Lecture 1: Inflammatory and Infectious Diseases of the Pericardium and Myocardium

Pericardium: made of visceral and parietal pericardium

 Visceral pericardium is the epicardium
o Made of mesothelial cells over a thin layer of fibro-elastic CT connected to myocardium by adipose tissue
 Parietal pericardium is the fibrous sac
o Inner serous layer  made of mesothelial monolayer
o Outer fibrous layer  made of fibro collagenous tissue
 Pericardial fluid  normally 30-50cc of thin clear straw-colored fluid
Causes of Pericarditis:
 Infectious  MOST COMMONLY VIRUSES, bacteria, tuberculosis, fungi, parasites
 Immunological
o Rheumatic fever [Group A strep: strep pyogenes can lead to this; has molecular mimicry initiated an autoimmune response]
o Systemic Lupus Erythematosus
o Scleroderma
o Postcardiotomy [some heart surgery and autoimmune reaction to that]
o Postmyocardial Infarction [Dressler] syndrome
 Occurs weeks after an infarction and usually after a transmural infarction
o Drug hypersensitivity
o Uremia
o Neoplasia
o Trauma
o Radiation
Pericardial Effusions
 Can be serous, blood, pus
 Slowly accumulating effusions
o The pericardium slowly stretches and can accumulate large volumes [can get up to 500cc]
 Acute accumulations of fluid
o Occurs after myocardial trauma or aortic dissections leading the hemopericardium
o These acute changes may result in cardiac tamponade at lower volumes in which the pressure of the fluid around the heart prevents the heart from filling with
blood
 Reducing cardiac output
Pericarditis:

Serous Pericarditis  serous fluid [[rarely any fibrous adhesions occurring]

 Typically caused by a VIRAL infection, collagen vascular disease, uremia, tumors
-Hx of recent viral illness
 Mild inflammatory response in the EPICARDIAL FAT with lymphocytes [mononuclear infiltrate]
Symptoms: Clinical Findings:
- Pleuritic substernal chest pain - Low grade fever, tachycardia, and atrial ectopy
- Worse in the supine and lateral left decubitus - ST segment elevation
position - Severe effusion: low QRS voltage and electrical
- Better when sitting upright alternans and “water bottle heart” on imaging
- Electrocardiogram is the diagnostic imaging of
choice

Fibrinous and Serofibrinous pericarditis

- The MOST FREQUENT type of pericarditis
- Pericardial friction rub***
- Commonly caused by: acute MI, Dressler’s, uremia, radiation, surgery, rheumatic fever, SLE, trauma
Fibrinous: more fine, granular appearance

Shaggy
rough Strands of
looking and the fibrin
rough [not attaching the
nice mesothelium
smooth
and
glistening]

Microscopically, the pericardial surface here shows strands of

pink fibrin extending outward. There is underlying
inflammation. Eventually, the fibrin can be organized and
Serofibrinous: more inflammatory infiltrate [RBCs and Leukocytes] plus the fibrin yellow brown turbid fluid cleared, though sometimes adhesions may remain.
Purulent or Suppurative pericarditis [think neutrophils]
- Caused by
 Extension from an empyema (a collection of pus in the pleural cavity caused by bacteria), pneumonia, mediastinal infection, or ring abscess of the heart (valves)
 Pericardial seeding from a bacteremia
 Lymphatic extension
 Direct introduction through procedure
- Reddened, granular serosal surface coated with exudate
- Fibrinous exudate with acute inflammatory response [NEUTROPHILS]
- It can infiltrate the mediastinum  mediastinoperidcarditis
- Can also lead to constrictive pericarditis or scarring

Nice layer
of fat,
don’t see a And
fibrinous
lots of
heart here fibrin bugs
but
purulent

Hemorrhagic
fibrinous
pericarditis 
yellow film you
can see some
pus mixed in
with the fibrin Gram +
[would see diplococci
neutrophils and [strep
pneumo]
bacteria on a
histological slide]

Hemorrhagic pericarditis- blood mixed with a fibrinous or purulent effusion

 Caused by: tumors, bacterial infections, bleeding, disorders, post-surgical

• The pericarditis here not only has

fibrin, but also hemorrhage.
Thus, this is called a
"hemorrhagic pericarditis". It is
really just fibrinous pericarditis
with hemorrhage.

• Without inflammation, blood in

the pericardial sac would be
called "hemopericardium”.

Chronic or healed pericarditis

 Mild healed pericarditis: “soldiers plaque” plaque like fibrous thickening of the epicardium [commonly seen on autopsy] few thin delicate adhesions from sac to epicardium
 Adhesive pericarditis: delicate stringy adhesions completely obliterate the pericardial space with NO FUNCTIONAL interference

 Adhesive mediastinopericarditis : pericardial sac obliterated and adhesions of external sac to surrounding mediastinal structures
 Increase the workload of the heart with systolic retraction of the rib cage and diaphragm

 Constrictive Pericarditis: heart is encased in a dense, fibrous, or fibrocalcific scar, that may be up to 1.0 cm thick with obliteration of the pericardial space [may resemble
a plastic mold]
 Limit diastolic expansion and cardiac output [cardiac output may be reduced at rest and not adjust to increased demand when not
at rest]
 Cardiac hypertrophy and dilation CANNOT OCCUR
 Caseous pericarditis [#1 is TB, and can be other fungal causes]
 Results in constrictive pericarditis [heart cannot expand because of the fibrotic band around the heart

Positive acid-fast stain

for Myocabacterium
[bacilli]

 Waxy
bacterium this
is why they
stain pink

Myocarditis = NON- ischemic myocardial inflammation

 Causes: Infections, immune mediated and unknown
o An inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with
coronary artery disease
Viral Myocarditis: in the US is the most common cause of myocarditis
 Direct myocardial injury caused by the virus or an immune response injury
 Coxsackieviruses A and B (picornoviruses) and other enteroviruses are most common
 Adenovirus, CMV, influenza, echoviruses, HIV, Hepatitis C in Japan, and Parvovirus
Clinical findings: Treatment:
 Recent febrile illness followed by  Supportive care
chest pain  angina-like chest pain,  Pharmacological intervention and
dyspnea, or arrhythmias hemodynamic support [if there is left
 Elevated troponin levels ventricular dysfunction)
Necrosis of the myocardiocytes  Immune mediated 
 Increased viral titers immunosuppressive drugs
 Endomyocardial biopsies [but only
reveal a dx ~10-20% of the time]

Lymphocytic infiltrate with

myocyte necrosis

-Most people do actually

survive this and may end up
with a dilated cardiomyopathy
or chronic ventricular
dysfunction and that is what
kills you [arrhythmic death]

May have to get a heart

transplant
 Other infectious diseases
 Bacterial
- Lyme disease [Borrelia Burgdorferi: spirochete]: from deer ticks [rodents to people via the ticks (ixodes scapularis)]; northeast and midwest USA
- Myocarditis occurs ~5% of the time with conduction abnormalities and may require a temporary pacemaker
- Skin, CNS, joint, and cardiac manifestations [target lesion of erythema migrans]
- Corynebacterium diphtheriae: toxin mediated
- Neisseria meningitides
 Protozoa
- Chagas Disease [trypanosoma cruzi]: caused by an intracellular protozoa
- Endemic in parts of Central and Southern America
- Transmitted to humans through via feces breaks in the skin from “kissing bugs” [reduviid bugs]
- At the site of entry, may get a chagoma, if around the eye = Romano’s sign (transitory red nodule)

T. cruzi amastagotes in
the cardiomyocytes

-serological testing for

antibody, PCR, or
immunohistochemistry
can be used to detect
T.cruzi [though a
negative result does not
rule out infection

Acute Chagas: Chronic Chagas:

 Rarely have acute myocarditis
 With clusters of amastigotes in the myocardial fibers
[intracellular pseudocysts]
 Myocardial necrosis and extensive inflammation
 Immune mediated dilated cardiomyopathy with chronic inflammatory
infiltrates histologically
- RBBB and/ or left anterior fascicular block can occur
 Colon and esophageal dilations  destruction of the mesenteric plexus =
megacolon and megaesophagus
 Usually develops 5-5 years after the initial infection

 Immune mediated myocarditis

o Systemic Lupus Ertyhmatosis  pancarditis
o Drug hypersensitivity [methyldopa, thiazides, sulfonamides [infiltrate composed of eosinophils and mononuclear cells; predominantly locoalize to
perivascular and expanded interstitial spaces]

o Post viral
o Rheumatic fever [post streptococcal]
o Transplant rejection
 Unknown causes
o Giant cell myocarditis
- Wide-spread inflammatory cellular infiltrate containing multinucleate giant cells interspersed with lymphocytes, eosinophils, plasma cells, and macrophages

o Sarcoidosis
 Other causes
o Hyperthyroidism and hypothyroidism
o Direct drug toxicity [catecholamines, cocaine with scattered foci of myocardial necrosis with contraction bands often associated with a sparse mononuclear
inflammatory infiltrate mostly of macrophages
o Takotsubo cardiomyopathy [sudden intense emotional stress can induce an acute left ventricular dysfunction due to myocardial stunning]
o Amyloidosis
o Iron overload

Lecture 2 Myocarditis, Pericarditis, and Endocarditis Infectious Agents

Myocarditis - Inflammation of the myocardium
 Major cause of sudden death in adults less than 40y/o
 Variable disease presentation, most often ASYMPTOMATIC (no left ventricular dysfunction)
 Fever, malaise, fatigue, arthralgias, myalgias, and skin rash
 Heart symptoms result from diastolic of systolic ventricular dysfunctions  tachyarrhythmias and bradyarrhythmia’s
 Dyspnea, fatigue, decreased exercise tolerance, palpitations
 Chest discomfort is common [35%]; typically pericardial in nature – heavy, dull ache because of the viral replication
 Systemic and pulmonary thromboemboli have also been noted
 40 % of people who die from a myocarditis infection has an infection with Coxsackie B [picornovirus that is stable in the environment]

Outcomes: Pathogenesis [Triphasic Disease]

1. Early death due to multisystem failure fulminant
myocarditis] 1. Phase I: Viral Infection and Replication
2. Ventricular arrhythmias - Direct injury to cardiomyocytes by the viral infection [due to viral lysis of the
3. Complete recovery [spontaneous ~50-57% of the time] infected cells]
4. Long-term evolution to Dilated Cardiomyopathy - Often goes unnoticed and is limited by an effective immune system
2. Phase II: Autoimmunity and Injury
Physical Exam findings - The protective immune response becomes dysregulated
 Tachycardia, hypotension, fever of unknown origin - This is triggered by the initial cardiomyocyte damage and now both the cellular
- The tachycardia may be disproportionate to the degree and humoral response begin to induce damage
of fever - Molecular mimicry
 Bradycardia is possible but not commonly seen [HR <60) (streptococcus pyogenes has molecular mimicry)
 Narrow pulse pressure - During this phase, cytokines activate the matrix metalloproteinases
 Murmurs of mitral or tricuspid regurgitation, S3 or S4 gallops [gelatinase, collagenase, and elastase]
may also be heard 3. Phase III: Dilated Cardiomyopathy
 Distended neck veins, pulmonary crackles, wheezes, gallops, - The viruses may also cause myocyte apoptosis
and peripheral edema may be detected [may see a sock line - In the later stages of immune activation
on their legs or an imprint of their watch]  Cytokines play a leading role
 Adverse remodeling and progressive heart failure
- Cardiomyopathy developed despite the absence of viral proliferation
Endomyocardial Biopsy [EMB] (was correlated with the elevated levels of cytokines*** such as TNF)
- GOLD STANDARD for diagnosis of myocarditis
- Has risks, so routine use is not recommended, it is
usually reserved for those with severe symptoms
- Multiple clippings needed
1. Because it has limited sensitivity and specificity
2. Sensitivity increased with multiple biopsies
[standard is 4-5 biopsies]
3. Risk of false negatives (55%)
4. Risk of false positives [due to lymphocytes in the
myocardium or difficulty differentiating between
cell types]
5. Wide observer variability in histologic
interpretations
6. Only 25-50% of biopsies contain viral mRNA
7. If the mRNA is present, often confers a poor
prognosis
- For patients with unexplained new onset heart failure
<2 weeks duration [fulminant]**
- Normal sized or dilated left ventricle [in addition to
hemodynamic compromise]
- Early AV block, arrhythmias, or refractory heart failure
 Recommended with unexplained onset [2weeks Heart failure with eosinophilia has a poor prognosis
to 3 months that does not respond to usual
therapy]
Dallas Criteria (not the gold standard, but used more often because Imaging:
it is less invasive)  Echocardiography
1. An inflammatory infiltrate of the myocardium - To exclude other causes of heart failure
2. Positive for injury to adjacent myocytes - Evaluate the degree of cardiac dysfunction [usually slow due to decreased
3. Borderline myocarditis is made when the infiltrate is elasticity [hypokinesis and diastolic dysfunction]]
not accompanied by myocyte injury  Allow gross localization of the extent of inflammation
Laboratory results  May distinguish between fulminant and acute myocarditis
- CBC- leukocytosis *Fulminant myocarditis: increased septal thickness in fulminant myocarditis with marked
 May have increased eosinophils [>450/microL) improvement in systolic function in time
- Elevated ESR & C-reactive protein *Acute myocarditis: increased left ventricular diastolic dimensions and normal septal thickness
- Rheumatological screening to rule out systemic  Electrocardiogram
inflammation
- Often non-specific [sinus tachycardia, nonspecific ST or T-wave changes]
- Elevated Creatine Kinase or cardiac troponins [Troponin
- Occasionally will see a heart block [may indicate poorer prognosis]
I or T elevated in 50% of patients]
- Arrthymia is common in Chagas disease [RBBB with or without bifascicular
- Serum viral antibody titers for viral myocarditis
[coxsackie B, HIV, Hepatitis B & C, CMV, influenza, EBV] block]
 Rarely indicated because of the delay in rise -
Normal borderline active myocarditis
of the viral titers and its low specificity
 It also does not impact therapeutic
decisions
 The presence of viral genome on EMB lacks
specificity because they can also be found
in healthy controls
 The most common viral genomes found
[parvovirus and herpes simplex]
Endocarditis : inflammation of the endocardium [usually refers to infection of the valves of the heart]
 Subactute (slower and less pronounced symptoms; may have large spleen), or acute (more severe and quick)
 Fever, anemia, abnormal heartbeat  sometimes appearing similar to a heart attack
 Abdominal or side pain may be reported
 Petechiae over the upper half of the body and under the fingernails may be present
 HIGH mortalitly rate (20-50%)
 Frequent causes include mitral valve prolapse, aortic sclerosis, and bicuspid aortic valvular heart disease
 FEVER OF UNKNOWN ORIGIN + murmur *****
 Splinter hemorrhages, Osler nodes, Roth hemorrhages, and Janeway lesions

Duke criteria: must have one of the major criteria and 3 minor criteria
– Two major criteria
• Typical organism [staph strep bacteremia]
• Persistent bacteremia
• Positive serology for Coxiella brunetii [most infectious organism,
only needs 1]
• Positive echocardiographic results for vegetations, abscess, or
valve
– Positive culture or histology of a vegetation or intracardiac abscess
dehiscence
– Five minor criteria
• Valvular heart disease
• History of IV drug abuse
• Fever higher than 38° C (100.4 ° F) of unknown origin
• Vasculitis, skin lesions; little ecchymoses
• suggestive echocardiographic results (but not definitive)
• Single positive blood culture

Septicemias (often termed bacteremia)

 Occurs when organisms are actively multiplying in the blood [most often bacteria, but can be fungi)
 FEVER is the prominent symptom
 Patients appear very ill and may have:
- Altered mental state
- Shaking chills
- GI symptoms
- Increased breathing rate and respiratory alkalosis
- Low blood pressure [hypotension and hypovolemia]
 Most often caused by gram negative bacteria  they have LPS [Lipid A]  triggering an inflammatory response and leading to endotoxic shock

Sepsis
• 50-62% gram negative
• E. coli, Klebsiella sp, and Pseudomonas are most common
• 37-47% gram positive
• Staphylococcus aureus, Streptococcus pneumoniae, coagulase negative
staphylocci and Enterococus sp.
• 5% anaerobes [smell]
• Bacteroides fragilis, Clostridium sp, generally polymicrobial
• 8-19% fungi
• Candida sp. Also Cryptococcus, Coccidioides, Fusariu, and Aspergillus
• Risk Factors: abdominal surgery, poorly controlled diabetes mellitus,
prolonged granulocytpoenia, broad spectrum ABX, corticoid steroid tx,
prolonged hospitalization, central venous catheter, TPN, hematologic
malignancy
Infectious Causes of Myocarditis Infectious causes of endocarditis
Viral = MAJOR CAUSES of myocarditis and dilated cardiomyopathy Native valves (normal valves)
1. Coxsackie virus, mainly B[50%] [picornoviridae  enterovirus] 1. Oral streptococcus #1 (enterococcus)
- ssRNA +, no envelope, vesicular lesion on hand foot and mouth a. Catalase negative
disease 2. Staph aureus
- Enters cardiomyocytes and macrophages and Cleaves host proteins - Coagulase positive
by the production of viral proteases 2A - Catalase positive
 Induce an immune response and migration of immune cells 3. Staphylococcus epidermidis, saprophyticus
into the cardiac tissue - Coagulase negative
- Mouth is the portal of entry - Catalase positive
- Spread to heart, CNS, lungs, and skin
 Pericarditis, myocarditis, neonatal myocarditis, pleurdynia
 Pleurodynia: abrupt onset of fever and severe abdominal  GAS: pyogenes [beta hemolytic] 
and chest pain molecular mimicry, M-protein, rheumatic
- Incubation period is 1-2 weeks and the virus is shed from the fever
throat for 1 week and feces for 3 weeks  GBS: aglactiae [beta hemolytic &CAMP +]
- Fecal oral transmission  HANDWASHING!!!!  Viridans streptococcus: step mutans and
- Supportive care and analgesics for the myocarditis inflammation
2. ECHO [enteric cytopathic enteric orphan picornavirus] strep sanguis [dental carries  valve
3. Adenovirus disease]
4. Parvovirus B18 (fifths disease): face slap rash  Strep pneumo
5. HHV6 (human herpes virus 6)  goes latent  Staph and strep are associated with
6. Influenza/ paramyxovirus [more likely to die in the elderly and more BIOFILMS on the valves
likely to get in the very young] Gram negative
- SsRNA-negative, helical, enveloped
- F protein [fusion of the viral envelope with the cell] grow on
- HN protein [hemagglutinating/neuraminidase] 4. HACEK
- Responsible for the development of croup - Gram negative rods McKonkey’s
(barking cough, stridor, wheezing)
7. CMV / herpes viridae[can be reactivated after a transplant later in life]
agar!!!!
- dsDNA, linear, envelope of inverted repeats
- intranuclear inclusion (owl’s eye)
- cotton wool spots (retinitis in AIDS)
- hepatosplenomegaly and microcephaly is congenital (pregnant
woman)
8. 50% of HIV patients have myocarditis on autopsy
- Clinically silent : if symptomatic  chest pain and cardiomegaly
- Unspecified myocarditis and lymphocytic infiltration of the
myocardium
- Pericarditis is usually non-specific [Kaposi sarcoma,
mycobacterium TB, Cryptococcus neoformans]
- Tx: diuretic, ACE inhibitor, ARB, beta blocker
Bacterial
1. Corynebacterium diphtheria
- Gram positive bacillus
 Eikinella corrodens smells like bleach
- Club shaped [Chinese characters]
 Most common cause of gram negative endocarditis in NON-
- Not acid fast and NO CAPSULE
IV drug users
- EXOTOXIN
5. Candida
- Grey/black pseudomembrane  asphyxiation IV Drug user
- Bulls neck from edema 1. Staph aureus #1
2. Neisseria meningitidis 2. Oral strep (enterococcus)
- Gram negative diplococci, oxidase positive, aerobe, superoxol 3. HACEK
negative 4. CANDIDA
- Grows on chocolate agar 5. Coagulase negative staphylococcus
- Ferments glucose and maltose on CTA Prosthetic valves [early]
3. Borrelia burgdorferi 1. Coagulase negative staphylococcus #1
- Gram negative Spirochete - Epidermidis, saprophyticus, and pyogenes
- Ticks from the NE 2. Staph aureus
- Circular target/bulls eye rash/Erythema chronicum migrans 3. HACEK
- Bells palsy 4. Oral streptococcus and enterococcus
- Migratory arthritis 5. Candida
Fungal Prosthetic valves [late]
1. Candida [not common, usually immunosuppression allowing it to go 1. Oral streptococcus #1 (enterococcus)
systemic) 2. Coagulase negative staphylococcus
Protozoan 3. Staph aureus
1. Trypanosoma cruzi 4. HAECEK
- Transmitted through feces of the Triatomid bug 5. Candida
- Parasites prefer to infect cardiac, smooth, and skeletal muscle
- The parasites DO NOT undergo antigenic variation [no cyclic fever HACEK group infections
= not remitant]
- Cardiomyopathy (heart dilates)  CHF and GI megacolon and
megaesophagus due to damage of the autonomic nervous system
Metazoan
1. Worms  trichonella (eating undercooked meat)
Lecture 3: Pharmacology of Cardiovascular Infectious Disease
Amoxicillin
Cephalexin
Clindamycin
Azithromycin
Vancomycin; renally cleared
Gentamicin
Rifampin: potent in vitro anti-staphylococcal activity; effective against things adherent to foreign material
 Resistance develops quickly if used alone so use it with vancomycin
 Potent CYP inducer: things that are metabolized by CYP will be metabolized more quickly and you will see symptoms of the disease
Daptomycin: gram + only ; binds cell membrane causing depolarization, disruption of functions and death; renally cleared
 MSSA/MRSA skin infections or bacteremia and right sided endocarditis [inactivated by pulmonary surfactant so it CANNOT BE USED FOR PNEUMONIA]
 Usually use when someone is Vancomycin resistant
 ADE: myopathy (monitor CK levels) and nerve conduction deficits
Ceftriaxone
Levofloxacin

Dental Prophylaxis: viridans streptococcal (mutans and sanguis) can cause endocarditis post dental work [anything that involves manipulation of gingival tissues of periapical region of
teeth or perforation of oral mucosa]
 High risk patients:
- Prosthetic valce
- Previous infectious endocarditis
- Congenital heart disease
- Cardiac transplant recipients
 TX:
- Amoxacillin oral [if unable to take oral ampicillin or cefazolin or ceftriaxone]
- If allergic to penicillin [type I reaction]  clindamycin or azithromycin [NO CEPHALOSPORINS!!!] Clindamycin  overgrowth of C. diff
- If allergic to penicillin but not type I reaction  cephalexin or clindamycin or azithromycin
Endocarditis treatment [empiric therapy]
1. Vancomycin + ceftriaxone OR vancomycin + gentamicin [gentamicin covers gram negative]
2. Vancomycin or possibly daptomycin  gram + only [IV Drug users or MRSA spiders]
3. Vancomycin + gentamicin + rifampin
- Rifampin is generally used later to decrease the likelihood of emerging RESISTIANCE so susceptibility to resistance should be there before rifampin is
required
- Highly skilled at killing staph and things attached to devices

Pharmacokinetic in Critically ill patients

 Sepsis can affect drug distribution
 Vd (volume of distribution) can be increased [because of fluid accumulation from leaky capillaries and/or altered protein binding]
- Hydrophilic antimicrobials (aminoglycosides, beta lactams, carbapenems, and vancomycin)can result in lower peak serum concentrations with usual
disease
- They go where water goes so they are no longer circulating, instead the drugs are sitting in tissues
 As sepsis progresses, organ perfusion decreases  significant myocardial depression and multiple organ dysfunction
- Decreased clearance of antimicrobial agents, prolonged elimination half life and accumulation of metabolites

See Think DO NOT Think

Methicillin-
Oxacillin, nafcillin, dicloxacillin, cloxacillin, amoxicillin-clavulanic acid, cefazolin or
sensitive Staphylococcus Amoxicillin, ampicillin, ceftriaxone or vancomycin
cephalexin
aureus (MSSA)
Methicillin- Sulfamethoxazole-trimethoprim doxycycline, tigecycline, clindamycin, vancomycin,
Ceftriaxone, piperacillin-tazobactam, cefepime, carbapenems or
resistant Staphylococcus daptomycin, telavancin, dalbavancin, oritavancin, ceftaroline, linezolid, tedizolid or
fluoroquinolones
aureus (MRSA) quinupristin/dalfopristin

Pan-sensitive Enterococci Ampicillin or amoxicillin Vancomycin

Ampicillin-resistant Enterococci Vancomycin –

Vancomycin-resistant Enterococci
Daptomycin, linezolid or tigecycline Vancomycin
(VRE)

Beta-hemolytic Streptococi Penicillin –

Alpha-hemolytic Streptococci
Pseudomonas aeruginosa
Ceftriaxone, levofloxacin, amoxicillin-clavulanic acid [beware penicillin & azithromycin
resistance] –
Piperacillin-tazobactam, ceftazidime, cefepime, ceftazidime-avibactam, ceftolozane-
tazobactam, meropenem, doripenem, imipenem-cilastatin, aztreonam, ciprofloxacin, Tigecycline, ertapenem or moxifloxacin
levofloxacin, amikacin, gentamicin, tobramicin, polymyxin E (colistin), polymyxin B

Stenotrophomonas maltophilia Sulfamethoxazole-trimethoprim or levofloxacin Carbapenems

Metronidazole, clindamycin, ampicillin-sulbactam, amoxicillin-clavulanic acid,

Anaerobes Cefazolin, ceftriaxone or cefepime
piperacillin-tazobactam, cefoxitin, cefotetan, moxifloxacin or tigecycline
Clostridium difficile Metronidazole, oral or rectal vancomycin, or fidaxomicin Intravenous vancomycin

Atypical organisms Macrolides or fluoroquinolones –

Candida albicans Fluconazole Echinocandins or amphotericin B
Candida krusei Echinocandin Fluconazole

Cryptococcus neoformans Amphotericin B, fluconazole –

Aspergillus sp. Voriconazole –
Lecture 4: Congenital Heart Disease
 Congenital Heart disease: abnormalities of the heart or great vessels which are present from birth
o 85% of infants born with CHD reach adulthood
 Lesions which may not be detected in childhood and present later in life
 Bicuspid aortic valve [most common]
 Secundum atrial septal defects
 Coarctation of the aorta
 Ebstein anomaly of the tricuspid valve
 Congenitally corrected transposition
 Coronary artery anomalies
o Environmental factors alone or in combination with genetic factors causes or contributes to the development of CHD:
 congenital rubella infection
 exposure to teratogens including therapeutic drugs
 folate deficiency
 MATERNAL DIABETES
 Categories of CHD in adults
o Survive to adulthood with NO intervention
o Survive to adulthood with curative surgical or nonsurgical intervention
 Nonsurgical intervention includes: valvuloplasty (the younger the better), stenting, occlusion device for septal defects and PDA
o Survive to adulthood with palliative surgical or nonsurgical intervention

Obstructive 1. Congenital aortic stenosis [mostly bicuspid aortic valve]

cardiovascular defects in  The most common congenital heart anomaly in adults
adults  Usually occurs in the form of a bicuspid aortic valve in adults
- Congenital AS may be subaortic, supra-aortic or valvular
 More common in males
 Complications:
- Mildly obstructed nonlaminar (disturbed flow or turbulent) flow across the abnormal valve.
- Progressive wear and tear will cause calcification and progressive stenosis or regurgitation.
 LV hypertrophy with increased pressure load
 High-velocity jet of blood through stenotic lesion may impact aortic wall causing dilation and/or dissection
- Endocarditis risk.
- Bicuspid valve associated with coarctation of aorta.
 Pathologic findings in bicuspid valve
- Raphe caused by commissural fusion of two leaflets
- Valve is dysplastic with thickened rolled and calcified leaflets
 Symptoms
- Asymptomatic unless there is a significant amount of stenosis and/or regurgitation
- If there are symptoms: [poor prognosis when symptomatic; need valve replacement]
 Chest pain
 Dyspnea
 Exertional syncope
 There will be abnormal heart sounds on physical exam
2. Pulmonary valve stenosis
 Many are mild and require no treatment.
 May co-exist with other cardiac anomalies (ASD, VSD, PDA or tetralogy of Fallot).
 Associated with Noonan syndrome (an autosomal dominant heterogeneous malformation syndrome)
- Isolated congenital stenosis due to bicuspid valve in 20% of cases
- Dysplastic valve with myxomatous changes and severe thickening in 10% of cases.
- Abnormal trileaflet valve in remaining.
- May be associated with subpulmonic stenosis.
- May have post-stenotic dilation of pulmonary artery due to injury to the wall by jetting of blood.
 Symptoms
- Asymptomatic
- Exercise intolerance [exertional fatigue, dyspnea, cheat pain, or syncope]
- RV hypertrophy with failure late in disease
- Physical exam shows systolic murmurs and clicks
- Right heart failure if severe and untreated
 25 year survival is greater than 95%
 Tx with valvuloplasty
3. Coarctation of the aorta
 A congenital narrowing or constriction of the aorta.
 Secondary cause of HTN in 20’s and 30’s.
 Predominates in males but seen in Turner’s syndrome (45XO karyotype).
 Coexisting defects may include congenital mitral valve disease, saccular or berry aneurysms of the circle of Willis (25%), and
bicuspid aortic valve.
 Two classic forms
- Infantile
 Pre-ductal with tubular hypoplasia of the aortic arch proximal to a patent ductus arteriosus [usually
symptomatic early in life]
- Adult
 Juxta-ductal, post-ductal, or middle aortic form with a distinct ridge like infolding of the aorta opposite
the ligamentum arteriosum distal to the subclavian
 Complications
- HYPERTENSION results from decreased vascular compliance in the proximal aorta and activation of the renin-
angiotension system in response to renal hypo-perfusion.
- May result in left ventricular hypertrophy and CHF in longstanding hypertension.
- Additional complications generally occurring between ages 14 and 40 are aortic dissection or aneurysm, infective
endarteritis at coarctation, cerebral hemorrhage from berry aneurysm, premature coronary artery disease.
 Dx:
- Elevated systolic BP in the arms [always in the right] and reduced in lower extremities and sometimes in left arm
- Radial femoral pulse delay
- A late systolic murmur is present, best heard between the scapulae to the left of the spine
- Rib notching and 3 sign on CXR, possible LVH
- Imaging of the aorta
 Tx:
- Surgery after age 15 may be problematic due to aortic atherosclerosis and large intercostal aneurysms near the aortic
shelf
- 50% of those with uncorrected coarctation  50% die
 Symptoms
- Asymptomatic
- Symptoms of CHF from long-standing HTN, exertional dyspnea, leg fatigue
- In infancy:
 With PDA, unsaturated blood going into the distal aorta may cause lower body cyanosis
 If ductus closes, development of sudden CHF is possible
Left to Right Shunts 1. Atrial Septal Defects
 Abnormal fixed opening in the atrial septum due to incomplete tissue formation with communication of blood flow between the
atria.
 Ostium secundum defect in the region of the fossa ovale (90% of ASD’s) with female predominance.
 This defect arises from inadequate formation of the septum secundum, excessive resorption of the septum primum, or a
combination
 Ostium primum are defects in the lower portion of the septum and are part of AV (atrioventricular) canal defects.
 Sinus venosus defects are in the upper part of the septum near the superior vena cava (SVC) entrance and may have an associated
anomalous pulmonary venous return to the right atrium or SVC.
 ASD association with disease
- Down’s syndrome: secundum or primum with AV canal defect
- Holt-Oram Syndrome: ASD and limb defects
- Familial ASD: with associated atrioventricular conduction abnormalities
 Pathophysiology of ASD
- Left to right shunt with pulmonary blood flow being up to 2 to 4 times greater than normal.
- Murmur results due to increase blood flow through the pulmonary valve.
- Development of irreversible pulmonary hypertension is unusual.
 Clinical for secundum ASD
- Usually asymptomatic until adulthood and present in the 3rd or 4th decades of life.
- Exertional dyspnea and atypical chest pain.
- Right sided heart failure.
- With increasing age, may have atrial arrhythmias.
- Physical exam shows fixed split S2 and systolic ejection murmur caused by increased flow across the pulmonic valve.
 Complications
- Pulmonary hypertension with right heart failure
- Paradoxical embolization
- Atrial arrhythmias
 Treatment
- Closure in adult is based on size and type of defect
- Closure of ASD reverses the hemodynamic abnormalities and prevents complications of irreversible pulmonary
hypertension.
- Need repair if history of cryptogenic TIA or stroke.
 Because of the paradoxical emboli forming and travelling through the patent openings
- Transcatheter closure of a secundum ASD.
 Prognosis
- Survive to adulthood and once they reach 40 they have a decreased life expectancy
- Pulmonary systolic pressure > 40mm at the time of surgery have poorest survival rate [especially if older]

2. Patent foramen ovale

 The flap of tissue covering the fossa ovale is forced shut at birth and remains permanently closed in 80% of people.
 In patent foramen ovale, this flap of tissue may be forced open if right atrial pressure exceeds left atrial pressure.
- Pulmonary hypertension may cause it to open or even transient increases in pressure caused by coughing, sneezing,
bowel movement.
 Risk of paradoxical embolism.
 Primary closure is indicated only if anticoagulation therapy has failed or is ineffective or if there are contraindications to
anticoagulation.
3. Ventricular septal defects
 Defect in the ventricular septum allowing communication of blood between the left to right ventricles.
 Most common congenital heart defect at birth frequently associated with other cardiac anomalies like Tetralogy of Fallot while
20 to 30% are isolated.
 Usually hemodynamically significant VSDs diagnosed and repaired prior to adulthood.
 The ones that may remain undetected until adulthood are small.
 Large VSDs cause significant left to right shunting increasing chance of irreversible Pulmonary HTN.
 3 groups in adults:
- First group with small asymptomatic VSDs.
 Minimal to no left to right shunt
 Loud pansystolic murmur
 Frequently don’t need surgery, depends on pulmonary vascular resistance.
 Need bacterial endocarditis prophylaxis.
- Second group with moderate sized defect with a combination of pulmonary hypertension and left sided volume
overload (may develop systolic LV dysfunction and dilation) because of significant left to right shunt.
- Third group are surgically uncorrected large VSDs with Eisenmenger’s complex
 A large left to right shunt causes irreversible pulmonary hypertension with resultant right to left shunt
and cyanosis developing before puberty).
- Not surgical candidates if severe pulmonary HTN already present.
- A right to left shunt may develop causing cyanosis when pulmonary vascular resistance exceeds systemic vascular
resistance.
 Other complications
- Bacterial endocarditis [ALL VSDs need prophylaxis]
- Valvular problems
- Rhythm disturbances after surgical closure of VSDs

4. Patent ductus arteriosus

 Remnant of normal fetal circulation, usually closes at birth.
 Uncommon in adults with continuous machinery like murmur.
 Complications are:
 Heart failure from pulmonary overcirculation.
 Eisenmenger’s syndrome.
 Infectious endarteritis (may occur even with tiny defect)
 Need to close surgically or by transcatheter methods unless pulmonary hypertension is too far advanced
 In infants, can close with IV administration of anti-prostaglandin; indomethacin or ibuprofen administration

5. Congenitally corrected transposition of the great arteries (C-TGA)

 Rare.
 The right and left ventricles are switched; however, because the aorta and pulmonary artery are still properly providing blood to
the systemic and pulmonary circulations respectively this lesion is acyanotic and may not present unless there are complications
in adulthood or associated heart anomalies.
 Associated anomalies are VSD and valvular anomalies
 Complications:
- Complete heart block
- Systemic ventricle becomes hypertrophied and may develop failure
- Surgery
Ebstein’s Anomaly  Characterized by deformity of the tricuspid valve with apical displacement of the septal and posterior leaflets and their adhesion to the right
ventricular wall.
Atrialization of the right  Anterior leaflet is “sail-like”.
ventricle  Right ventricle proximal to the leaflets is atrialized.
 Right ventricle is small.
 ASDs are most common associated anomaly occurring in 80 to 90%.
 Clinical:
 May be asymptomatic or symptomatic because of supraventricular tachyarrhythmias associated with accessory pathways like
Wolf-Parkinson-White (WPW).
 Cyanosis (may be only exercise induced) due to right to left shunting across an ASD in the presence of tricuspid regurgitation or
elevated right atrial pressures.
 Older patients with long standing right ventricular volume overload and right atrial distention have heart failure.
 Prognosis and treatment
 50% chance of surviving to age 50, dependent on the degree of anatomic and physiologic abnormalities.
 Treated with tricuspid valve reconstruction or valve replacement.
 With exercise-induced cyanosis, closure of the ASD may be adequate.

Cyanotic Congenital  Usually, adults have had surgical intervention for cyanotic heart defects from childhood.
Heart Disease  Eisenmenger syndrome – development of pulmonary hypertension and shunt reversal in the presence of a congenital defect such as a VSD,
PDA, ASD (initially left to right shunt becoming right to left with cyanosis).
Tetralogy of Fallot (Blue baby)
 Most common form of cyanotic congenital heart defect.
 Four main features:
 Obstruction of the right ventricular outflow tract (subpulmonic stenosis from narrowing of the infundibulum
 Ventricular septal defect (VSD)
 An aorta overiding the VSD.
 Right ventricular hypertrophy.
 Most patients die in childhood without surgical intervention.
 Associated with DiGeorge syndrome – this chromosome 22q11.2 microdeletion present in 8 to 35% of patients with TOF.
 Subpulmonary stenosis:
 Clinical consequences of Tetralogy of Fallot (TOF) are dependent on the severity of the pulmonary arterial obstruction.
 Additional pulmonary obstruction can be from pulmonary valvular stenosis, complete atresia of the pulmonary valve and portions
of the pulmonary arteries.
 With severe or complete obstruction of pulmonary blood flow, survival is dependent on a patent ductus arteriosus and/or dilated
bronchial arteries.
 Clinical
 Childhood history of exercise intolerance with squatting.
 Cyanosis results from right to left shunt, may have clubbing of nailbeds
 May have “pink” Tetralogy of Fallot if only mild pulmonary obstruction.
- But can get spells of blue when they cry
 Pulmonic stenosis murmur if sufficient pulmonary blood flow.
 Mild RVH
 Surgery: anastomosis of the subclavian artery to the side of the pulmonary artery
Transposition of the great arteries (TGA)
 The aorta arises from the right ventricle and the pulmonary artery from the left ventricle.
 There is separation of the systemic and pulmonary circulation and is incompatible with life unless a shunt exists to mix the oxygenated with
unoxygenated blood.
 An infant with TGA and a VSD may have a stable shunt.
 If only a PDA and or patent foramen ovale, shunt may close physiologically and immediate surgical intervention needed.
 Prostaglandin E1 can be administered to keep the ductus arteriosis open****
Prognosis and treatment
 Without treatment, isolated transposition of the great arteries has a mortality of >90% in the first year of life but is better if infants have VSD
or large PDA or ASD.
 Treatment in the 1960’s was an atrial switch procedure to re-direct pulmonary and venous return (RV still supplies systemic circulation with
complications of failure along with arrhythmias.)
 Since the 1980s, an arterial switch procedure has been done which reestablishes the LV as systemic ventricle.
Systemic Complications of Chronic Cyanosis
 Secondary erythrocytosis with hyperviscosity when HCT is greater than 65%.
 Bleeding disorders with a variety of clotting factor deficiencies and qualitative and quantitative platelet disorder may be present.
 Iron deficiency due to bleeding or phleb0tomy.
 Neurologic complications including cerebral hemorrhage due to hemostatic defects and inappropriate anticoagulation therapy and
paradoxical cerebral emboli.
 Pulmonary complications from chronic hypoxemia with hemorrhage and arterial thrombosis.
 Renal dysfunction
 Rheumatologic including gout and hypertrophic osteoarthropathy, clubbing.
Lectures 5 & 6: Genetics
Familial Gene: LDLR
Hypercholesterolemia  Dysfunction of the LDL receptor results in an increase of LDL in the blood, leading to early CAD
Mode of Inheritance: Autosomal Dominant
 Homozygotes: make no normal LDL receptors
- Severe hypercholesterolemia at BIRTH and develop xanthomas by age 4
 Heterozygotes: make half the number of normal LDL receptors
- Usually asymptomatic until age 30-40
Liddle Syndrome Gene: SCNN1B or SCNN1G
 Encoding subunits the of the epithelium sodium channel (ENaC) preventing the degradation of the protein
 GAIN OF FUNCTION mutation
 Leads to increased sodium channels and hypertension and hypokalemia
Mode of Inheritance: Autosomal Dominnt
Features:
 Symptoms appear in childhood
Familial Gene: Fusion of CYP11B1 & CYP11B2 [chimeric fusion of 11 beta hydroxylase promoter to the coding region of aldosterone synthase]
Hyperaldosteronism Mode of Inheritance: Autosomal Dominant
Features:
“Glucocorticoid  Leads to retention of sodium and hypertension
remediable
aldosteronism
Marfan Gene: FBN-1 [either reducing the amount or function of fibrillin- 1]
 Decreased ability to sequester TGF-beta  increased cell growth
Mode of Inheritance: Autosomal dominant
 Variable expressivity
 No gender preference
 25% of cases arise from spontaneous mutations
Features:
 Aortic root aneurysm or dissection
 Ectopic lentis (abnormal lens position)
 Tall stature, arm length > height
 Arachnodactyly with joint hypermobility

Loeys-Dietz Gene: TGFBR1, TGFBR2, or SMAD3

 Loss of function mutations
Mode of Inheritance: Autosomal Dominant
Features:
 Similar to Marfan’s
 Aortic aneurysm
 Mitral valve prolapse
 Long fingers
 Chest wall deformities
 Dural ectasia
 NO ECTOPIC LENTIS
 Wide spaced eyes, cleft palate, bifid uvula, scoliosis, club foot, osteoporosis
 Cardiac symptoms are MORE SEVERE than Marfan
- Aortic rupture at an earlier age and at smaller aneurysm dimensions
Ehlers Danlos Gene: COL3A1
 Mutation in type III collagen
Mode of Inheritance: Autosomal Dominant
Features:
 Hyperextensible skin
 Hypermobile joints
 Fragile skin prone to easy lacerations
 Can cause rupture of the colon or large arteries
 Facial features: thin pinched nose, thin lips
Trisomy 21 Chromosome Abnormality: 3 copies of chromosome 21
Downs Mode of Inheritance: aneuploidy / trisomy’s
Features:
 Dysmorphic facial features
 Short neck
 Single transverse palmar crease
 Wide gap between 1st and 2nd toe
 Cognitive delay
 Hearing loss
Cardiac Abnormalities:
 ASD
 VSD
 PDA (patent ductus arteriosus)
Trisomy 18 Chromosome Abnormality: 3 copies of chromosome 18
Edwards Mode of Inheritance: aneuploidy / trisomy’s
Features:
Worse prognosis that  Intrauterine growth retardation  low birth weight
Downs  Malformations of the brain  intellectual disability, microcephaly, prominent occiput
 Low set ears that are rotated backwards
 Small mouth and chin
 “rocker bottom” feet  rounded plantar surface
Cardiac Abnormalities:
 Polyvalvular heart disease
 VSD
 AVSD
Trisomy 13 Chromosome Abnormality: 3 copies of chromosome 13
Patau Mode of Inheritance: aneuploidy/ trisomy’s
Features:
 Holoprosencephaly (failure of the brain development)
 Cleft lip/palate
 Renal abnormalities
 Cutaneous scalp defects
Cardiac Abnormalities
 Mostly VSD
 Distribution of the cardiac position
Turner Syndrome Chromosome abnormality: only 1 copy of the X chromosome (45,X)
Mode of Inheritance: Aneuploidy
Features:
 Short stature
 Webbed neck
 Gonadal dysgenesis
 NO INTELLECTUAL IMPAIRMENT
Cardiac Abnormalities:
 Bicuspid aortic valve (30%)
 Coarctation of the aorta
 Valvular aortic stenosis
 Mitral valve prolapse
 Left sided heart defects
DiGeorge Syndrome Genetic abnormality: 22q11.2 deletion
 One of the genes deleted includes a transcription factor in heart development: TBX1
Mode of Inheritance: Most common autosomal deletion [25-30 genes]
Features: “CATCH22”
 Cleft palate
 Hypocalcemia
 Thymic hypoplasia (no T-cells)
 Developmental delay
 Abnormal Facies
Cardiac Abnormalities: 80% will have a congenital heart defect
 Tetralogy of Fallot
 VSDs
 Interrupted aortic arch
Williams Syndrome Genetic abnormality: 7q11.23 deletion
Mode of Inheritance: deletion of about 17 genes
Features:
 “cocktail party” behavior
 Malar flattening
 Periorbital fullness
 Heavy sagging cheeks
 Short nose
 Poorly developed cupid’s bow on upper lip
Cardiac Abnormalities:
 More common in men with this syndrome
 1/3 of them are Supraventricular Aortic Stenosis and progresses with age
- Defects in ELN (elastin gene) most likely causes the SVAS
 Peripheral pulmonary artery stenosis
Noonan Syndrome Gene: PTPN11, SOS1, RAF1 (all encode proteins in the developmental pathways)
Mode of Inheritance: Autosomal Dominant
Features:
 Appears similar to Turner’s
- Short stature
- Distinctive craniofacial features
- DEVELOPMENTAL DELAY (one of the ways you can distinguish it from Turner’s)
- Bleeding disorders
- Skeletal malformations
Cardiac defects:
 Right sided heart defects (Turner’s is left sided heart defects)

Alagille Syndrome Gene: JAG1 or NOTCH2

 Genes involved in the Notch signaling pathway which is very important for development
Mode of Inheritance: autosomal dominant
Features:
 Abnormalities in the bile ducts  liver damage
 Facial features include prominent forehead, deep-set eyes, small and pointed chin
Cardiac Defects:
 Pulmonary artery stenosis
 VSDs
 Tetralogy of Fallot
Holt-Oram Syndrome Gene: TBX5
 LOSS OF FUNCTION
Mode of Inheritance: autosomal dominant
Features:
 Abnormal development of limbs
 Triphalangeal thumbs
 Carpal bone abnormalities
 Short forearm
 NO INTELLECTUAL DISABILITY
Cardiac defects:
 ASD
 VSD
 Cardiac conduction disease  bradycardia or fibrillation
Ellis-van Creveld Gene: EVC or EVC2
Syndrome  LOSS OF FUNCTION mutation disrupting the Sonic Hedgehog pathway
Mode of Inheritance: Autosomal RECESSIVE
 Common in the Amish population of Lancaster county, PA
Features:
 Dwarfism, polydactyly, abnormal hair and nails, dental abnormalities
Cardiac defects: 50% have congenital heart defects
 Common atrium [the absence of the interatrial septum]
- Due to failure of formation of septum primum and secundum

 Atrioventricular canal defect “endocardial cushion defect + atrioventricular septal defect”

- Abnormal valve and septum formation
- May be associated with Down’s and Ellis Van-Creveld

 ASD
 VSD

Dilated Genes associated with DCM:

Cardiomyopathy ***  MYH7 (B-myosin heavy chain)
 LMNA (lamina A/C)
 DMD (dystrophin)
Dilated cardiomyopathies can also be seen with mitochondrial conditions, metabolic, and other disorders
 Can follow ALL types of inheritance patterns
Muscular Dystrophy Gene: DMD
Mode of Inheritance: X-linked recessive
Features:
 Elevated creatine kinase levels in the plasma (>1000 U/L)
 Official dx by genetic testing
 Delayed motor skill development (walk at 18 months)
 Unstable gait
 Mean age of dx = 4y/o
 Gower maneuver to stand
Cardiac defects: 95% have some cardiac defect
 Dilated cardiomyopathy
 ECG abnormalities
Hypertrophic Genes associated with HCM:
Cardiomyopathy***  MYH7 (B-myosin heavy chain)
 MYBPC3 (myosin binding protein C)
 TNNI3 (Troponin I)
 TNNT2 (Troponin T)
Loss of function or missense mutations can lead to HCM
Long QT Syndrome Gene: KCNQ1, KCNH2, SCN5A (in order of most common to least common)
Channelopathy  Mutations in genes encoding ion channels
 Prolonged ventricular repolarization
Mode of Inheritance: Autosomal dominant
Short QT Syndrome Gene: KCNH2, KCNJ2, KCNQ1
Channelopathy  All encode potassium channel proteins
 Shortened ventricular repolarization
Mode of Inheritance: autosomal dominant
Features:
 Dizziness, syncope, cardiac arrest, death
 No other health problems associated with this syndrome

Wolf-Parkinson- Gene: PRKAG2

White Syndrome  Encodes AMP-activated protein kinase (AMPK)
 Very common in the Chinese population
Features:
 Widened QRS with delta wave, shortened PRI (<0.12)
Sick sinus syndrome Gene: Most commonly SCN5A (sodium channel protein) and HCN4 (potassium channel protein)
 May have increased risk of developing this syndrome with polymorphisms in MYH6 which encodes cardiac alpha myosin heavy chain
Mode of Inheritance:
Features:
 Intrinsic SA node dysfunction that causes inappropriate bradycardia
 Dizziness, confusion, or syncope
Catecholaminergic Gene: RYR2 (most common) ; CASQ2
polymorphic  Mutations involve intracellular calcium handling
ventricular  Arrhythmia induced by exercise or emotional arousal [delayed after-depolarizations]
tachycardia Mode of Inheritance:
(CPVT)  RYR2: autosomal dominant
- Encodes ryanodine receptor which form calcium channels
 CASQ2: autosomal recessive
- Encodes calsequestrin 2 involved in storage and transport of calcium
Brugada Gene: SCN5A
 Encoding sodium channel subunit
Mode of Inheritance: autosomal dominant
Features:
 Prominent ST elevation in leads V1-V3
 Determined as the same disease as SUDDEN UNEXPLAINED NOCTURNAL DEATH SYNDROME (SUNDS)
- Originally linked to the ASIAN population
Lecture 7: Congenital Heart Disease

 Congenital Heart disease= altered structural development of the heart from the third week of embryonic life which may be the result of the following factors:
o Abnormal structural development
o Failure of embryological progression
o Modification of flow pathway
o Rhythm disturbances
o Defects of contractility
 Congenital heart disease are the most common form of birth defects
 Risk factors
o MATERNAL DIABETES, family hx, rubella, toxoplasmosis, HIV, toxins, medication, substance abuse, genetic mutations
o Known cardiac teratogens
 Alcohol
 Hydantoin (anticonvulsant)
 Lithium (psychotropic)
 Thalidomide (antinausea)
Acyanotic 1. Atrial Septal Defect (ASD)
 Communication between the atria
Left to Right Shunts  Three types:
1) Most common type is secundum
2) Ostium primum – associated with Down’s Syndrome
3) Sinus Venosus
 Pathophysiology: LR shunt. Enlargement of right atrium and right ventricle.
 Remember blood flows areas of high resistance to areas of low resistance.
 Tx: Usually have no symptoms in childhood, now can be surgically closed in the cardiac catheterization lab without the chest being
opened; closure is needed to prevent right sided heart failure

2. Ventricular Septal Defect (VSD)

 Bacterial Endocarditis can develop due to communication between the ventricles
 About 50-75% of small VSD’s that are less than 5 mm, close spontaneously and require no intervention.
 Persons with larger VSD’s, have progressive heart failure between 6 weeks and 2 to 3 months of life.
 Tx: medicines may be used until surgical closure
- Peri-membranous VSD’s are the most common of all VSD’s.
- Harsh holosystolic murmur at LSB
- By age 2 50% of small or moderate size will close spontaneously
- Surgical correction during first few months if heart failure or pulmonary HTN

3. Patent Ductus Arteriosus (PDA)

 Connects the pulmonary artery to the aorta.
 Increased incidence in preterm infants
 ******Machinery like continuous murmur LUSB heard best at Left subclavicular area
 The patent ductus arteriosus undergoes functional closure at one day of life and anatomic closure at one week of life.
 Kid was doing great and then on day 3 is deteriorating, DO NOT GIVE FLUIDS
 Signs and symptoms:
- If a person presents with bounding pulses, (>30mm) widened pulse pressure and a continuous murmur, a chest x-ray and
echocardiogram should be obtained. Left ventricular hypertrophy will be present.
- Lower extremity cyanosis and clubbing if Eisenminger syndrome develops signifying advanced stage disease.
- Closure of the PDA is done in the cardiac cath lab.
 Medical Management:
- Small PDA’s will frequently close spontaneously.
- These are very common in small premature infants.
- Indomethacin (does not treat the underlying problem)
 Trying to maintain the patient until you can do surgery
- Surgical repair is often not necessary
4. Aortic stenosis “obstruction lesion”
 Aortic Stenosis is caused by abnormal structural development of the valve leaflets
 M:F = 4:1
 20% present with second abnormality such as coarctation of the aorta
 Often a result of fibrosed or calcified bicuspid Aortic valves
 Auscultation reveals a harsh crescendo-decrescendo systolic murmur loudest at base and radiates toward neck.
 In severe disease the prolonged ejection time causes a delay in closure of the aortic valve resulting in “paradoxical splitting of S2”
 Aortic stenosis represents a variety of lesions, and children tend to be asymptomatic unless
- s/s of heart failure before age one (i.e. tachycardia, tachypnea, failure to thrive and poor feeding).
 A harsh systolic murmur and/or diastolic murmur may be heard together or separately.
 Chest x-ray findings are normal, and the ECG shows left ventricular hypertrophy.
 Repair is done in the catheterization laboratory with angioplasty, or surgically with a valvotomy.

5. Pulmonary Stenosis
 Results from destruction of right ventricular outflow tract.
 Mild disease rarely progresses.
 Untreated, severe, P.S. results in right sided failure and (R) ventricular hypertrophy (presenting with dyspnea with exertion,
exercise intolerance, and decompensation, abdominal fullness and pedal edema.
 Most children with this defect will present without cyanosis, and perhaps a loud systolic murmur.
 Auscultation reveals a loud crescendo/decrescendo systolic ejection murmur @ left upper sternal border. May experience
splitting of P2. Rarely a pulmonic click may be heard prior to the murmur.
 Chest x-ray and ECG show right atrial and ventricular enlargement. ECG - RVH and R axis deviation. The diagnosis is made with an
echocardiogram.
 Angioplasty in the cardiac cath lab (transcatheter balloon valvuloplasty) relieves the stenosis, so no other surgery is necessary.
6. Coarctation of Aorta
 Most commonly occurs in patients with Turner Syndrome (45,XO)
 Causes increased left ventricular pressure due to increased afterload
 S/S: Present shortly after birth with symptoms of heart failure, claudication (pain in lower extremities following exercise),
femoral pulses weak or decreased. Pressure in upper arms 15-20 mmHg greater than in legs.
 CXR: Notching of the inferior surface of the posterior ribs secondary to enlarged intercostal vessels which supply collateral
circulation.
 Initial management is to give IV prostaglandin E to open ductus. Neonates with severe coarctation depend on a R->L shunt
through the PDA.
 Physical findings in this defect are variable, as a murmur may or may not be present, and the person may be asymptomatic.
 A chest x-ray may show rib notching and the ECG may show left or right ventricular hypertrophy, depending on the age of the
child.
 Most lesions can be corrected in the catheterization laboratory, and will not require an open approach.
 Surgical - “ROSS” procedure replaces aortic valve with patients own Pulmonic valve.

7. Endocardial Cushion Defect (AVC/Atrioventricular Septal defect)

 Children usually present with cardiac failure with this defect at 6 weeks to 3 months of age.
 A very harsh systolic murmur is heard, and subsequent chest x-ray and echocardiogram reveals pulmonary vascular disease as a
result of the increased pulmonary pressure.
 Down’s Syndrome
 Surgical closure by open heart surgery is done before one year of age.
Cyanotic 1. Tetralogy of Fallot (TOF)
 The features of Tetralogy of Fallot are:
Right to Left Shunts - Severe pulmonary stenosis
- Right ventricular hypertrophy
- Large VSD
- Overriding aorta
 All have a harsh systolic ejection murmur at LUSB created by turbulent flow through the stenotic left ventricular outflow tract.
 Classic “boot-shaped heart” on x-ray, and ECG changes.
 “Tet spells” following exertion, feeding or crying***
 TX:
- Elective repair at 6-12 months of age
- Antibiotic prophylaxis is required
- Complete surgical repair is considered at 3 to 6 months of age.

2. D-Transposition of the Great Arteries (D-TGA) Aorta and pulmonary artery are switched
 Most common cause of cyanosis in the neonatal period
 Newborns having this defect are extremely hypoxic, cyanotic and acidotic**
 PDA is of paramount importance as two systems operating in parallel
 A murmur may not be present, but the chest x-ray will show an “egg on a string” shaped heart with right ventricular hypertrophy.
 RVH on ECG.
 TX: medical emergency. Prostaglandins asap.
 Surgical repair is done in the first week of life, and includes a septostomy and arterial switch procedure. Rashkind procedure
creates temporary intra-arterial communication followed by “Arterial Switch” Jatene procedure.

3. Tricuspid Atresia (TA) Almost no right ventricle and almost always have VSD
 This lesion causes severe cyanosis not relieved by inhaled oxygen.
 A continuous PDA murmur is usually heard, and other signs are variable, as is the heart size of chest x-ray.
 Echocardiogram and ECG help make the diagnosis.
 An ASD or PFO is always present. Often has VSD allowing L->R shunt through pulmonary artery.
 DX: No murmur if intact VSD.
 ECG – Left Axis Deviation, right atrial enlargement and LVH - the only cause of these findings with cyanosis in the newborn period.
 Medical management assures that the PDA remains open with PGE1 until shunt placed.
 Surgical management involves placing a Gore-Tex shunt between the subclavian and pulmonary arteries. Fontan (redirect of IVC
and SVC to pulmonary artery) with a bidirectional Glenn shunt (superior vena cava to pulmonary artery) procedure at 3-6 y.o. or
15kg.
 4. Truncus Arteriosus (TrA) one central source for pulmonary and aortic roots
 Occurs when the aorta and pulmonary artery originate from a common artery the truncus.
 A VSD is usually present
 This defect may imitate the findings of a PDA, and include congestive heart failure due to excessive blood flowing to the lungs.
 A diastolic murmur may be heard as well as a SEJM at base.
 Chest x-ray is not very descriptive.
 ECG may reveal left atrial enlargement, but echocardiogram is diagnostic.
 Medical management includes treatment of congestive heart failure.
 Surgical management includes creating a conduit between the right ventricle and the pulmonary arteries with closure of the
VSD.

5. Total Anomalous Pulmonary Venous Return (TAPVR)

 All four pulmonary veins do not connect normally to the left atrium. Instead the four pulmonary veins drain abnormally to the
right atrium (right upper chamber) by way of an abnormal (anomalous) connection.
 There are 4 different types of Total Anomalous Pulmonary Venous Return, and most (50%) are supra-cardiac.
 Depending on the degree of pulmonary venous obstruction, murmurs may be present or not.
 Chest x-ray will reveal a “snowman” shaped heart, ECG will reveal right ventricular hypertrophy, and echocardiogram will show
right heart enlargement.
 Congestive heart failure and pulmonary edema will need to be treated.
 Surgical redirection of the pulmonary veins is curative.

Clinical Pearls:
Clinical Subtypes 1. Ebstein Anomaly commonly have a patent foramen ovale
 Cyanosis may be common, but intermittent.
 Symptoms may not present until adulthood, and then worsen rapidly.
 Heart sounds may be widely split, and there may or may not be a murmur.
 A chest x-ray will have variable findings and an ECG will show an increased PR interval and abnormal P waves.
 Echocardiograms are diagnostic.
 Surgical correction of the abnormal tricuspid valve is curative.
 Ablation of any accessory pathways may also be necessary.

2. Hypoplastic Left Heart Syndrome (HLHS)

 Obstructive lesion, left sided, cyanotic
 This lesion may be diagnosed before birth, and until recently was considered uniformly lethal.
 This lesion is still the most common cause of cardiac death in the first month of life.
 The diagnosis is made by prenatal and postnatal echocardiogram.
 Surgical repair is done in stages in the newborn period, at 2 to 3 months, and completed at 2 to 3 years of age.

3. Eisenminger Syndrome
 Severe pulmonary vascular obstruction resulting form L->R shunting. Leads to elevated pulmonary vascular resistance. This in
turn causes reversal of the original shunt. R->L with accompanying systemic cyanosis.
 S/S:
- Exertional dyspnea and fatigue. Decreased Hgb saturation -> BM to increase RBC volume leading to hyperviscosity
syndrome, headaches, and increased risk of stroke. Digital clubbing with cyanosis. JVD
 CXR: Proximal pulmonary artery dilatation with peripheral tapering
 ECG: Right ventricular hypertrophy and right atrial enlargement
 Pregnancy is especially dangerous if they have this-20 – 40% spontaneous abortion rate and 45% maternal mortality
 RX: pulmonary vasodilators
1) Endothelin receptor antagonists
2) Prostacyclin analogs
3) Phosphodiesterase inhibitors
 SX: Lung / Heart Lung Transplant
Lecture 8: EKG lesson 6
 One of the most common symptoms of errors in conduction is UNEXPLAINED SYNCOPE; MUST do a 12 lead EKG

Long QT Syndrome • Normal QT = < 440ms (two large squares) – prolonged QT > 450ms; should not be greater than 500 [more than 2 large squares]
• Produces prolonged ventricular repolarization  predisposes to malignant ventricular arrhythmias
• Beginning of Q wave up to the end of T wave
Causes:
• Drugs: amiodarone, TCA’s, many antibiotics, fluconazole, erythromycin, metoclopramide, quinidine, haloperidol, droperidol, methadone,
ondansetron, SSRI’s
• Genetic: cardiac ion channel mutation (Na+, K+) - Romano Ward Syndrome
• Myocardial disease: MI, RF, 3rd degree HB, cardiomyopathy
• Electrolytes: low Ca2+, low K+, low Mg2+
Management:
• beta-blockade
• avoidance of increased sympathetic tone
• cardiac pacing
• treat cause
• ICD
QT-corrected (QTc)
• The corrected QT interval (QTc) estimates the QT interval at a heart rate of 60 bpm.*****
• This allows comparison of QT values over time at different heart rates and improves detection of patients at increased risk of arrhythmias.
• Bazett’s formula is the most commonly used due to its simplicity. It over-corrects at heart rates > 100 bpm and under-corrects at heart rates <
60 bpm, but provides an adequate correction for heart rates ranging from 60 – 100 bpm.
Wolff-Parkinson-White • Wolff-Parkinson-White (WPW) Syndrome is a combination of the presence of a congenital accessory pathway and episodes of
Syndrome tachyarrhythmia.
• Associated with a small risk of sudden cardiac death.
• In WPW the accessory pathway is often referred to as the Bundle of Kent, or atrioventricular bypass tract.
- The bundle of Kent is an abnormal extra or accessory conduction pathway between the atria and ventricles that is present
in a small percentage (between 0.1% and 0.3%) of the general population.
- This pathway may communicate between the left atrium and the left ventricle, in which case it is termed a "type A pre-
excitation", or between the right atrium and the right ventricle, in which case it is termed a "type B pre-excitation".
• Associated with atrial fibrillation [electricity is the best choice of treatment]
- Do not treat with adenosine ; treated with cardiac ablation
ECG
• PR interval <120ms
• Delta wave – slurring slow rise of initial portion of the QRS
• QRS prolongation >110ms

orthodromic

Antidromic; QRS is much wider

Brugada Syndrome
Arrhythmogenic Right
ventricular Dysplagia
Treatment
Brugada Syndrome is an ECG abnormality with a high incidence of sudden death in patients with structurally normal hearts.
In a nutshell, Brugada syndrome is due to a mutation in the cardiac sodium channel gene.
Diagnostic Criteria
◦ Type 1 (Coved ST segment elevation >2mm in >1 of V1-V3 followed by a negative T wave) is the only ECG abnormality that is
potentially diagnostic. This has been referred to as Brugada sign.
◦ If this is seen, the person needs a defibrillator immediately ; also implantable cardioverter-defibrillator
Could be an
incomplete
bundle branch
block, left
ventricular
hypertrophy, but
DEFINITELY
Brugada
An inherited myocardial disease associated with paroxysmal ventricular arrhythmias and sudden cardiac death.
Characterized pathologically by fibro-fatty replacement of the right ventricular myocardium.
◦ Floppy right ventricle [decreased CO]
The second most common cause of sudden cardiac death in young people (after HCM), causing up to 20% of sudden cardiac deaths in patients
< 35 yrs of age.
◦ Epsilon wave (most specific finding, seen in 30% of patients)
◦ T wave inversions in V1-3 (85% of patients)
◦ Prolonged S-wave upstroke of 55ms in V1-3 (95% of patients)
Medication
◦ Beta Blockers
◦ Ace Inhibitors
◦ Amiodarone
Implantable Cardioverter Defibrillators (ICD)
Catheter Ablation
Hypertrophic
Cardiomyopathy
Treatment
Dilated Cardiomyopathy
Wellen’s Syndrome
• Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiac disorders (affecting ~ 1 in 500 people) and is the number
one cause of sudden cardiac death in young athletes. Annual mortality is estimated at 1-2 %.
• Left ventricular hypertrophy results in increased precordial voltages and non-specific ST segment and T-wave abnormalities.
• Asymmetrical septal hypertrophy produces deep, narrow (“dagger-like”) Q waves in the lateral (V5-6, I, aVL) and inferior (II, III, aVF) leads.
These may mimic prior myocardial infarction, although the Q-wave morphology is different: infarction Q waves are typically > 40 ms duration
while septal Q waves in HCM are < 40 ms. Lateral Q waves are more common than inferior Q waves in HCM.
 Septal Myectomy- to make the chamber bigger
 Ablation
 Medications
 ICD
• Dilated cardiomyopathy (DCM) is a myocardial disease characterized by ventricular dilatation and global myocardial dysfunction (ejection
fraction < 40%).
• Patients usually present with symptoms of biventricular failure, e.g. fatigue, dyspnea, orthopnea, ankle edema.
• Associated with a high mortality (2-year survival = 50%) due to progressive cardiogenic shock or ventricular dysrhythmias (sudden cardiac
death).
• Can be divided into ischemic and non-ischemic.
• Ischemic - Dilated cardiomyopathy commonly occurs following massive anterior MI due to extensive myocardial
necrosis and loss of contractility.
• Non Ischemic - Most cases are idiopathic. Up to 25% are familial (primarily autosomal dominant, some types are X-
linked) .
• There are no ECG features unique to DCM, although the ECG is usually abnormal.
• The most common ECG abnormalities are those associated with atrial and ventricular hypertrophy — typically, left
sided changes are seen but there may be signs of biatrial or biventricular hypertrophy.
• Wellens’ syndrome is a pattern of deeply inverted or biphasic T waves in V2-3, which is highly specific for a critical stenosis of the left anterior
descending artery (LAD).
• Patients may be pain free by the time the ECG is taken and have normally or minimally elevated cardiac enzymes; however, they are at
extremely high risk for extensive anterior wall MI within the next few days to weeks.
• Due to the critical LAD stenosis, these patients usually require invasive therapy, do poorly with medical management and may suffer MI or
cardiac arrest if inappropriately stress tested.
• Deeply-inverted or biphasic T waves in V2-3 (may extend to V1-6)
 severely ischemic
Tx: Cath lab
Electrical Alternans • Massive pericardial effusion
• Consecutive, normally-conducted QRS complexes alternate in height.
• The heart swings backwards and forwards within a large fluid-filled pericardium.
• Patients with this ECG pattern need to be immediately assessed for clinical and echocardiographic evidence of tamponade.
Lecture 9 Pathology of Valvular Disorders I

Valvular heart disease

 Acquired or congenital.
◦ Acquired
 Aortic Stenosis (most common)
 Aortic Insufficiency/ regurgitation
 Mitral Stenosis
 Mitral Insufficiency
 Isolated (one valve) or combined disease more than one valve).
 Stenosis or insufficiency or both.
◦ Stenosis - Blood flow forward is impeded because of failure of valve to open completely with acquired stenoses of mitral and aortic valves accounting for 2/3’s of all
valve disease.
◦ Insufficiency - Blood flows backward due to valve failing to close completely.
 Functional regurgitation – valve is normal but supporting structures are abnormal
Acquired Aortic Valve  Aortic stenosis is the most common acquired valvular disease.
Disease  Prevalence estimated at 2% of the population.
 Present clinically in 7th to 9th decade of life with bicuspid valves presenting at a younger age.
 Senile calcific aortic stenosis - Degenerative changes from “wear and tear” of normal valves (or bicuspid) with subsequent calcification
producing less pliant valve, stiffening and ultimately stenosis.
 May get a systolic murmur that radiates to the neck
Causes of Aortic Stenosis
 Degenerative changes to the valve from normal “wear and tear” to which bicupsid valves are more susceptible.
- Initially have aortic valve sclerosis with early calcification but no significant pressure gradient across the valve
 Possible chronic injury due to hyperlipidemia, hypertension, inflammation (i.e., rheumatoid valvulitis in rheumatoid arthritis).
 Rheumatic heart disease (mitral valve usually also involved)
 Congenital
Morphology of Senile Calcific Aortic Stenosis
 The hallmark of nonrheumatic calcific aortic stenosis is calcified masses in the cusps preventing opening.
◦ Calcified nodules within the Sinuses of Valsalva
 Valve area (the orifice of the valve in severe stenosis is 0.5 to 1 cm2 (normal is 3-4 cm2) with valve gradients up to 75 to 100mm Hg in severe
cases (usually valve gradient is only a few mmHg)
 There is no fusion of the commissures as seen in rheumatic heart disease.
- Rheumatic fever post-streptococcal infection
Complications
 Left ventricular hypertrophy which may decompensate into dilation over time. (Diastolic and systolic dysfunction)
 Myocardial ischemia due to decreased microcirculatory perfusion [angina]
◦ Increased oxygen demand from LVH as well
Clinical Findings
 Classic symptoms are
- Angina, syncope, and congestive heart failure
 Treatment is surgical valve replacement.
◦ Otherwise, death (sudden)
Diagnosis and Treatment
 Systolic ejection murmur radiating to the neck.
 Echocardiogram.
 The only medical therapy indicated is antibiotic prophylaxis for bacterial endocarditis per Cecil’s Medicine.
 Treatment is valve replacement surgery.
 Balloon valvuloplasty may be used in poor surgical candidate but not nearly as effective or TAVR (transcatheter aortic valve replacement)
Aortic
Insufficiency/Regurgitation
Symptoms
Chronic Aortic Regurgitation
Acute Aortic Regurgitation
Causes:
 Leaflet abnormalities
◦ Infective endocarditis
◦ Rheumatic heart disease
◦ Bicuspid aortic valve
 Aortic root dilation
◦ Degenerative aortic dilation (i.e., due to HTN)
◦ Aortic dissection
◦ Marfan syndrome (fibrillin-1 mutation) and other connective tissue defects due to genetic mutations
◦ Syphilis
◦ Ankylosing spondylitis
◦ Rheumatoid arthritis
 Dyspnea
 Orthopnea
 PND or paroxysmal nocturnal dyspnea
 Angina
 Syncope
 Volume overload on the left ventricle.
 The heart compensates for the increased volume by development of concentric and eccentric left ventricle hypertrophy
 Increased stroke volume causes a hyperdynamic circulation, inducing systolic hypertension.
◦ Compensated aortic regurgitation has reduced peripheral vascular resistance
◦ Diastolic systemic pressure is low due to LV accommodating a large regurgitant volume, therefore, diastolic pressure is low.
 Minimal blood remains in aorta at diastole
 A widened pulse pressure is a hallmark of AR ****
◦ Pulse pressure = systolic – diastolic arterial pressure
 Diastolic blowing murmur
 Austin Flint murmur: regurgitant jet impinges on the mitral valve causing it to vibrate.
 Hyperactive displaced apical impulse.
 Signs due to wide pulse pressure.
o Quincke pulse (nail finding of systole and diastole)
o De Musset’s sign (head bobbing)
o Corrigan’s pulse or “water-hammer” pulse (sharp upstroke and rapid decline of carotid pulse)
o Bisferiens pulse: Double systolic impulse in carotid or brachial artery
o Duroziez’s sign (combined systolic and diastolic bruits created by compression of the femoral artery with the stethoscope)
o Hill’s sign (An increase in femoral systolic pressure of 40mm of Hg when compare with brachial artery pressure).
 Tx: requires surgery when evidence of LV dysfunction even in asymptomatic patients.
 Acute – Most common causes of acute regurgitation is aortic dissection and infective endocarditis.
 The heart has not had time to develop compensatory mechanisms and develop heart failure and ischemia.
 Short diastolic blowing murmur
 Reduced intensity of S1 from mitral valve preclosure (the mitral valve closes early in diastole due to high diastolic LV pressure; only the
tricuspid component of S1 is heard when ventricular systole occurs,)
 Tx: with heart failure has a 75% mortality rate. May treat emergently with nitroprusside to reduce afterload with emergency surgery
required.
Mitral valve Stenosis  Practically all cases caused by rheumatic heart disease- an immunologically mediated disease occurring weeks after a group A streptococcal
pharyngitis.
 Occasionally caused by severe calcification of the mitral valve annulus.
 More common in women developing at ages 40 to 50’s.
Chronic Mitral Valve Stenosis
 In rheumatic heart disease, it’s the only valve affected in 65 to 70% of cases.
 Morphologic changes include
 Leaflet thickening
 Commissural fusion with shortening,
 Linear opening
 Thickening and fusion of the tendinous cords.
 May have a “fish mouth” or “buttonhole” appearance.

Pathophysiology
 The left atrium progressively dilates due to obstruction of the mitral valve and may develop atrial fibrillation with formation of thrombi.
 Pulmonary venous pressure increases and ultimately pulmonary hypertension develops and right ventricular failure.
 In one third of patients, LV performance is reduced despite normal muscle function due to reduced preload and increased afterload (due to
reflex vasoconstriction caused by reduced cardiac output).
 Murmur: Opening snap followed by the classic low-pitched early diastolic mitral stenosis rumble, increasing in length as stenosis progresses.
 Complications:
- Pulmonary hypertension with right sided heart failure
- Atrial fibrillation.
Atrial thrombi Diagnosis and Treatment
 Echocardiography is an important tool in
diagnosis.
 Asymptomatic patients in sinus rhythm
require no therapy.
 Diuretics for mild symptoms.
 Anticoagulation for atrial fibrillation along
with ventricular rate controlling drugs.
 Indications for surgery (open
commissurotomy, balloon valvotomy or
valve replacement) are the appearance of
more severe symptoms, pulmonary
hypertension and persistent atrial
fibrillation.

Symptoms
 Dyspnea
 Orthopnea
 PND (paroxysmal nocturnal dyspnea)
 Hemoptysis – Rupture of pulmonary –bronchial venous connections secondary to pulmonary venous hypertension from markedly elevated
left atrial pressures
 Hoarseness – the large left atrium impinges on the recurrent laryngeal nerve and cause hoarseness (Ortner’s syndrome)
 Edema
 Ascites
Mitral Regurgitation  Mitral valve components are the mitral annulus, the leaflets, the chordae tendinae and the papillary muscles.
 Abnormalities in any of these structures can lead to regurgitation.
Pathophysiology
 Causes a volume overload on the LV with subsequent hypertrophy and dilation to increase stroke volume with eventual systolic dysfunction.
Signs and Symptoms
 Dyspnea, orthopnea, PND.
 Holosystolic apical murmur radiating to the axilla.
 S3 with heart failure
Treatment
 Medical therapy
◦ Acute regurgitation
 Arterial vasodilators to reduce peripheral vascular resistance and increase forward flow
◦ Chronic symptomatic regurgitation
 ACE inhibitors reduce LV volume but surgery preferred over medical therapy
 Surgical therapy
◦ Symptomatic patients and asymptomatic patients with LV dysfunction.
◦ Valve repair or replacement.

Mitral valve prolapse  A condition in which one or both mitral valve leaflets prolapse (balloon back) into the left atrium during systole
 May be physiologic or due to myxomatous degeneration of the valve.
 Gross –
- Hooding of the affected leaflets which are enlarged, redundant, thick and rubbery with enlongated and thinned
chordae** and the annulus may be dilated.
- Tricuspid, aortic and pulmonic valves may also be affected.
 Histologic findings –
- Attenuation of collagenous fibrosa layer and marked thickening of the spongiosa layer from deposition of mucoid
materialor proteoglycans (myxomatous)
Secondary Heart changes from mitral valve prolapse
 Changes are due to injury from the excessive billowing leaflets.
◦ Friction induced fibrous thickening of the mitral valve leaflets, the endocardium in the left ventricle (from long chordae and
valve leaflets) and left atrium (from valve leaflets)
◦ Thrombi may form at sites of injury on the atrial surface of the mitral leaflets and left atrium.
◦ Focal calcifications at the base of posterior mitral valve leaflet.
 Pathogenesis
 Unknown
 MVP may be seen in inherited connective tissue disorders like Marfan’s (Fibrillin-1 mutation)
 Mild mitral valve myxomatous change may occur secondary to regurgitation from other etiologies.
Clinical Features
 Most patients are asymptomatic with an incidental mid-systolic click (caused by chordae tendinae being stretched taut by the prolapsing
valve) found on routine exam.
◦ May have late systolic murmur from regurgitation.
 Symptomatic patients may have palpitations, syncope and chest pain.
◦ Palpitations and syncope may be linked to autonomic dysfunction (seen more frequently in patients with MVP)
◦ Chest pain: possibly excessive tension on papillary muscles increases oxygen consumption and causes ischemia.
Complications
 Serious complications are rare but more common in men and increasing age:
◦ Infective endocarditis
◦ Mitral insufficiency, sometimes with chordal rupture
◦ Stroke
◦ Arrhythmias
◦ Sudden death
Treatment
 None.
 Endocarditis prophylaxis if regurgitation present (possibly in abnormal valve)
 Symptomatic individual may use beta blockers.
 Possibly aspirin to prevent thrombosis in some patients.
 Surgery for severe regurgitation.
Mitral Annular  Degenerative calcific deposits develop in the fibrous ring supporting the mitral valve.
Calcification  Usually asymptomatic.
 May cause:
◦ Regurgitation
◦ Stenosis
◦ Arrhythmias and sudden death (penetration of calcium deposits into AV conduction system)
◦ Calcific nodule may be a site for endocarditis and thrombi.
 Acquired Tricuspid  Secondary to a hemodynamic load on the right ventricle as in pulmonary hypertension of various causes.
regurgitation ◦ Ebsteins anomaly can be a cause
 Acquired valve diseases.
◦ Infective endocarditis (drug abuse, unsterile injections).
◦ Carcinoid syndrome
◦ Rheumatic heart disease
◦ RV infarction
◦ Myxomatous degeneration
◦ Mishaps with endomyocardial biopsy
Tricuspid Stenosis  RARE, and usually due to Rheumatic heart disease
 Carcinoid syndrome
 Infective endocarditis (very large vegetations may cause obstruction)
Acquired Pulmonary Valve  Pulmonary hypertension (due to dilation of the valve ring by enlarged pulmonary artery)
Insufficiency  Valvular abnormality
◦ Infective endocarditis
◦ Myxomatous degeneration
◦ Carcinoid syndrome
◦ Rarely rheumatic heart disease
Acquired Pulmonic stenosis  Carcinoid syndrome
 Rarely rheumatoid heart disease.
 Stenoses are mostly congenital

Lecture 10 & 11 High impact nutrition in cardiac patients

 Metabolic Syndrome
o Also known as Syndrome X/Insulin Resistance Syndrome/ PCOS
o Central Features
 Insulin resistance
 Visceral adiposity (central obesity)
 Atherogenic dyslipidemia
 Increased LDL
 Endothelial dysfunction
 Affects RAAS

 Body Mass Index (BMI) = kg/m2

o Impacts joints, and back, increases inflammation, decreased vitamin D, worsens symptoms of GERD, CAD, peripheral vascular disease, HTN
 Prediabetes  diabetes Type 2 within 10 years Seen in insulin resistance

Can precede diabetes – can mimic discoid lupus

 Disorder of collagen degeneration Diabetic Ulcer
 Can get fat deposition and ulceration Check:
• Sensory
• Circulation
• Skin
• Structure (hammertoe and foot
deformities  foot ulcer because of
shoe problems)
 Type Ia Familial Hyperchylomicronemia
 Increased chylomicrons – pancreatitis**/eruptive skin xanthomas/ hepatosplenomegaly – rare
Type Ib Familial Apoprotein CII deficiency
 LDL receptor deficiency – increased LDL – xanthelasma/arcus senilis/tendon xanthomas – 1 in 500 for heterozygotes
Type IIa Familial hypercholesterolemia
 Decreased LDL receptor and increased Apo B – increased LDL & VLDL – 1 in 100
Type IIb* Familial Combined Hyperlipidemia
 defect in Apo E2 synthesis – increased IDL – tubo-eruptive xanthomas & palmar xanthomas*****
Type III Familial dysbetalipoproteinemia
Type IV* Familial hypertriglyceridemia
 increased VLDL production and decreased elimination – can cause pancreatitis***
Type V Rare (increased VLDL and chylomicrons)
 increased VLDL production and decreased LPL (lipoprotein lipase)

*Most common
Creamy top layer in tube found in Type I,III, IV, V Fredrickson hyperlipidemias

ApoE2
Foam cells
C-reactive protein (CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are two markers of
inflammation that can be measured in the circulation. They’re additive in their ability to predict
atherosclerosis risk.

Short-lived cytokines , proteins that serve as messengers between cells, come from various parts of
the body that are inflamed, such as joints and muscle. Some also come from the arterial wall. The
short-lived cytokines stimulate CRP production in the liver. Short-lived cytokines may promote
atherosclerosis even though the origin is not in the artery wall.

Though CRP and Lp-PLA2 are distinct from each other, they are both markers of inflammation in the
circulation that can help predict atherosclerosis risk. CRP is an index of inflammation and presents
the potential for atherogenesis. Lp-PLA2 is located primarily in the artery wall and has a prooxidative
function. Lp-PLA2 generates inflammatory molecules and thereby, enhances inflammation in the
artery and possibly elsewhere.
Carbohydrates Fructose increases triglycerides so stay away from fructose [goes
 Simple = sugars right to the liver]; better off with glucose
o includes naturally found in fruits, vegetables and milk
o includes added sugars in processing and refining High fructose corn syrup [more rapidly metabolized in the liver
o Monosaccharides and Disaccharides and is so high density that it floods the metabolic paths and
o Monosaccharides increase TG synthesis and storage] increased risk of BP increase,
 Glucose: fruits and plants fatty liver disease, and excess uric acid, and complications in
 Fructose: fruits, root vegetables, cane sugar, honey
diabetes
 Galactose: part of milk sugar (combined with glucose)
o Disaccharides
Sugar substitutes actually increase insulin resistance and can lead
 Sucrose: sugar cane stems, sugar beet roots, root vegetables (glucose & fructose)
to CNS issues, bloody diarrhea, and many other side-effects
 Maltose: grains, during digestion of starch
 Lactose : milk
 Complex = starches and dietary fiber
o Oligosaccharides
 3-10 simple sugars
 Prebiotic
o Polysaccharides
 Starches
 Fiber
 Dietary fiber = non-starch polysaccharides and plant components (resistant starch, resistant dextrins, inulin, lignin, waxes, chitins, pectins,
beta-glucans, oligosaccharides)
 Produce healthful compounds during fermentation of soluble fiber, inulin, oligosaccharides, resistant starch
o Soluble fiber is readily fermented in the colon
 Increase bulk, soften stool and shorten transit time with insoluble fiber
o Metabolically inert bulking
 Gas production/bloating - disadvantage
 Constipation if insufficient fluid with high-fiber diet
 Primary Mechanisms – bulking/ viscosity/ fermentation
 Binds bile acids in small intestine
 Attenuates absorption of sugar [how it decreases the glycemic index]
 Produces short-chain fatty acids as byproducts in colon
 Reduces diabetes risk (insoluble fiber-mechanism unknown)
 Resistant starch – directly increases insulin sensitivity
 Increases food volume (without calories)/ increased satiety

Glycemic Index

• Measurement of glucose blood level increase from carbohydrate consumption relative to pure glucose (two hour response curve)
• Glucose glycemic index = 100
– Low Index ≤ 55 [this is good, slowly absorbed]
The lower the index the lower the insulin
– Medium Index = 56-69
demand
– High Index = 70 or above [white breads, melons, potatoes, corn flakes, desserts]
-fat delays gastric emptying
-one alcoholic drink before a meal, reduces
the glycemic index
-fiber lowers glycemic index
- Al dente pasta also has lower glycemic index
than fully cooked
Salt intake and Influence
• Increased BP - result of excess sodium and water
• Normal amounts: 5 grams of salt per day [~2 grams of sodium
• Obesity enhances the hypertensive effect of salt
• Diabetes increases salt sensitivity/volume expansion
• Improved salt excretion with K⁺ / Ca⁺ / Mg⁺
• Sodium-sensitivity is individualized
• Groups impacted by salt intake
Children and adolescents –
Obese – children/adolescents/adults
Elderly
African-Americans with HTN
Chronic Kidney Disease patients
Potassium deficient
• US diet – high in sodium – mostly processed foods
• Average/United States – 3400 mg/d
• Natural diet/no added salt= 600 mg
• 95% of ingested sodium – absorbed from GI tract
• Mostly eliminated by renal excretion
• Extra-renal loss rarely significant (massive diarrhea/sweating)

Effects of Dietary Salt Restriction for CVD

• Studies need large numbers and long-term follow-up
Participants usually resume regular (high salt) diet
• Recommended for ˃ 51 years of age
African-Americans
HTN/DM/CKD
• Children and Adolescents (Pediatrics Sept 17, 2012)
– Salt intake is positively associated with high blood pressure especially if they are overweight

Fats intake and Influence

• Types of Fats
• Sources of Fats
• Essential Fatty Acids
• End Products of n-3 and n-6
• Byproducts/Deficiencies when intake skewed
• Vitamins and Minerals in Metabolism of EFAs
Types of Dietary fats
• Solid fats
• Saturated fats
• sausage/ hotdogs/ bacon/ lard/ butter/coconut/ palm & tropical oils When they say low sugar  high fat
• Trans fats – animal or through food processing/partial hydrogenation of unsaturated fats
• Raises cholesterol levels When they say low fat  high sugar
• Increases risk of DM
• Sources Low HDL may be linked to memory loss
• margarines/ snack foods/ cookies & cakes/ meat & dairy
•
• Liquid fats
• Monounsaturated fats
• olive/ peanut/ canola oils/ avocado/ poultry, nuts and seeds
•
• Polyunsaturated fats
• Improves cholesterol levels
• Benefits insulin levels
• Sources
• vegetable oils (safflower, corn, sunflower, soy, cottonseed)/ nut oils, poultry, nuts and seeds
• Omega-3 fatty acids – fatty, cold-water fish/ ground flaxseed/ flax oil/ walnuts
• Cholesterol – eggs/ beef/ seafood/dairy/ butter/ lard =animal products
Lecture 12 Pathology of Valvular Disorders II

Endocarditis
 Infective Endocarditis
o Infection of endocardial surface of the heart, usually valves but may be mural.
o Acute – infection of previously normal heart valve by highly virulent organism
o Subacute – insidious infection of deformed valves with less virulent organisms
o Most commonly affected valves in descending order of frequency:
 Mitral and aortic valves (mitral valve used to be #1 because of rheumatic heart disease which is decreasing)
 Tricuspid valve
 Mixed right and left-sided infection
 Pulmonic valve.
o More common predisposing conditions.
 Mitral valve prolapse with thickened valves and regurgitation
 Degenerative valvular disease
 IV drug abuse
 Prosthetic valve
 Congenital heart disease
o Less common predisposing conditions
 Rheumatic heart disease
 Hypertrophic obstructive cardiomyopathy
 Previous endocarditis
 Pulmonary-systemic shunts (i.e., surgically constructed subclavian-pulmonary artery shunt used in in Tetralogy of Fallot)
o Physical Findings
 Acute symptoms versus insidious
 Fever in 80 to 95% of cases
 Audible murmur, 85%
 New or changed murmur 15 to 47%
 Embolic phenomena
 Petechiae
 Osler’s nodes
o Small painful nodules found most often on the palmar surfaces of the finger and toes that wax and wane and may be an
immunologic phenomenon (immune complexes) initiated by microemboli
 Janeway lesions
o Erythematous or hemorrhagic nontender macules on palms or soles
 Splinter hemorrhages
 Roth’s spots
o Oval retinal hemorrhages with pale centers, immunologic phenomenon
 Neurologic abnormalities (from emboli)
 Splenomegaly
o Dukes Criteria for diagnosis of infective endocarditis
 Pathologic Criteria –
 Microorganisms, demonstrated by culture or histologic examination, in a vegetation, embolus from a vegetation, or intracardiac abscess.
 Histologic confirmation of active endocarditis in vegetation or intracardiac abscess.
 Clinical Criteria
 Major – Positive blood cultures, Echo identification, new valvular regurgitation.
 Minor – Predisposing heart lesion or IV drug use, fever, vascular lesions, immunological phenomena, microbiologic evidence (single culture
pos), ECHO c/w but not diagnostic.
 If clinical criteria are used, 2 major, 1 major + 3 minor, or 5 minor criteria are required for Dx.
o Conditions required for pathogenesis of Infectious endocarditis
 1) Endocardial surface injury
 2) Thrombus formation at site of injury,
 3) Bacterial entry into the circulation
 4) Bacterial adherence to the injured endocardial surface
 The first two conditions provide an environment favorable to infection
 The last two permit implantation of organism on the endocardial surface
 The most common cause of endothelial injury is turbulent blood flow from pre-existing cardiac abnormalities
o Gross morphology
 Friable, bulky vegetations on the heart valves with possible valve destruction.
 Vegetation may be single or multiple and involve more than one valve.
 Vegetations may erode into the underlying myocardium (ring abscess).
 Emboli from the vegetations may occur causing septic infarcts or mycotic aneurysms.
o Histology
 Histology of the vegetation in acute endocarditis show acute inflammatory cells (neutrophils) and fibrin with bacterial colonies present.
 With time, granulation tissue develops with a chronic inflammatory infiltrate, fibrosis and calcification.
 Half of the cusp is just gone  acute
regurgitation and acute CHF

o Complications of infective endocarditis

o Direct valvular damage and consequences of local invasion.
o Embolic complications
o Metastatic infections from bacteremia
o Immunologic phenomena (glomerulonephritis)
o Prognosis
o Fatal if untreated.
o Treated, mortality ranges from 17 to 36% with a lower risk of death from less virulent organisms (strep viridans)
o Death generally results from heart failure and CNS events.
o Relapse rate is 12 to 16% and is greater in the elderly, IV drug abusers, and patients with prosthetic valves.
 Noninfective Endocarditis
o Nonbacterial thrombotic endocarditis (NBTE)
 Characterized by the deposition of small sterile thrombi (1 to 5 mm) on the leaflets of the cardiac valves.
 Thrombotic vegetations occur along the line of closure of the mitral valve most commonly with aortic and tricuspid valves next in frequency.
 Loosely attached and not invasive but may be a source of emboli.
 Associated diseases are cancer (especially mucinous adenocarcinomas), sepsis, and hypercoagulable states.
 Endocardial trauma to the right heart form indwelling catheters
Very loosely attached

o Libman-Sacks endocarditis
 Endocarditis of Systemic Lupus Erythmatosus
 Mitral and tricupsid valvulitis with small sterile vegetations (1 to 4 mm in diameter) sometimes seen in lupus.
 Vegetations of the mitral and tricuspid valve on both sides of the leaflets, the chordae and of the mural endocardium, singly or multiple, pink with a
warty or verrucous appearance.
 Mitral more frequently involved than the aortic valve
 Histology - finely granular, fibrinous eosinophilic material that may contain hematoxylin bodies (remnants of nuclei damaged by anti-nuclear
antibodies).
 Valvulitis may be present with fibrinoid necrosis of the valve.
 Anti-phospholipid syndrome in lupus may cause thrombotic lesions also. [NBTE also]
 Rheumatic Fever/heart disease
o an immunologically mediated multisystem inflammatory disease occurring as a result of a Group A streptococcal pharyngitis
o Major manifestations are
 (1) migratory polyarthritis of the large joint
 (2) pancarditis
 (3) SQ nodules
 (4)erythema marginatum of the skin and
 (5) Sydenham chorea
o Antibodies to strep cross react to heart antigens and CD4+ T cells specific for strep react to the heart.
o Acute manifestations occur 10 days to 6 weeks after strep pharyngitis with manifestations of a PANCARDITIS, affecting pericardium, myocardium and endocardium.
 Clinical cardiac features may include pericardial friction rubs, tachycardia, arrhythmias, mitral insufficiency and heart failure
o Increased susceptibility to additional attacks if re-infected with strep.
o Develop chronic valvular lesions over time, years to decades, i.e. mitral stenosis.
o Gross morphology
 Acutely, small vegetations called verrucae (1 to 2 mm) are along the line of closure overlying necrotic foci on the valves
 McCallum’s plaques – subendocardial irregular thickenings in left atrium.
 Possibly due to mitral regurgitation with jets of regurgitant blood hitting the atrial wall
 Chronically, the mitral valve is most commonly affected (65 to 70% of cases with both aortic and mitral in an additional 25% of cases)with leaflet
thickening, commissural fusion and shortening and thickening and fusion of the tendinous cords.
 “Fish mouth” lesion of mitral stenosis
 Also, “buttonhole”
o Histology
 PANCARDITIS with endocardium, myocardium and pericardium affected with inflammation and ASCHOFF bodies.
 ASCHOFF bodies – Foci of lymphocytes, occasional plasma cells and plump activated macrophages (ANITSCHKOW cells which are pathognomonic for
rheumatic fever)*******.
 Anitschkow cells called “caterpillar cells” because nuclear chromatin appears as a central, slender, wavy ribbon.
 Type of granuloma in rheumatic fever
 Acute
 Valves and endocardium have fibrinoid necrosis with fibrin vegetations
 Chronic
 Organization of the acute inflammation with subsequent diffuse fibrosis and neovascularization (normal valve is avascular)
 Lecture 13: Valvular Heart Disease
History
 Chest pain
 SOB
 Exercise intolerance
 Swelling
 Chronic cough
 Syncope
 Palpitations
Physical findings
 Aside for the murmur
 JVD
 S3 or S4
 Blood pressure
 Pulse
 PMI
 Edema
Maneuvers:
• Inspiration – increases venous
return to right atrium, increases
intensity of right heart sounds
• Hand grip – increases afterload,
increases intensity of mitral
regurgitation, Aortic
regurgitation and VSD
- Aortic stenosis does not
increase
• Valsalva and standing up –
decreases preload, decreases
intensity of most murmurs,
increases intensity of
hypertrophic cardiomyopathy
murmur
• Rapid squatting – increases
venous return and increases
preload, decreases
hypertrophic cardiomyopathy
murmur (young athletes),
increases aortic stenosis
murmur (older people)
Echocardiography
• When do you order it?
• Asymptomatic patients with benign flow DO NOT need
• Cardiac symptoms, diastolic murmur (Always needs echo), grade 3 or
greater, systolic murmur with other abnormal finding (systolic click,
etc.)
Murmurs
 Murmurs occur when turbulent blood flow moves
across a valve
o Flow across obstruction
o Increased flow through normal structure
o Ejection into a dilated chamber
o Regurgitation across an incompetent
valve
o Abnormal shunting from one chamber to
another
 Timing
o Systolic (midsystolic, holosystolic, early
systolic, late systolic)
 In beat with the pulse
o Diastolic (early diastolic, mid diastolic,
late diastolic)
 Offset to the radial pulse
 More pathologic but less
frequent
 Intensity **
o Overall declines with obesity,
emphysema and pericardial effusion
 Pitch
o High or low, harsh, rumbling, scratchy,
grunting, blowing, squeaky and musical
 Shape
o Crescendo, decrescendo, diamond shape,
uniform
 Location**
o Maximum intensity
o Where is it the loudest so that we know
what valve it is
 Radiation
o Related to direction of turbulent flow
 Response to maneuvers
Innocent murmurs
• Anemia, pregnancy, and thyrotoxicosis.
• As an example, a pulmonic murmur is
present in over 80 percent of normal
pregnant women.
Systolic
• Grade I - faintest murmur that can be heard (with difficulty)
• Grade II - faint murmur but can be identified immediately
• Grade III - moderately loud
• Grade IV - loud and is associated with a palpable thrill
• Grade V - very loud but cannot be heard without the
stethoscope.
• Grade VI - loudest and can be heard without a stethoscope away
from the bedside
Diastolic
• Grade 1 – Barely audible
• Grade 2 – Faint but immediately heard
• Grade 3 – easily heard
• Grade 4 – Very loud
Will not be on this test but know that it exists
• Systolic
• Aortic stenosis
• Mitral regurgitation
• Pulmonic stenosis
• Mitral valve prolapse
• Tricuspid regurgitation
• Diastolic
• Aortic regurgitation
• Mitral stenosis
• Pulmonary regurgitation
• Tricuspid stenosis
 Right sided Valve disease Mitral Stenosis
• Primary right sided valve disease RARE • Low pitched Late diastolic murmur
• Remember pressure on the right side of the heart is • Heard best at apex, left lateral decubitus
much lower than the left. • Most common cause – rheumatic fever due to commissural fusion
• Most right sided valve disease will be associated with • Congenital stenosis – rare in adults, generally presents in infants and children
other valve disease • Prominent calcifications – common, but rarely leads to hemodynamically significant MS
• Respiration will generally augment right sided heart • Fused commissures
murmurs • Endocarditis
• Radiation
• Fabry’s disease, Whipple’s disease, carcinoid
• Mitral facies
• Severe MS, cardiac output is diminished cutaneous vasoconstriction results in pink/purple
patches on the cheeks
• Lung exam might reveal rales/crackles
Acute Rheumatic Fever • Prominent a wave
• Group A streptococci (GAS) infection • Atrial pulses are reduced in volume (decreased stroke volume)
• Jones criteria • Opening snap – heard at the apex if the leaflets are still mobile
• children age 5-15 • Diastolic murmur – low pitched, prominent at the apex
• Occurs 2-3 weeks after a GAS throat • Best heard in a quiet room, patient left lateral position, using the BELL
infection • Normal valve orifice is 4 to 6 cm2
• Exact mechanism unknown, it DOES NOT • Stenosis become significant if less than 2 cm2
involve direct bacterial infection of the heart • Almost all patients are symptomatic when the valve area is reduced to 1.0 cm 2
• Not seen very commonly in USA anymore, • Many severe MS patients are not symptomatic because of the gradual progression of the disease.
but remember older patients may have had • Disease Progression
rheumatic fever • Varies
Jones Criteria*** • Can take 15-40 years from infection to onset of clinical symptoms
• Major • Without intervention disease progression will occur
• Carditis • Cause of death is usually related to progressive right sided heart failure or pulmonary edema
• Polyarthritis • Remaining are thromboembolic events
• Sydenham chorea • Clinical Symptoms
• erythema marginatum • Dyspnea (70%)
• Subcutaneous nodules • Increased left atrial pressure, inability to increase cardiac output
• Minor criteria • Hemoptysis
• Migratory arthralgia • Increased pulmonary pressure and vascular congestion
• Fever • Atrial fibrillation
• Increase acute phase reactant – • Increased left atrial pressure and size
ESR, CRP, leukocytosis • Thromboembolism – 30% over course of the disease
• Prolonged PR interval on EKG • Generally left atrium  cerebral
• Required • Right atrium if PHTN, R atrial and ventricular dilatation present  pulmonary
• ASO titers embolism
• Positive throat culture for GAS • Right Heart failure symptoms
• Diagnostic : 1 Required, 2 Major, 0 Minor • Chronic pulmonary hypertension leads to increased right ventricular and right
• Diagnostic : 1 Required,1 Major, 2 Minor atrial pressure
Rheumatic Heart Disease • EKG – non specific and not routine for diagnosis [structural and rhythms stuff]
• Acute rheumatic heart disease • left atrial enlargement
• Pancarditis – involves pericardium, • Right ventricular hypertrophy if pulmonary hypertension exists
myocardium and endocardium • Atrial fibrillation
• Tachycardia, decreased left ventricular • Echocardiography
contractility, pericardial friction rub, • Thickened mitral leaflets
transient murmur of aortic or mitral • Left atrial enlargement
regurgitation, mid diastolic murmur • Valve area
• Carey-Coombs murmur – • Cardiac Catheterization
absence of opening snap, • Only if we can’t get valve area based on echo [body habitus]
patient in left lateral position, • Can be used to calculate valve area
bell of stethoscope, resolves • ? Pulmonary hypertension or coronary artery disease
• Chronic rheumatic heart disease
•
• Deformity or impairment of one of more
valve
• Most common valve – mitral stenosis
• 25% aortic stenosis

Tricuspid Stenosis
• RARE and not very clinically significant
• Diastolic and soft rumble, heard at the left lower
sternal border
• Long term consequence of rheumatic fever
• Least common of the valvular stenosis lesions
• Often accompanied with MS
• Murmur intensifies with inspiration
• Other causes
• Carcinoid syndrome, endocarditis,
endomyocardial fibrosis, SLE, and
congenital tricuspid atresia
• 1% of the population
• Found in 15% of rheumatic heart disease
patients, clinically significant in 5%
• Associated with fatigue (CO limited), systemic venous
congestion
• Peripheral edema and ascities
Aortic Regurgitation/Insufficiency Right Ventricular hypertrophy
• Blowing, diastolic decrescendo
• heard best at left sternal border with patient leaning forward
• Radiation to the cardiac apex
• Increases with squatting or sitting up
• Causes
• Congenital (bicuspid valve), endocarditis, rheumatic
• Aortic aneurysm, aortic dissection, annuloaortic ectasia, syphilis
• Symptoms
• Dyspnea on exertion, fatigue, decreased exercise tolerance, uncomfortable
sensation of forceful heartbeat
• Acute AR
• LV is normal size
• LV diastolic pressure rises
• Considered a surgical emergency
• Chronic AR
• LV compensatory dilatation
• Pressure normal to mildly elevated
• Symptoms
• Palpitations
• Uncomfortable awareness of the heartbeat
• Shortness of breath
• Chest pain
• Sudden cardiac death
• Wide pulse pressure****
• Difference between systolic and diastolic pressure
• Diastolic pressures often below 60 mm Hg and pulse pressures
exceeding 100 mm Hg
• Crazy pulses in weird places
• Bisferiens pulse
• Double systolic impulse in carotid or
brachial artery
• Corrigan pulse
• “water-hammer” pulse with marked
distention and collapse
• De Musset sign
• Bobbing of the head in synch with heart
beat
• Duroziez sign
• Diastolic murmur over the femoral
artery
• Hill sign
• Popliteal systolic pressure more than 60
mm Hg greater than brachial pressure
• Muller sign
• Bobbing of the uvula during systole
• Quincke sign
• Capillary pulsations at the lip or
proximal nail bed
• Traube sign
• systolic and diastolic “pistol shot”
sounds heard while auscultating over
the femoral artery.

Pulmonic Regurgitation

• Primary causes include iatrogenic, infectious, rheumatic heart disease, carcinoid and
congenital
• Secondary most commonly develops with severe pulmonary hypertension
• High pitched diastolic decrescendo murmur at the left sternal border
• Indistinguishable from AR
• Echocardiogram differentiates the two
 Right axis deviation of +110° or more.
• Trivial or mild PR is common
• Nothing to do  Dominant R wave in V1 (> 7mm tall or R/S ratio >
• Leads to right heart failure but tolerated for a long time 1).
• What would an ECG show? Right ventricular hypertrophy, right bundle branch blocks  Dominant S wave in V5 or V6 (> 7mm deep or R/S
ratio < 1).
 QRS duration < 120ms (i.e. changes not due to
RBBB).
Mitral regurgitation
• Sometimes confused with Aortic stenosis due to ischemic papillary
muscle dysfunction – regurgitation may be directed to anterior left
atrial wall
• Clench fists – systemic vascular resistance increases and
the murmur increases Mitral Valve prolapse
• Murmur decreases with standing or Valsalva • Last systolic crescendo murmur with midsystolic
• Chronic click
• Holosystolic, high pitched blowing murmur • Click occurs due to sudden tightening of
• Loudest at apex, radiates toward axilla the chordae tendineae
• Causes • Most frequent valvular lesion – 2%
• Myxomatous degeneration of the valve • Redundancy of valve tissue
• Infective endocarditis • Can be inherited
• Rheumatic fever • Primary autosomal dominant with
• Hypertrophic obstructive cardiomyopathy variable penetrance
• Idiopathic rupture of chordae tendineae • Associated with other diseases – Marfan
• Ischemic heart disease syndrome, Ehlers-Danlos
• Mitral valve prolapse • Generally asymptomatic
• Degenerative mitral valve disease (mitral • Chest pain, palpitations, shortness of breath or
valve prolapse) syncope
• Rheumatic heart disease • Diagnosis confirmed by echocardiogram
• Infective endocarditis • Treatment is watchful waiting and looking for
• Trauma progression into MR
• Drugs – ergotamine (migraines),
bromocriptine (Parkinson’s/pituitary
tumors), pergolide (Parkinson’s), cabergoline
(pituitary tumors)
• Congenital malformations Aortic Stenosis
• Mitral annual calcifications • Causes
• Secondary causes – CAD, dilated • Degenerative calcific changes of the valve
cardiomyopathy, hypertrophic • Congenital deformed valve – bicuspid
cardiomyopathy • Chronic rheumatic disease
• 70% of adults have trivial MR • Late peaking systolic ejection murmur
• Systolic murmur • Heard best at the right upper sternal border
• Timing, quality, intensity, location and radiation are variable based on • Radiates to the right supraclavicular area
etiology • Presence of S4 [best heard at the apex]
• Heard best over the apex • Obstruction of AS develops gradually, LV compensates with
• Radiates to the axilla or posterior left thorax concentric hypertrophy
• Most often blowing and high pitched in quality • Symptoms
• Minimal variation with respiration • Syncope – ventricular hypertrophy increases
• Management pressure, it does not increase cardiac output, during
• Symptomatic patient with chronic MR with EF <60%  exercise there is vasodilatation, combo of cardiac
Beta Blocker, ACEI, aldosterone antagonist, diuretics output and vasodilation results in decreased cerebral
• Surgery is usually needed when patient become perfusion
symptomatic • Angina – myocardial oxygen mismatch
• Asymptomatic patients with EF between 30 -60%  • Dyspnea on exertion
recommended to have surgery • Once symptoms are present decreased survival if the
Bicuspid Aortic Valve valve is not replaced
• Acute
One of the most common types of congenital heart disease – 1% of the • Rthese symtpoms occur because the heart is not
•
general Causes
population compensating properly
• •
2-3:1 Ruptured
male mitralpredominance
to female chordae tendineae • Valve anatomy (surface area)
• Can be autosomal• Papillary muscle
dominant rupture
inheritance with variable penetrance • Normally 3-4 cm2
• •
Calcification occurs Dynamic left ventricular
more rapidly as compared outflow obstruction
to tricuspid aortic valves • Mild > 1.5 cm2
• • it related
Is Symptoms are more
to another severe than chronic MR due to the inability
disease? • Moderate 1 to 1.5 cm2
•of the Ascending
left atriumaortic
and ventricle
aneurysm to adapt • Severe less than 1 cm2
• •Considered a cardiac
Mutation emergency 9q
on chromosome  pulmonary edema, • Echo – LVH, valve area
•hypotension
Turner and cardiogenic shock
syndrome • Bicuspid valve
• •May mimic an acute
Loeys-Dietz pulmonary process (infection or acute
syndrome • Cardiac Catheterization – sometimes used for severity and rule
•respiratory distress
Familial syndrome)
thoracic aortic aneurysm syndrome due to ACTA2 out concurrent CAD
• Physical exam and MAT2A mutations
mutations
• Screening • Pulmonary edema, pallor, diaphoresis
• •
First Arterial
degree pulse isfor
relatives rapid and low
bicuspid amplitude
aortic valve
• • Systolic murmur – can be early, mid or holosystolic
Echocardiogram
normal
• Can be asymptomatic for •a LONG Soft,
timelow pitched and decrescendo
• Can lead to aortic stenosis• or regurgitation
Heard best left sternal border
• Higher risk for endocarditis • May radiate to the back
• Associated with • Can be confused with acute ventricular
• septal defect
Coarctation of the aorta
• •Management
Aortic dilation and dissection
• Considered a surgical emergency
• Nitroprusside can reduce MR
• Vasodilators are limited due to systemic
hypotension
• Do not give vasodilators it will worsen
their hypotension
• High surgical mortality, but medical management
alone is higher ***
•

• EKG
• Left atrial enlargement
• Left ventricular hypertrophy
• Echocardiography
• Identifies structural cause
• Grade of severity
• Cardiac catheterization
• Ischemic causes
 Tricuspid Regurgitation
• Harsh holosystolic
• Best heard at the diaphragm, lower left 2nd and 3rd
interspaces on the left sternal border
• Maximum intensity – cardiac apex
• Usually functional – right ventricular enlargement,
secondary to pulmonary hypertension
• Rare cause – carcinoid syndrome
• Increases with inspiration or pushing on the liver

Pulmonic Stenosis
• RARE
• Diamond shaped, systolic
• Heard best at left upper sternal border
• Congenital deformity
• Symptoms occur with severe obstruction include
• Dyspnea, fatigue, syncope and chest pain
• Most patients are asymptomatic

Idiopathic Hypertrophic SubAortic Stenosis

• Harsh, diamond shaped, mid systolic murmur
• Can be confused with aortic stenosis
• Heard best at left sternal border
• Softer with squatting
• Louder with standing
• Causes – subvalvular muscular ring or obstructive
cardiomyopathy

Valve repair
• Mechanical
• Requires life long anticoagulation
• Coumadin used to be the only one, newer ones are
now being approved
• Longer durability
• Generally preferred for younger patients [exception is primarily
pregnancy and the patients wishes]
• Bio prosthetic
• Porcine, bovine or human homograft
• Limited durability, structural failure at 15 years
• Low rate of thromboembolism
• Pregnant women should not be on coumadin so preferably
bioprosthetic
• Preferred for patietns older than 65 or patients with
contraindications to anticoagulation
Antibiotics and Heart valves
• Highest risk — People with the following conditions are considered to be at the
highest risk of developing IE. Preventive antibiotics are generally recommended
for people with the following conditions before certain procedures:
• A prosthetic heart valve
• Valve repair with prosthetic material
• A prior history of IE
• Many congenital (from birth) heart abnormalities, such as single
ventricle states, transposition of the great arteries, and tetralogy of
Fallot, even if the abnormality has been repaired. Patent foramen
ovale, the most common congenital heart defect, does not require
prophylaxis.
• Moderate Risk – DO NOT REQUIRE ABX
• Valve repair without prosthetic material
• Hypertrophic cardiomyopathy
• Mitral valve prolapse with valvular regurgitation and/or valvular
thickening
• Most other congenital cardiac abnormalities not listed above
• Unrepaired ventricular septal defect, unrepaired patent ductus
arteriosus
• Acquired valvular dysfunction (eg, mitral or aortic regurgitation or
stenosis)
OMM
• Atrial septal defect, ventricular septal defect, or patent ductus
arteriosus that was successfully closed (either surgically or with a • Parasympathetics are controlled by the vagus
catheter-based procedure) within the past six months • OA release
• Low risk • Sympathetic T1-T6
• Physiologic, functional, or innocent heart murmurs • Techniques to remember
• Mitral valve prolapse without regurgitation or valvular leaflet • Pectoral traction release
thickening • Rib raising
• Mild tricuspid regurgitation
• If life threatening situation fix the patient but remember OMT for
• Coronary artery disease (including previous coronary artery bypass
graft surgery) supplemental treatments
• Simple atrial septal defect
• Atrial septal defect, ventricular septal defect, or patent ductus
arteriosus that was successfully closed (either surgically or with a
catheter-based procedure) more than six months previously
• Previous rheumatic fever or Kawasaki disease without valvular
dysfunction
• People with pacemakers or defibrillators
 Lecture 14: Pediatrics
Innocent Cardiac murmurs Nearly 90% of all infants, children and adolescents will have a heart murmur at some time.

Result from turbulent blood flow and are not caused by structural heart Less than 5% of these murmurs are considered pathologic.
disease. Upwards of 50% children have an innocent murmur.
Approximately 50-70% of individuals screened for school or sports exams have a murmur.
 Still’s murmur – most common innocent murmur in children. It
is a benign systolic ejection murmur due to flow arising from Cardiac examination of children should involve observation, auscultation, and palpation.
turbulent flow in the LV outflow tract. It presents as a musical or
vibratory murmur at mid to LSB toward the apex.
 Pulmonary flow murmur – two types include infantile and
childhood types. This murmur is a result of turbulence in the RV
outflow tract.
Cardiac Examination
 Supraclavicular flow murmur – the result of turbulent flow from
arterial branches off the aortic arch. Heard best above the
clavicles. Often associated with a palapable carotid thrill.
 Venous hum – This murmur is caused by blood cascading down
the jugular vein. It is best auscultated in the right infra-clavicular
region in seated or standing position. It disappears when supine
or with gently pressure over the jugular vein
 Mammary souffle – this murmur is heard only in pregnant
and/or lactating women, due to the turbulent blood flow in the
dilated breast blood vessels.

Pathologic Murmurs

All diastolic murmurs with exception of venous hum are

pathologic.
- Systolic ejection murmurs
LV outflow stenosis
RV outflow stenosis
ASD, TAPVR
- Regurgitant systolic murmurs
mitral regurge
- Early and late diastolic murmurs
- Continuous pathologic murmurs

Causes of Chest Pain

 Pericarditis – is the most

common cardiac cause
 Coronary artery abnormalities
(congenital and acquired)
 Mitral valve prolapse
 Myocarditis
 Left ventricular outflow tract
obstruction
 Dysrhythmias
 Pulmonary hypertension,
endocarditis, acquired cardiac
disease
Costochondritis vs Tietze

 Chostochondritis is the most common cause of chest pain in children at 15-31%.

o Sharp stabbing pain upper two constochondral junctions, and is exacerbated by deep breathing.
o Pain lasts few seconds to few minutes and can be reproduced.
 Tietze syndrome – usually a single joint, 3rd rib most commonly, affected.
o There is localized warmth, edema, and tenderness at site.

Treatment :

 Rib raising is very effective in costochondritis. Examination may also find a rib that is out of place, as a cause for chest pain. This is also amenable to osteopathic manual medicine.
 Reassurance
 Analgesia
 Rest
 Steroids and anti-inflammatory If pericarditis is present

Management

If cardiac origin is suspected, a cardiologist should be consulted, and care initiated immediately with
echocardiography.

For musculoskeletal sources of chest pain, several osteopathic techniques are available for
treatment.

Bradydysrhythmias Tachydysrhythmias
 These arrythmias include supraventricular tachycardia (SVT), atrial flutter,
 usually caused by sinus node dysfunction, and include second and third degree AV atrial fibrillation, ventricular tachycardia, and ventricular fibrillation.
block.  In hemodynamically stable SVT, vagal maneuvers may be tried, and if not
 Bradycardia from AV block can be caused by drugs, acute myocarditis, or congenital successful, adenosine may be used.
heart block. Bradycardia is also a response to hypoxia in neonates, but may signal  DC cardioversion is the treatment of choice in unstable SVT, followed by
impending cardiac arrest in older children or adolescents. adenosine.
 Treatment should include adequate ventilation and oxygenation, epinephrine and  SVT is an abnormally accelerated heart rhythm originating proximally to
perhaps atropine if indicated. the bundle of HIS. It is the most common dysrhythmia in childhood. Wolf
Parkinson White – most common re-entry tachycardia and may result in
sudden death.
 Heart block is delayed or interrupted conduction of sinus or arterial impulses to the
ventricles.  NEVER USE CALCIUM CHANNEL BLOCKERS (VERAPAMIL) TO TREAT:
a) first degree – prolongation of the PR interval o INFANTS
b) second degree – o ANYONE WITH WOLFF-PARKINSON-WHITE SYNDROME
Type I – wenckebach – progressive o CHILDREN WITH CONGESTIVE HEART FAILURE
prolongation of the PR leading to failed AV conduction o CHILDREN TAKING BETA-BLOCKERS
Type II – abrupt failure of AV conduction without  Profound hypotension and cardiac arrest may occur if these drugs are
prolongation or progression of the PR interval. used in the above people.
c) Third degree- complete block, may be congential, postsurgical, or associated with  Management
bacterial endocarditis o Children with rhythm disturbances should be evaluated by a
 Long QT syndrome – pediatric cardiologist in consultation with an
electrophysiologist.
 Prolongation of QT interval which increases the risk of lethal ventricular
o Most of these children do well, and have a normal life.
arrhythmias such as Torsades de pointes.
o Follow up testing that is used most often, is ECG 24 hour
A) autosomal recessive –Jervell – Lange –Nielsen Holter monitor testing.
associated with congenital deafness. o Stress testing may be indicated in some individuals, especially
B) Autosomal dominant – Romano- Ward syndrome those having chest pain or rhythm disturbances during
C) Drugs physical activity.
1) Phenothiazines
2) Tricyclic antidepressants

3) Erythromycin

4) Terfinadine
o May present with syncope or sudden cardiac arrest.
Syncope
- Sudden loss of consciousness and postural tone due to transient cerebral under perfusion with spontaneous recovery
- Noncardiac Causes
o Neurally mediated –
 Vasovagal syncope is the most common noncardiac type.
 he episode lasts less than one minute, and has a prodrome of dizziness, pallor, nausea, diaphoresis and hyperventilation.
 This type accounts for up to 75% of all cases. The cause is not well known.
 Reflex or situational syncope occur in conjunction with grooming, micturition, defecation, coughing, stretching or swallowing.
 The cause is thought to be a sudden increase in vagal tone.
 Neurologic disorders such as seizures, tumors, and familial dysautonomia account for syncopal episodes. These types occur more often in younger
children.
 Miscellaneous causes can include anemia, electrolyte imbalances, hypovolemia, toxin inhalation and ingestions.
 Psychiatric disorders such as conversions reactions and malingering.
 Toddlers can have breath-holding spells that end in a syncopal episode.

- Cardiac Causes
o Cardiac syncope may be the result of
 Structural heart disease
 Arrhythmia
 Myocardial dysfunction.
o *Cardiac syncope is the usual cause associated with syncope during exercise.

Signs and Symptoms

 Pre-syncope –weakness, sweating, warm rushing feeling, dizziness, headache, palpitations, visual disturbances, nausea, pallor without complete loss of consciousness.
 True syncope – Patient becomes completely flaccid and does not remember.

Diagnostic Test
Laboratory evaluation should include:
- hemoglobin
- electrolytes
- glucose
- toxicology screening
- urinalysis
Other tests should include and ECG, possibly an echocardiogram, stress test, and Holter monitor

EVALUATION
This cardiac
cause of
syncope was
discovered
on a 24 hour
Holter
monitor
recording
-Bradycardia
and it comes
back followed
by reflex
tachycardia

Management
 Reassurance is very important for families of children having neurally mediated syncope.
 Medical treatment is determined by the cause, and may include hospitalization or fluid and salt intake should be improved.
 The help of a cardiologist should be enlisted whenever cardiac syncope is suggested

Medical Treatment
Vasovagal syncope usually does not require any treatment. Repeated episodes will need to be treated based on the underlying etiology.
Some of the medicines that can be used for prevention of vasovagal syncope include:
- pseudoephedrine
- metoprolol
- fludrocortisone
- disopyramide
- scopolamine
Red flags for syncope
 Recurrent, atypical or unexplained episodes.
 Syncope with exercise
 Syncope with palpitations or chest pain
 History of cardiac abnormalities
 Abnormal cardiac physical exam or ECG
 Neurologic deficits
 History or family history of neurologic disorders.
 Lecture 15: Acquired Heart Disease
Rheumatic Fever
- An autoimmune inflammatory disease that follows infection with specific strains
of GAS (beta hemolytic)
- 5-15 years; F > M; mitral valve prolapse and chorea occur more often in females.
African American > Caucasian
- History of sore throat 1-5 weeks prior in 2/3 of cases
- Throat cultures for strep are negative by the time a patient is symptomatic with
acute rheumatic fever [possible synovial fluid analysis]
- Major Criteria
o Carditis- is the most serious consequence of RF. Inflammation may
involve valves, myocardium, or pericardium. [all layers of the heart
are affected]
 Most commonly mitral valve affected. Leading to
sequelae of MV insufficiency. Mitral stenosis is a late
complication 20 years later.
 Aortic valve is second most commonly affected leading
to Aortic Insufficiency. Aortic stenosis is a late
complication 20 years later.
o Polyarteritis – large joints (knees, wrists, hips, elbows and shoulders)
in migratory fashion.
 Common in 80% of patients
 Starting in the lower limbs in 75%of cases.
o *Sydenham Chorea – involuntary movements with ataxia and slurring
of speech. May last up to three months. May occur months to years
later.
o *Erythema Marginatum – macular erythematous, serpiginous rash
with a well demarcated border on trunk and extremities sparing
face.
o Often confused with ring worm
o Subcutaneous nodules – joints, scalp, and spinal column. Up to 2 m,
non-tender, and freely mobile.
DO NOT USE TETRACYCLINES OR SULFONAMIDES TO TREAT GROUP A BETA HEMOLYTIC
STREP.
Kawasaki = mucocutaneous lymph nose syndrome
- A self-limited vasculitis that occurs in childhood and has an unknown etiology
- More frequently observed in Japan
- 80% of cases occur in children less than 5y/o
- Children of higher socioeconomic status
- More common in males
- Periodic epidemics occurs in the winter and spring
- The cardiovascular manifestations are the most important complications, and a reason for
hospitalization of affected children.
o Coronary artery aneurysms, myocarditis, pericardial effusions, dysrhythmias, and
congestive heart failure
- This illness is the leading cause of acquired heart disease in children in the U.S.
- Fever or greater than 5 days duration
- Many of these children present with classic symptoms of ear and throat infections, and many get
antibiotic therapy.
- The onset of this disease is abrupt, and a stiff neck may raise the possibility of meningitis. The lips
become red and fissured and a bilateral conjunctivitis is present. Most children have what is
known as a “strawberry” tongue. This finding also occurs in streptococcal infections.
- 3 distinct phases
1. Acute febrile phase (1-11 days)
a. Fever, arthritis, bilateral conjunctival non-purulent inflammation,
polymorphous rash, cervical lymphadenopathy
2. Subacute phase (11-21 days)
a. Platelet counts as high at 1 million (normal is up to 500,000)
b. Children are at the highest risk of sudden death
c. Desquamation and aneurysms
3. Convalescent phase (21-60 days)
a. Coronary artery aneurysms
- There is also a chronic phase for children developing cardiac complications
- Treatment
o Immediate management is the key to a good outcome. Since most of the
pathophysiology involves inflammation, anti-inflammatory therapy does improve
the outcome, and may be life-saving.
o The drug used is intravenous immune globulin (IVIG), 2 g/kg intravenously over 10-
12 hours in a single dose. This may be repeated if the response is less than optimal.
o Aspirin has a synergistic effect with IVIG to increase the anti-inflammatory
response, and to inhibit platelet aggregation. The initial dose of aspirin in 80-100
mg/kg/day divided 4 times a day for 2 weeks. After that, 3-5 mg/kg/day once a day
for 6-8 weeks (taper).
 Aspirin should be given long term in children with cardiac
complications, such as an aneurysm.
o These two therapies are effective in decreasing the incidence of coronary artery
dilatation and aneurysm formation.
o
Infective Endocarditis
- An infection of the endocardial surface of the heart
- Bacterial and fungal infections of the endocardium are rare and often involve congenital abnormalities of the heart, septic states, and indwelling catheter use.
- Patients having experienced a prior episode are at higher risk.
- Common organisms are streptococcal viridans (30-40%), Staph aureus (25-30%) and fungal agents (5%).
- Although transient bacteremia is frequent with such activities as eating, brushing teeth, flossing, or using a toothpick, an inciting incident is often not identifiable.
- Frequently presents as indolent manner with fever, malaise, and weight loss, joint pain and vomiting.
- Physical signs often include changing murmur, splenomegaly and hepatomegaly.
- May have Osler’s nodes (tender nodules on finger), Janeway lesions (nontender hemorrhagic macules on palms and soles, and Roth spots (retinal hemorrhages).

Cardiomyopathies

1. Hypertrophic cardiomyopathy
- Genetic disorder that has variable presentation and is the most important cause of sudden death in children and adolescents
- Slightly more common in males than females, but the inheritance pattern is autosomal dominant, with gender predilection. It usually present earlier in females than males., and
females are more symptomatic.
- In adults, the most common time of presentation is during the third decade of life. Children’s cases peak in the second decade of life.
- In hypertrophic cardiomyopathy, mutations may impair myosin binding protein C and other protein interactions, resulting in ineffectual contraction of the sarcomere .
- The feature of this disorder that attracts the greatest attention is the pressure gradient across the left ventricular outflow tract.
o The result of this pressure is diastolic dysfunction, leading to abnormal calcium kinetics, and subendocardial ischemia.
- Clinical findings
o Many persons affected by hypertrophic cardiomyopathy are asymptomatic, however, here is a list of symptoms that may be present, together or individually:
 most common arrhythmia is ventricular fibrillation
 dyspnea, is the most common presenting symptom****
 syncope, a very common symptom
 palpitations
 dizziness, common in children
 paroxysmal nocturnal dyspnea, uncommon in children
 presyncope( “graying out” spells”), predicts increased risk for sudden death
 angina and chest pain
o Treatment:
 Beta-blockers can be given to decrease outflow obstruction and increase ventricular compliance.
 Calcium channel blockers are an alternative to beta-blockers and improve diastolic relaxation, and decrease the outflow gradient. Use great caution in
younger children.
 Amiodarone is used exclusively for life-threatening arrhythmias, such as ventricular tachycardia
o Follow up
 Persons affected by hypertrophic cardiomyopathy should be advised NOT to participate in strenuous activity of any type.
 Regardless of pacemaker placement, in persons with following types of problems, COMPETITIVE SPORTS ARE CONTRAINDICATED:
 - significant outflow gradient
 - ventricular or supraventricular arrhythmias
 - marked left ventricular hypertrophy
 - history of sudden death from cardiac arrest in relatives having hypertrophic cardiomyopathy
2. Dilated Cardiomyopathy
- Left and right ventricular dysfunction with subsequent ventricular dilation and heart failure.
- 60-70% of pediatric cardiomyopathies
- Incidence: 5-20: million children
- Etiology:
o Viral cause in up to 15% of cases.
o Genetic cause common. Autosomal dominant, autosomal recessive, x-linked and mitochondrial inheritance patterns.
- Mechanism of Injury: circulating catacholamines in response to decreased or inadequate cardiac output. BNP, renin, angiotensin II and others cause excessive vasoconstriction,
intravascular volume expansion, hypertrophy of myocytes and dilatation of the chambers
- Presentation suggest congestive heart failure [if they present like CHF usually given something like a diuretic to handle fluid]
o gallops, dyspnea, liver margins extended, bad xray
- ECG shows sinus tachycardia
- CXR: Cardiomegaly and pleural effusion
- Echo: ventricular dilation
 Presyncope
 Lightheadedness
Lecture 16: Syncope/Pre-syncope  A feeling of being warm or cold
 Sweating
Syncope  Palpitations
 Transient loss of consciousness , generally from decreased cerebral perfusion from a drop in systemic blood pressure.  Nausea or non-specific abdominal discomfort
 1% of all hospital admissions are related to syncope  Visual "blurring" occasionally proceeding to temporary darkening or
 1-3% of all ER visits are related to syncope "white-out" of vision
 Causes  Diminution of hearing and/or occurrence of unusual sounds (particularly
o Neurocardiogenic (vasovagal) a "whooshing" noise)
 Passed out after they donated blood  Pallor reported by onlookers
o Orthostatic
o Cardiac
o Neurogenic Vasovagal
 Things that mimic Syncope ● Cold and clammy
o Disorders with partial or complete loss of consciousness, but without global cerebral hypoperfusion ● Normal neuro
 Epilepsy ● Can get hot and sweaty
 Metabolic disorders including hypoglycaemia, hypoxia, hyperventilation with hypocapnia ● No chest pain
 Intoxication ● No palpitation before-hand
 Vertebrobasilar TIA ● After exercise
o Disorders WITHOUT impairement of consciousness ● ECG is normal
 Cataplexy [Can’t talk during that period of muscle giving out] ● Coughing, swallowing, defecations, fear can cause this
 Drop attacks ● Young healthy people
 Falls Cardiac
 Functional (psychogenic pseudosyncope) ● Chest pain, SOB, palpitations (before)
 TIA or carotid origin ● During exercise
 Before you do anything ● Passed out while laying flat more likely cardiac cause (all others are
o Is the patient stable? standing up)
o Blood pressure ok? ● ECG may be abnormal
o Heart rate ok? ● Maybe a murmur
o breathing? Orthostatic
o If not… fix that first ● Standing/ changing positions
 Look for things that kill people ● Laying down to seated and seated to standing are possible
o Ischemic heart disease ● Diagnosis is based on blood pressure  drop in BP [can be caused by
o Fatal arryhtmias dehydration, blood loss, neurogenically/autonomic dysfunction
o CVA (Parkinson’s, POTS, diabetes)]
o Pulmonary embolism Neuro
o Hemorrhage ● Least likely of all of them
o Subarachnoid hemorrhage ● Neuro exam will have a deficit present
Comprehensive H&P ● Stroke symptoms [not confused]
 Number frequency, and duration of episodes Reflex (neutrally mediated) syncope
 Onset of syncope Vasovagal:
 Position Mediated by emotional distress: fear, pain, instrumentation, blood phobia
 Provocative factors Mediated by orthostatic stress
o During or immediately after exercise [cardiac syncope during exercise; vasovagal after exercise] Tilt testing  confirm vasovagal
o During or immediately after urination, defecation, coughing or swallowing [vasovagal]  Leg-crossing with simultaneous tensing of leg, abdominal,
o While in a warm and/or crowded place [could be any, mostly vasovagal] and buttock muscles
o During prolonged standing [vasovagal] ; orthostatic immediately after standing  Handgrip, which consists of maximum grip on a rubber ball
o During the post-prandial period or similar object
o In association with emotional stress, fear, or intense pain  Arm tensing, which involves gripping one hand with the
o Immediately following abrupt neck movements [reflex, vasovagal] other while simultaneously abducting both arms
 Preceding syncope o Reassurance
o Nausea o Avoid situation
o Vomiting Situational:
o Feeling cold or clammy [more with vasovagal, but can see with others] Cough, sneeze
o Visual auras or blurry vision Gastrointestinal stimulation (swallow, defecation, visceral pain)
o Palpitations [cardiac cause more likely] Micturition (postmicturition)
o Shortness of breath Post-exercise
o Chest pain Postprandial
 Post event associated symptoms Others (eg, laughter, brass instrument playing, weightlifting)
o Fatigue Carotid sinus syncope
o Injury -Neck movement****
o Nausea Orthostatic
o Vomiting Primary autonomic failure:
o Feeling cold or clammy Pure autonomic failure, multiple system atrophy, Parkinson's disease with
o Palpitations autonomic failure, Lewy body dementia
 If they have palpitations before and after, probably not a cardiac cause [vasovagal will have Secondary autonomic failure:
palpitations after] Diabetes, amyloidosis, uraemia, spinal cord injuries
o Shortness of breath [cardiac] Drug-induced orthostatic hypotension:
o Chest pain [cardiac] Alcohol, vasodilators, diuretics (can also be a cause of volume depletion),
 Review medication phenothiazines, antidepressants
o Calcium channel blockers Volume depletion:
o Beta blockers Hemorrhage, diarrhea, vomiting, etc
o Alpha blockers Tx:
o Nitrates  Immediately replace volume
o Antiarrhythmics [may induce V. tach?]  Normal saline or blood
o Diuretics  Increase salt and water intake
o QTc medications  Decrease medication dose or adjust
 Family Hx:  Adjust posture, compression stockings
o Sudden cardiac death  Sit until you feel steady with older people [take longer to
o Arrhythmias change positions]
o Ischemic disease  Medications - for me not expected to know at this time.
 Vital Cardiac
o Blood pressure Bradycardia:
 Check “orthostatics” Sinus node dysfunction (including bradycardia/tachycardia syndrome)
 Blood pressure measured - laying flat, sitting up, and standing  pacemaker
 Start supine for 5 minutes Atrioventricular conduction system disease
 Standing for 3 minutes Implanted device malfunction
 Drop in systolic blood pressure more than 20 mmHg or diastolic 10 mmHg Tachycardia:
 PE Supraventricular
o Carotids Ventricular (idiopathic, secondary to structural heart disease or to
o Cardiac exam channelopathies)
o Pulmonary exam Drug-induced bradycardia and tachyarrhythmias
o Oral exam Structural disease:
o Neurologic exam  Cardiac: cardiac valvular disease (aortic stenosis)
o +/- rectal o Acute myocardial infarction/ischaemia, hypertrophic
 ECG cardiomyopathy, cardiac masses (atrial myxoma, tumors,
o Cheap and easy to do etc),
o Low diagnostic value (2-7%) o Pericardial disease/tamponade, congenital anomalies of
o Arrhythmia coronary arteries [syncope in a child], prosthetic valves
o Ischemic heart disease dysfunction
 Others: pulmonary embolism, acute aortic dissection, pulmonary
hypertension