Cardiovascular Toxicity in

Cancer Treatment:
CASES
ANTONELLO D’ANDREA
PhD - FESC – EACVI
Chair of Cardiology – Luigi Vanvitelli University –
Monaldi Hospital - Naples - Italy
Valves
CASE 1

ASYMPTOMATIC…!!
after 1 year of treatment..!
LV EF : 23%
LV GLS : 6 %
“Cancer therapeutics-related cardiac
dysfunction (CTRCD) is defined as a decrease
in the LVEF of >10 percentage points, to a
value below the lower limit of normal (50%)”.

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity

developed under the auspices of the ESC Committee for Practice Guidelines
In our patient the final cardiotoxic effect
resulted from a combined action

Association between antineoplastic agents and

systolic disfunction:

Doxorubicin +++
Trastuzumab +++
Cyclophosphamide +
 NO
FIBROSIS!
 …a heart failure pharmacological treatment was orally
introduced (bisoprolol 3,75 mg, enalapril 10 mg, canreonate 50
mg, furosemide 50 mg).
After 6 months of medical
treatment..
After medical treatment..

LV EF : 48 %
 After medical treatment..
 Due to a severe progression of disease,
trastuzumab was resumed and continued for
more than one year, without cardiac demage

DOX ✢TRA
LEP
TRA
 Cancer Therapeutics-Related Cardiac
Dysfunction (CTRCD)

Ewer and Lippman classification (2005):

 Type 1: myocyte injury, dose related,

irreversible
 ANTHRACYCLINES
 Type 2: absence of ultrastructural
abnormalities, lack of dose relationship,
reversibility with cessation of treatment
 TRASTUZUMAB
This classification has been queried because:
 Anthracyclines cardiotoxicity may be
reversible with an early initiation of
neurohormonal antagonists
 Trastuzumab cardiotoxicity is not always
reversible
 Anthracyclines and Trastuzumab are rarely
administered as sole agents, and are usually
preceded or followed with other classes of
drugs (synergic/combined action)
 Case 2: Past medical history

 70 year-old woman

 No cardiovascular risk factors

 No pre-existing cardiac disease

 Past medical history

 Diagnosis of non-Hodgkin lymphoma 10 years

before  CHOP chemotheraphy:
Cyclophosphamide, Doxorubicin
(Hydroxydaunorubicin), Vincristine (Oncovin)
and Prednisone + mediastinal radiotherapy

 Diagnosis of chronic myeloid leukemia 1 year

before  chemotheraphy: Imatinib mesylate
 Recent medical history
Access to the emergency room with severe
dyspnoea: acute pulmonary edema effectively
treated with diuretics and non-invasive
mechanic ventilation

SEVERE FUNCTIONAL MITRAL REGURGITATION

Admission to our cardiology department

Trans-thoracic 2D Echocardiography:
assessment of LV function

Impaired LV systolic function

Trans-thoracic 2D Echocardiography:
biplane modified Simpson's method

LV EF: 26%
Trans-thoracic 2D Echocardiography:
GS in APLAX
In our patient the final cardiotoxic effect
resulted from a combined action of
Doxorubicin, Cyclophosphamide and Imatinib.

Association between antineoplastic agents and

systolic disfunction:

Doxorubicin +++
Imatinib ++
Cyclophosphamide +
Trans-thoracic 2D Echocardiography:
aortic stenosis
Transesophageal echocardiography:
aortic stenosis
Transesophageal echocardiography:
mitral regurgitation
Frequency of Severe Valvular Disease Caused by Mediastinal Radiation
Among Patients Undergoing Valve Surgery in a Community‐Based,
Regional Academic Medical Center

Aortic valve specimen - Pathological findings consisted of

nodular thickening and calcification

Clinical Cardiology
Volume 36, Issue 4, pages 217-221, 14 MAR 2013 DOI: 10.1002/clc.22106
http://onlinelibrary.wiley.com/doi/10.1002/clc.22106/full#clc22106-fig-0002
Frequency of Severe Valvular Disease Caused by Mediastinal Radiation Among Patients
Undergoing Valve Surgery in a Community‐Based, Regional Academic Medical Center

Clinical Cardiology
Volume 36, Issue 4, pages 217-221, 14 MAR 2013 DOI: 10.1002/clc.22106
http://onlinelibrary.wiley.com/doi/10.1002/clc.22106/full#clc22106-fig-0001
Valvulopathy after Radiation
Stress Echo and Valvulopathies: When?

EACVI position paper 2016

Dobutamine stress echocardiography:
assessment of AoS severity in low-
gradient AoS with impaired LV function
“When mitral regurgitation is associated with
severe aortic stenosis, its severity may be
overestimated…”

“As long as there are no morphological leaflet

abnormalities surgical intervention on the
mitral valve is in general not necessary”

“In patients with severe mitral regurgitation,

combined or sequential TAVI and percutaneous
mitral edge-to-edge repair have been
demonstrated to be feasible, but there is not
enough experience to make recommendations”
2017 ESC/EACTS Guidelines for the management of valvular heart disease
Transthoracic echocardiography
after TAVI
Transthoracic echocardiography
after TAVI

GLS 6%
2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy
 Transthoracic echocardiography:
LV function 1 year after CRT

Significant improvement of LV systolic function

Transthoracic echocardiography:
LV function 1 year after crt

EF 51% GLS 16%

 Transthoracic echocardiography:
mitralic rigurgitation 1 year after crt
 CASE 3: Clinical History
 Male, 61-year old.
 Permanent atrial fibrillation, Hypertension,
Diabetes Mellitus, Chronic kidney disease
(stage III), iatrogenic hyperthyroidism.
 Carpentier’s reconstructive mitral valve
surgery in 2005.
 PMK implantation in 2005.
 High levels of erythropoietin, Hb 17,5 g/dl-
>ongoing genetic analysis for the mutation
V617F di JAK-2 (Polycythemy vera?)
 Recent clinical hystory
 NYHA Class III.
 Recent hospitalization (2017,
August) for worsening dyspnea and
intense asthenia.
 Therapy: Furosemide 25 mg 3
tb/day, Ramipril, Warfarin, beta
blockers, digitalis, insulin.
 Labile INR.
 PET/CT
For evidence of pulmonary
lesion, the patient practiced
PET /CT.

“Moderata metabolic parenchymal

hyperactivity at the pulmonary
medium lobe. Metabolic
hyperactivity of lymph nodes. No
further areas of metabolic
hyperactivity at the level of the
remaining body segments examined».

Pulmonary Adenocarcinoma !
TTE
MITRAL REGURGITATION ++/++++
Mass occupying approximately 50% of the volume of the left
atrium, probably thrombotic nature ......
…… and further oval-shaped formation,
approximately 36 mm in length, with no LV inflow
obstruction.
TROMBOSIS IN NEOPLASIA
 Virchow’s triad
Blood flow
- Blood stasis (AF; EF <20%).
alterations - LA dilatation

-High levels of erythropoietin

Hyper (Polycytemy vera??)
coagulability -Lung neoplasia
-Platelet activation, due to the flow
turbolence.

Endothelial
Dysfunction -AF; Mitral regurgitation.
 Treatment of AF in cancer patients is a challenge,
particularly in terms of antithrombotic therapy for stroke
prevention.

 History of cancer has not been incorporated in the

thromboembolic risk prediction scores such as CHA2DS2
-VASc
 Some anticancer therapies and in particular the novel
angiogenesis inhibitors have been related to
thromboembolic complications
 Some malignancies , such as primary or metastatic
intracranial tumors and hematological malignancies,
pose an increased risk of hemorrhage.
1 month follow-up

subcutaneous twice-daily enoxaparin (1.0 mg/kg)
TEE
Before…. ….after
 TAKE-HOME MESSAGES (1)

• Classically, we consider two different

chemotherapy drugs depending on the
reversibility of the myocardial injury, although
this classification is not very useful in clinical
practice.
• Cancer patients habitually receive a “cocktail”
of chemotherapy drugs, so it is sometimes
difficult to determine the specific mechanism.
 TAKE-HOME MESSAGES (2)

• The  presence  of  cancer  has  been  seen  to 

produce  myocardial  injury  and  vascular 
trombosis independent of the treatment. 
• Radiotherapy also produces cardiac damage, 
including  myocardial  injury  and  affection  of 
other  structures,  such  as  valves,  which  may 
also progress to HF. 
 TAKE-HOME MESSAGES (3)

 Finally, the existence of cardiovascular risk

factors in cancer patients can accelerate the
development of cardiovascular disease.
CARDIAC TOXICITY IN CANCER