Left Ventricular Hypertrophy

Detection, significance and treatment

Pathophysiology of LVH

High BP LV wall stress Wall stress 1/ wall thickness LV wall thickening wall stress Myocyte hypertrophy and collagen matrix Mediators:

Mechanical: preload & afterload Neurohormonal: angiotensin II, sympathetic NS

Methods of detecting LVH

Clinical examination Chest radiography Electrocardiography Echocardiography (CT, MRI)

Definition of LVH

Healthy cohort of subjects No high BP, diabetes, CV disease, obesity LVH defined as LVMI > mean + 2SD

Framingham Study LVMI > 131g/m2 males; > 100g/m2 females Cornell, New York LVMI > 134g/m2 males; > 110g/m2 females
Levy et al. Am J Cardiol 1987;59:956-60. Devereux et al. JACC 1984;4:1222-30.

Risk factors for LVH

Age Gender Race Genetic factors Blood pressure Obesity Physical activity

Clinic versus mean 24 hour systolic BP and LVMI

Relationship between mean 24 hour SBP and LVMI

Clinic SBP v. LVMI: (r=0.28, p<0.05)

Clinic SBP (mmHg)
200 150 100 50 0 0 100

Linear (Relationship between mean 24 hour SBP and LVMI) Linear (Relationship between mean 24 hour SBP and LVMI)

24 hour SBP (mmHg)

250

24 hour mean SBP v. LVMI (r=0.48, p<0.01)

250 200 150 100 50 0 0 100 200 300

LVMI (g/m2)

200

300

LVMI (gm2)

Mayet al et. J Cardiovasc Risk 1995;2:255-61.

12-lead ECG showing LVH and strain

Sensitivity and specificity of ECG criteria for LVH

Sensitivity Specificity Sokolow-Lyon Cornell voltage Minnesota code 3-1 Framingham criteria 15-30 7-45 3-15 3-17 73-100 93-100 85-99 88-99 98-100

Romhilt-Estes point score 6-50

Devereux et al 1983, Murphy et al 1985, Levy et al 1990, Lee et al 1992, Devereux et al 1993, Schillaci et al 1994, Crow et al 1995, Norman et al 1995, Chapman et al (in press)

Determinants of specificity of ECG criteria for LVH

Age Race Sex Smoking Obesity

Cardiothoracic ratio and CHD mortality: Whitehall study

Cardiothoracic ratio Hazard ratio for CHD* <0.4 0.4-0.439 0.44-0.449 0.45-0.469 0.471.0 1.02 (0.61-1.73) 1.02 (0.60-1.74) 1.33 (0.81-2.20) 1.65 (1.01-2.70)
Hemingway et al. BMJ 1998; 316: 1353-4.

*Adjusted for age, BP, HR, cholesterol, smoking, angina and ECG ischaemia

Cardiovascular risk in subjects with ECG-LVH: Framingham

Age-adjusted risk-ratio

Cardiovascular outcome Coronary heart disease Stroke Peripheral arterial disaese Cardiac failure
*P<0.0001

Men 3.0* 5.8* 2.7 15.0*

Women 4.6* 6.2* 5.3* 12.8*

Kannel. Eur Heart J 1992; 13 (suppl D): 82-88

Risks of X-ray and ECG LVH: Framingham

Age-adjusted biennial rate per 1000
No X-ray enlargement X-ray enlargement No ECG-LVH ECG-LVH 171 669 253 1072

Data include men and women, aged 35-94

Kannel. Eur Heart J 1992; 13 (suppl D): 82-88

Echocardiography

Advantages

sensitivity improved correlation with morbidity & mortality assessment of function (systolic and diastolic) addition to individuals risk profile
skilled operator time cost

Disadvantages

Echocardiographic LVH and prognosis

Ref. Levy et al 1990 Levy et al 1989 Population N General General Follow-up End-points RR with LVH CAD CVD All death Casale et al 1986 HTN Koren et al 1991 HTN 140 280 4.8y 10.2y CVD Men: 1.67 Women 1.60 Men 1.49 Women 1.57 Men 1.73 Women 2.12 Men 3.83 1911 4y 3220 4y

CVD All 2.17 CVD death All 14.0 All death All 3.5

Sheps and Frohlich. Hypertension 1997; 29: 560-563.

M-mode echocardiograms

LVH

Normal

Penn convention for M-mode measurements

Septum (SWT)

Peak of QRS Endocardium excluded from SWT and PWT Endocardium included in LVID

LV cavity (LVID)
LV mass = 1.04[(SWT+LVID+PWT)3 - (LVID)3 - 14g Divide by body surface area to get LV mass index

Posterior wall (PWT)

Devereux & Reichek Circulation 1977;55:613-8

ASE guidelines for M-mode measurements

Septum (SWT)

Start of QRS Endocardium included in SWT and PWT Endocardium excluded from LVID

LV cavity (LVID)
LVM = 0.8{1.04[ (SWT+LVID+PWT)3 - (LVID)3]} + 0.6 g

Posterior wall (PWT)

Divide by body surface area to get LV mass index

Devereux et al. Am J Cardiol 1986;57:450-8

Area-length method for calculation of LV mass

LVmass=1.05[5/6(A1xL1)-5/6(A2xL2)] Divide by body surface area to get LV mass index

Reichek et al. Circulation 1983;67:348-52

4-year age-adjusted incidence of cardiovascular disease according to LVMI

18 16 14 12 10 8 6 4 2 0 <75 75-94 95-116 117Males Females

LVMI (g/m2)

Redrawn from Levy et al; NEJM 1990; 322: 1561-6.

Incidence of cardiovascular mortality according to presence or absence of LVH

5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Men Women

No LVH LVH

P<0.001

P=ns
Redrawn from Levy et al, NEJM 1990; 322: 1561-6.

Echocardiographic LVH and prognosis

Ref. Levy et al 1990 Levy et al 1989 Population N General General Follow-up End-points RR with LVH CAD CVD All death Casale et al 1986 HTN Koren et al 1991 HTN 140 280 4.8y 10.2y CVD Men: 1.67 Women 1.60 Men 1.49 Women 1.57 Men 1.73 Women 2.12 Men 3.83 1911 4y 3220 4y

CVD All 2.17 CVD death All 14.0 All death All 3.5

Sheps and Frohlich. Hypertension 1997; 29: 560-563.

Risks associated with LVM and geometry

Total mortality*
40

Cardiovascular events

% patients

30 20 10 0 >125 <125 >125 <125 >0.45 <0.45

RWT

LVMI (g/m2) *P<0.001, P=0.03

LVMI (g/m2)
Koren et al. Ann Int Med 1991; 114: 345-352.

Regression of LVH by drug treatment: meta-analysis of RCTs

0 -2 -4 -6 -8 -10 -12 -14 Diuretics B-blockers CCB's ACE-I

Between treatment P<0.01

Schmieder et al. JAMA 1996; 275: 1507-1513

LVH regression: LIVE study

1 0

% from baseline

-1 -2 -3 -4 -5 -6 PWT IVST LVID LVMI

Sheridan and Gosse 1998

Indapamide SR Enalapril

*P<0.05 for LVMI

Prognostic significance of Echo LVM regression

Events/ 100 patient years
7 6 5 4 3 2 1 0 All Regressors LVH Non-regressors

*P=0.04, P=0.0004 after adjustment for age.

Verdecchia et al. Circulation 1998; 97: 48-54

Prognostic significance of ECG voltage changes: Framingham

OR for CV events (2 years)
2 1.5 1 0.5 0 Decreased voltage Males Increased voltage Females

*P<0.05

Levy et al. Circulation 1994; 90: 1786-1793

Who to refer for echocardiography?

Patients with borderline BP:

LVH may influence decision to treat

LVH may lead to other interventions e.g. lipid lowering therapy

Patient with multiple risk factors:

Possible white coat hypertension ? To stratify class of antihypertensive agent to be used (increasing data suggesting LVH regression should be a goal of treatment)