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
Linear (Relationship between mean 24 hour SBP and LVMI)
Clinic SBP v. LVMI: (r=0.28, 24 hour mean SBP v. LVMI
Linear (Relationship between mean 24 hour SBP and LVMI)

p<0.05) (r=0.48, p<0.01)

250 250

24 hour SBP (mmHg)

200 200
Clinic SBP
(mmHg)

150 150
100 100

50 50

0 0
0 100 200 300 0 100 200 300
LVMI (g/m2)
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 15-30 73-100
Cornell voltage 7-45 93-100
Romhilt-Estes point score 6-50 85-99
Minnesota code 3-1 3-15 88-99
Framingham criteria 3-17 98-100

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 1.0
0.4-0.439 1.02 (0.61-1.73)
0.44-0.449 1.02 (0.60-1.74)
0.45-0.469 1.33 (0.81-2.20)
0.47- 1.65 (1.01-2.70)
*Adjusted for age, BP, HR, cholesterol, smoking, angina and ECG ischaemia
Hemingway et al. BMJ 1998; 316: 1353-4.
Cardiovascular risk in subjects with ECG-LVH:
Framingham
Age-adjusted risk-ratio
Cardiovascular outcome Men Women

Coronary heart disease 3.0* 4.6*

Stroke 5.8* 6.2*
Peripheral arterial disaese 2.7 5.3*
Cardiac failure 15.0* 12.8*

*P<0.0001 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 171 253

ECG-LVH 669 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
Disadvantages
skilled operator
time
cost
 Echocardiographic LVH and prognosis
Ref. Population N Follow-up End-points RR with LVH

Levy et al 1990 General 1911 4y CAD Men: 1.67

Women 1.60
Levy et al 1989 General 3220 4y CVD Men 1.49
Women 1.57
All death Men 1.73
Women 2.12
Casale et al 1986 HTN 140 4.8y CVD Men 3.83

Koren et al 1991 HTN 280 10.2y 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
Peak of QRS
Septum (SWT) 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

Start of QRS
Septum (SWT) 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
Males
8
Females
6
4
2
0
<75 75-94 95-116 117-

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 No LVH
2 LVH
1.5
1
0.5
0
Men Women

P<0.001 P=ns
Redrawn from Levy et al, NEJM 1990; 322: 1561-6.
 Echocardiographic LVH and prognosis
Ref. Population N Follow-up End-points RR with LVH

Levy et al 1990 General 1911 4y CAD Men: 1.67

Women 1.60
Levy et al 1989 General 3220 4y CVD Men 1.49
Women 1.57
All death Men 1.73
Women 2.12
Casale et al 1986 HTN 140 4.8y CVD Men 3.83

Koren et al 1991 HTN 280 10.2y 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* Cardiovascular events

40
% patients

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

LVMI (g/m2) LVMI (g/m2)

*P<0.001, P=0.03
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
Indapamide SR
-3
* Enalapril
-4
-5
*P<0.05 for LVMI
-6
PWT IVST LVID LVMI

Sheridan and Gosse 1998

Prognostic significance of Echo LVM regression
Events/ 100 patient years

7
6
5
4
3
2

1
*
0
All LVH

Regressors 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)

1.5
*
1

0.5
*
0
Decreased voltage Increased voltage

Males 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
Patient with multiple risk factors:
LVH may lead to other interventions e.g. lipid
lowering therapy
Possible white coat hypertension
? To stratify class of antihypertensive agent to
be used (increasing data suggesting LVH
regression should be a goal of treatment)