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

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

0

50

100

150

200

250

0 100 200 300

LVMI (gm2)2

4 h

our

SB

P (

mm

Hg)

Relationship between mean 24 hour SBP and LVMI

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

p<0.05)

0

50

100

150

200

250

0 100 200 300LVMI (g/m2)

Clin

ic S

BP

(m

mH

g)

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

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*

Age-adjusted risk-ratio

*P<0.0001 Kannel. Eur Heart J 1992; 13 (suppl D): 82-88

Risks of X-ray and ECG LVH:Framingham

No X-ray enlargement X-ray enlargement

No ECG-LVH 171 253

ECG-LVH 669 1072

Data include men and women, aged 35-94

Age-adjusted biennial rate per 1000

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 individual’s 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: 1.67Women 1.60

Levy et al 1989 General 3220 4y CVD

All death

Men 1.49Women 1.57Men 1.73Women 2.12

Casale et al 1986 HTN 140 4.8y CVD Men 3.83

Koren et al 1991 HTN 280 10.2y CVDCVD deathAll death

All 2.17All 14.0All 3.5

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

M-mode echocardiograms

LVH Normal

Penn convention for M-mode measurements

Peak of QRS Endocardium excluded from SWT

and PWT Endocardium included in LVID

LV mass = 1.04[(SWT+LVID+PWT)3 - (LVID)3 - 14g

Divide by body surface area to get LV mass index

LV cavity (LVID)

Septum (SWT)

Posterior wall (PWT)

Devereux & Reichek Circulation 1977;55:613-8

ASE guidelines for M-mode measurements

Start of QRS Endocardium included in SWT and

PWT Endocardium excluded from LVID

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

Divide by body surface area to get LV mass index

LV cavity (LVID)

Septum (SWT)

Posterior wall (PWT)

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

0

2

4

6

8

10

12

14

16

18

<75 75-94 95-116 117-

Males

Females

LVMI (g/m2)

Ag

e-a

dju

ste

d i n

c id

enc

e/ 1

00 s

ub

ject

s

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

Incidence of cardiovascular mortality according to presence or absence of LVH

00.5

11.5

22.5

33.5

44.5

5

Men Women

No LVH

LVH

4-y

ea

r ag

e-a

dju

ste

dca

rdio

vasc

ula

r m

ort

ality

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: 1.67Women 1.60

Levy et al 1989 General 3220 4y CVD

All death

Men 1.49Women 1.57Men 1.73Women 2.12

Casale et al 1986 HTN 140 4.8y CVD Men 3.83

Koren et al 1991 HTN 280 10.2y CVDCVD deathAll death

All 2.17All 14.0All 3.5

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

Risks associated with LVM and geometry

0

10

20

30

40

>125 <125 >125 <125

<0.45

>0.45

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

RWT

Total mortality* Cardiovascular events†

% p

atie

nts

Koren et al. Ann Int Med 1991; 114: 345-352.*P<0.001, †P=0.03

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

-14

-12

-10

-8

-6

-4

-2

0

Diuretics B-blockers CCB's ACE-I

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

Mea

n %

in

LV

MI

Between treatment P<0.01

LVH regression: LIVE study

-6

-5

-4

-3

-2

-1

0

1

PWT IVST LVID LVMI

Indapamide SR

Enalapril

*P<0.05 for LVMI

*

%

from

bas

elin

e

Sheridan and Gosse 1998

Prognostic significance of Echo LVM regression

0

1

2

3

4

5

6

7

All LVH

Regressors Non-regressors

Eve

nts/

100

pat

ient

yea

rs

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

*

†

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

Prognostic significance of ECG voltage

changes: Framingham

0

0.5

1

1.5

2

Decreased voltage Increased voltage

Males FemalesOR

for

CV

eve

nts

(2 y

ears

)

*

*

*P<0.05Levy 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)