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Harvard Medical School Hypertensive Heart Disease Gene Bukhman January 12th, 2005 Epidemiology I • Number of Patients with Hypertension in the United States: 50 million • Number of Patients with Heart Failure: 5 million • Percent of Heart Failure Patients with Hypertension: 75% JNC 7. 2004 Jessup and Brozena. NEJM. 2003 Harvard Medical School Mosterd et al. NEJM. 1997 Harvard Medical School Mortality in Hypertension • 50% from ischemic heart disease or heart failure • 33% from cerebrovascular disease • 10 to 15% from renal failure Kaplan in Zipes, Libby, Bonow, and Braunwald. 2005 Harvard Medical School Hypertensive Heart Disease • Coronary Artery Disease • Heart Failure – Diastolic Dysfunction • Impaired relaxation • Left ventricular myocyte hypertrophy • Interstitial fibrosis – Systolic Dysfunction • Ischemic cardiomyopathy • Late consequence of afterload • Arrhythmias – Atrial fibrillation • Left atrial enlargement – Ventricular Arrythmias Kaplan in Zipes, Libby, Bonow, and Braunwald. 2005 Harvard Medical School Left Ventricular Hypertrophy I • Concentric increase in LV mass • Compensatory response to increased afterload • Collagen • Myocyte hypertrophy Lorell and Carabello. Circulation. 2000 Harvard Medical School Left Ventricular Hypertrophy II • Effect of mechanical loading most clear in rapid regression following aortic valve replacement • In systemic hypertension confounded by role of angiotensin II and sympathetic hormones • LVH often develops after other signs of diastolic dysfunction in HTN • LVH also seen to precede development of systemic HTN Lorell and Carabello. Circulation. 2000 Harvard Medical School Jessup and Brozena. NEJM. 2003 Harvard Medical School Consequences of LVH • • Although initially compensatory, LVH ultimately associated with risk of cardiovascular events similar to history of prior myocardial infarction Ischemia – Decreased coronary reserve with increased LV mass • angina – Greater risk of death following myocardial infarction • Heart Failure – Depressed LV systolic and diastolic function • Arrhythmia – Atrial fibrillation – Ventricular arrhythmias • • • • Nonuniform action potential prolongation Altered repolarization Specific vulnerability to torsades Ischemic ventricular arrhythmia Dunn and Pfeffer. NEJM. 1999 Harvard Medical School Echocardiography Findings in Systemic HTN • Left atrial enlargement • Mitral annular calcification – Mild to moderate mitral regurgitation • Aortic root dilatation • Aortic valve sclerosis – Mild aortic regurgitation • Diastolic dysfunction – Impaired relaxation – Restrictive pattern • Reduced ejection fraction – Usually late consequence with ventricular dilatation • Symmetric left ventricular hypertrophy Otto. 2000 Harvard Medical School Aurigemma and Gaasch. NEJM. 2004 Harvard Medical School Diastolic Dysfunction Aurigemma and Gaasch. NEJM. 2004 Redfield. NEJM. 2004 Harvard Medical School Possible Role of LVH determination in systemic HTN 1. 2. 3. Selection of patients for treatment Choice of treatment agent Monitoring Harvard Medical School Echocardiographic evaluation of LVH • Framingham adds echocardiography in 1979 • ECG probably has 1/8th the sensitivity of echocardiography • Probably 20 percent prevalence in those over 40 years old • Present in 20 to 30 percent of otherwise low risk patients with HTN Lorell and Carabello. Circulation. 2000 Harvard Medical School Multiple methods of echocardiographic left ventricular mass calculation • LVM = 0.8 x [1.04 x (LVID + LVPWT + IVST)3 –LVID3] • Limits set by 2 standard deviations of the Framingham cohort mean • Poor reproducibility • Possible advantage of cardiac MR (Manning 2004) Lorell and Carabello. Circulation. 2000 Harvard Medical School Treatment of Hypertension and Absolute Cardiovascular Risk • Benefit of treatment proportional to overall cardiovascular risk • Risk increases with level of blood pressure without clear threshold MacMahon. NEJM. 2000 Harvard Medical School LVH and treatment of HTN • Regression of LVH with treatment by all classes of agents except direct vasodilators • Possible superiority of ace inhibitors and angiotensin receptor blockers • Not clear if benefit to LVH regression independent from overall benefit of blood pressure reduction Harvard Medical School Losartan Intervention for endpoint reduction (LIFE) trial Dahlof et al. Lancet. 2002 Harvard Medical School ACC/AHA/ASE 2003 Guidelines: Echocardiography in HTN I Class I Indications: 1. When assessment of resting LV function, hypertrophy, or concentric remodeling is important in clinical decision making 2. Detection and assessment of functional significance of concomitant CAD by stress echocardiography. 3. Follow-up assessment of LV size and function in patients with LV dysfunction when there has been a documented change in clinical status or to guide medical therapy. Cheitlin et al. ACC/AHA/ASE. 2003 Harvard Medical School ACC/AHA/ASE 2003 Guidelines: Echocardiography in HTN II Class IIa Indications: 1. Identification of LV diastolic filling abnormalities with or without systolic abnormalities. 2. Assessment of LV hypertrophy in a patient with borderline hypertension without LV hypertrophy on ECG to guide decision making regarding initiation of therapy. A limited goal-directed echocardiogram may be indicated for this purpose. Cheitlin et al. ACC/AHA/ASE. 2003 Harvard Medical School ACC/AHA/ASE 2003 Guidelines: Echocardiography in HTN III Class IIb Indications: 1. Risk stratification for prognosis by determination of LV performance. Class III Indications: 1. Re-evaluation to guide antihypertensive therapy based on LV mass regression. 2. Re-evaluation in asymptomatic patients to assess LV function. Cheitlin et al. ACC/AHA/ASE. 2003 Harvard Medical School Common indications for echocardiography in HTN • Borderline hypertension with no other risk factors – As many as 30 percent of patient with low to medium risk HTN will have LVH – Pharmacologic treatment preferred • Patients with severe hypertension in the office, but not on initial ambulatory monitoring – If no LVH suggests either white coat hypertension – Or HTN of recent onset – Continued ambulatory monitoring • Heart Failure Harvard Medical School Role of Limited echocardiography • Cost – $600 for complete echocardiogram – $150 for limited study including m-mode and doppler – $70 for ECG Harvard Medical School Worker’s Compensation • Hypertension considered an occupational injury for selected professions in some states if can show end organ damage Harvard Medical School For example, Virginia Code Section 65.2-402(B) "hypertension or heart disease causing the death of, or any health condition or impairment resulting in total or partial disability of (i) salaried or volunteer firefighters, (ii) members of the State Police Officers' Retirement System, (iii) members of county, city or town police departments, (iv) sheriffs and deputy sheriffs, (v) Department of Emergency Services hazardous materials officers, and (vi) city sergeants or deputy city sergeants of the City of Richmond shall be presumed to be occupational diseases, suffered in the line of duty, that are covered by this title unless such presumption is overcome by a preponderance of competent evidence to the contrary." Harvard Medical School Future directions for LVH assessment in patients with HTN • If absolute risk approach adopted more extensively, question of role of LVH assessment as an independent risk factor • Question of superiority of some anti-hypertensive agents for patients with LVH • Improvements in accuracy of LV mass assessment with cardiac MR Harvard Medical School References • • • • • • • • • • Aurigemma and Gaasch. Clinical Problem Solving. Diastolic Heart Failure. NEJM. 2004. Cheitlin et al. ACC-AHA-ASE 2003 Guideline Update for the Clinical Application of Echocardiography. 2003. Dahlof et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE). a randomised trial against atenolol. Lancet. 2002. Dunn and Pfeffer. Left Ventricular Hypertrophy in Hypertension. NEJM. 1999. Kaplan. Systemic Hypertension: Mechanisms and Diagnosis. Zipes, Libby, Bonow, Braunwald. Braunwald’s Heart Disease. 2005. Lorrell and Carabello. Left Ventricular Hypertrophy. Pathogenesis, Detection, and Prognosis. Circulation. 2000. Jessup and Brozena. Medical Progress. Heart Failure. NEJM. 2003. MacMahon. Blood Pressure and the Risk of Cardiovascular Disease. NEJM. 2000. Mosterd et al. Trends in the prevalence of hypertension, antihypertensive therapy, and left ventricular hypertrophy from 1950 to 1989. NEJM. 1997. Otto. Textbook of Clinical Echocardiography. 2000. Harvard Medical School