Diastolic Heart Failure

A Disorder of the Elderly Patient
M Chadi Alraies, MD
Chief Medical Resident St. Vincent Charity Hospital/Case Western Reserve University

Diastolic Heart Failure Defined1:

Clinical presentation and symptoms of heart failure with preserved LV systolic function Stiff ventricle equals decreased compliance and impaired relaxation leading to ↑ LVEDP

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Prevalence: as of 2004, 4.8 million Americans are affected by diastolic heart failure (HF)1,2,3 Diastolic HF prevalence increases with age4,5,6,7: < 50 years old: 15% 50-70 years old: 33% > 70 years old: 50%
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Background (cont.)

Incidence: about 500,000 new cases diagnosed per year1,2,3,4 HF is the leading cause of hospitalization in persons over the age of 654,8

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Background (cont.)

More than 50% of patients with HF have preserved LV function4,9 Mortality rates for patients with diastolic HF:
Advanced disease: 30-40% mortality in 5-10 years4,10  Mortality rates are comparable to those seen in systolic HF4,9

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A 68-year-old woman is hospitalized with palpitations and shortness of breath. She has a history of hypertension and chronic atrial fibrillation, and her medications include furosemide, candesartan, and warfarin. On physical examination, the heart rate is 120/min with an irregularly irregular rhythm, and blood pressure is 130/80 mm Hg; she has an elevated jugular venous pulse, crackles in both lungs, and marked lower extremity edema. Echocardiography shows left ventricular hypertrophy, an ejection fraction of 70%, and no significant valvular disease. She is treated with intravenous diuretics, with improvement in her symptoms and resolution of peripheral edema and of crackles on lung examination. Her heart rate is now 99/min and her blood pressure is 120/75 mm Hg. Which of the following would be the most appropriate medication to add?  A Lisinopril M Chadi Alraies 6

Risk Factors for Diastolic 4,11 HF :
  

Elderly Female Hypertensive

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Long-standing HTN with LVH12:

A hypertensive hypertrophic cardiomyopathy with LVEF >75% in the elderly6

  

Aortic Stenosis with normal LVEF13 Severe aortic or mitral regurgitation Ischemic Heart Disease

Regional wall motion abnormalities

Restrictive Cardiomyopathy – Idiopathic vs. Infiltrative

Sarcoidosis, Amyloidosis, Hemochromatosis

6. 7.

HOCM Hypothyroidism M Chadi Alraies


Asymptomatic Diastolic HF:
 

More common than symptomatic diastolic HF Mayo Clinic study of 2,042 subjects > age 45:
Prevalence of symptomatic HF: 2.2%  Of those, 44% had diastolic HF  In subjects without symptoms of HF, 28% had diastolic HF by echo criteria4,15.

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Diastolic Function



Myocardial Relaxation Elasticity
- An active process - Requires energy energy - A passive process - Requires no

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Pathophysiology (cont.)17:

Normally, LV relaxation during diastole creates a negative LA to LV pressure gradient, thereby augmenting diastolic filling Decrease in LV relaxation and distensibility causes increased LA, LV, PV, and PCW pressures Increase in LV filling during late diastole, increase in dependence on atrial contraction
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Cardiac Cycle

Reproduced from: Gutierrez C, Blanchard DG. Diastolic Heart Failure: Challenges of Diagnosis and Treatment. Am Fam Physician 2004;69:2609-16. M Chadi Alraies


Pathophysiology (cont.)17
Why do patients with diastolic dysfunction have poor exercise tolerance? During normal exercise, increase in HR associated with increase in SV → ( CO = HR x SV ) Increased HR leads to compensatory increase in relaxation rate, maintaining normal LVEDP & PCWP Increased LVEDV normally leads to increased SV due to Frank-Starling mechanism Normal LV distensibility allows normal LVEDP to be maintained at increased LVEDV

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 

Increased PCWP During Exercise in Pts. With Diastolic HF

Data from Kitzman, DW, Higginbotham, MB, Cobb, FR, et al, J Am Coll Cardiol 1991;
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Pathophysiology (cont.)

Why is diastolic dysfunction more common in elderly persons? Age-related changes18,19:
Increased collagen cross-linking  Increased smooth muscle content  Loss of elastic fibers

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Clinical Manifestations :
  

Similar to systolic HF AF poorly tolerated due to loss of atrial kick Tachycardia poorly tolerated due to shortening of late diastolic filling time Elevated systemic blood pressure increases LV wall stress and further impairs relaxation Acute-on-chronic diastolic dysfunction caused by ischemia
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Diagnosis :

Controversy: does clinical HF + normal LVEF = diagnosis of diastolic HF? Most patients with overt clinical HF and normal LV systolic function have some element of diastolic dysfunction A study of 63 HF patients with LVH and normal systolic function by echo found that 100% of patients had at least one index of diastolic
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Diagnosis (cont.)1

Gold standard for diagnosis is cardiac catheterization:
Direct measurement of LVEDP  Risk outweighs benefit for routine use in diagnosing diastolic dysfunction

Doppler Echocardiography: the primary diagnostic modality for diagnosis
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Doppler Echocardiography1

Tau = time constant of LV pressure decay during isovolumetric relaxation that correlates with LV stiffness Diastolic trans-mitral valve blood flow:

Measurement of peak velocities during early diastolic filling: 1) E wave = Early diastolic filling 2) A wave = Atrial Alraies M Chadi contraction


Spectrum of Diastolic Dysfunction1

 

E wave > A wave Ratio 1.5:1.0

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Spectrum of Diastolic Dysfunction1

Early Diastolic Dysfunction:

Abnormal Relaxation
 

E-to-A ratio reverses to < 1.0 Increased isovolumetric relaxation time (stiff heart takes longer to relax) Abnormal relaxation is a nonspecific finding

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Advanced Diastolic Dysfunction:

Spectrum of Diastolic Dysfunction (cont.)1

Pseudonormal Pattern
 

Abnormal relaxation & ↑ LVEDP “Pseudonormalization” can occur with decompensated HF and ↑ LA pressure, common triggers include tachyarrhythmias, especially AF, uncontrolled HTN

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Spectrum of Diastolic Dysfunction (cont.)1

Severe Diastolic Dysfunction:

Restrictive Pattern

↑ LVEDP → LV diastolic filling occurs mostly during early diastole because LVEDP so high that atrial kick unable to effectively contribute to LV filling E-to-A ratio > 2.0 → poor prognosis

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Normal Trans-Mitral-Valve Spectral Doppler Flow Pattern

Reproduced from: Gutierrez C, Blanchard DG. Diastolic Heart Failure: Challenges of Diagnosis and Treatment. Am Fam Physician 2004;69:2609-16. Alraies M Chadi


Abnormal Relaxation

Reproduced from: Gutierrez C, Blanchard DG. Diastolic Heart Failure: Challenges of Diagnosis and Treatment. Am Fam Physician 2004;69:2609-16. M Chadi Alraies


Severe (Restrictive) Diastolic Dysfunction

Reproduced from: Gutierrez C, Blanchard DG. Diastolic Heart Failure: Challenges of Diagnosis and Treatment. Am Fam Physician 2004;69:2609-16. M Chadi Alraies 26

Doppler Echocardiography (cont.)

Adapted from: Zile MR. Clinical manifestations and diagnosis of diastolic heart failure. http://www.utdol.com/diastolic heart failure/clinical manifestations and diagnosis of diastolic heart failure. 3/2/07

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BNP elevated in patients with both systolic and diastolic HF, but cannot be used to differentiate between the two21-24 A study of 357 patients referred for echocardiography based on clinical suspicion for heart failure revealed the following mean BNP levels25:
Diastolic Dysfunction = 373 (+/- 335)  Systolic Dysfunction = 550 (+/- 602)  Combined Dysfunction = 919 (+/- 604) M Chadi Alraies

Brain Natriuretic Peptide (BNP)4


BNP (cont.)


A study of 400 randomly selected patients referred for echo to evaluate LV function21:
With normal LV function – mean BNP was 30  BNP of 75: sensitivity of 85% and specificity of 97% in detecting ventricular dysfunction  In the patients with normal LV systolic function, BNP of 57 detected 28 patients M Chadi Alraies with isolated diastolic dysfunction with 29

BNP (cont.)


A study of 294 patients with echocardiographically normal LV systolic function23:

Mean BNP:
All diastolic dysfunction = 286; normals = 33  Impaired relaxation = 202  Pseudonormal = 294  Restrictive = 402

For diagnosis of diastolic dysfunction, BNP of 62: sensitivity 85%; specificity 83%
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BNP (cont.)

ACE-Is, ARBs, Spironolactone, and Diuretics: ↓ BNP levels26 Thus, monitoring of BNP levels may be a useful method of assessing response to treatment

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Treatment :

Trial data limited compared with systolic HF Aim of therapy is to prevent or control hemodynamic stressors.

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Treatment (cont.)


2) 3) 4) 5)

2005 ACC/AHA Task Force Guidelines on Management of Chronic Diastolic HF: Control of systolic and diastolic HTN Control of VR in patients with AF Control of pulmonary edema and peripheral congestion with diuretics Coronary revascularization in CAD patients if ischemia thought to be contributing to diastolic dysfunction
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Pharmacologic Therapy

Patients with small, stiff LV chamber are sensitive to excessive preload reduction Diuretics, Nitrates, Dihydropyridine CCBs, ACE-Is – use with caution due to potential to cause LV underfilling Frank-Starling curve has a steeper slope Monitor for symptoms of weakness, lightheadedness, syncope
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 

No survival benefit29 DIG ancillary trial: role of digoxin in patients with HF and EF >45%

At 37-month follow-up, no effect on all-cause or CV hospitalization with digoxin

A study examining the effect of IV digoxin on echocardiographic diastolic parameters demonstrated a significant decrease of trans-mitral peak E and E-to-A ratio, and a significant lengthening of deceleration time30 However, consensus is that digoxin should be avoided in diastolic HF M Chadi Alraies 35

27 β -blockers

β -blockers

Can cause regression of LVH and improvement of diastolic function Can ↓ HR, ↑ diastolic filling time, ↓ oxygen consumption, ↓ BP1 Carvedilol has been shown to improve Eto-A ratio31

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Calcium channel blockers27

Non-dihydropyridine CCBs (diltiazem, verapamil) - more potent negative inotropes CCBs - can cause regression of LVH and improvement of diastolic function Verapamil

May have a “lusitropic” (relaxation-enhancing) effect27 A study on 20 patients with diastolic HF taking verapamil:
 

↓ signs and symptoms of HF ↑ LV diastolic filling rate and treadmill exercise time32

Amlodipine - a study of 59 patients with 37 M Chadi Alraies


Afterload reduction not as important as with systolic HF, but some evidence of benefit ACE-Is – can cause regression of LVH and improvement of diastolic function ACE-Is – improve NYHA functional class, QOL, and may prevent myocardial fibrosis associated with LVH
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Angiotensin II Receptor Blockers27
 

ARBs - can cause regression of LVH and improvement of diastolic function CHARM-Preserved trial34:

3023 patients with symptomatic HF and LVEF > 40% Randomly assigned to receive candesartan or placebo x mean 37 months Small but almost significant reduction in incidence of primary endpoints of CV death and hospitalization for HF in the candesartan group
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Antihypertensives and LVH27
 

Regression of LVH may improve diastolic function35 2003 meta-analysis examining the efficacy of various antihypertensives in reversal of LVH36 Relative reductions in LV mass index:
    

ARBs – 13% CCBs – 11% ACE-Is – 10% Diuretics – 8% β-blockers – 6%
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Regression of LVH

M Chadi Alraies 41 Reproduced from: Zile MR. Treatment and prognosis of diastolic heart failure. www.utdol.com. 3/2/07 www.utdol.com.



Varies with symptomatic vs. asymptomatic HF Framingham Heart Study and V-HeFT trials showed better prognosis with diastolic HF than with systolic HF, but worse than controls 37-39 A study of 522 patients showed similar 5-year mortality for diastolic vs. systolic HF (25% vs. 42%)40
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Reproduced from: Zile MR. Treatment and prognosis of diastolic heart failure. www.utdol.com. 3/2/0743 www.utdol.com. M Chadi Alraies

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References (cont.)
26. Doust J, Lehman R, Glasziou P. The role of BNP testing in heart failure. Am Fam Physician 2006 Dec 1;74(11):1893-8. 27. Zile MR. Treatment and prognosis of diastolic heart failure. www.utdol.com. 3/2/2007. www.utdol.com. 28. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 2005; 112:e154. 29. Ahmed A, Rich MW, Fleg JL, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation 2006; 114:397. 30. Giunta A, Maione S, Arnese MR, Giacummo A, Liucci GA, Palma M, de Campora P, Cangianiello S, Condorelli M. Effects of intravenous digoxin on pulmonary venous and transmitral flows in patients with chronic heart failure of different degrees. Clin Cardiol 1995 Jan;18(1):27-33. 31. Bergstrom A, Andersson B, Edner M, et al. Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish Doppler-echocardiographic study (SWEDIC). Eur J Heart Fail 2004; 6:453. 32. Setaro JF, Zaret BL, Schulman DS, et al. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol 1990; 66:981. 33. Zaliunas R, Bradzionyte J, Zabiela V, Jurkevicius R. Effects of amlodipine and lacidipine on heart rate variability in hypertensive patients with stable angina pectoris and isolated left ventricular diastolic dysfunction. Int J Cardiol 2005 Jun 8;101(3):347-53. 34. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved leftventricular ejection fraction: the CHARM-Preserved trial. Lancet 2003; 362:777. 35. Watchtell K, Bella JN, Rokkedal J, et al. Change in diastolic left ventricular filling after one year of antihypertensive treatment: The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study. Circulation 2002; 105:1071. 36. Klingbeil AU, Schneider M, Martus P, Messerli FH. A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med 2003; 115:41. 37. Vasan, RS, Larson, MG, Benjamin, EJ, et al. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: Prevalence and mortality in a population-based cohort. J Am Coll Cardiol 1999; 33:1948. 38. Cohn, JN, Johnson, G, and Veterans Administration Cooperative Study Group. Heart failure with normal ejection fraction. The V-HeFT Study. Circulation 1990; 81:III48. 39. Gottdiener, JS, McClelland, RL, Marshall, R, et al. Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study. Ann Intern Med 2002; 137:631. 40. MacCarthy PA, Kearney MT, Nolan J, et al. Prognosis in heart failure with preserved left ventricular systolic function: prospective cohort study. BMJ 2003; 327:78.

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