DESCRIPTION

Diastolic mechanisms contribute importantly to the pathogenesis of most instances of heart failure seen in the U.S. Some reasons for this are:

• HTN is an underlying risk factor in most patients with CHF, and a high proportion of patients with chronic HTN, particularly those with LV hypertrophy, have diastolic dysfunction.
• Roughly 1/3–1/2 of patients hospitalized with congestive failure have normal systolic ejection fraction at the time of hospitalization or thereafter.
• Most patients with heart failure and normal ejection fraction have demonstrable abnormalities in diastolic function and an elevated LV end-diastolic pressure.

PATHOPHYSIOLOGY

• LV diastolic filling occurs in two phases: Passive filling followed by atrial systole. Normal diastolic filling may be characterized as the ability of the ventricle to fill optimally at normal pressures. This capability is influenced by both the active (energy requiring) and passive (compliance) properties of the LV.
• Underlying mechanisms:
  • Filling occurs as the LV relaxes and pressure decays; this filling takes place during isovolumic relaxation (time between the aortic 2nd sound and mitral valve opening) and during the early part of diastole, during which rapid filling takes place.
  • The rapid pressure decay in the LV, in association with untwisting and elastic recoil of the LV, promotes a pressure gradient (diastolic suction).
  • Because the ventricular myocardium is relaxed and distensible during diastole, pressures are low in what is effectively the common chamber, comprising the LV, left atrium, and pulmonary veins. Therefore, filling in the normal ventricle is associated with a low or normal pulmonary capillary wedge pressure.
  • Atrial systole, an active process whereby blood is pumped into the LV, assumes greater importance as aging or myocardial disease renders the LV myocardium less distensible (increasing stiffness, decreasing compliance).
  • Major influences on the compliance of the LV myocardium include the extent of fibrosis (scar from prior infarction, unrelieved pressure and/or volume overload) and whether hypertrophy is present:
    • LV and therefore left atrial, pulmonary vein, and pulmonary capillary pressures are also influenced by LV volume. Because even the normal LV does not have infinite compliance, a much larger than normal LV volume will result in abnormal elevation in LV diastolic pressures.
• As implied by the preceding discussion, the 2 major pathophysiologic problems comprise abnormalities in relaxation and abnormalities in LV compliance.
• Some of the more common underlying abnormalities include:
  • Myocardial hypertrophy (generally associated with long-standing HTN)
  • Interstitial fibrosis
  • Ischemia contributes directly and indirectly to diastolic dysfunction, the latter acting by decreasing the ability of the myocardium to relax and compromising the normal decay in diastolic pressure. Ischemia also increases LV chamber stiffness and thereby alters the normal pressure–volume relationship. Thus, in the ischemic LV, the ability of the heart to fill at normal pressure is compromised.

Outline

• Description
• Pathophysiology

DIAGNOSTIC TESTS & INTERPRETATION

Imaging

• In the heart failure patient, bedside clinical assessment may not completely distinguish the heart failure patient with normal systolic function from the patient with systolic dysfunction. In both, individual signs of increased central venous and pulmonary venous volume may be present. Therefore, additional testing is necessary.
• Echo is generally the test of choice in the assessment of the patient with heart failure and is the most common clinical test ordered to assess LV diastolic function.
• The presence of a normal ejection fraction greatly increases the likelihood that diastolic dysfunction is the underlying cause of heart failure.
• Doppler echo is used in everyday practice to assess LV filling and to determine the mechanism of CHF.
• The Doppler inflow pattern consists of 2 velocity profiles:
  • Early (E) wave, which corresponds to passive filling
  • Late (A) wave, which corresponds to atrial systole
• In normal subjects, the ratio of early to late filling is 1 because the atrial contraction tends not to be particularly forceful.
• With advancing age, the ratio of peak E velocity to peak A velocity approaches 1 in normal individuals at around age 70.
• As noted above, diastolic dysfunction generally comprises 1 or both pathophysiologic mechanisms, abnormal relaxation, and abnormalities in ventricular diastolic compliance.
• Both of these abnormalities are demonstrable by Doppler echo, when a comprehensive exam is performed. Such a comprehensive exam includes transmitral flow velocities, exam of the pulmonary venous velocities, and measurement of the velocities of the mitral annulus during the rapid phase of ventricular filling using tissue Doppler echo.
• After a decade of use of tissue Doppler echo in concert with Doppler velocity measurements of the transmitral flow, we have come to appreciate that tissue Doppler indices are relatively load independent.
• Specific patterns:
  • Abnormalities in myocardial relaxation are generally associated with a diminution in the E wave and a prolongation in the time from peak E to zero velocity (diastasis). There is often an accompanying increase in A velocity as the atrial contraction increases in force. This may correspond to the 4th heart sound (S4) on physical exam. Pulmonary venous velocities will show a normal ratio of systolic to diastolic flow, and tissue Doppler velocities are lower than normal.
  • Compliance abnormalities generally reflect more advanced disease, reflective of myocardial fibrosis. The Doppler pattern associated with compliance abnormalities includes a decrease in the time from peak E to diastasis (deceleration time <140 msec) and a diminution in the A velocity, reflecting increased atrial afterload. Thus, the E to A ratio may increase and approach that seen in normal, healthy adults. In this regard the deceleration time of the E wave will distinguish a pseudo-normal E/A ratio from the LV with severe compliance abnormalities.
  • In the instance of reduction in LV diastolic compliance, the tissue Doppler velocities will be low.

ADDITIONAL TREATMENT

General Measures

• Management is predicated on making the proper diagnosis. Accordingly, an assessment of systolic function, presence of valvular heart disease, extent of hypertrophy, and LV filling is essential. Echo generally provides these data noninvasively. Regional wall-motion abnormalities present on the resting echo imply that coronary heart disease may be a contributing mechanism.
• Once the diagnosis is established, the following measures are in order:
  • Manage presenting symptoms generally including HTN and coronary artery disease.
  • Maintenance of normal sinus rhythm and the avoidance of tachycardia have beneficial results.
  • Reduce congested state: Diuretics, salt restriction, angiotensin inhibitors (or angiotensin II receptor blockers)
  • Avoid tachycardia and promote bradycardia; this is usually accomplished with -blockers and rate-lowering calcium channel blockers.
  • Treat ischemia.
• As of now, there is no specific, targeted therapy to improve diastolic function. HTN trials, such as the Antihypertensive and Lipid-Lowering Trial (ALLHAT) and the Systolic HTN in the Elderly Program (SHEP) have shown that successful BP lowering is associated with a reduction in heart failure.
• Clinical trials of therapy for patients with heart failure and normal ejection fraction are in progress. Those published to date have tested the role of ARBs to favorably impact outcome in heart failure with a normal EF. Thus far, the studies have shown only limited utility of these medications in patients with heart failure and preserved ejection fraction.
• The benefit of candesartan in patients with heart failure and preserved EF was limited to a modest reduction in hospitalization for heart failure. The i-Preserve trial showed no improvement in a combined endpoint of death or cardiac hospitalization.
• The VALIDD trial, by contrast, tested the ability of valsartan to improve diastolic function in a group of patients with HTN-related diastolic dysfunction. This trial demonstrated that treatment both with valsartan or the positive control medication, amlodipine, led to reduction in BP and improvement in diastolic filling, as assessed by tissue Doppler imaging.

CODES

ICD9

• 428.30 Diastolic heart failure, unspecified
• 428.31 Diastolic heart failure, acute
• 428.32 Diastolic heart failure, chronic
• 428.33 Diastolic heart failure, acute on chronic

SNOMED

• 418304008 diastolic heart failure (disorder)
• 443343001 acute diastolic heart failure (disorder)
• 441530006 chronic diastolic heart failure (disorder)
• 443344007 acute on chronic diastolic heart failure (disorder)
• 3545003 diastolic dysfunction (finding)

ADDITIONAL READING

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• Gaasch WH. Diagnois and treatment of heart failure based on left ventricular diastolic function. JAMA. 1994;271:1276–1282.
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• Levy D, Larson MG, Vasan RS, et al. The progression from hypertension to congestive heart failure. JAMA. 1996;275:1557–1562.
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• Massie BM, Carson PE, McMurray JJ, et al. I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359(23):2456–2467.
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• Vasan RS, Levy D. Defining diastolic heart failure: A call for standardized diagnostic criteria. Circulation. 2000;101:2118–2121.
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• Yusuf S, Pfeffer MA, Swedberg K, et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362(9386):777–781.
• Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I: diagnosis, prognosis, and measurements of diastolic function. Circulation. 2002;105:1387–1393.
• Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure, II: Causal mechanisms and treatment. Circulation. 2002;105:1503–1508.
• Zile MR, Gaasch WH, Carroll JD, et al. Heart failure with a normal ejection fraction: Is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure? Circulation. 2001;104:779–782.

Gerard P. Aurigemma