IS IT DIASTOLIC HEART FAILURE A SEPARATE DISEASE? Tamara Goda Department of Cardiology and Cardiac Surgery UHC “Mother Theresa” Tirana, Albania October 20, 2007

• When a patient presents with signs and symptoms of HF, clinician expect to see a dilated poorly contractile left ventricle. Yet almost one-half of all patients presenting with HF have a normal EF and comprise an unique subset known as diastolic heart failure

Diastolic Heart Failure

• DHF occurs when the ventricle is unable to accept an adequate volume of blood in diastole at normal diastolic pressures and at volumes sufficient to maintain stroke volume and cardiac output. The low stroke volume and cardiac output are manifested as fatigue whereas the increased left ventricular end-diastolic pressure is transmitted back to the pulmonary circulation causing dyspnea • Patients with DHF appear to have both an abnormal active relaxation and increased passive stiffness

Rony L. Shammas

2006

Diastolic Dysfunction and Diastolic Heart Failure

• Diastolic dysfunction indicates an abnormality of diastolic distensibility, filling, or relaxation of the left ventricle, regardless of whether the EF is normal or abnormal and whether the patient is symptomatic or asymptomatic. Diastolic dysfunction refers to abnormal mechanical (diastolic) properties of the ventricle and is present in virtually all patients with heart failure. • The term diastolic heart failure is used to describe patients with the signs and symptoms of heart failure, a normal EF, and LV diastolic dysfunction. Gerard P. Aurigemma Circulation 2006;113:296-304

Diastolic Heart Failure

• Conventionally, LV diastolic dysfunction is implicated as a major factor responsible for the clinical syndrome of HF in these patients, provided that valvular heart disease, cor pulmonale, volume overload conditions, and noncardiac causes of symptoms are excluded

Diastolic Heart Failure

• Most common prevalence sited in the literature is 40– 50%. The prevalence is substantially less in younger patients and can rise to over 70% in elderly patients. Age is probably the single most important factor influencing the prevalence. Coronary artery disease, hypertension, atrial fibrillation and diabetes are all conditions that are known to be associated with DHF

Diastolic Heart Failure: Effects of Age on Prevalence and Prognosis Zile, M Circulation 2002;105;1387-1393

• Women are more likely to have DHF than men.

• Most agree that CHF with preserved EF has a lower mortality than CHF with diminished EF but a significantly higher mortality than the general population. Advanced age adversely affects outcome in both groups. • In general, the annual mortality rate is quoted as 5%–8% compared to 10%–20% for those with systolic heart failure. • Morbidity for DHF is not much better than systolic heart failure Rony L. Shammas

2006

Diastolic Heart Failure • The gold standard for evaluating LV diastolic function remains direct measurement of LV pressures via a catheter. Echocardiography plays a central role in evaluating these patients. There are several echocardiographic parameters that are used to help in the diagnosis of diastolic dysfunction. • Increased left atrial volume in the presence of normal EF has also been suggested as a marker for diastolic dysfunction by itself . • The measurement of BNP has been proposed as an adjunct for the diagnosis. There is a close relation between the BNP and myocyte hypertrophy. Rony L. Shammas

2006

Combined Systolic and Diastolic Heart Failure

• Patients with DHF have a predominant (although not isolated) abnormality in diastolic function. Patients with SHF have a predominant (although not isolated) abnormality in systolic function. • DHF can occur alone or in combination with SHF • Therefore, virtually all patients with symptomatic HF have abnormalities in diastolic function • Those with a normal EF have isolated DHF • Those with a decreased EF have combined systolic and diastolic HF Zile 2002

Is it DHF a separate disease?

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The division of patients with HF into two groups has evolved over the past 50 years and has included forward versus backward failure, systolic heart failure (SHF) versus DHF, and more recently, HF with depressed versus preserved EF.

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Diastolic heart failure has emerged over the last decades as a separate clinical entity

Diagnostic Criteria for Diastolic Heart Failure (according to European Study Group on DHF, 1998 )

¾ Signs or symptoms of CHF (effort dyspnea, pulmonary rales/edema, CPX-test VO2 max 120bpm

Rigorous Criteria for identifying heart failure based on clinical history and physical findings were developed for the Framingham study. However, heart failure may not be recognized in up to 40% of patients due to the limited reliability of these findings.

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The similarities in clinical symptoms characterizing SHF and DHF belie significant pathophysiologic differences between the 2. The pathophysiology of chronic SHF is characterized by progressive eccentric remodeling of the left ventricular (LV) chamber leading to progressive dilatation and resultant decrease in LV ejection fraction (LVEF). Diastolic HF has been characterized by predominantly concentric remodeling with normal LV end-diastolic volume. The primary abnormality in patients with DHF is diastolic dysfunction (DD). This syndrome has been defined as impaired LV filling capacity because of abnormalities of active relaxation and passive stiffness of the myocardium. Hemodynamically, these changes present as an upward- and leftward-shifted end-diastolic pressure-volume relationship, and abnormalities in mechanical function during diastole lead to increasing LV stiffness. These abnormalities can occur independently of the HF syndrome and with preserved or diminished systolic function.

• Concentric hypertrophy is characteristic of diastolic HF. In concentric hypertrophy, myocyte width is increased more than the length and the sarcomeres are deposited in parallel, allowing the increase in wall thickness. In concentric hypertrophy, increased myocyte protein synthesis has been documented. The changes in the extracellular matrix and the abnormalities of collagen synthesis and degradation occur in both types of HF. However, the matrix architectural changes are likely to be different since, despite fibrosis.The abnormalities of activation of the matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) have been identified in both types of HF.

Heart Failure With a Normal Ejection Fraction Is It Really a Disorder of Diastolic Function?

A large proportion of patients who present with symptomsof heart failure have a left ventricular ejection fraction within the normal range. Although some have postulated that ventricular systolic function is impaired, most investigators have concluded that the fundamental abnormality in these patients is a disorder of diastolic (rather than systolic) function,and in fact, these patients are frequently referred to as having diastolic heart failure. The use of such a term is troublesome, however, because it presumes that we understand the mechanisms leading to this disorder and therefore can justify the substitution of a mechanistic term for a descriptive phrase. There is still no evidence to support the hypothesis that pathologically shifted EDPVRs are present in most patients with heart failure and a normal ejection fraction. The increase in left ventricular filling pressures seen in these patients may be the cause (and not the result) of the abnormalities of diastolic filling that have been observed in this disorder. Such a conclusion would present a direct challenge to the diastolic dysfunction hypothesis, and we expect such a proposal to generate considerable controversy. The diastolic dysfunction hypothesis is so widely accepted and is so ingrained in our thinking that it has formed the sole basis of both basic research and clinical trials of new treatments for HFNEF for the past 30 years.Yet, despite detailed studies of the biochemistry and molecular biology of ventricular relaxation, this research has yet to lead to a single effective treatment for HFNEF. Have we failed because diastolic dysfunction is too difficult to understand or manage, or is it because HFNEF has nothing to do with diastolic dysfunction at all? Daniel Burkhoff,Circulation 2003;107:656-658.

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Diastolic dysfunction can occur in the absence of LVH due to ischemia, myocardial infiltration (e.g., amyloidosis), or pericardial constriction. The most common form of heart failure, that due to coronary artery disease, often reflects a combination of systolic and diastolic dysfunction. Systolic dysfunction is due to prior infarction and ischemia-induced decrease in contractility. Diastolic dysfunction is due to chronic replacement fibrosis and ischemia-induced decrease in distensibility.