ReviewDiastolic heart failure and left ventricular diastolic dysfunction: What we know, and what we don't know!
Introduction
Over 5 million people in the United States have heart failure and over 500,000 cases are diagnosed each year [1]. Heart failure is the most common discharge diagnosis in elderly patients and one of the most common causes for readmission [2]. The cost to the society is enormous and ranges from 28 to 50 billion dollars per year [1], [3]. About 40%–50% of patients with congestive heart failure (CHF) have preserved ejection fraction (EF) [4], [5], [6]. Some prefer to use the term heart failure with preserved left ventricular systolic function instead of diastolic heart failure (DHF). This confusion is due in part to difficulty in measuring diastolic function and absence of clear diagnostic criteria for DHF. When the left ventricular EF is low, the diagnosis of CHF is seldom questioned and physicians are more likely to label these patients as CHF. However, the same physicians are less likely to commit to a diagnosis of CHF when the EF is normal.
Section snippets
Definition
Heart failure is the pathophysiological state in which the heart is unable to pump blood at a rate commensurate with the requirement of the metabolizing tissue or can do so only from an elevated filling pressure [7]. In patients with systolic heart failure (SHF), the primary abnormality is reduced contractile reserve of the left ventricle causing reduction in the stroke volume and cardiac output. DHF, however, occurs when the ventricle is unable to accept an adequate volume of blood in diastole
Pathophysiology
Patients with DHF have increased left ventricular (LV) diastolic pressures and pulmonary venous pressures with secondary limitation in exercise tolerance. These patients appear to have both an abnormal active relaxation and increased passive stiffness of the LV [9], which explains the large changes in LV diastolic pressure with small or barely detectable changes in ventricular volume making it impossible for the ventricle to accept additional venous return without high diastolic pressure and
Prevalence
The prevalence of both systolic and diastolic heart failure increases with age with an estimated 10% over 70 years [13]. The proportion of heart failure patients with DHF has ranged from 13% to 80% [5], [6], [14], [15], [16]. Most common prevalence sited in the literature is 40–50%. The variation is due in part to absence of unified definition of DHF, difficulty in diagnosis, different EF cutoff used to define preserved EF, age of population studied and the setting they are studied in (i.e.
Diagnosis
Diagnosing DHF has been challenging mainly due to lack of consensus on specific criteria and absence of a ‘single’ non-invasive test to confirm diagnosis. Clinical findings are non-specific and cannot differentiate DHF from systolic heart failure (Table 1) [10]. Diastolic heart failure describes a clinical syndrome whereas diastolic dysfunction describes a mechanical abnormality of the left ventricle. Indexes of diastolic dysfunction may be present without the “clinical syndrome” of diastolic
Prognosis
Reports about morbidity and mortality have varied widely depending on many factors including age, EF cutoff, underlying disease process causing DHF and presence of coexistent pathology (Table 3). Some community-based studies have reported very high, up to 60%, 3 year mortality rates for DHF especially in advanced age and in patients with NYHA class 3 and 4 heart failure [47]. Few others implied similar prognosis between DHF and heart failure with reduced EF [16]. However, most agree that CHF
Treatment
Although up to half of patients with CHF may have preserved EF, few treatments have specifically been evaluated in such patients. The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM-Preserved) [52] is perhaps the only completed large scale prospective randomized trial to specifically address the impact of certain pharmacotherapy on outcome in a subgroup of patients with CHF and preserved EF. Until now most of the treatments used in DHF focus on treating
Diuretics
Diuretics are usually the initial treatment in DHF with volume overload. Such treatment can also lower blood pressure which is an exacerbating factor for the development and propagation of DHF. Due to the stiffness of the left ventricle in these cases and the increased dependency on preload to maintain adequate cardiac output, aggressive diuresis may result in hypotension.
Digoxin
Digoxin is not specifically indicated for the treatment of diastolic heart failure. In the ancillary arm of the DIG study, digoxin reduced hospitalization rate in patients with CHF and EF over 45% [54]. Any benefits for digoxin in DHF may be related to controlling heart rate especially in the presence of atrial arrhythmias.
Beta-blockers
Beta-blockers may be helpful in several ways. Treatment with beta-blockers has been associated with regression of LV hypertrophy [53]. In addition beta-blockers may help by decreasing the incidence of tachycardia which can exacerbate DHF by shortening the filling time of the left ventricle. Furthermore, beta-blockers may improve LV diastolic properties in patients where ischemia is present and also by controlling blood pressure. Carvedilol has been associated with improvement of the echo
Calcium channel blockers
Like beta-blockers, calcium channel blockers may be beneficial by controlling heart rate, lowering blood pressure and treating ischemia. Also, by causing regression of left ventricular hypertrophy [57], [58] calcium channel blockers may improve the diastolic properties of the left ventricle. In patients with DHF, clinical status, exercise tolerance and diastolic filling were all improved by verapamil [59]. In this small, prospective study the improvement was evident at 2 weeks using a mean
Angiotensin converting enzyme inhibitors (ACE-I)
In contrast to the large body of evidence linking ACE-I to lower morbidity and mortality in patients with decreased EF, very little information is available about the effect of ACE-I in diastolic heart failure. The PEP-CHF is a large prospective trial evaluating the benefits of Perindopril in elderly patients with DHF [61]. The final results of this study are still pending. ACE-I, like many other antihypertensive agents, have been shown to cause regression of left ventricular hypertrophy [62],
Angiotensin receptor blockers
The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM-Preserved) is perhaps the only completed randomized prospective trial that evaluated pharmacotherapy in a subgroup of patients with DHF [52]. Over 3000 patients with CHF and EF > 40% were enrolled in this study and followed for 3 years. Treatment with Candesartan was associated with decreased heart failure hospitalization and a trend in favor of candesartan in combined mortality and heart failure
Aldosterone blockers
The RALES (Randomized Aldactone Evaluation study for CHF) showed benefit of aldactone in patients with systolic heart failure [67]. There is evidence to suggest that aldosterone may play a role in fibrosis and hypertrophy. In the RALES study, patients with the highest serum levels of marker for collagen turnover had the worst prognosis and these patients had the greatest response to spironolactone [68]. Elprelenone has been shown to cause regression of left ventricular hypertrophy with
Conclusion
DHF is a common condition that is responsible for significant morbidity and mortality. It is more common in elderly hypertensive women and should be suspected in patients with normal EF who present with CHF without any other explanation especially if there is LVH and left atrial enlargement on the echocardiogram. In contrast to CHF with decreased EF, very little data is available about the long term benefits of specific interventions. Candesartan appears to have a modest long term benefit.
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