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【medical-news】舒张型心力衰竭治疗
Heart 2008;94:971-972;
In around half of patients diagnosed with heart failure, a relatively preserved systolic function (left ventricular ejection fraction (LVEF) >0.40–0.50) is found. These patients are generally diagnosed with diastolic heart failure or heart failure with preserved ejection fraction. Owing to an ageing population and an increased incidence of hypertension and diabetes, this percentage is expected to increase in the near future.
The diagnosis of diastolic heart failure is challenging. In a consensus statement of the European Society of Cardiology, the definition of diastolic heart failure is based on signs and symptoms of heart failure, a relatively preserved left ventricular systolic function (LVEF >0.40–0.50), evidence of diastolic dysfunction on echocardiography and raised natriuretic peptides.1
Treatment of diastolic heart failure is hampered by the absence of evidence for a specific drug that can reduce mortality and morbidity in these patients. Theoretically, a number of treatments might benefit patients with diastolic heart failure. First, in symptomatic patients, diuretics will reduce fluid overload and symptoms. Second, heart rate lowering and negative inotropic agents, such as (some) calcium channel blockers and β blockers, will increase left ventricular filling time and might improve relaxation. Third, every agent that will decrease blood pressure is expected to reduce left ventricular hypertrophy and therefore improve relaxation. Of particular interest are blockers of the renin–angiotensin system, such as ACE inhibitors, angiotensin receptor blockers (ARBs) and aldosterone antagonists. Their potential benefit can be explained by a reduction in both pre- and afterload, a reduction in left ventricular hypertrophy, a reduction in interstitial collagen deposition and fibrosis and, possibly, a favourable effect on relaxation. However, strong evidence for a beneficial effect of ACE inhibitors or ARBs in patients with diastolic heart failure is still lacking.
The ARB candesartan did not significantly reduce cardiovascular death or heart failure hospitalisation in 3024 patients with heart failure and a (relatively) preserved systolic function (LVEF >0.40) who were included in the "effects of candesartan in patients with chronic heart failure and preserved left ventricular ejection fraction" (CHARM-Preserved) trial.2 Of note, patients enrolled in CHARM-Preserved only needed to have an LVEF >0.40 and a history of previous admission to hospital (at any time) for a cardiac condition. Although the investigators were also asked to state that the patient’s signs and symptoms were primarily due to heart failure and not explained by other conditions, these criteria may have "polluted" the population. In fact, in an echocardiographic substudy, it was shown that 33% of patients included in CHARM-Preserved did not have any sign of diastolic dysfunction.3
The ACE inhibitor perindopril did not reduce death or heart failure hospitalisation in patients with diastolic heart failure (LVEF 0.40) who were included in the Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) study.4 Unfortunately, many patients withdrew from perindopril and placebo and started taking open-label ACE inhibitors, which severely jeopardised the power of this study.
In the Valsartan In Diastolic Dysfunction (VALIDD) trial, patients with hypertension and diastolic dysfunction were assigned to valsartan or placebo.5 After 9 months of treatment, blood pressure was lowered similarly and diastolic function improved similarly in both groups. However, VALIDD did not specifically study patients with diastolic heart failure.
Considering the drawbacks of the studies mentioned above, the Hong Kong diastolic heart failure study, recently published in the May issue of Heart is of particular interest.6 In this prospective, multicentre, randomised, open-label with blinded end point (PROBE) trial, 150 patients with diastolic heart failure were randomly assigned to diuretics alone, diuretics plus irbesartan (75 mg/day) or diuretics plus ramipril (10 mg/day). End points of the study were symptoms and quality of life and diastolic function on echocardiography. After 1 year, reduction of blood pressure was not significantly different between the groups. In addition, no significant differences between the groups were observed in quality of life, 6 min walk test, or diastolic function. This study has several strengths and weaknesses.
A strong point of this study is its design. This is the first comparative study between an ACE inhibitor and an ARB, compared with no additional treatment in patients with diastolic heart failure who were treated with a diuretic. The study aimed to answer clinically relevant questions, and although the open-label design might seem inferior, the blinded end point evaluation enables objective evaluation of the results. Second, the patient population is well defined. Patients were included on the basis of a thorough clinical diagnosis of heart failure and an LVEF >0.45. Although inclusion of the patients did not need evidence of diastolic dysfunction on echocardiography, it appeared that diastolic function was considerably worse than in an age- and sex-matched control population. Third, diastolic function was well assessed using both the "classical" mitral inflow parameters and several colour tissue-derived myocardial velocities.
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作者:admin@医学,生命科学 2011-04-18 17:14
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