Prognosis in diastolic heart failure

Diastolic dysfunction and the clinical syndrome of diastolic heart failure have become well recognized as contributors to the overall burden of congestive heart failure. This increasing awareness has led to several recent investigations into the impact of diastolic abnormalities on morbidity and mortality. This article reviews the current state of knowledge regarding the prognosis of patient populations with diastolic dysfunction and diastolic heart failure.     

Advances in diastolic heart failure

More than 50% of people living with congestive heart failure have diastolic heart failure (DHF). Most of them are older than 70 years, and female. The prevalence of DHF has increased with time. DHF is caused by left ventricular (LV) diastolic dysfunction (DD) which is induced by diastolic dyssynchrony. Cardiac and extracardiac factors play important roles in the development of heart failure (HF) symptoms. The diagnosis of DHF is generally based on typical symptoms and signs of HF, preserved or normal LV ejection fraction, DD and no valvular abnormalities on examination, using noninvasive and invasive methodologies. The outcomes with pharmacological therapy in patients with DHF are frequently neutral in clinical trials, and prognosis still remains poor with a 5-year mortality of 42.3% after hospitalization for HF. Further trials are necessary.     

Diagnosing diastolic heart failure

BACKGROUND: increasing evidence supports the existence of left ventricular diastolic dysfunction as an important cause of congestive heart failure, present in up to 40% of heart failure patients. AIM: to review the pathophysiology of LV diastolic dysfunction and diastolic heart failure and the currently available methods to diagnose these disorders. RESULTS: for diagnosing LV diastolic dysfunction, invasive hemodynamic measurements are the gold standard. Additional exercise testing with assessment of LV volumes and pressures may be of help in detecting exercise-induced elevation of filling pressures because of diastolic dysfunction. However, echocardiography is obtained more easily, and will remain the most often used method for diagnosing diastolic heart failure in the coming years. MRI may provide noninvasive determination of LV three-dimensional motion during diastole, but data on correlation of MRI data with clinical findings are scant, and possibilities for widespread application are limited at this moment. CONCLUSIONS: in the forthcoming years, optimal diagnostic and therapeutic strategies for patients with primary diastolic heart failure have to be developed. Therefore, future heart failure trials should incorporate patients with diastolic heart failure, describing precise details of LV systolic and diastolic function in their study populations.     

Primary diastolic heart failure

Diastolic heart failure is defined clinically when signs and symptoms of heart failure are present in the presence of preserved left ventricular systolic function (ejection fraction >45%). The incidence and prevalence of primary diastolic heart failure increases with age and it may be as high as 50% in the elderly. Age, female gender, hypertension, coronary artery disease, diabetes, and increased body mass index are risk factors for diastolic heart failure. Hemodynamic consequences such as increased pulmonary venous pressure, post-capillary pulmonary hypertension, and secondary right heart failure as well as decreased cardiac output are similar to those of systolic left ventricular failure, although the nature of primary left ventricular dysfunction is different. Diagnosis of primary diastolic heart failure depends on the presence of preserved left ventricular ejection fraction. Assessment of diastolic dysfunction is preferable but not mandatory. It is to be noted that increased levels of B-type natriuretic peptide does not distinguish between diastolic and systolic heart failure. Echocardiographic studies are recommended to exclude hypertrophic cardiomyopathy, infiltrative heart disease, primary valvular heart disease, and constrictive pericarditis. Myocardial stress imaging is frequently required to exclude ischemic heart disease. The prognosis of diastolic heart failure is variable; it is related to age, severity of heart failure, and associated comorbid diseases such as coronary artery disease. The prognosis of severe diastolic heart failure is similar to that of systolic heart failure. However, cautious use of diuretics and/or nitrates may cause hypotension and low output state. Heart rate control is essential to improving ventricular filling. Pharmacologic agents such as angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers are used in selected patients to decrease left ventricular hypertrophy. To decrease myocardial fibrosis, aldosterone antagonists have a potential therapeutic role. However, prospective controlled studies will be required to establish their efficacy in primary diastolic heart failure.     

心肌细胞凋亡在老年性心衰发生中的作用

目的探讨心肌细胞凋亡在老年心衰发生中的作用。方法制备大鼠心肌缺血／再灌注（MI／R）模型。雄性SD大鼠被分为4个实验组：青年假手术组（2个月,16只）、老年假手术组（24个月,16只）、青年手术组（2个月,16只）和老年手术组（24个月,16只）。心肌缺血／再灌注组大鼠的左冠状动脉近中段被阻断30rain后恢复血流再灌注3h和24h。通过MillarMikro—Tip导管压力换能器对大鼠左心室（LV）功能指标进行检测,从而对sD大鼠心脏功能进行评价。采用原位末端标记检测（TUNEL）法和Caspase-3活性检测评价心肌细胞凋亡水平,同时测定大鼠血浆中凋亡标志物sFas、TNF—α和IL-6水平。对大鼠心肌组织使用伊文氏蓝-TTC染色并测定血浆cTnI水平以确定心肌坏死程度。结果与青年大鼠相比,老年大鼠在心肌缺血／再灌注后心功能明显降低,同’时心肌细胞凋亡水平及心肌细胞坏死程度显著增加。血浆凋亡标志物的检测结果也表现出相同的趋势。结论年龄导致了缺血／再灌注后心功能的显著降低,心肌细胞凋亡水平的增加可能是引发上述现象的主要原因。     

Clinical trials in diastolic heart failure

Forty percent to 50% of patients with chronic heart failure have normal or relatively normal left ventricular ejections fractions. These are much more frequently women and tend to be older than those with reduced ejection fractions. In most, left ventricular diastolic dysfunction plays a major role in the genesis of heart failure. Until recently, these patients have been systematically excluded from heart failure trials, so that there are no proven treatments for this group. This article reviews the recent and ongoing trials in patients with diastolic heart failure, which hopefully will lead to improved treatment and outcomes.     

Clinical advances in diastolic heart failure

Congestive heart failure is a common cardiovascular disorder among adults and is a major cause of morbidity and mortality worldwide. Diastolic heart failure (DHF) is implicated in 1/3 to 1/2 of all heart failure cases and results from an abnormality of ventricular relaxation, compliance or filling. DHF differs from heart failure with reduced ejection fraction in epidemiology, pathophysiology, and natural history. Recent advances have improved our understanding of DHF. This review summarizes these advances and discusses their clinical implications as they pertain to the diagnosis and management of patients with DHF.     

舒张性心力衰竭的研究进展

舒张性心力衰竭或射血分数正常的心力衰竭约占临床慢性心力衰竭的一半左右,以往被视为与收缩性心力衰竭完全不同的表现形型,经越来越深入的研究后表明,两者是不可分割的有机整体,前者是后者的一部分。进一步从病理生理角度提出慢性心力衰竭诊断的新思路。对于舒张性心力衰竭的治疗仍然缺乏循证依据。     

Therapy for diastolic heart failure

There is little objective to guide the therapy of patients with diastolic heart failure. Because of the similarities of pathophysiology abnormalities in diastolic and systolic heart failure, it is a reasonable inference to suggest that the proven therapy for systolic heart failure may also be of benefit in patients with diastolic heart failure. Treatment of underlying or exacerbating conditions in diastolic heart failure, such as hypertension, left ventricular hypertrophy, ischemia, diabetes, anemia, obesity and pulmonary disease is an important means of managing diastolic heart failure. Control of systolic blood pressure is effective in improving and preventing the development of diastolic heart failure. Treatment of diastolic heart failure is most effective when it is associated with hypertension. Production of systolic arterial pressure acutely reduces pulmonary congestion, ischemia, and chronically may lead to regression of left ventricular hypertrophy. Patients with diastolic heart failure in the absence of hypertension are very difficult to treat.     

Diagnosis of diastolic heart failure

Nearly half of patients with heart failure (HF) have a normal ejection fraction (EF) and have been labeled as having diastolic HF. Diastolic HF is characterized by a normal EF, a variable amount of concentric left ventricular hypertrophy, and abnormal diastolic function. Differentiating diastolic HF from HF with a reduced EF (systolic HF) is important because these two forms of HF have different pathophysiology and thus might require different therapeutic approaches. Nevertheless, patients with diastolic HF and those with systolic HF have similar clinical symptoms and signs. Thus, clinical history and physical examination do not differentiate between diastolic and systolic HF. There is accumulating evidence that diastolic dysfunction is related to the severity of HF and prognosis regardless of EF. Thus, it is important to evaluate both systolic and diastolic function not only to differentiate between diastolic and systolic HF but also to identify high-risk patients.     

Hypertension and diastolic heart failure

In patients with hypertension, pressure overload leads to left ventricular hypertrophy (LVH), myocardial fibrosis, and impaired diastolic filling without systolic dysfunction. Presently, diastolic heart failure accounts for about 50% of the heart failure population. Fatigue, dyspnea, reduced exercise tolerance, and peripheral edema are common presenting complaints. As a group, patients with diastolic heart failure are older and predominantly female. Diuretics are effective for treating congestive symptoms. β Blockers and heart rate-lowering calcium blockers show benefit in smaller studies but have not been evaluated in definitive clinical trials. Renin-angiotensin-aldosterone system blockers reduce blood pressure, LVH, and myocardial fibrosis; however, long-term studies with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers demonstrate little effect on symptoms or survival, and inconsistent effects on heart failure hospitalization. At present, evidence-based treatment includes antihypertensive therapy to reduce progression from hypertension to heart failure. In patients with established heart failure, diuretics and other empiric treatments are used to control symptoms.     

Epidemiology of diastolic heart failure

Heart failure (HF) is a major public health problem. Clinical studies suggest that a significant proportion of patients with HF have preserved ejection fraction, a clinical syndrome commonly referred to as diastolic HF (DHF). One of the purposes of epidemiological studies is to identify unmet public health needs in a population and to quantify the magnitude of the problem in a manner that is free from the referral bias inherent in clinical studies. We review current epidemiological data estimating the prevalence of DHF, highlight the challenges posed by existing data, and suggest focus for future studies on the epidemiology of DHF. We limited the review to studies that met our definition of population-based studies (eg, studies drawing participants from a defined community or all consecutive referrals to a health facility that is the sole provider to a defined community). Studies relevant to the epidemiology of each stage of DHF (American College of Cardiology/American Heart Association stages A-D) were reviewed. These epidemiological studies clearly define the magnitude of this health care problem and underscore the urgent need for studies elucidating the natural history, pathophysiology, and optimal diagnostic and management strategy for this extremely common clinical syndrome.     

Statins and diastolic heart failure

Although nearly 50% of patients with heart failure have normal ejection fraction, there are only few studies for guiding the treatment of this patient population. We emphasize the possible clinical benefit of statins therapy in these patients.     

舒张性心力衰竭的诊治进展

50%以上的心力衰竭为舒张性心力衰竭(dias-tolic heart failure,DHF)。DHF的比例随年龄而增加,其发病率在45岁以下人群中为46%,而85岁以上为59%;DHF的主要危险因素有长期高血压、老年、女性、肥胖、糖尿病、慢性肾病以及冠状动脉疾病〔1〕。有研究表明,DHF的住院率与收缩性心力