细说舒张性心力衰竭
定义 舒张性心力衰竭（心衰）又被称为收缩功能正常的心衰或收缩功能保留的心衰。过去，人们认为慢性心衰主要由收缩功能不全引起，而近十年的调查显示，不少心衰患者保留了正常的心脏收缩功能，左室射血分数（LVEF）正常或接近正常。有学者称这类心衰为舒张性心衰（DHF），也有学者称之为收缩功能正常的心衰（HF-NEF）或收缩功能保留的心衰（HF-PSF）。
当高血压引起左室向心性重构和左室肥厚时，左室舒张特性发生变化，左室松弛和充盈受损，即发生舒张功能不全。左室舒张功能不全常发生在收缩功能改变之前，患者初期可能无症状，但一旦出现心衰症状和体征，则称之为舒张性心衰。
有学者认为很少有单纯舒张性心衰，因为应用组织多普勒成像技术测定左室壁心肌纵向运动时发现，所谓单纯舒张功能不全的患者已存在左室壁心肌纵向运动异常，因此，他们认为将舒张性心衰命名为HF-NEF或HF-PSF为妥。
流行病学
舒张性心衰在心衰患者中所占比例为40％~71％。
1999年发表的弗雷明汉心脏研究显示，LVEF≥50％的心衰占所有心衰的51％。2003年欧洲心衰调查显示，在因心衰入院患者中，49％的男性和72％的女性LVEF≥40％。总体而言，舒张性心衰常见于老年患者，女性多见，病因以高血压和心房颤动为多（多于冠心病）。调查人群年龄、性别不同，研究所定义的正常或接近正常的LVEF范围不同，这可能是舒张性心衰流调结果各异或相差甚远的原因。
http://www.cmt.com.cn/article/090226/c0201.jpg
诊断
舒张性心衰的诊断包括临床表现和辅助检查。心导管检查依然是诊断舒张功能不全最有价值的方法，但在临床实践中常用无创的超声检查，当超声检查存在技术困难时，可应用核素或心室造影等方法。
临床表现
当患者出现乏力、呼吸困难、水肿、颈静脉充盈、肝大等心衰症状时，我们很难区分是收缩性还是舒张性心衰，因此需要进行临床鉴别（见上表）
超声心动图
多普勒二尖瓣血流频谱
舒张早期血流峰速度（E）与舒张晚期血流峰速度（A）的比值（E/A）和E峰减速时间（DT） 二尖瓣血流频谱由舒张性早期快速充盈E峰和舒张晚期充盈A峰组成。正常情况下E/A>1，左室松弛异常时，E降低而A代偿性增高，E/A<1，E峰DT延长。如果左室顺应性降低或左心房压力明显增高，则快速充盈DT缩短。DT和肺毛细血管楔压（PCWP）存在很好的负相关关系，DT<130 ms提示PCWP>20 mmHg。
等容舒张时间（IVRT） IVRT是主动脉瓣关闭至二尖瓣开放的间期，其变化一般和DT平行，在左室松弛异常时延长，在充盈压力增加时缩短。
三种异常的左室充盈模式 ①松弛受损（DD Ⅰ型，轻度舒张功能不全）：E峰下降，A峰增高，E/A减小，IVRT 延长，DT延长；②假性正常化充盈（DD Ⅱ型，中度舒张功能不全）：E/A和DT正常，IVRT较DD Ⅰ型时缩短；③限制型充盈（DD Ⅲ、Ⅳ型，重度舒张功能不全）：E/A显著增加（2∶1），IVRT和DT缩短。
提示 E和A受年龄、心脏前后负荷、血容量、心率及二尖瓣解剖结构和功能影响。由于存在假性正常化类型，二尖瓣血流频谱评价左室舒张功能有一定局限性。
肺静脉血流速度
正常肺静脉血流的脉冲式多普勒可记录到正向收缩期血流速度（PVs）和舒张期血流速度（PVd）。在舒张晚期记录到逆向血流峰值速度（PVa）。PVa和间期（PVa dur）是重要的测量参数，当左室舒张末期压力（LVEDP）增加时，两者均增加。
组织多普勒二尖瓣瓣环速度
舒张早期速度（E’）和舒张晚期速度（A’） 舒张功能不全时，二尖瓣环E’/A’<1。(顶图)
对于心肌松弛受损的患者，基础状态时E’减低，且不像正常人一样随前负荷增加而增高。因而，E’降低是舒张功能不全的最早期表现之一，并存在于其后所有阶段。E’随年龄增加而降低，甚至比二尖瓣流入道血流速度E降低更早出现。在充盈压增加时，E’仍降低而E增高，因此E/E’比值与左心室充盈压及PCWP相关性良好。从内侧瓣环记录E’，E/E’≥15时表明PCWP≥20 mmHg。
其他辅助诊断
心电图 舒张性心衰的心电图可能显示左室肥厚、心肌缺血、心肌梗死或心房颤动心律。
血浆钠尿肽（BNP）和N末端钠尿肽前体（NT-proBNP） 血浆BNP和NT-proBNP的正常值为<100 pg/ml和<400 pg/ml。舒张性心衰时，BNP和NT-
proBNP水平均增高。
胸片 舒张性心衰患者胸片可见肺淤血、肺水肿。心脏大小正常或略扩大。
诊断标准
综合国内外指南建议，舒张性心衰的诊断须满足以下条件：①有心衰症状和体征；②左室收缩功能正常或接近正常，即LVEF>50%，左室舒张末期容积指数（LVEDVI）<97 ml/m2；③具有左室舒张功能不全的证据，即有创评价显示LVEDP>16 mmHg或PCWP>12 mmHg或无创组织多普勒显示E/E’>15。当E/E’为8~15时，需要另一个无创性左室舒张功能不全的诊断证据，如DT、二尖瓣或肺静脉血流频谱、左室质量指数等。
(北京协和医院 朱文玲 中国医学论坛报) Diastolic Heart Failure: Challenges of Diagnosis and Treatment
CECILIA GUTIERREZ, M.D, and DANIEL G. BLANCHARD, M.D., University of California, San Diego, School of Medicine, La Jolla, California
http://www.aafp.org/afp/images/acf.gif? This article exemplifies the AAFP 2004 Annual Clinical Focus on caring for America's aging population.
Diastolic heart failure, a major cause of morbidity and mortality, is defined as symptoms of heart failure in a patient with preserved left ventricular function. It is characterized by a stiff left ventricle with decreased compliance and impaired relaxation, which leads to increased end diastolic pressure. Signs and symptoms are similar to those of heart failure with systolic dysfunction. The diagnosis of diastolic heart failure is best made with Doppler echocardiography. Based on current knowledge, pharmacologic treatment of diastolic heart failure should focus on normalizing blood pressure, promoting regression of left ventricular hypertrophy, avoiding tachycardia, treating symptoms of congestion, and maintaining normal atrial contraction when possible. Diuretic therapy is the mainstay of treatment for preventing pulmonary congestion, while beta blockers appear to be useful in preventing tachycardia and thereby prolonging left ventricular diastolic filling time. Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers may be beneficial in patients with diastolic dysfunction, especially those with hypertension. Evidence from adequately powered randomized controlled trials, however, is not available yet. The outcomes of ongoing clinical trials may provide much-needed information to move from intuitive treatment to therapy based on evidence that matters: decreased morbidity and mortality and improved quality of life. (Am Fam Physician 2004;69:2609–16. Copyright ? 2004 American Academy of Family Physicians.)
Heart failure affects approximately 4.8 million persons in the United States, with about 500,000 new cases diagnosed each year.1,2 It is the leading cause of hospitalization in patients older than 65 years.3 In spite of significant advances in the treatment of heart failure, mortality rates remain high: 30 to 40 percent of patients with advanced disease and 5 to 10 percent of patients with mild symptoms die within five to 10 years.4
Heart failure can arise from any condition that compromises the contractility of the heart (systolic heart failure) or that interferes with the heart's ability to relax (diastolic heart failure). Hospital- and community-based reports indicate that about one fourth to one half of patients with heart failure have normal left ventricular systolic function.5,6 Observational studies5–7 indicate that diastolic heart failure is more common in women and elderly persons. Although patients with diastolic heart failure have a lower annual mortality rate than patients with systolic heart failure, they have a higher rate than the general population. They also have hospitalization rates similar to those of patients with systolic heart failure. These observations emphasize diastolic heart failure as an important contributor to morbidity, mortality, and health care costs, and highlight the need for further research and clinical trials examining this condition.
Pathophysiology
Diastole is the process by which the heart returns to its relaxed state; it is also the time for cardiac perfusion. During diastole, drastic changes in cardiac pressure-volume relationships occur. The relaxation process has four identifiable phases: isovolumetric relaxation from the time of aortic valve closure to mitral valve opening; early rapid filling after mitral valve opening; diastasis, a period of low flow during mid-diastole; and late filling of the ventricles from atrial contraction (Figure 1).
In patients with isolated diastolic heart failure, the heart often is able to meet the body's metabolic needs, but at higher diastolic pressures. The left ventricle is stiff, with decreased compliance and impaired relaxation. Transmission of the higher end-diastolic left ventricular pressure to the pulmonary circulation may lead to pulmonary congestion, dyspnea, and other symptoms of heart failure.8,9
Diastole is a complex process that is affected by a number of factors, including ischemia, heart rate, velocity of relaxation, cardiac compliance (i.e., elastic recoil and stiffness), hypertrophy, and segmental wall coordination of the heart muscle.
http://www.aafp.org/afp/2004/0601/afp20040601p2609-f1.jpg FIGURE 1.Cardiac cycle, showing changes in left atrial pressure, left ventricular pressure, aortic pressure, and ventricular volume; the electrocardiogram (ECG); and the phonocardiogram.
HYPERTENSION
Chronic hypertension is the most common cause of diastolic dysfunction and failure. It leads to left ventricular hypertrophy and increased connective tissue content, both of which decrease cardiac compliance.10 The hypertrophied ventricle has a steeper diastolic pressure-volume relationship; therefore, a small increase in left ventricular end-diastolic volume (which can occur with exercise, for example) causes a marked increase in left ventricular end-diastolic pressure.
ISCHEMIA
Relaxation of the ventricles involves the active transport of calcium ions into the sarcoplasmic reticulum, which allows the dissociation of myosinactin crossbridges. Hypoxia inhibits the dissociation process by altering the balance of the adenosine triphosphate–to–adenosine diphosphate ratio, which may contribute to diastolic dysfunction.11
HEART RATE
The heart rate determines the time that is available for diastolic filling, coronary perfusion, and ventricular relaxation. Tachycardia adversely affects diastolic function by several mechanisms: it decreases left ventricular filling and coronary perfusion times, increases myocardial oxygen consumption, and causes incomplete relaxation because the stiff heart cannot increase its velocity of relaxation as heart rate increases. Patients with diastolic dysfunction do not tolerate tachycardia or exercise well.
ATRIAL FIBRILLATION
Patients with heart failure are at increased risk for atrial fibrillation.12 As the ventricle stiffens and develops higher end-diastolic pressures, the atria are distended and stressed; this situation often results in atrial fibrillation. The loss of atrial contraction worsens the symptoms of heart failure, because patients with diastolic dysfunction often are dependent on atrial filling of the left ventricle (“atrial kick”). Atrial fibrillation also can worsen symptoms if the ventricular rate is uncontrolled.
VENTRICULAR LOAD
At the end of normal systole, a small residual volume of blood remains in the left ventricle. If this residual volume increases, it interferes with the normal elastic recoil of the heart, the relaxation of the heart, and the development of a negative pressure gradient between the ventricle and atria. As a result, rapid early diastolic filling is impaired.
AGING
Diastolic dysfunction is more common in elderly persons, partly because of increased collagen cross-linking, increased smooth muscle content, and loss of elastic fibers.13,14 These changes tend to decrease ventricular compliance, making patients with diastolic dysfunction more susceptible to the adverse effects of hypertension, tachycardia, and atrial fibrillation.
Diagnosis
The signs and symptoms of heart failure are nonspecific (dyspnea, exercise intolerance, fatigue, weakness) and often can be attributed to other conditions, such as pulmonary disease, anemia, hypothyroidism, depression, and obesity. Furthermore, it is difficult to distinguish diastolic from systolic heart failure based on physical findings or symptoms (Table 115–17).15,18–20 Systolic heart failure is defined as a left ventricular ejection fraction of less than 45 percent, but diagnostic criteria for diastolic dysfunction are still controversial.
Cardiac catheterization remains the gold standard for demonstrating impaired relaxation and filling, because it provides direct measurement of ventricular diastolic pressure. However, the balance of benefit, harm, and cost argue against its routine use in diagnosing diastolic dysfunction.
Doppler echocardiography has assumed the primary role in the noninvasive assessment of cardiac diastolic function and is used to confirm the diagnosis of diastolic heart failure. For example, echocardiographic measurement of tau, the time constant of left ventricular pressure decay during isovolumetric relaxation, can be performed to assess left ventricular stiffness.
More importantly, Doppler echocardiogra phy is used to evaluate the characteristics of diastolic trans–mitral-valve blood flow. The peak velocities of blood flow during early diastolic filling (E wave) and atrial contraction (A wave) are measured, and the ratio is calculated. Under normal conditions, the early-filling E-wave velocity is greater than the A-wave velocity, and the E-to-A-wave ratio is about 1.5 (Figure 2). In early diastolic dysfunction, this relationship reverses, because the stiffer heart relaxes more slowly, and the E-to-A-wave ratio drops below 1.0 (Figure 3). As diastolic function worsens and left ventricular diastolic pressure rises, left ventricular diastolic filling occurs primarily during early diastole, because the left ventricular pressure at end-diastole is so high that atrial contraction contributes less to left ventricular filling than normal. At this point, the E-to-A-wave ratio rises, often to greater than 2.0 (Figure 4). This so-called “restrictive pattern” confers a poor prognosis.21 Recent studies also have shown that Doppler evaluation of myocardial velocities during ventricular relaxation predict elevated filling pressure.
TABLE 1
Prevalence of Specific Signs and Symptoms in Patients with Systolic or Diastolic Heart Failure The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication.
The E- and A-wave velocities are affected by blood volume and mitral valve anatomy and function. Furthermore, these wave velocities are less useful in the setting of atrial fibrillation. Despite these limitations, Doppler echocardiography provides essential information about the anatomy and function of the heart, chamber size, hypertrophy, valvular function, regional wall abnormalities, and chamber pressures. It also allows the physician to identify and rule out other potential causes of the patient's symptoms, such as valvular lesions, pericardial disease, and pulmonary hypertension.
http://www.aafp.org/afp/2004/0601/afp20040601p2609-f2.jpg FIGURE 2.Normal trans–mitral-valve spectral Doppler flow pattern. The E-to-A-wave ratio is approximately 1.4 to 1.0.
The serum level of B-type natriuretic peptide is an accurate tool for establishing the diagnosis of heart failure in patients with dyspnea, but the test cannot distinguish diastolic from systolic heart failure.22,23 A B-type natriuretic peptide level greater than 100 pg per mL was found to be 95 percent sensitive but only 14 percent specific for detecting systolic heart failure in a mixed group of patients with systolic or diastolic heart failure.24
http://www.aafp.org/afp/2004/0601/afp20040601p2609-f3.jpg FIGURE 3.Trans–mitral-valve Doppler flow tracing in a patient with mild diastolic dysfunction (abnormal relaxation). The E-to-A-wave ratio is less than 1.0.
In an attempt to establish diagnostic criteria, the European Study Group on Diastolic Heart Failure25 proposed three obligatory conditions for the diagnosis of diastolic heart failure: the presence of signs and symptoms of heart failure; the presence of normal or mildly abnormal left ventricular systolic function (ejection fraction of greater than 45 percent); and evidence of abnormal left ventricular relaxation, filling, diastolic distensibility, or diastolic stiffness. The criteria have been criticized, however, because symptoms of heart failure are nonspecific, significant variability exists in eliciting and reporting symptoms of heart failure, and it is impractical to obtain evidence of abnormal relaxation in daily clinical practice.
One investigative team26 proposed classifications of definite, probable, and possible diastolic heart failure, depending on the presence of three stratified conditions: definite evidence of heart failure; objective evidence of normal left ventricular systolic function measured within 72 hours of the heart failure event; and objective evidence of left ventricular diastolic dysfunction by cardiac catheterization. If all three conditions are present, the diagnosis of diastolic heart failure is definite. If the first two conditions are present, the diagnosis is probable. If only the first condition is present or only partial evidence of the second condition is present, the diagnosis of diastolic heart failure is considered possible. A recent prospective study of 63 patients with symptoms of heart failure based on the Framingham criteria27 and a normal ejection fraction found that more than 90 percent of the patients had abnormal diastolic function on evaluation with both Doppler echocardiography and cardiac catheterization. The results of this study call into question the need for objective measurement of diastolic dysfunction, but confirmation is required before this approach is adopted more widely.
http://www.aafp.org/afp/2004/0601/afp20040601p2609-f4.jpg FIGURE 4. Trans–mitral-valve Doppler flow pattern in a patient with severe (restrictive) diastolic dysfunction. The E-to-A-wave ratio is abnormally high, and the A-wave velocity is extremely low.
Treatment
The treatment of diastolic heart failure is less well defined than the treatment of systolic heart failure. Current recommendations are based on disease-oriented evidence, including pathophysiology, extrapolation of knowledge about other aspects of cardiovascular disease, data from small studies, and expert opinion. None of the treatment recommendations have been validated by randomized controlled trials (RCTs). Evidence-based guidelines from the American College of Cardiology/American Heart Association (ACC/AHA)28 and the Institute for Clinical Systems Improvement (ICSI)29 provide guidance until RCTs can be completed.
NONPHARMACOLOGIC INTERVENTIONS
Lifestyle modifications are recommended to reduce the risk of all forms of cardiovascular disease. Measures include weight loss, smoking cessation, dietary changes, and exercise. Identification and treatment of comorbid conditions, such as high blood pressure, diabetes, and hypercholesterolemia, are important in reducing the risk of subsequent heart failure.28,29
PHARMACOLOGIC THERAPY
Pharmacologic treatment of diastolic heart failure is directed at normalizing blood pressure, promoting regression of left ventricular hypertrophy, preventing tachycardia, treating symptoms of congestion, and maintaining atrial contraction.28–30 The basis for drug therapy remains empiric, and the recommendations discussed in this section come from the ACC/AHA guidelines and the ICSI evidence-based practice guideline.28–30
Treatment with diuretics and vasodilators often is necessary to reduce pulmonary congestion. However, caution is required to avoid excessive diuresis, which can decrease preload and stroke volume. Patients with diastolic dysfunction are highly sensitive to volume changes and preload.
The potential benefits of beta blockers stem from their ability to decrease heart rate, increase diastolic filling time, decrease oxygen consumption, lower blood pressure, and cause regression of left ventricular hypertrophy. The Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure31 is evaluating the effect of the beta blocker nebivolol in the treatment of elderly patients with diastolic heart failure.
The multiple benefits of angiotensin-converting enzyme (ACE) inhibitors in the treatment of cardiovascular disease make them highly promising therapeutic agents. ACE inhibitors cause regression of left ventricular hypertrophy, decrease blood pressure, and prevent or modify cardiac remodeling; these actions provide strong theoretic support for the use of these agents in patients with diastolic dysfunction. So far, there have been few studies of ACE inhibitors in patients with diastolic dysfunction.32 The Perindopril for Elderly People with Chronic Heart Failure study33 is the largest ongoing trial of the benefits of perindopril in patients with diastolic failure.
Strength of Recommendations
Key clinical recommendations for patients with diastolic dysfunctionStrength of recommendationReferencesTreat blood pressure to achieve a goal of less than 130/85 mm Hg.
A
28,29
For patients with concomitant atrial fibrillation, control ventricular rate or restore sinus rhythm.
C
28
Coronary revascularization is recommended in patients with coronary artery disease in whom symptomatic or demonstrable myocardial ischemia is judged to have an adverse effect on diastolic function.
C
28
Use diuretics to control pulmonary congestion and peripheral edema.
C
28,29
Use digitalis to minimize symptoms of heart failure.
C
28
Use beta blockers for rate control, especially in patients with atrial fibrillation or symptoms of heart failure. Start with a low dosage; higher dosages can be used in patients with diastolic dysfunction than in patients with systolic dysfunction.
C
28,29
Use angiotensin-converting enzyme inhibitors to control symptoms of heart failure.
C
28,29
One arm of the Candesartan in Heart Failure-Assessment of Reduction of Mortality and Morbidity trial34 studied the effect of candesartan in patients with preserved systolic function. After an average of 36.6 months follow-up, the study found no difference in cardiovascular mortality but a small decrease in hospitalization for worsening heart failure among patients taking candesartan as compared with placebo. In 1999, a small trial showed that losartan improved exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise.35 The Irbesartan in Heart Failure with Preserved Systolic Function study is currently evaluating the utility of angiotensin-receptor blockers in patients with diastolic heart failure.
In theory, the use of calcium channel blockers may be beneficial, because these agents decrease blood pressure, decrease oxygen demand, and dilate coronary arteries. However, data are lacking on patient-oriented outcomes such as morbidity and mortality. Calcium channel blockers should be used with caution in patients with coexisting systolic and diastolic dysfunction. The long-acting dihydropyridine class of calcium channel blockers is safe for use in patients with systolic heart failure, but nondihydropyridine agents should be avoided.
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