Diastolic heart failure: The forgotten manifestation of hypertensive heart disease

Heart failure (HF) is a progressively debilitating disorder characterized by frequent hospital admissions and high annual mortality rates. Coronary artery disease (CAD), hypertension, and aging are major risk factors for the development/ progression of HF. For years, most of the attention has been focused on HF caused by reduced left ventricular (LV) systolic function, largely attributable to CAD. It is now generally accepted that nearly 50% of elderly patients with HF might have normal or preserved LV systolic function. This condition is commonly referred to as a distinct type of HF caused by LV diastolic dysfunction, and it often accompanies hypertensive heart disease. Isolated diastolic HF is increasingly recognized as the dominant cause of symptoms and hospitalizations from HF in a large proportion of individuals aged 65 and older. However, the clinicians caring for patients with diastolic HF do not fully understand its cause, how it progresses, or how it could be appropriately diagnosed and treated. Because varying degrees of systolic and diastolic dysfunction might coexist in any individual patient, and given the limitation of current diagnostic tools, the overall impact of isolated diastolic HF continues to evolve. Ongoing clinical trials are testing new strategies for treatment of diastolic HF.     

Prevalence and prognosis of asymptomatic left ventricular diastolic dysfunction in ambulatory patients with coronary heart disease

The association of asymptomatic left ventricular (LV) diastolic dysfunction with cardiovascular outcomes in ambulatory patients with coronary heart disease (CHD) and no history of heart failure (HF) was examined. LV diastolic HF predicts adverse cardiovascular outcomes. However, the prevalence and prognosis of asymptomatic LV diastolic dysfunction in patients with established CHD in the absence of clinical HF is unknown. Six hundred ninety-three patients with stable CHD, normal systolic function (LV ejection fraction>or=50%), and no history of HF were evaluated. Echocardiography was used to classify LV diastolic function, and Cox proportional hazards models were used to evaluate the association of LV diastolic dysfunction with cardiovascular outcomes during 3 years of follow-up. Of 693 subjects with normal systolic function and no history of HF, 455 (66%) had normal LV diastolic function, 166 (24%) had mild LV diastolic dysfunction, and 72 (10%) had moderate to severe LV diastolic dysfunction. After multivariable adjustment, the presence of moderate to severe LV diastolic dysfunction was strongly predictive of incident hospitalization for HF (hazard ratio 6.3, 95% confidence interval 2.4 to 16.1, p=0.0003) and death from heart disease (HR 3.9, 95% confidence interval 1.0 to 14.8, p=0.05). In conclusion, moderate to severe LV diastolic dysfunction was present in 10% of patients with stable CHD with normal ejection fraction and no history of HF and predicts subsequent hospitalization for HF and death from heart disease. Patients with asymptomatic LV diastolic dysfunction may benefit from more aggressive therapy to prevent or delay the development of HF.     

Diastolic dysfunction and heart failure with a preserved ejection fraction: Relevance in critical illness and anaesthesia

Epidemiological and clinical studies suggest that HF with a preserved ejection fraction will become the more common form of HF which clinicians will encounter. The spectrum of diastolic disease extends from the asymptomatic phase to fulminant cardiac failure. These patients are commonly encountered in operating rooms and critical care units. A clearer understanding of the underlying pathophysiology and clinical implications of HF with a preserved ejection fraction is fundamental to directing further research and to evaluate interventions. This review highlights the impact of diastolic dysfunction and HF with a preserved ejection fraction during the perioperative period and during critical illness.     

Role of angiotensin II in the evolution of diastolic heart failure

More than half of all persons with heart failure (HF) have diastolic HF. The prevalence of diastolic HF increases from 46% in persons younger than 45 years to 59% in those 85 years and older. The annual mortality rate associated with diastolic HF is >10%. Diagnosis is based on signs and symptoms of HF, elevated plasma B-type natriuretic peptide, preserved left ventricular systolic function, and evidence of diastolic dysfunction by Doppler examination on two-dimensional echocardiography. Approximately 80% of patients with diastolic HF have increased left ventricular mass and a history of hypertension. Neurohormonal activation is a key aspect of this condition. Studies suggest that activation of the renin-angiotensin-aldosterone system, specifically direct cardiac effects of angiotensin II and aldosterone, contributes to the pathogenesis and progression of diastolic dysfunction. Hence, there is a rationale for use of agents that antagonize the renin-angiotensin-aldosterone system, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists, in patients with heart failure.     

Prevention of heart failure

Heart failure (HF) is a progressive process and the objective of treatment should be to prevent progression. Treatment should begin at the stage of asymptomatic left ventricular dysfunction (LVD), not only to reduce mortality but also to preserve exercise capacity and quality of life. To prevent clinical progression in patients with asymptomatic LVD or HF, left ventricular remodelling and dilatation must be prevented. The SOLVD prevention trial-the only clinical trial on the prevention of HF-showed that ACE inhibition significantly reduced the development of HF, but did not significantly reduce mortality. Plasma norepinephrine is elevated in patients with asymptomatic LVD, is further elevated in patients with overt HF, and is correlated with increased mortality. Inhibition of the sympathetic nervous system by administration of beta-blocking agents is therefore a logical treatment for patients with HF or asymptomatic LVD. Clinical trials have shown that beta-blocking agents increase left ventricular ejection fraction and reduce left ventricular dimensions in patients with HF, indicating regression of left ventricular remodelling. Almost all the patients in these studies were receiving an ACE inhibitor as part of their background medication, therefore the relative efficacy of beta-blocking agents and ACE inhibitors in the regression of remodelling is not known. CARMEN, a double-blind, randomised, parallel group study of carvedilol versus enalapril versus carvedilol + enalapril in 450 patients with mild HF, will provide this information.     

Heart failure with preserved ejection fraction

Progressive aging of the population and prolongation of life expectancy have led to the rising prevalence of heart failure (HF). Despite the improvements in medical therapy, the mortality rate of this condition has remained unacceptably high, becoming the primary cause of death in the elderly population. Almost half of patients with signs and symptoms of HF are found to have a nearly normal ejection fraction, which delineates a distinct clinical syndrome, known as HF with preserved ejection fraction (HF-PEF). While early research focused on the importance of diastolic dysfunction, more recent studies reported the pathophysiological complexity of the disease with multiple cardiovascular abnormalities contributing to its development and progression. HF-PEF is a challenging major health problem with yet no solution as there is no evidence-based treatment which improves clinical outcomes. This review summarizes the state of current knowledge on diagnosis, prognosis and treatment of HF-PEF, with particular insights on the pathological characteristics in the elderly population.     

Aging and heart failure: changing demographics and implications for therapy in the elderly

The elderly population (age ≥65) is increasing and with it morbidity, hospitalizations, costs and mortality due to heart failure (HF). HF is a progressive disorder that is superimposed on an on-going aging process. The two broad categories of HF, HF with left ventricular (LV) systolic dysfunction or low ejection fraction (HF/low-EF) and HF with preserved ejection fraction (HF/PEF) are equally prevalent in the elderly. Trials of therapy for HF/low-EF in primarily non-elderly patients showed mortality benefit in elderly patients. In contrast, trials for HF/PEF have not shown mortality benefit in elderly or non-elderly patients. HF pharmacotherapy in the elderly is challenging and needs to be individualized and consider several aging-related changes. More research into the biology of aging and more clinical trials in elderly patients are needed to improve morbidity and mortality in elderly HF patients.     

Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome

The prevalence of heart failure (HF) is increasing. A distinction is made between diastolic HF (preserved left ventricular ejection fraction (LVEF)) and systolic HF (reduced LVEF). Advanced glycation end-products (AGEs) are crystallized proteins that accumulate during ageing, but are particularly increased in patients with diabetes mellitus and in patients with renal failure. Through the formation of collagen crosslinks, and by interaction with the AGE-receptor, which impairs calcium handling and increases fibrosis, AGE-accumulation has pathophysiologically been associated with the development of diastolic and renal dysfunction. Interestingly, diastolic dysfunction is a frequent finding in elderly patients, diabetic patients and in patients with renal failure. Taken together, this suggests that AGEs are related to the development and progression of diastolic HF and renal failure. In this review, the role of AGEs as a possible pathophysiological factor that link the development and progression of heart and renal failure, is discussed. Finally, the role of AGE intervention as a possible treatment in HF patients will be discussed.     

Diastolic dysfunction and heart failure with preserved ejection fraction: rationale for RAAS antagonist/CCB combination therapy

A large number of patients who present with signs or symptoms of heart failure (HF) do not have evidence of left ventricular systolic dysfunction. As a result, HF in the presence of normal or preserved ejection fraction, or diastolic HF, is increasingly recognized as a health care challenge. Guidelines have been issued for the classification, diagnosis, and prevention of HF from diastolic dysfunction, but treatment of this condition remains problematic. Antihypertensive agents that have been proven in clinical trials to improve outcomes in HF with systolic dysfunction, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers, have not yet demonstrated comparable benefits in patients with diastolic dysfunction. Combination therapy using an antagonist of the renin-angiotensin-aldosterone system and a calcium-channel blocker has potential advantages over monotherapy and is being explored in several ongoing clinical trials.     

Screening for ventricular remodeling

Current guidelines emphasize the importance of preventing heart failure (HF) by targeting people with preclinical forms of the disease. Accordingly, there is considerable interest in identifying left ventricular (LV) remodeling, the fundamental substrate for HF, in asymptomatic individuals in the community. Increased LV mass and asymptomatic LV systolic and LV diastolic dysfunction are the remodeling phenotypes that could be potentially considered for population-wide screening. Plasma levels of natriuretic peptides (NP) have been extensively investigated for such screening purposes. However, a majority of investigations suggest that their performance characteristics are suboptimal for identifying LV remodeling phenotypes unless high-risk individuals (eg, older men with hypertension) are targeted. In general, the prevalence of LV systolic dysfunction in women is too low to justify screening. In recent reports, sequential screening strategies combining urine and plasma NP or plasma NP and hand-held portable echocardiography have been advocated as potential approaches to identify asymptomatic LV systolic dysfunction in a cost-effective manner. Additional studies are warranted to confirm these findings.     

Uncovering a hidden epidemic: a study of the current burden of heart failure in Australia

BACKGROUND: Australia, like other countries, is experiencing an epidemic of heart failure (HF). However, given the lack of national and population-based datasets collating detailed cardiovascular-specific morbidity and mortality outcomes, quantifying the specific burden imposed by HF has been difficult. METHODS: Australian Bureau of Statistics (ABS data) for the year 2000 were used in combination with contemporary, well-validated population-based epidemiologic data to estimate the number of individuals with symptomatic and asymptomatic HF related to both preserved (diastolic dysfunction) and impaired left ventricular systolic (dys)function (LVSD) and rates of HF-related hospitalisation. RESULTS: In 2000, we estimate that around 325,000 Australians (58% male) had symptomatic HF associated with both LVSD and diastolic dysfunction and an additional 214,000 with asymptomatic LVSD. 140,000 (26%) live in rural and remote regions, distal to specialist health care services. There was an estimated 22,000 incidents of admissions for congestive heart failure and approximately 100,000 admissions associated with this syndrome overall. CONCLUSION: Australia is in the midst of a HF epidemic that continues to grow. Overall, it probably contributes to over 1.4 million days of hospitalization at a cost of more than 1 billion dollars. A national response to further quantify and address this enormous health problem is required.     

Systolic and diastolic functions in elderly patients with and without heart failure

BACKGROUND: A considerable number of patients with heart failure (HF) have a normal left ventricular ejection fraction (LVEF). In these subjects, HF has usually been related to diastolic heart failure (DHF), still a frequently overlooked clinical entity. METHODS: This study reports the clinical, instrumental, and conventional echocardiographic evaluation of 159 consecutive, hospitalized elderly patients, 87 admitted with HF and 72 admitted for other reasons without overt HF. RESULTS: All of the 87 HF patients had signs of diastolic dysfunction (DDYS), yet 44.8% of them had a normal LVEF. Forty-four of the 72 patients admitted without overt HF (61.1%) had mild DDYS and 14 (19.5%) also had a reduced LVEF. There was a clear relationship between LVEF reduction and the severity of DDYS. CONCLUSIONS: HF is often a combination of diastolic and systolic function abnormalities. DHF may be difficult to detect in HF subjects with normal LVEF because their DDYS is often mild. However, there are signs of DDYS in all HF patients that increase in severity as LVEF decreases. DDYS could be considered a marker for all forms of HF, especially in elderly patients.     

Frequent non-cardiac comorbidities in patients with chronic heart failure

Heart failure (HF) in elderly patients is associated with more diffuse symptoms and signs due to the presence of other noncardiac comorbidities. This can cause difficulties in assessing the correct diagnosis and initiating appropriate therapy. The four most frequently occurring noncardiac comorbidities and therapies used to treat them are discussed in the present paper. Hypertension is an important precursor of HF, and is still the most common risk factor for HF in the general population. About 50% of patients with untreated hypertension will develop HF. Pressure overload leads to the development of left ventricular hypertrophy (LVH) and diastolic dysfunction. Diabetes, which occurs in about 20-30% of patients with HF, is an important comorbidity resulting in morphological and metabolic disturbances affecting myocardial blood flow and hormonal regulation leading to a poor outcome and necessitating aggressive conventional treatment. Chronic obstructive pulmonary disease (COPD), occurs in approximately 20-30% of heart failure patients, and may complicate HF treatment, it is therefore important to recognize and treat it effectively. Finally, the early detection of anemia, which occurs in 20-30% of HF patients, is important since it is associated with functional impairment and increased mortality and morbidity. Combined treatment with erythropoietin and intravenous iron has shown beneficial effects on clinical symptoms and morbidity. In conclusion early detection of concomitant diseases in patients with HF is important and should be considered carefully when initiating therapy.     

Contribution of left ventricular diastolic dysfunction to heart failure regardless of ejection fraction

Heart failure (HF) has been classified as systolic and diastolic based on the left ventricular ejection fraction. We hypothesized that left ventricular diastolic dysfunction is an important element of HF regardless of ejection fraction. Two hundred six patients who had clinical HF were compared with 72 age-matched controls. Diastolic dysfunction, as assessed by the mitral filling pattern and tissue Doppler imaging, was present in >90% of patients who had HF regardless of ejection fraction and was more frequent and severe than in age-matched controls (p <0.001). In patients who had HF, B-type natriuretic peptide correlated with diastolic dysfunction (r = 0.62, p <0.001) but not with ejection fraction or end-diastolic volume index (EDVI). The degree of diastolic dysfunction influenced survival rate (risk ratio 1.64, p <0.05), whereas ejection fraction and EDVI did not. Systolic function measured by systolic mitral annular velocity was decreased in patients who had HF and an ejection fraction /=0.50 (6.6 +/- 1.8 cm/s) compared with control subjects (8.0 +/- 2.1 cm/s, p <0.01). Patients who had HF and an ejection fraction >/=0.50 had an increased ratio of ventricular mass to EDVI. Patients who had HF and an ejection fraction /=0.50 is associated with mild systolic dysfunction and an increased ratio of left ventricular mass to EDVI. In HF with an ejection fraction 相似文献   

AMPK与心力衰竭发病机制和治疗的研究进展

心力衰竭（heart failure,HF）作为心血管疾病的终末阶段,是一种复杂的临床综合征,主要表现为心脏的收缩和舒张功能障碍。虽然治疗HF的药物在不断更新,但其病死率仍维持在较高水平,因此人们需要不断探索HF新的治疗靶点。近年来的研究表明单磷酸腺苷活化蛋白激酶（AMP-activated protein kinase,AMPK）参与HF的发生发展,可调控HF时的心肌代谢、心肌纤维化、氧化应激等。现对AMPK保护HF的机制及其相关药物的研究进展作一综述。     

Targeting Preclinical Diastolic Dysfunction to Prevent Heart Failure: Contemporary Insights

Diastolic dysfunction encompasses both those who are asymptomatic and those who have heart failure symptoms. Preclinical diastolic dysfunction (PDD), defined as diastolic dysfunction with preserved ejection fraction (EF) without the presence of heart failure symptoms, is prevalent and may progress to heart failure with preserved EF (HFpEF). While the causative factors of HFpEF are multifactorial, targeting PDD and its associated comorbidities prior to development of symptoms can reduce development of heart failure. Diabetes, coronary artery disease, hypertension, and renal dysfunction are targets of treatment in those with diastolic dysfunction that may decrease the risk of heart failure development. This review will focus on PDD, its epidemiology, pathophysiology, comorbid conditions, and management that may prevent development of heart failure.     

Heart failure, diastolic dysfunction and atrial fibrillation; mechanistic insight of a complex inter-relationship

Atrial fibrillation (AF) and heart failure (HF) commonly coexist, and their co-presence is associated with adverse outcomes relating to thromboembolic events, HF progression, hospitalisation and death. Diastolic dysfunction (DD) is also frequently present in patients with HF and is an independent predictor of hospitalisation and mortality. The presence of DD is a strong predictor of incident AF in patients with HF. In this review, we provide mechanistic insight into pathophysiological processes that frequently promote the occurrence of AF, HF and DD and outline the yin-yang relationship between AF, DD and HF. More recently, invasive studies have also shown that asymptomatic paroxysmal atrial fibrillation (PAF) is a common phenomenon in HF patients. We examine complex inter-relationships between PAF, HF and DD and speculate upon the possible clinical influence of undiagnosed PAF in HF patients.     

Treatment of asymptomatic left ventricular dysfunction

Opinion statement  Patients with abnormalities of left ventricular (LV) systolic or diastolic function may have no symptoms, especially in the early stages. These patients are not uncommon in the community, and the prevalence of this condition increases in the presence of risk factors such as diabetes, hypertension, and coronary artery disease. Patients with asymptomatic LV dysfunction have a significantly increased risk of overt heart failure and mortality. Therefore, it is of prime importance to identify and treat these patients to prevent progression of the disease. Echocardiography is an excellent tool to characterize systolic and diastolic properties of the left ventricle. However, its cost and lack of widespread availability have limited its usefulness in screening the general population. Careful clinical assessment coupled with electrocardiography and natriuretic peptide level assessment can identify higher-risk patients who should be referred for detailed evaluation of LV function. The goal of therapy is to halt and even reverse LV remodeling. Neurohormonal blockade, now the cornerstone of heart failure therapy, has been shown to have salutatory effects in patients with asymptomatic LV systolic dysfunction, both in reversing remodeling and reducing adverse clinical outcomes. Except for risk factor control, there is no evidence to advocate any specific therapy for asymptomatic patients with LV diastolic dysfunction.     

Women, men and heart failure: a review

Chronic heart failure (HF) is a major cause of morbidity and mortality, and is the reason for more than one in five of all hospital admissions in patients aged >65 years. Major advances in the diagnosis and treatment of HF over the last two decades have proven effective in reducing morbidity and mortality among both men and women, but with less improvement for women and elderly patients. Women and men with HF differ in several respects. Women tend to be older and more often hypertensive, but are less likely to demonstrate any clinical evidence of coronary heart disease (CHD) and more often have preserved ventricular function. Conversely, hypertension plays a greater role in the development of HF in women than in men. Sex differences in systolic and diastolic function in patients with hypertension have been demonstrated. Although men have higher incidence of HF at all ages, lifetime risk is similar in men and women because women live longer. Intervention studies have included far more men than women but in patients with reduced ventricular function there is no evidence to suggest that women benefit less than men from evidence-based treatments, and current guidelines do not differentiate between men and women. There is no consistent recent evidence that women receive poorer quality of care than men. Women with HF have better survival rates than men, which may be due to better systolic function or less CHD among women; however, mortality rates for HF are still very high regardless of sex. As most trials have been targeted towards patients with left ventricular systolic dysfunction, which is less typical for women than for men with HF, more research is needed to help define treatment aimed at improving prognosis for patients with HF and preserved systolic function. In light of these differences and ongoing uncertainties, future European guidelines should incorporate gender issues. Heart Fail Monit 2008;6(1):34-40.