Women and heart failure

Almost half of the patients affected with congestive heart failure (CHF) in the United States are women. However, past studies have included predominantly men and generalized results to women. Many women with CHF are older, have hypertension, and have higher ejection fractions. Survival differences have been reported previously with conflicting results. Although treatment for left ventricular dysfunction is somewhat standardized, treatment for diastolic dysfunction is less defined. Clinical trials for this group of patients, many of whom are women, have not been performed.In comparison with men, women have several cardiovascular differences as well as differences in electrical properties. In addition, response to medical (pharmacologic) therapy may differ in men and women.Finally, functional status has been shown to be compromised in both men and women with CHF; however, some studies have shown women to experience more exercise intolerance. This may be because more women than men have diastolic dysfunction. Few women have been included in exercise trials. Future trials must address women with CHF, many of whom are older and have normal (or near normal) left ventricular function or diastolic dysfunction.     

Inflammation, cytokines and anti-inflammatory therapies in heart failure

Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Certain categories in patients with dilated cardiomyopathy have shown the presence of humoral and cellular immunity activation suggesting a possible relation between myocarditis and dilated cardiomyopathy. Recent studies suggest a link between the circulating levels of cytokines (TNF alpha IL-1 et IL-6), the clinical status and prognostic. However, the mechanisms connecting heart failure and cytokine activation are unclear and the sites of cytokines production remain controversial. In the clinical setting, specific measurements of cytokines are not available. As tests of inflammation, erythrocyte sedimentation rate and C-reactive protein concentration appear to have interesting pronostic values. Current conventional therapy i.e. ACE inhibitors, type I angiotensin II antagonist and beta-blockers have shown some anti-cytokine properties. Recently, immunosuppressive therapies have shown their ability to improve symptoms and LV ejection in selected patients with dilated cardiomyopathy and clear sign of myocardium inflammation. Specific anti-cytokine therapy have been developed and showed interesting results in preliminary clinical studies. However large clinical trials testing this new therapy have been stoppel prematurely because of deterious effects.     

Surgical therapies for heart failure

Heart transplantation remains the best hope for patients with end-stage heart failure unresponsive to conventional therapy, but the number of transplant candidates continues to exceed the number of available donor hearts. Despite major advances in the medical management of heart failure, researchers continue to explore alternative surgical therapies designed to augment cardiac function. Many of these surgical therapies are still in the experimental or clinical trial phases. Surgical approaches include coronary revascularization, mitral valve repair or replacement, cardiomyoplasty, left ventricular volume reduction surgery, and bridging to recovery with the use of ventricular assist devices. Although cardiac surgeons have gained considerable experience in the treatment of patients with heart failure, many improvements and innovations lie ahead.     

New surgical therapies for heart failure

A growing number of patients present with heart failure. Some of them may qualify for surgical correction of their cardiac condition. Since heart transplantation will always be available to only a small number of patients, several new surgical techniques have been developed for approval in heart failure patients. Classic interventions such as revascularization, valve repair, or valve replacement have been improved and modified to meet the need of heart failure patients. Several of these techniques are currently under investigation in large clinical trials. These trials will definitely have an impact on the development of surgical treatment of patients with heart failure.     

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.     

Contemporary medical,surgical, and device therapies for end-stage heart failure

Opinion statement Despite recent advances in medical therapy, mortality remains high following the diagnosis of heart failure (HF). Cardiac transplantation is still the standard surgical treatment option for highly selected patients with severe end-stage HF; however, it is only available to a small percentage of patients. The small number of available donor hearts is an inherent limitation on the ability of cardiac transplantation to greatly impact the management of advanced HF. The increased incidence and prevalence of HF in an ever aging and medically complex population has paved the way for alternative surgical and device treatment strategies. Some of these treatment options include ventricular reduction/remodeling surgery, mitral valve repair, mechanical ventricular assist device implantation, implantable cardioverter-defibrillators, and cardiac resynchronization therapy. Several recent trials have demonstrated the effectiveness of these therapies with regard to improvement in primary cardiac end points, HF symptoms, and survival. Surgical and device techniques are usually combined with optimal medical management of HF. The total cost and actual cost-effectiveness of employing these new therapeutic modalities in a growing population of HF patients remains to be determined.     

New therapies in acute decompensated heart failure

PURPOSE OF REVIEW: Hospitalization and mortality rates associated with heart failure are persistently high. This is due partly to aging of the population but mostly to delayed progress in the pharmacological treatment of decompensated heart failure. We will review the current recommendations and most recent advancement in the pharmacological treatment of acute decompensated heart failure while providing a systematic approach to the management of this prevalent condition. RECENT FINDINGS: Loop diuretics, nitrates and inotropes such as dobutamine and milrinone are the current mainstay of acute heart failure management although their associated morbidity and possible mortality have raised serious concerns. Recent vasoactive agents such as Nesiritide, Tolvaptan and more recently the inotropic agent Levosimedan could offer improved hemodynamics and congestive relief to patients in acute pulmonary edema. SUMMARY: Despite the promising results of these agents, further clinical trials are required prior to their international approval as first-line therapy. Although we can be optimistic that these vasoactive drugs might have favorable clinical outcomes and improve the intricate management of decompensated heart failure, their associated mortality benefit remains unclear and controversial.     

Evolving cell-based therapies for heart failure patients

Heart failure (HF) represents the only cardiovascular disease (CVD) whose incidence continues to rise in the developed world. With recent advances in device and drug therapies, the prognosis is improving. Nevertheless, the mortality associated with HF remains high, with more than 50% of patients dying within 5 years after initial diagnosis. The loss of cardiac cells is a major contributor to the development and progression of HF, thus therapeutic interventions to repair or regenerate lost cardiac cells hold tremendous promise. During the past several years, cell-based therapy for CVD has moved at a rapid pace from animal studies to clinical trials. To date, populations enrolled in cell-based therapy trials have comprised patients with coronary artery disease and myocardial infarction, with a limited number of trials conducted in patients with congestive HF. Also, most trials have used autologous skeletal myoblasts or bone marrow cells (whole bone marrow or subpopulations). The outcomes from these studies have been largely mixed, ranging from clear beneficial effects of cell therapy to no observed improvement, although all trials demonstrated a reasonable degree of safety, at least within the study period. Several critical issues, such as the type of cells, number of cells, timing, delivery methods, and the mechanisms of action involved, remain to be elucidated. This article reviews the current status of the emerging field of cell-based therapies for CVD, with particular focus on HF treatment.     

Interventional therapies for heart failure in the elderly

The aging of a population replete with risk factors for heart failure (HF) (coronary heart disease, diabetes, and hypertension) coupled with a declining age-adjusted mortality rate for coronary artery and hypertensive heart diseases has created, and will continue to create, a literal explosion in the prevalence of HF in the United States. Despite advances in maximal medical therapy, however, most patients who have symptomatic HF can expect functional impairment, interludes of worsening symptomatology, and a shortened lifespan. This article updates the use of interventional therapies for the treatment of elderly patients who have HF caused by coronary artery disease, valvular heart disease, congenital heart disease, myocardial disease, and renal vascular disease.     

顽固性心力衰竭的治疗进展

近半个世纪来,药物治疗心力衰竭取得很大进展,尽管目前的治疗改善了心力衰竭患者的生存质量,降低其病死率,但顽固性心力衰竭患者预后仍很差,本文就顽固性心力衰竭的治疗进展做一述评。     

Interventional therapies for heart failure in the elderly

The aging of a population replete with risk factors for heart failure(HF) (coronary heart disease, diabetes, and hypertension) coupled with a declining age-adjusted mortality rate for coronary artery and hypertensive heart diseases has created, and will continue to create, a literal explosion in the prevalence of HF in the United States. Despite advances in maximal medical therapy, however, most patients who have symptomatic HF can expect functional impairment, interludes of worsening symptomatology, and a shortened lifespan. This article updates the use of interventional therapies for the treatment of elderly patients who have HF caused by coronary artery disease, valvular heart disease, congenital heart disease, myocardial disease, and renal vascular disease.     

Emerging therapies for heart failure: renal mechanisms and effects

Improved understanding of the pathophysiology of salt and water homeostasis has provided a foundation for explaining the renal mechanisms of emerging therapies for heart failure, as well as why renal function might potentially be improved or harmed. These aspects are reviewed in this article for a number of newer therapies including adenosine, endothelin, and vasopressin receptor antagonists, as well as extracorporeal ultrafiltration. An appreciation of the complexity and sometimes opposing pathways of these approaches may explain their limited efficacy in early trials, in which there has not been a substantial improvement in patient or renal outcomes. In that there is often a balance between beneficial and maladaptive receptor actions and neurohumoral responses, this physiologic approach also provides insight into the rationale for combining therapies. Multi-agent strategies may thus maximize their effectiveness while minimizing adverse effects and tolerance. In this paper, the theoretical impact of the emerging agents based on their mechanism of action and pathophysiology of the disease is initially addressed. Then, the available clinical evidence for each class of drugs is reviewed with special emphasis on their effect on kidney-related parameters. Finally, a general overview of the complexity of the interpretation of trials is offered along with a number of potential explanations for the observed results.     

New therapies for the management of acute heart failure

The standard treatment for acute heart failure (synonymous with pulmonary edema) is an upright posture, oxygen, morphine (often accompanied by an antiemetic), and intravenous diuretics. This treatment has remained unchanged for many years, and the precise mechanism by which each of these methods alleviates symptoms in patients is unclear. Nitrates, oral or intravenous, are also used with benefit, and have some hemodynamic advantages over intravenous diuretics. Recently, three new forms of treatment have been investigated. The use of milrinone, a phosphodiesterase inhibitor, for exacerbation of heart failure in patients with a background of chronic heart failure was not advantageous. The trials of levosimendan, a calcium sensitizer, in patients with pulmonary edema hinted at benefit. Nesiritide, a formulation of brain natriuretic peptide, does bring about hemodynamic improvement in acute heart failure, and is at least as effective as nitroglycerin, easier to prescribe, but prone to cause hypotension. These are small but important advances that increase our knowledge of the pathophysiology of acute heart failure, and also provide an indication of which drugs are preferable for the treatment of this distressing condition.     

Novel therapies for heart failure: vasopressin and selective aldosterone antagonists

Despite favorable improvements in mortality, heart failure (HF) remains a problematic illness due to the ever-present burden of hospitalization. Clearly, novel treatment strategies are needed. This review focuses on two newer pharmacologic targets: arginine vasopressin and aldosterone. Arginine vasopressin receptor antagonists will most likely serve as an adjunct to or replacement of standard diuretic therapy in selected patients. The safety and efficacy of chronic therapy with oral arginine vasopressin receptor antagonists in large groups of congestive HF patients is currently under investigation. Aldosterone antagonism is emerging as a treatment of severe congestive HF. Recent large-scale clinical trials using aldosterone antagonists have proven that those with HF or left ventricular dysfunction postmyocardial infarction derive a survival benefit from aldosterone antagonism. Whether aldosterone antagonism should be prescribed in all patients with HF is unclear; however, in carefully selected and managed patients, aldosterone antagonism is helpful.     

Atrial fibrillation in heart failure: catheter and surgical interventional therapies

Atrial fibrillation and heart failure commonly coexist in the same patient. Each may adversely affect the other. Atrial fibrillation leads to heart failure exacerbation, left ventricular function deterioration and an increase in thrombo-embolic risk. Therapeutic options targeting atrial fibrillation in heart failure patients include pharmacological and non-pharmacological means. Pharmacological therapy is directed at either rate control using nodal blocking agents or rhythm control using anti-arrhythmic agents, of which the options are limited in patients with heart failure. The landmark AF–CHF trial did not show any benefit of rhythm control strategy as opposed to rate control in patients with heart failure and atrial fibrillation. However, patients in this trial as well as in others used mostly amiodarone for rhythm control. This might have negated any positive effects of achieving normal sinus rhythm. Non-pharmacological therapy both for rate and rhythm control is appealing. This includes AV node ablation for rate control, catheter ablation of atrial fibrillation and surgical therapy of atrial fibrillation. This review will address non-pharmacologic treatment of AF in heart failure patients.     

Targeting myocardial remodelling to develop novel therapies for heart failure

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta‐adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca^{2 +} ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre‐clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.     

Novel therapies for heart failure: focus on anti-inflammatory strategies

The understanding of the pathomechanisms leading to heart failure has evolved from the simplistic pump-failure concept to the more complex syndrome involving neurohormonal and inflammatory systems. Anti-inflammatory therapy targeting specific cytokines, however, such as tumor necrosis factor-alpha, has failed to show clinical benefit. As a result, the focus has turned toward more broad-spectrum anti-inflammatory strategies. This review examines the various broad-spectrum anti-inflammatory modalities that have been used in heart failure: IV immunoglobulin administration, immune modulation therapy, immune adsorption, and plasmapheresis.     

The incidence of congestive heart failure associated with antidiabetic therapies

BACKGROUND: Increased risk for CHF in persons with type 2 diabetes is well established. Our objectives were to estimate the CHF risk associated with specific therapies for diabetes and to determine the differences in incidence rates of CHF associated with adding various antidiabetic agents. METHODS: Subjects were members of the Kaiser Permanente Northwest (KPNW) diabetes registry as of 1 January 1998, with no prior history of CHF (n = 8063). We identified their therapy as of that date and then defined the start of the subject study period as the date when their drug regimen changed, either by switching to or by adding another antidiabetic drug. We defined the new therapy as the index therapy and the date of initiating the new therapy as the index date. Follow-up on the patients was done until the index therapy was discontinued or changed, or until 31 December 2002, whichever came earlier. We calculated the incidence rate of CHF in patients on various therapeutic regimens adjusting for age, gender, diabetes duration, existing ischemic heart disease, hypertension, renal insufficiency and glycemic control (HbA(1c)). RESULTS: CHF incidence rates were highest in index therapy categories that included insulin and lowest in regimens that included metformin. When insulin was added to an initial therapy, CHF incidence was increased 2.33 times (p < 0.0001) and 2.66 times (p < 0.0001) compared to the addition of sulphonylurea or metformin respectively. CONCLUSIONS: Our findings support the theory that elevated serum insulin levels promote the development of cardiac disease. Consistent with the UKPDS, metformin may offer some protection from incident CHF relative to sulphonylurea or insulin.     

New and emerging drug therapies for the management of acute heart failure

Abstract
In recent times, there have been many developments in therapies for acute heart failure, in contrast to the preceding 20 years. These have been mainly fuelled by new and expanding knowledge about the pathophysiology of heart failure, which has allowed for insight into potential therapeutic strategies. This review will examine the key emerging therapies for acute heart failure, in light of available pathophysiological and clinical evidence. (Intern Med J 2003; 33: 515−520)