The effect of pregestational diabetes on fetal heart function

Pregestational diabetes affects nearly 2% of all pregnancies. Moreover, Type 2 diabetes in child-bearing women is on the rise because of the childhood obesity epidemic. Pregestational diabetes can affect the fetal heart in several ways. First, the risk of fetal congenital heart disease is markedly increased; second, fetal hypertrophic cardiomyopathy may occur even with good glycemic control; third, studies have shown impaired function of the hearts of some infants and fetuses of diabetic pregnancies, which can occur with and without septal hypertrophy. Small-for-gestational-age infants of diabetic mothers may have diminished cardiovascular health in the long term. This review mainly discusses methods to detect fetal diabetic cardiomyopathy prenatally. The focus is on the noninvasive diagnostic markers that can serve as an outcome measure for future therapeutic trials, which are still lacking. There is some experimental research on treatment strategies to prevent fetal heart disease in diabetic pregnancies but little clinical data.     

Trypanosomiasis,cardiomyopathy and the risk of ischemic stroke

American (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis.     

Diabetic heart muscle disease

Diabetic patients may have various abnormalities in left ventricular systolic and diastolic function not attributable to coronary heart disease, hypertension or other known cardiac disease. Although the exact causes of this diabetic heart muscle disease or "diabetic cardiomyopathy" are still incompletely understood, several mechanisms may contribute to it including disturbed myocardial energy metabolism, microvascular changes, structural changes in collagen, increased myocardial fibrosis, and cardiac autonomic neuropathy. Perhaps the most typical feature of diabetic heart muscle disease is an abnormal filling pattern of the left ventricle, suggesting reduced compliance or prolonged relaxation. Left ventricular systolic function is commonly normal at rest in asymptomatic diabetic patients, but it frequently becomes abnormal during exercise. The abnormalities in left ventricular systolic function may be partly reversible along with an improvement of metabolic control of diabetes. It is not known how frequently subclinical abnormalities in left ventricular function in diabetic patients result in clinically manifest heart failure.     

Heart failure: the frequent,forgotten, and often fatal complication of diabetes

There is a high frequency of heart failure (HF) accompanied by an increased mortality risk for patients with diabetes. The poor prognosis of these patients has been explained by an underlying diabetic cardiomyopathy exacerbated by hypertension and ischemic heart disease. In these patients, activation of the sympathetic nervous system results in increased myocardial utilization of fatty acids and induction of fetal gene programs, decreasing myocardial function. Activation of the renin-angiotensin system results in myocardial remodeling. It is imperative for physicians to intercede early to stop the progression of HF, yet at least half of patients with left ventricular dysfunction remain undiagnosed and untreated until advanced disease causes disability. This delay is largely because of the asymptomatic nature of early HF, which necessitates more aggressive assessment of HF risk factors and early clinical signs. Utilization of beta-blockade, ACE inhibitors, or possibly angiotensin receptor blockers is essential in preventing remodeling with its associated decline in ventricular function. beta-Blockers not only prevent, but may also reverse, cardiac remodeling. Glycemic control may also play an important role in the therapy of diabetic HF. The adverse metabolic side effects that have been associated with beta-adrenergic inhibitors in the diabetic patient may be circumvented by use of a third-generation beta-blocker. Prophylactic utilization of ACE inhibitors and beta-blockers to avoid, rather than await, the need to treat HF should be considered in high-risk diabetic patients.     

Vascular endothelial dysfunction in diabetic cardiomyopathy: pathogenesis and potential treatment targets

Cardiovascular complications account for significant morbidity and mortality in the diabetic population. Diabetic cardiomyopathy, a prominent cardiovascular complication, has been recognized as a microvascular disease that may lead to heart failure. Pathogenesis of diabetic cardiomyopathy involves vascular endothelial cell dysfunction, as well as myocyte necrosis. Clinical trials have identified hyperglycemia as the key determinant in the development of chronic diabetic complications. Sustained hyperglycemia induces several biochemical changes including increased non-enzymatic glycation, sorbitol-myoinositol-mediated changes, redox potential alterations, and protein kinase C (PKC) activation, all of which have been implicated in diabetic cardiomyopathy. Other contributing metabolic abnormalities may include defective glucose transport, increased myocyte fatty acid uptake, and dysmetabolism. These biochemical changes manifest as hemodynamic alterations and structural changes that include capillary basement membrane (BM) thickening, interstitial fibrosis, and myocyte hypertrophy and necrosis. Diabetes-mediated biochemical anomalies show cross-interaction and complex interplay culminating in the activation of several intracellular signaling molecules. Studies in both animal and human diabetes have shown alteration of several factors including vasoactive molecules that may be instrumental in mediating structural and functional deficits at both the early and the late stages of the disease. In this review, we will highlight some of the important vascular changes leading to diabetic cardiomyopathy and discuss the emerging potential therapeutic interventions.     

Restrictive Cardiomyopathy

Background: Restrictive cardiomyopathy is characterized by ventricular diastolic dysfunction with a clinical course in childhood that is often progressive despite medical therapy.
Methods: A review of the literature and clinical experience was used to summarize the natural history of this oftentimes devastating disease with a focus on diagnostic tools and therapeutic options.
Results: The clinical presentation of restrictive cardiomyopathy can be highly variable, ranging from asymptomatic to overt signs of heart failure with pulmonary hypertension. Emerging noninvasive diagnostic tools are increasingly helpful yet there remains a role for invasive studies including cardiac catheterization with or without endomyocardial biopsy. A significant risk of sudden death exists and may not be limited to those with more pronounced symptoms.
Conclusions: Children with restrictive cardiomyopathy require comprehensive evaluation with careful surveillance. Early listing for cardiac transplantation should be considered.     

Role of Echocardiography in the Diagnosis of Heart Failure with Preserved Left Ventricular Systolic Function: Update 2013

Heart failure and its complications are significant causes of mortality and morbidity in most societies. Major parts of the studies that constitute the base of modern treatment of heart failure have been limited to the study of heart failure associated with reduced left ventricular ejection fraction (HFrEF). Only during the past 10–15 years, heart failure associated with preserved left ventricular ejection fraction (HFpEF) or primarily right-sided heart failure have come more into focus as our understanding of the critical role of other etiologies for the clinical syndrome of heart failure than a reduced left ventricular (LV) ejection fraction has increased. Furthermore, whilst the powerful prognostic role of a reduced LV ejection fraction has long since been well validated, only relatively recently it was realized that patients with heart failure symptoms and preserved LV ejection fraction also have a substantially impaired prognosis. Previously, these patients had often been dismissed as not having "real heart failure". In parallel, it has become clear that diagnoses like hypertensive heart disease, diabetic cardiomyopathy and heart failure associated with atrial fibrillation, among others, can be understood as forms of HFpEF.     

Genetics of inherited cardiomyopathies

Cardiomyopathies are the most common disorders resulting in heart failure, with dilated cardiomyopathy being responsible for the majority of cases. Other forms of cardiomyopathy, especially hypertrophic forms, are also important causes of heart failure. The mortality rate due to cardiomyopathy in the USA is over 10,000 deaths per year, and the costs associated with heart failure are approximately US$200 million per year in the USA alone. Over the past few years, breakthroughs have occurred in understanding the basic mechanisms of these disorders, potentially enabling clinicians to devise improved diagnostic strategies and therapies. As at least 30 to 40% of cases are inherited, it is now imperative that the genetic basis for these disorders is clearly recognized by caregivers and scientists. However, it has also become clear that these diseases are genetically highly heterogeneous, with multiple genes identified for each of the major forms of cardiomyopathy, and most patients having private mutations. These data suggest that the genetic diagnosis of most patients with cardiomyopathy will be impractical with current technologies. However, there are a few exceptions, such as patients with X-linked cardiomyopathies, with or without the concomitant abnormalities of cyclic neutropenia and 3-methylglutaconic aciduria, or patients with cardiomyopathy associated with conduction disease: these appear to be associated with mutations in a small subset of genes, and can be investigated by certified diagnostic laboratories. This review will summarize current knowledge of the genetics of inherited cardiomyopathies and how findings from research laboratories may be translated into the diagnostic laboratory.     

Genetics of inherited cardiomyopathies

Cardiomyopathies are the most common disorders resulting in heart failure, with dilated cardiomyopathy being responsible for the majority of cases. Other forms of cardiomyopathy, especially hypertrophic forms, are also important causes of heart failure. The mortality rate due to cardiomyopathy in the USA is over 10,000 deaths per year, and the costs associated with heart failure are approximately 200 million US dollars per year in the USA alone. Over the past few years, breakthroughs have occurred in understanding the basic mechanisms of these disorders, potentially enabling clinicians to devise improved diagnostic strategies and therapies. As at least 30 to 40% of cases are inherited, it is now imperative that the genetic basis for these disorders is clearly recognized by caregivers and scientists. However, it has also become clear that these diseases are genetically highly heterogeneous, with multiple genes identified for each of the major forms of cardiomyopathy, and most patients having private mutations. These data suggest that the genetic diagnosis of most patients with cardiomyopathy will be impractical with current technologies. However, there are a few exceptions, such as patients with X-linked cardiomyopathies, with or without the concomitant abnormalities of cyclic neutropenia and 3-methylglutaconic aciduria, or patients with cardiomyopathy associated with conduction disease: these appear to be associated with mutations in a small subset of genes, and can be investigated by certified diagnostic laboratories. This review will summarize current knowledge of the genetics of inherited cardiomyopathies and how findings from research laboratories may be translated into the diagnostic laboratory.     

Diabetic cardiomyopathy

The purpose of this article was to review the clinical and experimental features of diabetic cardiomyopathy, with particular relevance to the Black population. One hundred thirty-seven studies were identified, of which 57 were selected as references for this article. Diabetes is associated with the development of cardiomyopathy, independent of coronary atherosclerosis. Pathological studies show myocardial hypertrophy and fibrosis; microvascular pathology is also present, but all of these pathological findings have an uncertain relationship to myocardial failure. Hemodynamic findings of both congestive and restrictive cardiomyopathy have been described. Noninvasive studies revealed abnormal systolic and diastolic function in many diabetic subjects, particularly in the presence of diabetic complications and/or hypertension. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. One year of diabetes in dogs resulted in decreased left ventricular compliance and increased interstitial connective tissue. Studies in the diabetic rat showed a marked slowing of contraction and relaxation. Chronic insulin therapy reversed the changes in the rat model. Combining hypertension with diabetes in the rat resulted in increased myocardial and coronary microvascular pathology and greater changes in isolated muscle function, electrophysiology, and contractile protein biochemistry. Many hypertensive diabetic rats died spontaneously, showing signs of congestive heart failure. Diabetic cardiomyopathy is a significant cause of heart failure in diabetic subjects and occurs more frequently in those with microvascular complications and/or hypertension. Clinical studies are needed to clarify the natural history of this disorder, focusing on the benefits of tight control of hyperglycemia and treatment of associated hypertension. Experimental studies will clarify the pathophysiology and contribute to improved therapy. The high prevalence of diabetes and hypertension in Blacks makes these considerations especially relevant to this population.     

Epidemiology of heart failure in sub-Saharan Africa

Heart failure has emerged as a dominant form of cardiovascular disease in Africa, and has great social and economic relevance owing to its high prevalence, mortality and impact on young, economically active individuals. The causes of heart failure in Africans remain largely nonischemic. Hypertension, cardiomyopathy, rheumatic heart disease, chronic lung disease and pericardial disease are the main contributors to the etiology of cardiac failure in sub-Saharan Africa, accounting for over 90% of cases. Hypertensive heart disease complications occur more frequently in Africans and the majority of affected patients are younger. Endemic cardiomyopathies include dilated cardiomyopathy, peripartum cardiomyopathy and endomyocardial fibrosis. Nonendemic cardiomyopathies apparently occur with the same frequency as in other parts of the world, and include hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Coronary artery disease and its complications remain uncommon in Africa, but the situation is changing due to modifications in lifestyle, risk-prone behavior, diet, cultural attitudes and other consequences of rapid urbanization. As the prevalence of heart failure is expected to rise substantially in sub-Saharan Africa, the authors call for population-based studies and registries of the epidemiology of heart failure in Africans and the urgent study of interventions that will decrease morbidity and mortality from the causes of heart failure, with a focus both on nonischemic and ischemic risk factors.     

Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways

Cardiovascular disease is the primary cause of morbidity and mortality among the diabetic population. Both experimental and clinical evidence suggest that diabetic subjects are predisposed to a distinct cardiomyopathy, independent of concomitant macro- and microvascular disorders. ‘Diabetic cardiomyopathy’ is characterized by early impairments in diastolic function, accompanied by the development of cardiomyocyte hypertrophy, myocardial fibrosis and cardiomyocyte apoptosis. The pathophysiology underlying diabetes-induced cardiac damage is complex and multifactorial, with elevated oxidative stress as a key contributor. We now review the current evidence of molecular disturbances present in the diabetic heart, and their role in the development of diabetes-induced impairments in myocardial function and structure. Our focus incorporates both the contribution of increased reactive oxygen species production and reduced antioxidant defenses to diabetic cardiomyopathy, together with modulation of protein signaling pathways and the emerging role of protein O-GlcNAcylation and miRNA dysregulation in the progression of diabetic heart disease. Lastly, we discuss both conventional and novel therapeutic approaches for the treatment of left ventricular dysfunction in diabetic patients, from inhibition of the renin–angiotensin–aldosterone-system, through recent evidence favoring supplementation of endogenous antioxidants for the treatment of diabetic cardiomyopathy. Novel therapeutic strategies, such as gene therapy targeting the phosphoinositide 3-kinase PI3K(p110α) signaling pathway, and miRNA dysregulation, are also reviewed. Targeting redox stress and protective protein signaling pathways may represent a future strategy for combating the ever-increasing incidence of heart failure in the diabetic population.     

An update on the management of Chagas cardiomyopathy

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, infects nearly 18 million people in Latin America and mainly affects the heart, causing heart failure, arrhythmias, heart block, thromboembolism, stroke and death. In this review, the clinical diagnosis and management of Chagas cardiomyopathy are discussed. Particular emphasis is placed on the clinical staging of patients and the use of various diagnostic tests that may be useful in individualizing treatment of the two most relevant clinical syndromes, that is, heart failure and arrhythmias. The relevance of specific treatments are discussed, stressing the important role of parasite persistence in disease pathogenesis. We also discuss new therapy modalities that may have a role in the treatment of Chagas cardiomyopathy.     

超声心动图评价糖尿病患者心脏损害的研究进展

糖尿病是一种以血糖升高为特征的代谢性疾病,可导致多种并发症,其中糖尿病心肌病等心血管并发症是糖尿病患者发生心力衰竭甚至死亡的主要原因。超声心动图可以全方位多角度地评价糖尿病患者的早期心脏损害,为临床干预提供依据,对改善患者预后具有重要作用。本文就超声心动图评价糖尿病患者心脏损害的研究进展进行综述。     

MRI检测糖尿病心肌病研究进展

糖尿病心肌病是表现为心室功能异常的糖尿病心血管并发症,早期检测和诊断糖尿病心肌病有助于预防不良心血管事件的发生,降低死亡率。目前心脏MRI技术飞速发展,新序列的开发不仅可有效地检测疾病本身,也有助于理解疾病产生的病理生理机制。本文就近年来心脏MRI检测糖尿病心肌病的研究进展进行综述。     

ACE inhibitor-induced bronchial reactivity in patients with respiratory dysfunction

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are often associated with an increased incidence of cough and bronchial responsiveness that may cause further deterioration of patients with impaired pulmonary function. OBJECTIVE: To review the available literature on the incidence of cough and bronchial responsiveness associated with ACE-inhibitor therapy in patients with asthma, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). DATA SOURCES: Literature was accessed through MEDLINE (1985-September 2001). Key search terms included cough, bronchospasm, asthma, congestive heart failure, chronic obstructive pulmonary disease, ACE inhibitors, and angiotensin II receptor blockers. DATA SYNTHESIS: The literature reports several cases of increased bronchial responsiveness associated with ACE inhibitors. Larger, controlled studies evaluating the increased risk in patients with pulmonary dysfunction are limited. Data from these trials are summarized in this article. CONCLUSIONS: The literature shows that patients with primary airway disease such as asthma and COPD are not at an increased risk of developing cough or bronchoconstriction as a result of ACE-inhibitor therapy. Despite the ability of ACE inhibitors to improve exercise tolerance, perfusion, and gas transfer, patients with CHF may be at higher risk of developing cough than the general population. Whether this cough is attributed to ACE inhibition or increased left-ventricular dysfunction remains uncertain. If increased bronchial responsiveness does occur, angiotensin II receptor antagonists are another reasonable option.     

An update on the management of Chagas cardiomyopathy

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, infects nearly 18 million people in Latin America and mainly affects the heart, causing heart failure, arrhythmias, heart block, thromboembolism, stroke and death. In this review, the clinical diagnosis and management of Chagas cardiomyopathy are discussed. Particular emphasis is placed on the clinical staging of patients and the use of various diagnostic tests that may be useful in individualizing treatment of the two most relevant clinical syndromes, that is, heart failure and arrhythmias. The relevance of specific treatments are discussed, stressing the important role of parasite persistence in disease pathogenesis. We also discuss new therapy modalities that may have a role in the treatment of Chagas cardiomyopathy.     

Sex‐ and Gender‐specific Research Priorities for the Emergency Management of Heart Failure and Acute Arrhythmia: Proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Research Workgroup

The emergency department (ED) is the point of first contact for patients with acute heart failure and arrhythmias, with 1 million annual ED visits in the United States. Although the total numbers of men and women living with heart failure are similar, female patients are underrepresented in clinical studies, with current knowledge predominantly based on data from male patients. This has led to an underappreciation of the sex‐specific differences in clinical characteristics and pathophysiology‐based management of heart failure. Similar disparities have been found in management of acute arrhythmias, especially atrial arrhythmias that lead to an increased risk of stroke in women. Additionally, peripartum and postpartum cardiomyopathy represent a diagnostic and treatment dilemma. This article is the result of a breakout session in the cardiovascular and resuscitation work group of the 2014 Academic Emergency Medicine consensus conference “Gender‐Specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes.” A nominal group technique was used to identify and prioritize themes and research questions using electronic mail, monthly conference calls, in‐person meetings, and Web‐based surveys between June 2013 and May 2014. Consensus was achieved through three rounds of nomination followed by the meeting on May 13, 2014, and resulted in seven priority themes that are essential to the common complex clinical syndrome of heart failure for both men and women and include the areas of pathophysiology; presentation and symptomatology; and diagnostic strategies using biomarkers, treatment, and mortality, with special consideration to arrhythmia management and pregnancy.     

Diabetic cardiovascular autonomic neuropathy: clinical implications

Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.     

Diabetic cardiovascular autonomic neuropathy: clinical implications

Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.