Form Of Congestive Heart Failure Research Articles

Increased expression of microRNA-378a-5p in acute ethanol exposure of rat cardiomyocytes.

Alcohol abuse is a risk factor for a distinct form of congestive heart failure, known as alcoholic cardiomyopathy (ACM). Here, we investigate how microRNAs may participate in the induction of cardiomyocyte apoptosis associated with ethanol exposure in vitro. Increasing the concentrations of ethanol to primary rat cardiomyocytes resulted in elevated apoptosis assessed by annexin V and propidium iodide staining, and reduced expression of an enzyme for alcohol detoxification aldehyde dehydrogenase 2 (ALDH2). These ethanol effects were accompanied by a substantial elevation of miR-378a-5p. Driving miR-378a-5p overexpression in cardiomyocytes decreased ALDH2. The specific interaction of miR-378a-5p with the 3'UTR of ALDH2 was examined by luciferase reporter assays, and we found that miR-378a-5p activity depends on a complementary base pairing at the 3'-UTR region of ALDH2 mRNA. Finally, ethanol-induced apoptosis in cardiomyocytes was attenuated in the presence of anti-miR378a-5p. Collectively, these data implicate a likely involvement of miR-378a-5p in the stimulation of cardiomyocyte apoptosis through ALDH2 gene suppression, which might play a potential role in the pathogenesis of ACM.

Birinci basamakta bir Peripartum Kardiyomiyopati vakası

Introduction: Peripartum cardiomyopathy (PKM) is a form of congestive heart failure that results from an enlarging of the heart and a weakening of the heart muscle in the last month of pregnancy and in the first five months of the postnatal period. Major risk factors include pregnancy at >30 years of age, multiparity, chronic hypertension and eclampsia. Patients suffering from PKM generally present with symptoms akin to heart failure, and the condition can be considered normal during the late period of pregnancy. A diagnosis of PKM can be made from anamnesis, a physical examination and echocardiography. Case Presentation: A 34-year old female patient, visiting the family medicine polyclinic for vaccinations of her 1-month-old infant, was noted to be suffering from shortness of breath, palpitations and coughing. There was no medical history of any disease or medication before or during the pregnancy. The patient’s blood pressure was 120/70 mmHg and her pulse was rhythmic at 122/min. There was no cardiac murmur, rales were present in both pulmonary bases and the results of an abdominal examination were normal. Pitting edemas were observed in both lower extremities, and a further anamnesis revealed that the patient’s palpitations had begun two weeks prior to the birth, and had increased in the first postpartum week. The patient was transferred to a cardiologist due to concerns of heart failure and a pulmonary embolism, and was then admitted to the intensive care unit for treatment with a diagnosis of acute decompensated heart failure. Conclusion: Given the higher incidence of disease in mothers >30 years, and the advanced average age of maternity in the present day, the odds of encountering PKM in the primary care is increasing. Family physicians can overcome this low-prevalence of the disease by investigating risk factors, following-up symptoms and consulting experts.

Correlation between endothelial dysfunction and redox-potential decreasing in patients with severe form of congestive heart failure

Correlation between endothelial dysfunction and redox-potential decreasing in patients with severe form of congestive heart failure

Favourable outcome after peripartum cardiomyopathy: a ten-year study on peripartum cardiomyopathy in a university hospital

Peripartum cardiomyopathy (PPCM) is an uncommon form of congestive heart failure, affecting obstetric patients around the time of delivery. The epidemiology of PPCM is infrequently reported. This study was undertaken to define the prevalence, presentation and outcome of PPCM among women giving birth in a teaching hospital in Malaysia. A retrospective case record analysis was conducted on all patients admitted and diagnosed with PPCM at the University Malaya Medical Centre, Kuala Lumpur, Malaysia, from 1 January 2000 to 31 December 2009. All deliveries were undertaken in the same hospital. A total of 12 patients were diagnosed with PPCM during the ten-year study period. The prevalence of PPCM was 2.48 in 100,000 (1 in 40,322) live births. Nine women were diagnosed with PPCM within five months of delivery. Three women had twin pregnancies. There was one death in the group (mortality rate 8.3%). The mean left ventricular ejection fraction at the time of diagnosis was 28.9% ± 8.5% (range 15%-40%). Following the index event, left ventricular function normalised in six of the nine patients (66.7%) who underwent subsequent echocardiography one year later. All patients were treated with standard heart failure therapy. Two patients with normalised left ventricular function had subsequent pregnancies - one pregnancy was terminated at seven weeks and the other patient delivered uneventfully at full term. PPCM is uncommon. The outcome in our series was favourable, with 66.7% of patients with PPCM recovering their left ventricular function. The mortality rate was 8.3%.

Predictors of Mortality or Heart Transplantation in Peripartum Cardiomyopathy

Predictors of Mortality or Heart Transplantation in Peripartum Cardiomyopathy Background Peripartum cardiomyopathy is an uncommon form of congestive heart failure with an unpredictable outcome. Very little is known about its real incidence and prevalence, and its etiology is still unknown, although a number of contributing factors, including diverse risk factors, have been proposed. Objective To analyze the predictors of mortality or need for heart transplantation. Methods Between 1992 and November 2011, 23 patients were retrospectively evaluated. Patients with decompensated heart failure were managed with hemodynamic monitoring. Median follow-up was of 7.3 years (3.2-17.5). Univariate Cox regression analysis was performed and overall survival was calculated using the Kaplan-Meier method. Results Mean age was 28.7±8.8 years; eight patients were multipara. Seventy three percent were in functional class III-IV. Systolic blood pressure and diastolic blood pressure were 103±23 and 67±11 mm Hg, respectively, and heart rate was 92±19 bpm. All the patients were in sinus rhythm. The cardiothoracic index was 0.56±0.07. End-diastolic and end-systolic left ventricular dimensions were 67.5±10.2 and 56.7±10.1 mm, respectively; left atrial dimension was 42.5±6 mm and left ventricular ejection fraction was 24.6%±10.8%. Mean pulmonary artery pressure was 25±9 mm Hg and pulmonary wedge pressure, was 18.4±7.8 mm Hg; cardiac index was 2.6±0.6 L/min/m2. Seven patients died and three patients underwent heart transplantation. Univariate analysis revealed that functional class, cardiac index, systolic and diastolic blood pressure, pulmonary wedge pressure and mean pulmonary artery pressure, cardiothoracic index and left atrial dimension were associated with mortality and heart transplantation. Survival at one, three and six years was of 91%, 82% y 64%, respectively. Conclusions In-hospital mortality was of 4.3% and the need for heart transplantation or mortality during follow-up was of 39%. The hemodynamic parameters at admission were the main predictors of mortality and transplant.

The vascular barrier-protecting hawthorn extract WS® 1442 raises endothelial calcium levels by inhibition of SERCA and activation of the IP3 pathway

WS® 1442 has been proven as an effective and safe therapeutical to treat mild forms of congestive heart failure. Beyond this action, we have recently shown that WS® 1442 protects against thrombin-induced vascular barrier dysfunction and the subsequent edema formation by affecting endothelial calcium signaling. The aim of the study was to analyze the influence of WS® 1442 on intracellular calcium concentrations [Ca2+]i in the human endothelium and to investigate the underlying mechanisms. Using ratiometric calcium measurements and a FRET sensor, we found that WS® 1442 concentration-dependently increased basal [Ca2+]i by depletion of the endoplasmic reticulum (ER) and inhibited a subsequent histamine-triggered rise of [Ca2+]i. Interestingly, the augmented [Ca2+]i did neither trigger an activation of the contractile machinery nor led to a barrier breakdown (macromolecular permeability). It also did not impair endothelial cell viability. As assessed by patch clamp recordings, WS® 1442 did only slightly affect endothelial Na+/K+-ATPase, but increased [Ca2+]i by inhibiting the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) and by activating the inositol 1,4,5-trisphosphate (IP3) pathway. Most importantly, WS® 1442 did not induce store-operated calcium entry (SOCE), but even irreversibly prevented histamine-induced SOCE. Taken together, WS® 1442 prevented the deleterious hyperpermeability-associated rise of [Ca2+]i by a preceding, non-toxic release of Ca2+ from the ER. WS® 1442 interfered with SERCA and the IP3 pathway without inducing SOCE. The elucidation of this intriguing mechanism helps to understand the complex pharmacology of the cardiovascular drug WS® 1442.

Peripartum cardiomyopathy

Peripartum cardiomyopathy is an uncommon form of congestive heart failure associated with systolic dysfunction of left ventricle. The onset is characterised by symptoms of heart failure occurring between the last month of pregnancy and 5-6 months postpartum. The early diagnosis and the institution of medical treatment for this disease are essential because the inadequate management may affect the patient’s long-term prognosis and can lead to severe complications, including death.Currently its aetiology is not completely understood. Many aetiopathogenetic hypotheses have been formulated: inflammation, viral agents, autoimmune processes. In the last years, evidences aroused for a role of prolactin and its 16 kDa metabolite in reducing cardiomyocite metabolic activity and contraction. In this article we have reviewed the current literature with special emphasis on the role of prolactin and the related current treatment strategies. In particular, bromocriptine appears promising, even if women need to be informed that the drug stops the production of breastmilk. Further researchers, such as large multicenter trials, are needed to decide the best treatment for the women suffering of this disease.

Peripartum cardiomyopathy

Peripartum cardiomyopathy is an uncommon form of congestive heart failure associated with systolic dysfunction of left ventricle. The onset is characterised by symptoms of heart failure occurring between the last month of pregnancy and 5-6 months postpartum. The early diagnosis and the institution of medical treatment for this disease are essential because the inadequate management may affect the patient’s long-term prognosis and can lead to severe complications, including death.Currently its aetiology is not completely understood. Many aetiopathogenetic hypotheses have been formulated: inflammation, viral agents, autoimmune processes. In the last years, evidences aroused for a role of prolactin and its 16 kDa metabolite in reducing cardiomyocite metabolic activity and contraction. In this article we have reviewed the current literature with special emphasis on the role of prolactin and the related current treatment strategies. In particular, bromocriptine appears promising, even if women need to be informed that the drug stops the production of breastmilk. Further researchers, such as large multicenter trials, are needed to decide the best treatment for the women suffering of this disease.

The Crataegus extract WS ® 1442 inhibits balloon catheter-induced intimal hyperplasia in the rat carotid artery by directly influencing PDGFR-β

Objective Effective systemic drugs against restenosis upon percutaneous transluminal coronary angioplasty (PTCA) are largely lacking. Polyphenols have been suggested to ameliorate post-angioplasty restenosis. Hawthorn ( Crataegus spp.) extracts, which are among the most frequently used herbal medicinal products against mild forms of congestive heart failure, contain polyphenols, but have not been investigated in this context. We aimed to assess the potential of the hawthorn extract WS ® 1442 to prevent balloon catheter-induced intimal hyperplasia and to elucidate the underlying mechanisms. Methods We analyzed the effects of WS ® 1442 on serum-induced vascular smooth muscle cell (VSMC) and endothelial cell (EC) growth and migration, growth factor-induced proliferation, growth factor receptor activity, and neointima formation in the rat carotid artery model. Results WS ® 1442 (100 μg/ml) decreased VSMC migration by 38% and proliferation by 44%, whereas EC migration and proliferation were unaltered. The extract inhibited VSMC DNA synthesis induced by platelet-derived growth factor (PDGF) (IC 50: 47 μg/ml), but not that of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Along this line, WS ® 1442 blocked recombinant human PDGF receptor (PDGFR)-β kinase activity (IC 50: 1.4 μg/ml) and decreased PDGFR-β activation and extracellular signal-regulated kinase (ERK) activation in VSMCs. In rats, orally administered WS ® 1442 significantly reduced neointima formation after balloon catheter dilatation of the carotid artery. Conclusion WS ® 1442 inhibits migration and proliferation of VSMCs, but not of ECs, and reduces balloon catheter-evoked neointima formation probably through inhibition of PDGFR-β. Thus, the present study suggests a novel adjunct pharmacological strategy to prevent angioplasty-related restenosis.

MiRNAs as Therapeutic Targets in Ischemic Heart Disease

Ischemic heart disease is a form of congestive heart failure that is caused by insufficient blood supply to the heart, resulting in a loss of viable tissue. In response to the injury, the non-ischemic myocardium displays signs of secondary remodeling, like interstitial fibrosis and hypertrophy of cardiac myocytes. This remodeling process further deteriorates pump function and increases susceptibility to arrhythmias. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression in a sequence-dependent manner. Recently, several groups identified miRNAs as crucial gene regulators in response to myocardial infarction (MI) and during post-MI remodeling. In this review, we discuss how modulation of these miRNAs represents a promising new therapeutic strategy to improve the clinical outcome in ischemic heart disease.

Peripartum Cardiomyopathy

Peripartum Cardiomyopathy (PPCM) is an uncommon form of congestive heart failure that affects women in late pregnancy or early puerperium. The disease causes a significant morbidity and mortality in women of child bearing age. The etiology is unknown and diagnosis is confined to a narrow period and requires echocardiographic evidence of left ventricular systolic dysfunction. Dyspnoea is the main presenting complaint but carries a broad differential diagnosis. Although PPCM is an uncommon disease it should be considered in the differential diagnosis in women presenting with dyspnoea in the late pregnancy or early puerperium. Treatment of PPCM is similar to that of other forms of congestive heart failure and included loop diuretics, beta blockers, vasodilators and digoxin. With early and effective treatment a significant number of patients improve but in others it carries a long term poor prognosis. We are presenting a case of PPCM in a 30-years old woman who presented with dyspnoea after fifteen days of parturition. Â Â Â Â Â University Heart Journal Vol.4(1) January 2008

Alcohol use and congestive heart failure: incidence, importance, and approaches to improved history taking

Alcohol use, abuse, and dependence have the potential to result in alcoholic cardiomyopathy (ACM). This distinct form of congestive heart failure (CHF) is responsible for 21-36% of all cases of nonischemic dilated cardiomyopathy in Western society. Without complete abstinence, the 4-year mortality for ACM approaches 50%. Therefore, accurate and detailed assessment of alcohol use in congestive heart failure is essential. The prevalence of problematic alcohol use is unrecognized by many clinicians. Clinical assessment of alcohol intake is often reduced to a simple question such as, "Do you drink?" Denial and minimization are hallmarks of alcohol abuse, with many individuals underreporting their use of alcohol. Clinicians can overcome these hurdles by implementing practical history taking measures to improve the accuracy of self-reported alcohol use. The data regarding the dangers of ongoing alcohol use in individuals with ACM make attempts to engage individuals in treatment to support abstinence essential. Suggestions for detailed and accurate assessment are discussed.

Prevalence and outcome of peripartum cardiomyopathy in Malaysia

Peripartum cardiomyopathy (PPCM) is an uncommon form of congestive heart failure, afflicting obstetric patients around the time of delivery. The epidemiology of PPCM is infrequently reported. To the best of our knowledge, there has been no report from Asia. To define the prevalence, presentation and outcome of PPCM in a major referral centre in Malaysia. Retrospective case record analysis of all patients admitted and diagnosed with PPCM at the University Malaya Medical Centre, Kuala Lumpur, over 5 years from 1st January, 2001 to 31st December, 2004. Eight patients were diagnosed with PPCM over the study period reflecting a prevalence of 34: 100,000 life births. Five were diagnosed within 5 months after delivery. Three were associated with twin pregnancies. There was one death (12.5% mortality). The mean left ventricular ejection fraction (LVEF) at the time of diagnosis was 27.1 +/- SD 6.4% (range: 17-35%). Following the index event, the left ventricular function recovered in three of the eight patients (37.5%) with restoration of normal LVEF (LVEF > 50%). Two patients had subsequent pregnancies. One was terminated at 7 weeks, and the other delivered uneventfully with a normal LVEF. Peripartum cardiomyopathy is uncommon in Malaysia. It appears to be associated with twin pregnancy. The outcome is variable with 37.5% recovering normal left ventricular function, 12.5% mortality and persistently impaired left ventricular function in the remainder.

Doxorubicin-Induced Cardiomyopathy: From the Cardiotoxic Mechanisms to Management

First isolated in the early 1960s, doxorubicin (DOX) remains among the most effective anticancer drug ever developed. However, this drug has proven to be a double-edged sword because it also causes a cardiomyopathy that leads to a form of congestive heart failure that is usually refractory to common medications. It is hoped that a better understanding of the mechanisms underlying DOX's cardiotoxicity will enable development of therapies with which to prevent and/or treat the heart failure it causes. Suggested contributors to DOX-induced cardiomyopathy include formation of reactive oxygen species, apoptosis, inhibited expression of cardiomyocyte-specific genes, and altered molecular signaling. And taking these various contributors into consideration, a variety of approaches aimed at preventing or mitigating the cardiotoxicity of DOX have been tried, but so far, the ability of these treatments to protect the heart from damage has been limited. That said, one recent approach that shows promise is adjuvant therapy with a combination of hematopoietic cytokines, including erythropoietin, granulocyte colony-stimulating factor, and thrombopoietin. We suggest this approach to preventing DOX-induced cardiomyopathy is worthy of serious consideration for clinical use.

Too Much Is Not Enough

When young healthy humans, and especially trained endurance athletes, perform activities like running, swimming, or cycling, mean arterial pressure (MAP) does not rise much.1,2 At first glance, this seems counterintuitive, because in normal subjects, cardiac output can increase 4- to 5-fold during heavy exercise, and in elite male athletes, cardiac output values in excess of 40 L/min have been reported.3 The “failure” of MAP to rise is even more puzzling in light of the large exercise-mediated increases in vasoconstricting sympathetic outflow directed at most vascular beds.2 In the athletes, stroke volume can reach 200 mL/beat, making the maintenance of MAP even more impressive. By contrast, in middle-aged subjects with hypertension, mean arterial blood pressure frequently rises markedly during exercise in spite of more modest increases in cardiac output and small stroke volumes.1 How does this happen, and what insight does the article by Zhao et al4 from the Thomas laboratory at University of Texas Southwestern provide on this observation and related phenomenon? First, young subjects are “protected” from a rise in MAP during exercise by marked peripheral vasodilation in the face of the increased sympathetic outflow. Because a high fraction of cardiac output during exercise is directed toward the active skeletal …

Pharmacological Prevention of Thromboembolism in Patients with Left Ventricular Dysfunction

Chronic left ventricular systolic dysfunction is a well recognized problem with an increasingly significant impact on healthcare in the form of congestive heart failure (CHF). Advances in medicine have led to improved survival after myocardial infarction (MI) and as a result, an increased prevalence of left ventricular systolic dysfunction. An increased incidence of thromboembolism, especially stroke, in patients with left ventricular systolic dysfunction is also well recognized. Pharmacological strategies to prevent stroke have been proposed in numerous studies. For example, anticoagulation in patients with atrial fibrillation and heart failure has been shown to reduce mortality rates and the incidence of stroke; however, its role in patients with left ventricular dysfunction and normal sinus rhythm is unclear and utilization of anticoagulation in these patients varies widely. The role of aspirin to prevent thromboembolism in patients with CHF is controversial. The relatively new pharmacological agent ximelagatran, which has an advantage of unmonitored oral administration has the potential to change the anticoagulation strategy in patients with heart failure. Important trials to define optimal therapy for reducing the risk of thromboembolism and death in patients with left ventricular systolic dysfunction and sinus rhythm include the recently reported WATCH (Warfarin and Antiplatelet Therapy in Chronic Heart failure) trial and the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial, which is currently underway. The WATCH trial failed to outline significant differences between aspirin (acetylsalicylic acid), warfarin, and clopidogrel in the primary composite endpoint of all-cause mortality, nonfatal MI, and nonfatal stroke. Combined data from WATCH and WARCEF may provide sufficient statistical power to clarify outcomes such as stroke and death in patients with reduced cardiac ejection fraction. The pooled data may also help define optimal preventative measures for thromboembolism in patients with left ventricular systolic dysfunction and sinus rhythm.

Renovascular Hypertension and Ischemic Nephropathy

Major improvements in imaging, medical therapy, and techniques of renal revascularization have changed the landscape of renovascular disease during the past decade. This has been particularly true for atherosclerotic renal artery stenosis, which remains one of the most common conditions known to accelerate hypertension and one of the most common incidentally detected vascular lesions. Despite, or perhaps because of, these developments, few clinical questions provoke more controversy and debate among cardiologists, internists, and nephrologists than decisions about the optimal management of patients with main renal artery stenosis. Even well-informed clinicians from different subspecialties hold widely divergent opinions about the role of renal revascularization, particularly for atherosclerotic disease. Studies of Medicare claims data indicate that application of peripheral intervention procedures varies >14-fold between various parts of the country.1 Some of those from interventional subspecialties (primarily interventional radiology and cardiology) emphasize the major benefits now available from endovascular procedures, including the use of stents. They argue that revascularization offers the potential to improve or reverse renovascular hypertension, to salvage or preserve the renal circulation and renal function, and to improve the management of patients with refractory forms of congestive heart failure.2 A recent review of the use of percutaneous renal artery procedures among Medicare beneficiaries confirms a rise from 7660 claims in 1996 to 18 520 claims in 2000, primarily because of a 2.8-fold increase in procedures by interventional cardiologists.3 Many in the nephrology community review the same published literature and reach nearly opposite conclusions. They argue that recent prospective studies fail to reveal major benefits of blood pressure control related to renal revascularization, that the risks of complications from interventional procedures are substantial, including uncommon but sometimes devastating loss of renal function resulting from atheroembolic disease.4 Despite a wave of enthusiasm in the early 1990s to identify …

Heart failure after Caesarean section for twin delivery

Heart failure after Caesarean section for twin delivery

Synthesis and Evaluation of Imidazolylmethylenetetrahydronaphthalenes and Imidazolylmethyleneindanes: Potent Inhibitors of Aldosterone Synthase

Elevated plasma aldosterone levels play a detrimental role in certain forms of congestive heart failure and myocardial fibrosis. We proposed aldosterone synthase (CYP11B2) as a novel target for the treatment of these diseases. In this study, the synthesis and biological evaluation of substituted E- and Z-imidazolylmethylenetetrahydronaphthalenes and E- and Z-imidazolylmethyleneindanes (compounds 1a,b-9a,b) is described. The compounds were prepared by a Wittig-like reaction. They were tested for activity using bovine CYP11B and human CYP11B2 expressed in fission yeast and V79 MZh cells. Selectivity was determined toward human CYP11B1, CYP19, and CYP17. Especially in the case of CYP11B1 (steroid 11beta-hydroxylase), selectivity is a crucial issue, since sequence homology between this enzyme and the target enzyme is very high (93%). On the basis of the X-ray structure of human CYP2C9, a protein model of CYP11B2 was developed and docking experiments with the title compounds were performed. The biological results revealed highly potent inhibitors of CYP11B2 (IC(50) = 4-93 nM). The Z-isomers usually were more active than the corresponding E-isomers. Different inhibitory profiles could be observed: rather selective inhibitors of CYP11B1, dual inhibitors of both enzymes, and rather selective inhibitors of CYP11B2. The chloro derivative 8b was found to be a highly potent CYP11B2 inhibitor (IC(50) = 4 nM) showing a 5-fold selectivity for CYP11B1 (IC(50) = 20 nM). This compound could be an interesting lead for further optimization as a therapeutic agent. It also could be used as well as the CYP11B1 selective compounds as a pharmacological tool.

Ryanodine receptor channelopathies

Ryanodine receptors (RyR) are the Ca 2+ release channels of sarcoplasmic reticulum that provide the majority of the [Ca 2+] necessary to induce contraction of cardiac and skeletal muscle cells. In their cellular environment, RyRs are exquisitely regulated by a variety of cytosolic factors and accessory proteins so that their output signal (Ca 2+) induces cell contraction without igniting signaling pathways that eventually lead to contractile dysfunction or pathological cellular remodeling. Here we review how dysfunction of RyRs, most commonly expressed as enhanced Ca 2+ release at rest (skeletal muscle) or during diastole (cardiac muscle), appears to be the fundamental mechanism underlying several genetic or acquired syndromes. In skeletal muscle, malignant hyperthermia and central core disease result from point mutations in RYR1, the skeletal isoform of RyRs. In cardiac muscle, RYR2 mutations lead to catecholaminergic polymorphic ventricular tachycardia and other cardiac arrhythmias. Lastly, an altered phosphorylation of the RyR2 protein may be involved in some forms of congestive heart failure.