Management Of Dilated Cardiomyopathy Research Articles

Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high-risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high-risk arrhythmogenic gene variants in DCM patients. In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non-sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high-risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF]<35%). During a median follow-up of 6 years (interquartile range 1.6-12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present. In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life-threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes.

Pragmatic electrocardiogram tracings in non-ischaemic dilated cardiomyopathy: diagnostic and prognostic role.

Dilated cardiomyopathy (DCM) is a primitive heart muscle disease characterized by a great heterogeneous aetiology and prognostic outcome. Dilated cardiomyopathy is an umbrella term encompassing different aetiologies that might require specific treatments. It principally affects young and male adults, with high-risk arrhythmic competitive risk. Unfortunately, the prevention of major ventricular arrhythmic events remains a clinical challenge. In the era of advanced multimodality imaging and widely available genetic testing, electrocardiogram (ECG) continues to represent a reliable diagnostic tool, for specific work up of every single patient. However, approaching DCM patients, only a cardiomyopathy-oriented reading makes the role of ECG central in the management of DCM, both for diagnosis, prognosis, and therapeutic management. In this paper, we present four ECGs of four different DCM patients, in order to guide a cardiomyopathy-oriented ECG reading, emphasizing its impact in an early, cost-effective, and personalized diagnostic and prognostic work up in this specific setting.

International practice heterogeneity in pre-transplant management of pulmonary hypertension related to pediatric left heart disease.

Elevated pulmonary vascular resistance (PVR) in the setting of left heart failure may contribute to poor outcomes after pediatric heart transplant (HTx), but peri-transplant management is variable. We sought to characterize international practice by surveying physicians at pediatric HTx centers. We received 49 complete responses from 39 centers in 16 countries. Most respondents are pediatric cardiologists (90%), practice at centers offering heart (86%) and lung (55%) transplant, and perform pre-HTx acute vasoreactivity testing (AVT, 88%) in patients with elevated PVR. Half (51%) reported defining a PVR cutoff for HTx eligibility as ≤6WU m2 (56%) post-AVT (84%). The highest post-AVT PVR ever accepted for HTx ranged from 3-14.4 (median 6) WU m2 . To treat elevated pre-transplant PVR, phosphodiesterase type 5 inhibitors are most common (65%) followed by oxygen (31%), nitric oxide (14%), endothelin receptor antagonists (11%), and prostacyclins (6%). Nearly a third (31%) do not routinely use pulmonary vasodilators without implantation of a left ventricular assist device (LVAD). Case scenarios highlight treatment variability: in a restrictive cardiomyopathy scenario, HTx listing with post-transplant vasodilator therapy was favored, whereas in a Shone's complex patient with fixed PVR, LVAD ± pulmonary vasodilators followed by repeat catheterization was most common. Management of dilated cardiomyopathy with reactive PVR was variable. Most continue vasodilator therapy until HTx (16%), PVR normalizes (16%) or ≤6 months. Management of elevated PVR in children awaiting HTx is heterogenous. Evidence-based guidelines are needed to allow for longitudinal determination of optimal outcomes and standardized care.

Dilated cardiomyopathy in children

Pediatric cardiomyopathies are infrequent diseases of the cardiac muscle, with an annual inciden ce of 1.1 to 1.2 per 100,000 children. Dilated cardiomyopathy (DCM) is the predominant form, characterized by ventricular dilatation and systolic dysfunction. Etiologies are multiple, with at least 50%-70% of cases being idiopathic. When assessing a child with DCM, secondary potentially reversible causes must be ruled out. The main diagnostic tool is the echocardiogram which allows the identification of cardiac phenotype, to establish the degree of functional compromise, and res ponse to medical therapy. Prognosis is limited but more favorable in infants younger than 1 year at the onset, post myocarditis, or with a lesser degree of ventricular dysfunction. At least 20% of patients may recover ventricular function in the first 2 years after the onset and 40%-50% may die or need heart transplant in the first 5 years. Medical therapy is mainly based on adult experience with limited scientific evidence in children. Heart transplant is the therapy of choice in patients with end-stage disease, with excellent short- and medium-term survival. A significant proportion of patients may require stabilization on the waiting list, including the use of mechanical circulatory support as a bridge to transplantation. The purpose of this revision is to update the available infor mation on etiology, physiopathological mechanisms, prognostic factors, and management of DCM in children.

The electrocardiogram in the diagnosis and management of patients with dilated cardiomyopathy.

The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. In approximately one third of cases, DCM is familial with a genetic pathogenesis and various patterns of inheritance. Although the electrocardiogram (ECG) has been considered traditionally non-specific in DCM, the recently acquired knowledge of the genotype-phenotype correlations provides novel opportunities to identify patterns and abnormalities that may point toward specific DCM subtypes. A learned ECG interpretation in combination with an appropriate use of other ECG-based techniques including ambulatory ECG monitoring, exercise tolerance test and imaging modalities, such as echocardiography and cardiovascular magnetic resonance, may allow the early identification of specific genetic or acquired forms of DCM. Furthermore, ECG abnormalities may reflect the severity of the disease and provide a useful tool in risk stratification and management. In the present review, we discuss the current role of the ECG in the diagnosis and management of DCM. We describe various clinical settings where the appropriate use and interpretation of the ECG can provide invaluable clues, contributing to the important role of this basic tool as cardiovascular medicine evolves.

Myocardial Deformation Pattern Differs between Ischemic and Non-ischemic Dilated Cardiomyopathy: The Diagnostic Value of Longitudinal Strains

Both ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) are characterized by left ventricular (LV) dysfunction and dilation. Differentiation between ICM and NICM using non-invasive image modalities is a clinical challenge. This study compared the myocardial deformation patterns of ICM and NICM using 2-D speckle tracking echocardiography (2-D STE) and sought to find parameters valuable in the diagnosis and management of dilated cardiomyopathy. The study population comprised 84 consecutive patients with LV end-diastolic dimension >55 mm and ejection fraction (EF) <45 %. Of these patients, 41 were diagnosed with ICM and 43 with NICM by coronary angiography. 2-D STE was performed in all patients. The LV dimension did not differ between ICM and NICM. Compared with patients with ICM, patients with NICM had lower EF (29.0% vs. 33.0%, p = 0.024), lower global longitudinal strain (–5.4 ± 2.6% vs. –7.0 ± 2.5%, p = 0.006) and lower global radial strain (7.5 ± 4.5% vs. 10.7 ± 4.7%, p = 0.019). In contrast, global longitudinal strains did not differ significantly. However, NICM patients had higher apical and lower basal longitudinal strains compared with those with ICM. The ratio of basal to sum of mid- and apical longitudinal strains could predict NICM with a sensitivity of 63.4% and specificity of 88.4% by receiver operating characteristic curve analysis (cutoff value: 0.47, area under the curve: 0.792). Moreover, the concomitant presence of non-significant coronary artery stenosis (>50% and <70%) had no significant influence on global longitudinal strain in NICM. In conclusion, LV dilation and systolic dysfunction, relative apical sparing and a basal worsening pattern of LV longitudinal strain by 2-D STE were observed in patients with NICM but not ICM. The ratio of basal to sum of mid- and apical longitudinal strains could help differentiate NICM from ICM.

P1662All cause mortality outcomes of various types of stem cell therapies in patients with dilated cardiomyopathy: an updated meta analysis and systematic review

Abstract Background Dilated Cardiomyopathy (ischemic and non-ischemic) has been associated with very high mortality despite maximal medical and device therapy. Recently, several clinical trials involving different types of stem cells for the management of dilated cardiomyopathy have shown significant improvement in cardiac function, however, these studies were not powered to calculate mortality benefit. A previous meta analysis included 17 randomized controlled trials, however, there has been new randomized trials published since last meta analysis, hence the need for an updated meta analysis. Purpose Comparison of all cause mortality rate between stem cell therapy group and standard therapy group in patients with Dilated Cardiomyopathy followed for 12 months or more. Methods We conducted a systematic search of Medline (Pubmed) and Cochrane Central Register of Controlled Trials for abstracts and fully published studies (from inception through April, 2018) comparing various types of stem cell therapies with standard of therapy for patients with dilated cardiomyopathy (ischemic and non-ischemic). Study selection Only fully published randomized clinical trials and abstracts of randomized trials comparing all cause mortality outcomes of various types of stem cell therapies and standard therapy for patient with dilated cardiomyopathy (ischemic and non-ischemic) followed over a period of 12 or more months were included in our meta-analysis. Total of 1392 studies were identified. Studies which were duplicate, non-randomized, included pediatric population, systematic reviews or meta-analysis, study designs or protocols, trials including gene therapy or had follow up of patients for less than 12 months were excluded. Data extraction and Synthesis: Data were abstracted by two independent reviewers. Using Mantel-Haenszal method, a random effect model was used to calculate weighted Risk ratio (RR). RevMan 5.3 was used for statistical analyses. Results Twenty eight fully published randomized clinical trials and one abstract of randomized controlled trial met inclusion criteria of our analysis. Using Mantel-Haenszel method, a random effect model was used to calculate the weighted risk ratios. Our analysis included a total of 1662 patients. Stem cell therapy group showed significant reduction in mortality compared to standard therapy group (risk ratio [RR], 0.68; 95% confidence interval, 0.53–0.87) Fig 1. Tests for statistical heterogeneity did not show any significant heterogeneity p-value = 0.80 (I2 = 0%). Limitations of our study include selection, attrition and performance biases in the included studies. Fig 2 shows distribution of the included studies. Conclusion Stem cell therapy is associated with significant mortality reduction in patients with dilated cardiomyopathy (ischemic and non-ischemic). Our meta-analysis underscores the importance of conducting large randomized clinical trial to assess the mortality outcomes of stem cell therapy.

Dilated cardiomyopathy and severe heart failure. An update for pediatricians.

Dilated cardiomyopathy is the main cause of heart failure leading to heart transplant. Its prognosis is variable and depends on the etiology, the patient's age at onset, and the severity. The management of dilated cardiomyopathy is aimed at minimizing symptoms and preventing disease progression; it requires a comprehensive screening for comorbidities and the prevention of complications to improve the overall status of these children and mitigate their prognosis. Here we present a review oriented at the multidisciplinary management that pediatricians should consider when seeing these patients.

Evaluation of add on effect of carvedilol on standard protocol of digoxin, frusemide and benazepril in the management of dilated cardiomyopathy in dogs

This is a prospective, controlled, randomized clinical trial in canine patients with overt Dilated Cardiomyopathy (DCM). We hypothesized that the addition of the third generation beta-blocker carvedilol to the standard treatment of diuretic (furosemide), inotropic support (digoxin) and ACE-inhibitor (benazepril) would have beneficial effects over cardiac function and quality of life (QoL) that would be measurable 90 days post-treatment. 16 dogs diagnosed with overt DCM were recruited. They underwent clinical examination, electrocardiography, echocardiography and neurohormonal profiling (NT-proBNP and NO). Dogs were divided in two groups, receiving standard therapy or standard therapy plus carvedilol and subjected to re-evaluation on 90 days post-treatment. Our results indicated that the addition of carvedilol to the standard therapy improved echocardiographic indices of systolic function (FS and EF), reduced NT-proBNP and NO serum levels and quality of life within the group but did not showed the significant improvement over standard therapy. This suggested that the addition of carvedilol to the standard therapy in canine patients with overt DCM might have beneficial effects in cardiac function and quality of life in the treatment was continued for longer period.

Dilated Cardiomyopathy: Genetic Determinants and Mechanisms.

Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subtypes. Moreover, cascade genetic testing in family members can identify those who are at risk or with early stage disease, offering the opportunity for early intervention. This review will address diagnosis and management of DCM, including the role of genetic evaluation. We will also overview distinct genetic pathways linked to DCM and their pathogenetic mechanisms. Historically, cardiac morphology has been used to classify cardiomyopathy subtypes. Determining genetic variants is emerging as an additional adjunct to help further refine subtypes of DCM, especially where arrhythmia risk is increased, and ultimately contribute to clinical management.

Particularities of the Pharmacological management of dilated Cardiomyopathy in Cluj-Napoca County Hospital

Particularities of the Pharmacological management of dilated Cardiomyopathy in Cluj-Napoca County Hospital

Reply to: Timothy A C Snow, Cara A Wasywich and Fiona M Stewart. A case of breathlessness during pregnancy: the difficulty in diagnosing heart failure Obstet Med OM.2012.120031; published ahead of print 20 December 2012, doi:10.1258/OM.2012.120031.

To the Editor, Reply to: Timothy A C Snow, Cara AWasywich and Fiona M Stewart. A case of breathlessness during pregnancy: the difficulty in diagnosing heart failure Obstet Med OM.2012.120031; I wish to thank Drs Snow et al. for their fascinating case report of cardiogenic shock with dilated cardiomyopathy in pregnancy. It raised several questions: (1) Could the subjects’ use of clomipramine have been a factor in her dilated cardiomyopathy? A case/non-case study in the French PharmacoVigilance database found a reporting odds ratio of 11.5 with exposure to clomipramine and occurrence of dilated cardiomyopathy.1 More than 20 cases of dilated cardiomyopathy have been reported after exposure to imipraminic antidepressants, left ventricular dysfunction resolving following drug withdrawal. A positive re-challenge was described in one case report.2 (2) Were other underlying aetiologies considered for the subjects’ presentation? Catastrophic antiphospholipid syndrome may be associated with cardiogenic shock, renal failure, digital infarction and intrauterine fetal demise. Phaeochromocytoma, especially tumours secreting predominantly adrenaline, may also present with refractory shock with dilated cardiomyopathy. Severe cardiogenic shock was reported in a patient with phaeochromocytoma provoked by the use of imipramine, known to block the postsynaptic reuptake of noradrenaline.3 (3) Is there a place for aldosterone antagonists in the management of dilated cardiomyopathy during pregnancy? Aldosterone antagonists have been shown to improve survival in both mild and severely symptomatic subjects with dilated cardiomyopathy, and with left ventricular dysfunction after myocardial infarction.4 It has been commonly stated that spironolactone is contraindicated in pregnancy since a study published in 1980 reported demasculinisation of the external genitalia in the male offspring of exposed rats.5 A similar study performed five years earlier, however, found no evidence of an antiandrogenic effect in male rats whose mothers were exposed to the human equivalent of 400 mg spironolactone per day from day 14 of pregnancy until delivery.6 To the best of my knowledge, demasculinisation of male infants has not been reported in human pregnancies where the mother was exposed to spironolactone, despite the medication being widely used for hypertension, pre-eclampsia, liver disease and myasthenia gravis prior to 1980. More recently, a further four human pregnancies have been reported where maternal treatment with spironolactone in doses of 25–400 mg per day caused no adverse effect on male offspring.7–9 The use of eplerenone has only been reported in two pregnancies to date, with no effect apparent on the fetus.10,11 I again thank Snow et al. for their thought-provoking article. Competing interests: None.

Management of dilated cardiomyopathy in children in India

Management of dilated cardiomyopathy in children in India

Current understanding and management of dilated cardiomyopathy in Duchenne and Becker muscular dystrophy

To review the current understanding of the pathophysiology of dilated cardiomyopathy (DCM) in patients with Duchenne and Becker muscular dystrophies, assessment of cardiac dysfunction for these patients, and the recommended pharmacological treatment options and ongoing research directions. Reviews and original research articles from scholarly journals and books. Duchenne and Becker muscular dystrophies are debilitating neuromuscular disorders, both caused by mutations in the dystrophin gene. Most patients develop DCM as part of the disease course; in fact, DCM is the leading cause of death among these patients. Cardiac surveillance, including routine monitoring of electrocardiograms, echocardiograms, and appropriate blood biomarkers, may detect early DCM development. Although previous studies have shown that early administration of cardiac medications may delay the development of DCM, current standard of care does not emphasize cardiac surveillance and timely treatment. This, in turn, limits clinicians, including advanced practice nurses, to be optimally engaged in providing the most aggressive and proactive patient care. Implementing a routine cardiac assessment and timely pharmacological treatment in primary or specialty care settings is highlighted as an important step to optimize cardiac health among patients with Duchenne and Becker muscular dystrophies.

Cardiac magnetic resonance imaging and management of dilated cardiomyopathy in a Duchenne muscular dystrophy manifesting carrier

JO N 3055 muscles. Most DMD boys initially present delayed motor milestones, elevated serum creatine kinase (CK), respiratory impairment and 25 % of those surviving the age of 15 present dilated cardiomyopathy and arrhythmias [3, 4, 8, 10]. Echocardiography describes left ventricular dysfunction, but cardiac magnetic resonance (CMR) can detect the earliest signs of cardiomyopathy: occult regional cardiac asynergy; tissue degeneration; fibrosis [1, 9, 12]. Standard therapy for heart failure is effective in DMD cardiomyopathy [7, 10]. Female carriers show a mosaic pattern of dystrophin-positive and dystrophin-negative muscular fibres. About 50 % of patients present skeletal muscular symptoms and 18 % present dilated cardiomyopathy, because of a “skewed Xinactivation”, with most cells having an active faulty X-chromosome [5, 6]. A 27-year old woman was referred to our hospital in 2005 because of fatigue, effort dyspnoea (NYHA class IIb), episodes of palpitations and near syncope. Two brothers with a typical history of DMD without heart involvement died in their teens due to respiratory failure. Her asymptomatic 6year old daughter had a mild increase of CK (640 U/L). DNA analysis revealed dystrophin gene deletion of exons 3–17. Electromyography showed small duration motor unit potentials and reduced amplitude interference pattern during voluntary contraction. In 2003, she had already been diagnosed with a dilated cardiomyopathy, with an echocardiographic ejection fraction (EF) of 40 %, treated discontinuously with carvedilol 6.25 mg b.i.d. She was a smoker (5 cigarettes/d) and showed only calf pseudohypertrophy. She had high plasmatic concentrations of CK (1745 U/L, n.v. 22– 269), normal levels of cardiac troA. Barison G. D. Aquaro C. Passino M. Falorni A. Balbarini M. Lombardi L. Pasquali M. Emdin G. Siciliano

Surgical Treatment for Heart Failure

Congestive heart failure has become a major problem and the only surgical treatment for end-stage heart failure caused by dilated cardiomyopathy (DCM) had been heart transplantation. However, because of the shortage of donors, several procedures for non-transplant surgery have been developed. Published literature on left ventricular (LV) restoration was searched to review the new surgical procedures for treating patients with ischemic or non-ischemic DCM. LV restoration was initiated in the 1980s for repairing LV aneurysm. In the 1990s several surgical procedures were introduced for treating DCM, and the new evolving surgical treatment plays an important role in the management of DCM in the 21st century.

Minimally invasive explantation of implantable left ventricular assist devices

J Thorac Cardiovasc Surg 2002;124:189-91

A practical approach for the diagnosis and management of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) refers to a group of conditions of diverse etiology in which both ventricles are enlarged with reduced contractility. Certain correctable conditions associated with ventricular dysfunction can masquerade as DCM. Most of them can be identified with relatively inexpensive and readily available tests. A typical diagnostic work-up for a child with DCM also includes a number of investigations to identify the underlying cause, some of which are expensive and sophisticated. The average center in the developing world often does not have the facilities to carry out these investigations. The results of many of these investigations typically do not translate into a specific management strategy that makes a difference to prognosis. A significant number of children with DCM will eventually develop end-stage heart failure that requires cardiac transplantation with or without bridging procedures. This is an unrealistic option for the developing world. The management strategy of childhood DCM in the developing world needs to be tailored to the resources available with in a manner such that the overall prognosis is not substantially affected.

Therapeutic management of dilated cardiomyopathy

The therapeutic approach to dilated cardiomyopathy (DCM) still remains nonspecific and symptomatic, since no specific etiology is identified. Nevertheless, the recent introduction of angiotensin converting enzyme (ACE) inhibitors and beta-blockers greatly improved the treatment of DCM. The poor prognosis of patients with DCM encourages maximal aggressive attempts to prevent progression of ventricular dysfunction rather than to wait for treatable symptoms. To achieve this goal, vasodilators, particularly ACE inhibitors, now appear to be essential for the treatment of DCM. Digitalis is added unless contraindicated by adverse effects. Diuretics should be used only to relieve congestive symptoms. In the presence of sinus tachycardia or ventricular arrhythmias, beta-blockers are the next choice in our practice. When congestive symptoms or low output state are not controlled with vasodilators, diuretics, and digitalis, inotropic agents are indicated, with or without mechanical assist devices. For severely ill patients unresponsive to maximal medical management, heart transplantation is needed.