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The paper describes the investigation of matrix metalloproteinase type 3 (MMP-3) -1171 5A/6A gene polymorphic alleles variants (rs35068180) in patients with dilated cardiomyopathy. A allele and 6А6А genotype of MMP-3 -1171 5A/6A gene (rs35068180) were determined as new genetic predictors of dilated cardiomyopathy development. Aim. To study the association of polymorphism -1171 5A/ of the MMP-3 gene with dilated cardiomyopathy of various origins. Material and methods. The main study group comprised 221 patients with dilated cardiomyopathy (DCM) of different origin. Their average age was 55.309.69 years. Among them there were 111 persons with DCM of ischemic origin, including 99 (89.2%) men and 12 (10.8%) women. The average age of the subjects with DCM was 51.739.74 years, the age of the male subgroup was 51.008.96 years, and the age of the female subgroup was 57.753.71 years. A total of 110 patients with idiopathic cardiomyopathy were included in the study. Among 221 patients, 110 persons did not demonstrated idiopathic dilated cardiomyopathy as the cause of myocardium dilation. This group comprised 100 (91.5%) male patients and 10 (8.5%) female patients. The control group of subjects (221 persons) was represented by healthy people without diseases of the cardiovascular system. The average age of control subjects was 53.64.8 years. We examined all patients in the main group using routine laboratory and instrumental methods, as well as coronary angiography. If myocarditis was suspected, we did an MRI of the heart. Genotyping of polymorphism -1171 5A/6A (rs35068180) of the MMP-3 gene was performed using PCR. Results. Among patients of the main group with dilated myocardial remodeling of various Genesis, the allele was documented in 65.8% of cases against 59.3% among the control group, p=0.044. The homozygous genotype of the MMP-3 gene in patients of the main group was verified in 42.1% of patients against 32.6% of cases in relatively healthy individuals (p=0.099). Conclusion. We have proved the predominance of 6A allele and 6А6А genotype of the MMP-3 gene in the group of patients with DCM. It seems that it is homozygous 6A allele that causes a decrease in the activity of the transcription process and change in the level of stromelysin in arterial walls. This contributes to the activation of type 1 procollagenase, extracellular matrix deposition and cardiac muscle remodeling.

Background The epidemiology of diabetes and idiopathic cardiomyopathy have limited data. We investigated the overall and the age-, sex-, and urbanization-specific incidence and relative hazard of idiopathic cardiomyopathy in association with type 2 diabetes and various anti-diabetic medications used in Taiwan. Methods A total of 474,268 patients with type 2 diabetes were identified from ambulatory care and inpatient claims in 2007–2009 from Taiwan’s National Health Insurance (NHI) database. We randomly selected 474,266 age-, sex-, and diagnosis date-matched controls from the registry of NHI beneficiaries. All study subjects were linked to ambulatory care and inpatient claims (up to the end of 2016) to identify the possible diagnosis of idiopathic cardiomyopathy. The person-year approach with Poisson assumption was used to estimate the incidence, and Cox proportional hazard regression model with Fine and Gray’s method was used to estimate the relative hazards of idiopathic cardiomyopathy in relation to type 2 diabetes. Results The overall incidence of idiopathic cardiomyopathy for men and women patients, respectively, was 3.83 and 2.94 per 10,000 person-years, which were higher than the corresponding men and women controls (2.00 and 1.34 per 10,000 person-years). Compared with the control group, patients with type 2 diabetes were significantly associated with an increased hazard of idiopathic cardiomyopathy (adjusted hazard ratio [aHR]: 1.60, 95% confidence interval [CI]: 1.45–1.77] in all age and sex stratifications except in those men aged > 64 years. Patients with type 2 diabetes aged Conclusions In Taiwan, diabetes increased the risk of idiopathic cardiomyopathy in both sexes and in all age groups, except in men aged > 64 years. Younger patients were vulnerable to have higher HRs of idiopathic cardiomyopathy. Some anti-diabetic medications may reduce the risks of cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy that is caused by heart failure secondary to a dysfunction of the left ventricle at the end of pregnancy or in the first months following childbirth. The diagnosis is performed by electrocardiogram, radiography of the thorax and increase of natriuretic peptides. Bedside radiography can contribute with data that help early diagnosis. Treatment is carried out following clinical guidelines for heart failure, taking into account potentially teratogenic drugs. The importance of this pathology lies in that it affects women at a fertile age and is potentially mortal, which is why there must be a high index of suspicion for its diagnosis and a differential diagnosis with other entities. In this clinical note we present a series of cases of PPCM with the goal of reviewing the diagnosis and treatment of this entity.

Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4+, CD8+, and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8+ T-cells were highly activated in CCC as compared to IDC, CD4+ T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.

Peripartum cardiomyopathy (PPCM) is defined as idiopathic cardiomyopathy which occurs at the end of pregnancy or in the first few months after delivery, with symptoms of heart failure (HF) secondary to left ventricular dysfunction, and at the same time no other cause for this condition. The pathomechanism of the disease has not yet been fully understood, but it is probably based on the interaction of complex factors. The clinical course of PPCM varies from life-threatening acute heart failure to mild symptoms mimicking the symptoms typical of the perinatal period. In Europe, PPCM is a rare disease but there are areas of the world where it occurs in one in every 300 cases. The treatment of PPCM is similar to that of HF with reduced ejection fraction. However, it is important to exclude drugs with teratogenic effects during pregnancy. The inclusion of bromocriptine in PPCM therapy seems to be justified, and in some cases improves the prognosis.

Advances in the diagnostics and treatment of cancer have led to improved survival of patients and decreased mortality. Cardiovascular complications (CVC) however, are among the most frequent side effects of anticancer treatment, which can have an adverse effect on the prognosis. This may be the result of cardiotoxicity, which involves direct effects of the radiation therapy and /or chemotherapy on the heart function and structure. Heart failure with cancer therapy was associated with a 3.5-fold increase in the risk of mortality compared with idiopathic cardiomyopathy. The cardiotoxicity risk assessment is often difficult, due to the different susceptibility of patients to drugs and their combinations, and coadministration of radiation therapy. Therefore, the likelihood of development and the time of occurrence of cardiotoxicity may vary and not always depend on the initial risk. Strategies for managing such patients are in most cases based on the expert opinion. This article provides recommendations for the prevention and therapy of cardiotoxicity, set out in the consensus of the European Society of Cardiology 2016.

Isolated left ventricular non-compaction (ILVNC) is a rare, congenital, idiopathic cardiomyopathy that may present in adulthood. There is no true gold standard for the diagnosis of ILVNC. Two-dimensional echocardiography with colour Doppler is the modality of choice to diagnose the condition. However, the diagnosis should be confi rmed with cardiac magnetic resonance imaging (CMRI), as well as either a positive family history, complications of ILVNC or confi rmatory genetic testing. We describe the clinical and echocardiographic features in 4 patients, each with a possible diagnosis of ILVNC, in the setting of potential alternative aetiologies for heart failure. Approval to present these cases was obtained from the institutional ethics committee and the patients also provided consent. Suffi cient transthoracic echocardiographic (TTE) evidence of ILVNC according to previously published criteria was found in all the cases, although it was not confi rmed with CMRI. This case series highlights the importance of routine echocardiography in all patients who present with heart failure – irrespective of associated risk factors. We caution against over-diagnosis of ILVNC with TTE alone, and recommend the use of CMRI as a second-line diagnostic investigation. Screening of family members and prevention of complications of confi rmed cases of ILVNC are important.

Background Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by clinical features including cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and exercise intolerance. It is often considered to be a paediatric disease, owing to most cases being diagnosed during childhood and mortality being the highest during the first few years of life. Case summary We report a case of dilated cardiomyopathy due to BTHS in a 27-year-old adult male patient, who initially presented with lightheadedness, dyspnoea, orthopnoea, and bilateral lower extremity oedema. Key findings from investigations included leukopenia, prolonged QTc interval, reduced left ventricular ejection fraction (LVEF), global enlargement of all heart chambers, patent coronary arteries, and mild pulmonary hypertension. The patient was diuresed to euvolemia and discharged with a LifeVest. Guideline-directed medical therapy was initiated and uptitrated as an outpatient. A repeat echocardiogram 2 years after initial presentation showed marked improvement in LVEF. Discussion It is possible that there are adult patients with idiopathic cardiomyopathy, which may be attributable to BTHS. In the absence of an obvious underlying cause, with the appropriate historical information, clinical exam, laboratory investigations, and imaging findings, BTHS should be considered as a likely cause of non-ischaemic cardiomyopathy.

Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing ( P =0.005 and P =0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first‐degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01873963.

Aim. To study the relationship of matrix metalloproteinase-3 (MMP3) genetic polymorphism and dilated ischemic cardiomyopathy (DCM), as well as idiopathic cardiomyopathy (ICM) of unknown etiology.Material and methods. A total of 221 patients with DCM and ICM were examined (mean age, 55,30±9,69 years). The group of ischemic DCM consisted of 111 people (99 men (89,2%) and 12 women (10,8%)). The mean age of DCM subjects was 51,73±9,74 years (male subgroup, 51,00±8,96 years; female subgroup, 57,75±3,71 years). The ICM group consisted of 110 people (100 men (91,5%) and 10 women (8.5%)). The mean age of ICM subjects was 58,68±8.38 years (male subgroup, 58,29±8.,6 years; female subgroup, 62,90±6,29 years). The control group of subjects (n=121) consisted of healthy people without cardiovascular diseases (mean age, 53,6±4,8 years). All patients of the experimental group underwent routine diagnostic tests, as well as coronary angiography. In case of suspected myocarditis, cardiac magnetic resonance imaging was performed. All patients underwent polymerase chain reaction to determine the MMP3-11715A/6A polymorphism (rs35068180).Results. In patients with cardiomyopathy, regardless of the disease origin, significant differences were verified in comparison with the control group. Allele 6A (65,8% vs 59,3%, p=0,044) and genotype 6A/6A (42,1% vs 32,6%, p=0,099) were found significantly more frequently in patients with cardiomyopathy than in the control group. In addition, despite various etiological factors, the pathogenetic involvement of MMP3 is likely to have a general direction.Conclusion. In all patients with cardiomyopathy, the prevalence of MMP3 gene A allele was shown. Due to decrease in the transcription activity in homozygous 6A allele, the stromelysin level in arterial walls also decreases. This promotes the activation of procollagenase-1, the deposition of extracellular matrix and cardiac remodeling

Coronavirus disease 2019 (COVID-19) is challenging the care for cardiovascular patients, resulting in serious consequences with increasing mortality in pre-diseased heart failure patients. In the current state of the pandemic, the physiopathology of COVID-19 affecting pre-diseased hearts and the management of terminal heart failure in COVID-19 patients remain unclear. We outline the findings of a young COVID-19 patient suffering from idiopathic cardiomyopathy who was treated for acute multi-organ failure and required cardiac surgery with implantation of a temporary right ventricular and durable left ventricular assist device (LVAD). For deeper translational insights, we used in-depth tissue analysis by electron and light sheet fluorescence microscopy revealing evidence for spatial distribution of severe acute respiratory syndrome coronavirus 2 in the heart. This indicates that in-depth analysis may represent a valuable tool in understanding indistinct clinical cases. We conclude that COVID-19 directly affects pre-diseased hearts, but the consequences can be treated successfully with LVAD implantation. OA Förderung 2020

BackgroundPeripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with acute heart failure during the peripartum period. It is common in patients of African ancestry. Currently, there is paucity of data on the burden, predictors and outcomes of PPCM in Uganda. This study aimed to investigate the prevalence, predictors and six-month outcomes of PPCM in an adult cohort attending a tertiary specialised cardiology centre in Kampala, Uganda.MethodsThis study consecutively enrolled 236 women presenting with features of acute heart failure in the peripartum period. Clinical evaluation and echocardiography were performed on all the enrolled women. PCCM was defined according to recommendations of the Heart Failure Association of the European Society of Cardiology Working Group on PPCM. Poor outcome at six months of follow-up was defined as presence of any of the following: death of a mother or her baby, New York Heart Association (NYHA) functional class III-IV or failure to achieve complete recovery of left ventricular function (left ventricular ejection fraction ≤55%).ResultsThe median age, BMI and parity of the study participants was 31.5 (25.5-38.0) years, 28.3 (26.4-29.7) and 3 (2-4) respectively. The prevalence of PPCM was 17.4% (n = 41/236). Multiple pregnancy was the only predictor of PPCM in this study population (OR 4.3 95% CI 1.16-16.05, p = 0.029). Poor outcome at six-months was observed in about 54% of the patients with PPCM (n = 4, 9.8% in NYHA functional class III-IV and n = 22, 53.7% with LVEF ConclusionPPCM is relatively common in Uganda and is associated with multiple pregnancy. Poor outcomes especially absence of complete recovery of left ventricular function are also common. Large studies to further investigate long-term maternal and foetal outcomes in Uganda are justified.

Background Syndromic dilated cardiomyopathy (DCM) includes a group of complex disorders with a very heterogeneous genetic etiology, leading to delay in definitive diagnosis. Conversely, an early genetic diagnosis is very important in determining the disease course, the prognosis, and may guide personalized treatments and family counseling. Methods We analyzed two brothers with a multisystemic disorder, including dilated cardiomyopathy, diabetes, bilateral neurosensorial hearing loss, and optic atrophy, using different genetic approaches, namely mitochondrial DNA sequencing, comparative genomic hybridization‐array (a‐CGH) and whole exome sequencing (WES). Results Sequencing of the wide mitochondrial genome revealed, in both brothers, the known homoplasmic variant rs2853826 in the subunit 3 of the NADH dehydrogenase gene (MT‐ND3), whose pathogenicity was conflicting. Comparative genomic hybridization‐array analysis revealed in both patients and their father two heterozygous deletions in Phosphodiesterase 4d‐Interacting Protein (PDE4DIP) and Protocadherin‐related 15 (PCDH15) genes, respectively. The use of WES detected a pathogenetic mutation in ALMS1, enabling the definitive diagnosis of Alström syndrome. Conclusion We demonstrated how the diagnosis of a complex heterogeneous disease may be difficult, due to several overlapping manifestations and the possible interaction of more genetic variants that could lead to a more severe and complex phenotype. This paper strongly evidences how genomics is revolutionizing the diagnosis of rare complex disease, representing one of the most essential steps to enable a definitive diagnosis and to establish the etiology for diseases, such as syndromic DCM., The diagnosis of a complex heterogeneous disease may be difficult, due to several overlapping manifestations and the possible interaction of more genetic variants. By using different genetic approaches we obtained a definitive diagnosis of Alström syndrome in two brothers with a multisystemic disorder.

Objective: Exercise-induced premature ventricular complexes (EiPVCs) are often considered as benign arrhythmias, although they are associated with a high risk of all-cause death in the general healthy population. However, an intermediate pathophysiological process remains unclear, particularly in patients with known cardiovascular disease. The aim of this study was to find an association between EiPVCs, the occurrence of life-threatening ventricular arrhythmias (LACO), and all-cause mortality in patients with cardiovascular disease. Methods: This was an observational study of a cohort of patients with coronary artery disease (CAD) or idiopathic cardiomyopathy (ICM). Stress testing was performed as a part of the routine cardiovascular evaluation. The occurrence of EiPVCs was evaluated during exercise testing (ET). At follow-up, long-term occurrence of LACO was evaluated. A bivariate and multivariate analysis was performed. Results: Out of the total of 1442 patients analysed, 700 (49%) had EiPVCs. During 14 years of following-up after ET, 106 LACO outcomes were observed. Long-term all-cause mortality was 4% (n = 61). A bivariate analysis showed that patients with EiPVCs had an increased risk for LACO (RR = 2.81, 95% CI; 1.9–4.3, P

Objectives This study sought to characterize ventricular tachycardia (VT) ablation outcomes across nonischemic cardiomyopathy (NICM) etiologies and adjust these outcomes by patient-related comorbidities that could explain differences in arrhythmia recurrence rates. Background Outcomes of catheter ablation of VT in patients with NICM could be related to etiology of NICM. Methods Data from 2,075 patients with structural heart disease referred for catheter ablation of VT from 12 international centers was retrospectively analyzed. Patient characteristics and outcomes were noted for the 6 most common NICM etiologies. Multivariable Cox proportional hazards modeling was used to adjust for potential confounders. Results Of 780 NICM patients (57 ± 14 years of age, 18% women, left ventricular ejection fraction 37 ± 13%), underlying prevalence was 66% for dilated idiopathic cardiomyopathy (DICM), 13% for arrhythmogenic right ventricular cardiomyopathy (ARVC), 6% for valvular cardiomyopathy, 6% for myocarditis, 4% for hypertrophic cardiomyopathy, and 3% for sarcoidosis. One-year freedom from VT was 69%, and freedom from VT, heart transplantation, and death was 62%. On unadjusted competing risk analysis, VT ablation in ARVC demonstrated superior VT-free survival (82%) versus DICM (p ≤ 0.01). Valvular cardiomyopathy had the poorest unadjusted VT-free survival, at 47% (p Conclusions Catheter ablation of VT in NICM is effective. Etiology of NICM is a significant predictor of outcomes, with ARVC, myocarditis, and DICM having similar but superior outcomes to hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis, after adjusting for potential covariates.

Peripartum cardiomyopathy (PPCM) is a rare idiopathic cardiomyopathy having an incidence of less than 0.1%. PPCM is associated with high morbidity and mortality rates ranging from 5 to 32%. In this review, the authors report a series of five PPCM cases. The case reports included pregnant women with PPCM, admitted in the hospital from October 1, 2017 to June 1, 2018 over a period of 9 months who required cesarean section. The authors aim to discuss the presentation, optimization, anesthetic management, and postoperative care of this rare condition. One of the cases was a booked case. The remaining four pregnant patients were referred in late pregnancy with features of congestive cardiac failure. One patient was in acute pulmonary edema, required intubation, and subsequently had cesarean section under general anesthesia. Four patients were managed with incremental epidural anesthesia. The need for proper preoperative optimization and intra- and postoperative management was discussed. The authors had one maternal mortality in our series. There was no neonatal mortality. Early diagnosis of PPCM, prompt treatment of heart failure, planning the delivery, and postpartum care can decrease maternal morbidity and mortality. Incremental epidural dosing can be used for cesarean section and has the advantage of stable hemodynamic status without the risks associated with general anesthesia.

Eosinophilic infiltration is a rare and underrecognized cause of myocarditis associated with prolonged eosinophilia. Before advanced imaging and routine biopsy, patients were diagnosed with an idiopathic cardiomyopathy with subsequent diagnosis made on autopsy. We present 3 cases of eosinophilic myocarditis diagnosed by cardiac biopsy classified as hypereosinophilic syndrome. Two patients presented with severe left ventricular dysfunction, and 1 patient presented with cardioembolic stroke. All patients were successfully treated with glucocorticoid therapy. Our cases highlight the importance of early diagnosis with endomyocardial biopsy and prompt immunosuppressive treatment. Résumé: L’infiltration par les éosinophiles est une cause rare et non reconnue de myocardite associée à une éosinophilie prolongée. Avant l’imagerie avancée et la biopsie systématique, le diagnostic de cardiomyopathie idiopathique était posé après l’autopsie des patients. Nous présentons 3 cas de myocardite à éosinophiles dont la biopsie cardiaque a permis de poser le diagnostic de syndrome d’hyperéosinophilie. Deux patients ont présenté une dysfonction grave du ventricule gauche, et 1 patient a présenté un accident vasculaire cérébral d’origine cardio-embolique. Le traitement par glucocorticoïdes s’est avéré réussi chez tous les patients. Nos cas montrent l’importance du diagnostic précoce par biopsie endomyocardique et du traitement immunosuppresseur hâtif.

Objectives This study sought to characterize the biatrial substrate in heart failure (HF) and persistent atrial fibrillation (PeAF). Background Atrial fibrillation (AF) and HF frequently coexist; however, the contribution of HF to the biatrial substrate in PeAF is unclear. Methods Consecutive patients with PeAF and normal left ventricular (NLV) systolic function (left ventricular ejection fraction [LVEF] >55%) or idiopathic cardiomyopathy (LVEF ≤45%) undergoing AF ablation were enrolled. In AF, pulmonary vein (PV) cycle length (PVCL) was recorded via a multipolar catheter in each PV and in the left atrial appendage for 100 consecutive cycles. After electrical cardioversion, biatrial electroanatomic mapping was performed. Complex electrograms, voltage, scarring, and conduction velocity were assessed. Results Forty patients, 20 patients with HF (mean age: 62 ± 8.9 years; AF duration: 15 ± 11 months; LVEF: 33 ± 8.4%) and 20 with NLV (mean age: 59 ± 6.7 years; AF duration: 14 ± 9.1 months; p = 0.69; mean LVEF: 61 ± 3.6%; p Conclusions HF is associated with significantly reduced biatrial tissue voltage, fractionation, and prolongation of PVCL. Advanced biatrial remodeling may have implications for invasive and noninvasive rhythm control strategies in patients with AF and HF.

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure due to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found. We report a case of a woman with PPCM who developed a critical cardiogenic shock with repeated cardiopulmonary resuscitation. We show for the first time that mechanical circulatory support combined with high-dose bromocriptine therapy to suppress systemic prolactin levels may serve as an effective therapeutic option in patients with fulminant PPCM and cardiogenic shock. Myocardial cathepsin D was overexpressed in our patient underscoring a potential role of cathepsin D-induced cleavage of prolactin in the pathophysiology of PPCM.

Aims Identification of metabolic signatures in heart failure (HF) patients and evaluation of their diagnostic potential to discriminate HF patients from healthy controls during baseline and exercise conditions. Methods Plasma samples were collected from 22 male HF patients with non-ischemic idiopathic cardiomyopathy and left ventricular systolic dysfunction and 19 healthy controls before (t0), at peak (t1) and 1 h after (t2) symptom-limited cardiopulmonary exercise testing. Two hundred fifty-two metabolites were quantified by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC)-MS/MS-based metabolite profiling. Results Plasma metabolite profiles clearly differed between HF patients and controls at t0 (P

Introduction Among patients who survive heart transplant, recurrent end-stage heart failure is a major cause of morbidity and mortality secondary to acute rejection, primary graft failure or coronary artery vasculopathy, and heart retransplantation (HRT) offers the potential for long-term survival. However, there is controversy about the appropriateness of retransplantation because of limited organ availability and outcomes that tend to be worse than in primary transplantation. Internationally, between 2 and 4% of the available donor hearts are distributed to retransplant patients.1 The aim of this study was to determine the mid-term survival after heart retransplantation. Methods After obtaining Institutional Review Board approval, the authors retrospectively studied all consecutive adult patients who underwent orthotopic heart transplantation between January 2009 and December 2018 at a tertiary care university hospital and followed them up until December 2019. Patients included in the analysis had undergone HRT and were 18 years or older. Recipient demographic data, hemodynamic profile and postoperative outcomes were analyzed. Results During the study period, 250 patients underwent orthotopic heart transplantation. Among these patients, 2% (n=5) underwent HRT. The end-stage heart failure diagnoses leading to first heart transplant in our study were hypertrophic cardiomyopathy (40%), idiopathic cardiomyopathy (40%) and myocarditis (20%); and the major indications for HRT were chronic rejection (60%) and cardiac allograft vasculopathy (40%). Grafts failed at a median follow-up of 9 (5) years after first heart transplantation. The majority of patients (80%) required combined simultaneous second cardiac and first renal transplantation. Heart-kidney combined transplantation were performed with organs coming from the same donor and with no-staged modality. Actuarial survival rate was 60%, after a median follow-up of 17.8 (39.6) months. Discussion Although HRT survival is still inferior to primary transplantation, it has improved over the decades and is a viable treatment option for patients with late failing allografts. Outcome after HRT strongly depends on the indication for retransplantation and the interval between first and second transplantation. Different studies suggest that a diagnosis of cardiac allograft vasculopathy or chronic rejection and an interval between first and second transplantation greater than 1 year have a significantly favorable impact on mortality.2 3 Judicious patient selection and careful perioperative care are of utmost importance considering limited allograft availability.

Background X-linked dilated cardiomyopathy (XLDCM) is a rare but rapidly progressive cardiomyopathy caused by dystrophin gene mutation. Mutations are more often associated with Duchenne and Becker Muscular Dystrophy, which are characterized by skeletal muscle weakness or limb girdle dystrophy. However, patients with isolated XLDCM have normal skeletal muscle but complete dystrophin loss in cardiac muscle resulting in isolated myocardial involvement without overt signs of skeletal myopathy. Case summary A previously well 16-year-old boy developed sudden onset dense left-sided weakness and facial droop. Computed tomography (CT) angiography and CT brain showed an occluded right internal carotid artery extending to the right middle cerebral artery. He underwent successful endovascular clot retrieval but developed frank pulmonary oedema and cardiogenic shock requiring inotropic support and intubation. Transthoracic echocardiography demonstrated severe left ventricular (LV) cardiomyopathy and an apical thrombus. Subsequent cardiac magnetic resonance (CMR) imaging confirmed the LV parameters and diffuse late gadolinium enhancement. Despite absence of skeletal manifestations, subsequent genetic testing revealed an X-linked dystrophin gene mutation [c.31+G>T (IVS1G>T)]. He was commenced on empirical heart failure therapy and underwent successful cardiac transplantation. Discussion X-linked dilated cardiomyopathy is a rare, rapidly progressing cardiomyopathy. Patients show normal skeletal muscle dystrophin but absent expression in cardiac muscle, resulting fibrosis, and atrophy. About 20% of affected young males have significantly reduced survival and thus the diagnosis must be considered in cases of idiopathic cardiomyopathy with CMR and genetic testing key to the diagnosis. Whilst evidence exists for empirical heart failure medications, cardiac transplantation remains the definitive treatment.

Aim: The aim of the study was to assess predictors of outcome in patients hospitalized for dilated cardiomyopathy (DCM) and severe left ventricular dysfunction. Patients & methods: 83 pediatric patients hospitalized for heart failure due to DCM with coexistent left ventricular dysfunction were enrolled.Results: Overall, 5-year survival free from heart transplantation was 69.8%. Normalization of left ventricular function was achieved in 39.8% of patients during follow-up: younger age, less necessity of inotropic support and other than idiopathic DCM predicted left ventricular function, while familial history for cardiac disease or sudden death and inotropic support during hospitalization were associated with poorer outcome. Conclusion: Almost 40% of patients with DCM experienced a complete normalization of cardiac function. Outcome was extremely variable according to the type of DCM.

In the third quarter of 2017, culprit only percutaneous coronary intervention (PCI) fares better in acute myocardial infarction with shock, guided de-escalation antiplatelet therapy seems noninferior, drug-eluting stent (DES) better in elderly patients undergoing PCI, DES with ultrathin struts proves superior, atrial fibrillation ablation improves left ventricular function in idiopathic cardiomyopathy, and edoxaban beneficial in preventing cancer-associated venous thromboembolism.

The individual amount of alcohol consumed acutely or chronically decides on harm or benefit to a person’s health. Available data suggest that one to two drinks in men and one drink in women will benefit the cardiovascular system over time, one drink being 17.6 ml 100 % alcohol. Moderate drinking can reduce the incidence and mortality of coronary artery disease, heart failure, diabetes, ischemic and hemorrhagic stroke. More than this amount can lead to alcoholic cardiomyopathy, which is defined as alcohol toxicity to the heart muscle itself by ethanol and its metabolites. Historical examples of interest are the Munich beer heart and the Tübingen wine heart. Associated with chronic alcohol abuse but having different etiologies are beriberi heart disease (vitamin B1 deficiency) and cardiac cirrhosis as hyperdynamic cardiomyopathies, arsenic poising in the Manchester beer epidemic, and cobalt intoxication in Quebec beer drinker’s disease. Chronic heavy alcohol abuse will also increase blood pressure and cause a downregulation of the immune system that could lead to increased susceptibility to infections, which in turn could add to the development of heart failure. Myocardial tissue analysis resembles idiopathic cardiomyopathy or chronic myocarditis. In the diagnostic work-up of alcoholic cardiomyopathy, the confirmation of alcohol abuse by carbohydrate deficient transferrin (CDT) and increased liver enzymes, and the involvement of the heart by markers of heart failure (e.g., NT-proBNP) and of necrosis (e.g., troponins or CKMb) is mandatory. Treatment of alcoholic cardiomyopathy consists of alcohol abstinence and heart failure medication.

An 18-year-old Hmong man sought medical care because of worsening performance on military training exercises. He had a previous syncopal episode with prompt recovery. His medical and developmental history were otherwise unremarkable. A chest radiograph revealed cardiomegaly and, after further cardiac tests, he was diagnosed with postinfectious or idiopathic cardiomyopathy. His cardiac function deteriorated and heart transplantation was pursued. During preoperative evaluation, his serum creatine kinase (CK) was noted to be persistently elevated in the 4,000s, prompting further investigation, but since he was not weak or otherwise symptomatic, definitive diagnosis and treatment were not pursued. When 19 years old, he underwent orthotropic heart transplantation. In the following years, he had multiple stents placed for coronary artery disease and developed type 1 diabetes mellitus, but he worked as an information specialist and cared for himself. The authors thank H. Brent Clark, MD, PhD, Department of Laboratory Medicine and Pathology, University of Minnesota, for his assistance preparing the figure.

In chronic heart failure, minute ventilation (V′E) for a given carbon dioxide production (V′CO2) might be abnormally high during exercise due to increased dead space ventilation, lung stiffness, chemo- and metaboreflex sensitivity, early metabolic acidosis and abnormal pulmonary haemodynamics. The V′Eversus V′CO2 relationship, analysed either as ratio or as slope, enables us to evaluate the causes and entity of the V′E/perfusion mismatch. Moreover, the V′E axis intercept, i.e. when V′CO2 is extrapolated to 0, embeds information on exercise-induced dead space changes, while the analysis of end-tidal and arterial CO2 pressures provides knowledge about reflex activities. The V′Eversus V′CO2 relationship has a relevant prognostic power either alone or, better, when included within prognostic scores. The V′Eversus V′CO2 slope is reported as an absolute number with a recognised cut-off prognostic value of 35, except for specific diseases such as hypertrophic cardiomyopathy and idiopathic cardiomyopathy, where a lower cut-off has been suggested. However, nowadays, it is more appropriate to report V′Eversus V′CO2 slope as percentage of the predicted value, due to age and gender interferences. Relevant attention is needed in V′Eversus V′CO2 analysis in the presence of heart failure comorbidities. Finally, V′Eversus V′CO2 abnormalities are relevant targets for treatment in heart failure.

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure (HF) secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of HF is found. The symptoms and signs of this rare disorder mimic those of the physiological changes of pregnancy or other cardiovascular diseases. Consequently, its diagnosis is frequently delayed, which worsens an already poor prognosis. Here, we report a young adult who was diagnosed with PPCM, early, with the help of focused cardiac ultrasonography, performed after presenting to the emergency department with nonspecific respiratory complaints, including dyspnea and hemoptysis, which suggested at first pulmonary embolism. Keywords: Acute heart failure, Echocardiography, Cardiomyopathy, Ultrasound

BACKGROUND: Dilated cardiomyopathy is a frequent disease responsible for 40-50% of cases of heart failure. Idiopathic cardiomyopathy is a primary disorder often related to familial/genetic predisposition. Before the diagnosis of idiopathic cardiomyopathy is made, clinicians must not only rule out viral and immune causes, but also toxic causes such as drugs, environmental agents, illicit substances and natural toxins. OBJECTIVE: The objective of this review is to present recent data on the mechanisms underlying toxic cardiomyopathy. METHODS: The US National Library of Medicine Pubmed database was searched from 1980 to December 2017 utilizing the combinations of the search terms "toxic cardiomyopathy", "drugs", "anticancer drugs", "azidothymidine", "rosiglitazone", "carbon monoxide", "alcohol", "illicit drugs", "cocaine", "metamfetamine", "metals", "venom". A total of 339 articles were screened and papers that dealt with the pathophysiology of toxic cardiomyopathy, either in animal models or in clinical practice were selected, with preference being given to more recently published papers, which left 92 articles. Anticancer drugs: The mechanisms of anthracycline-induced cardiotoxicity are primarily related to their mechanisms of action as anticancer drugs, mainly the inhibition of topoisomerase II β and DNA cleavage. Additional metabolic or oxidative stress factors may play a part, together with interference with iron metabolism. The more recent drugs, trastuzumab and imatinib, also influence stress pathways. Antiretroviral agents: Azidothymidine is cardiotoxic as a result of mitochondrial toxicity. In addition to energy depletion, azidothymidine also increases the production of mitochondrial reactive oxygen species (ROS). Antidiabetic drugs: The cardiotoxicity of thiazolidinedione antidiabetic drugs is still under investigation, though interference with mitochondrial respiration or oxidative stress is suspected. Cocaine: Among the multiple mechanisms involved in cocaine-related cardiotoxicity, excessive sympathetic stimulation with increased myocardial oxygen consumption is well documented in the acute form of left ventricular dysfunction. As for cocaine-related cardiomyopathy, the role of apoptosis and ROS is under investigation. Ethanol: The aetiology of ethanol-related cardiotoxicity is multifactorial, with individual susceptibility being important. It involves apoptosis, alterations of the excitation-contraction coupling in cardiac myocytes, structural and functional alterations of the mitochondria and sarcoplasmic reticulum, changes in cytosolic calcium flows, changes in calcium sensitivity of myofilaments, alterations of mitochondrial oxidation, deregulation of protein synthesis, decrease of contractile proteins and disproportion between the different types of myofibrils, changes in the regulation of myosin ATPase, up-regulation of the L-type calcium channels, increase of oxidative stress, and induction of ANP and p21 mRNA expression in ventricular myocardium. Metamfetamines: Catecholamine-mediated toxicity is the probable cause, with a possible role for genetic susceptibility. Carbon monoxide: In addition to hypoxic injury, carbon monoxide is also directly toxic to the mitochondria, with impairment of mitochondrial respiratory chain at the cytochrome c oxidase level, decrease of glutathione concentrations and of ATP production. There is no evidence for a delayed dilated cardiomyopathy in survivors of an acute exposure. Metals: Cobalt-related cardiomyopathy probably results from interference with energy production and contractile mechanisms, but additional factors (nutrition, hypothyroidism) are often required. Antimony may cause lethal oxidative stress and cell death mediated by elevation in intra-cellular calcium. Proposed mechanisms for mercury toxicity include glutathione depletion, production of ROS, and interruption in selenium-dependent endogenous enzymatic reactions. The existence of a lithium-induced cardiomyopathy is still debated. Scorpion venom: Catecholamine release is the probable cause of acute cardiomyopathy following scorpion envenomation. CONCLUSIONS: The mechanisms behind toxic cardiomyopathy are complex and multifactorial but include interference with myocardial cell bioenergetics and intracellular calcium handling, the generation of ROS, neurohormonal stress, and induction of apoptosis.

Apical hypertrophic cardiomyopathy (HCM) is a form of HCM that typically has a non-obstructive physiology and benign prognosis. It rarely occurs in transplanted hearts. 68-year-old female with past history of heart transplant in 2000 due to idiopathic cardiomyopathy, hypertension, and liver

Non-ischemic idiopathic dilated cardiomyopathy (DCM) patients with scar on Late Gadolinium Enhancement (LGE) cardiac MR (CMR) are at higher risk of developing VT or VF. However, many patients with no scar on LGE still experience VT/VF. CMR feature tracking (CMR-FT) allows quantification of mechanics

Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause for heart failure is identified. Outcome varies from full recovery to residual left ventricular systolic dysfunction and even death. Many women return to their physician to acquire information on their long- term prognosis, to seek medical advice regarding contraception, or when planning a subsequent pregnancy. This position paper summarizes current evidence for long-term outcome, risk stratification of further pregnancies and overall management. Based on the best available evidence, as well as the clinical experience of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy members, a consensus on pre- and postpartum management algorithms for women undergoing a subsequent pregnancy is presented.

Hypertrophic cardiomyopathy thickens heart muscles, reducing functionality and increasing risk of cardiac disease and morbidity. Genetic factors are involved, but their contribution is poorly understood. We used the hypertrophic heart rat (HHR), a unique normotensive polygenic model of cardiac hypertrophy and heart failure, to investigate the role of genes associated with monogenic human cardiomyopathy. We selected 42 genes involved in monogenic human cardiomyopathies to study: 1) DNA variants, by sequencing the whole genome of 13-wk-old HHR and age-matched normal heart rat (NHR), its genetic control strain; 2) mRNA expression, by targeted RNA-sequencing in left ventricles of HHR and NHR at 5 ages (2 days old and 4, 13, 33, and 50 wk old) compared with human idiopathic dilated cardiomyopathy data; and 3) microRNA expression, with rat microRNA microarrays in left ventricles of 2-day-old HHR and age-matched NHR. We also investigated experimentally validated microRNA-mRNA interactions. Whole-genome sequencing revealed unique variants mostly located in noncoding regions of HHR and NHR. We found 29 genes differentially expressed in at least 1 age. Genes encoding desmoglein 2 ( Dsg2) and transthyretin ( Ttr) were significantly differentially expressed at all ages in the HHR, but only Ttr was also differentially expressed in human idiopathic cardiomyopathy. Lastly, only two microRNAs differentially expressed in the HHR were present in our comparison of validated microRNA-mRNA interactions. These two microRNAs interact with five of the genes studied. Our study shows that genes involved in monogenic forms of human cardiomyopathies may also influence polygenic forms of the disease.

Learning objectives In 2010, the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy (PPCM) defined PPCM as ‘an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular (LV) systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found. It is a diagnosis of exclusion’1 (figure 1). It is important to appreciate that not all heart failure during pregnancy is due to PPCM. Other cardiovascular conditions can present during pregnancy; for example, pre-existing cardiomyopathies or previously undiagnosed congenital or valvular heart disease. Figure 1 European Society of Cardiology PPCM Working Group definition of peripartum cardiomyopathy. The incidence of PPCM varies between countries and between races within countries. In Africa, among predominantly black populations, the incidence is around 1 in 1000 live births.2 There are a few countries where PPCM appears to be much more common. For example, in Nigeria and Haiti, an incidence of 1 in 100 and 1 in 300 pregnancies respectively has been reported.3 4 In the USA, the incidence in predominantly white populations is between 1 in 1000 and 1 in 4000, but in African-American populations it is between 1 in 1000 and 1 in 2000.5–7 The incidence in Europe and Australasia is not well studied. The incidence does appear to be increasing—possibly due to increased awareness and diagnosis.8 It is striking that PPCM is often only recognised when patients are very sick with severe myocardial dysfunction. It seems likely that less severe forms of PPCM go undiagnosed, with symptoms being ascribed to the stresses around the arrival of a new child …

See Article by S. Lee et al Pregnancy-associated heart diseases substantially contribute to maternal morbidity and mortality. Among these, peripartum cardiomyopathy (PPCM), an idiopathic cardiomyopathy that causes heart failure with reduced left ventricular ejection fraction, represents one of the major life-threatening diseases in previously healthy women. The clinical course ranges from milder forms with slightly depressed left ventricular ejection fraction to severe forms with cardiogenic shock.1,2 Although greater awareness and understanding of PPCM have developed over recent years, major gaps remain about epidemiology, risk factors, pathophysiology, and targeted therapy. As such, the exact diagnosis of PPCM remains a fundamental challenge in both clinical practice and scientific analysis. In this issue of Circulation: Heart Failure, Lee et al3 present important data on the incidence and risk factors of PPCM in South Korea. The authors retrospectively analyzed a nationwide database that covers a total of 97% of the Korean population, hence expanding the knowledge of PPCM in Asian countries. The estimated incidence of PPCM in South Korea is 1:1741 (795 cases in 1 384 449 pregnancies; Figure). This compares well to the incidences reported in the United States and Germany but is markedly higher than those previously described in an analysis from Japan.4–6 The incidence of PPCM differs widely depending on the ethnic/racial and regional background of women. Interestingly, Africans and African Americans are at a higher risk for developing PPCM, with an estimated incidence of 1:100 in Nigeria and 1:299 in Haiti,1,3,7–9 whereas incidences in Caucasian populations range from 1:1000 in Germany to 1:10149 in Denmark.1,5,6,10 In a Japanese cohort, the incidence was as low as 1:20 00011; however, these results should be interpreted with caution because of methodological aspects, and …

Features of energy metabolism in children with cardiovascular diseases are of great practical importance. It is prognostically important to determine the status of the energy of cardiomyocytes to normalize bioenergetic deficit cardiomyocytes in rheumatoid arthritis, myocarditis, congenital heart diseases to decrease reduction in myocardial contractility and reduce precondition for the progression of heart failure. The experimental and clinical studies of the pathogenesis of idiopathic cardiomyopathy in children in recent years indicate directly the damage of oxidative phosphorylation in myocardial tissue due to decreased activity of the mitochondrial electron transport system. Numerous congenital diseases like syndrome Ivemark, Holt-Oram, Ellis-Van Creveld, Ivemark, Noonan, Greeg, Kugel-Stoloff, Werner, West, Adams-Stokes, MERRF include cardiomyopathy in their symptoms. Vibration-type model of hypoxic cell metabolism was suggested to estimate antihypoxant succinic acid as cardioprotective substance in in drug “Amber-antitoks” on rabbit cardiomyocytes. The experiment of bioenergy dependent reaction of native heart mitochondria was studied by polarographic method performed using a closed membrane Clarke’ electrode. Pharmacological drug “Amber-antitoks” in dose as 8.4 mg/kg prevents the formation of bioenergy dependent hypoxia of cardiomyocytes and restore the activity of NAD-dependent, and suppress hyperactivity suktsinat-degidrogenaze enzyme-substrate complex of the respiratory chain. It causes reduction of the severity of mitochondrial dysfunction and the degree of morphological myocardial tissue damage. The protective properties of drug “Amber-antitoks” allow to recommend it for using in the treatment in combination with other drugs of cardiovascular disease in children.