Primary Dilated Cardiomyopathy Research Articles

USE OF LIFE–VEST AND COMPLEX RE–IMPLANTATION OF CRT–D IN PATIENT WITH POCKET INFECTION BY MULTIRESISTENT S. AUREUS AND PERSISTENCE OF LEFT SUPERIOR VENA CAVA

Abstract Patient with primary hypokinetic dilated cardiomyopathy, previously underwent coronary angioplasty with stent implantation on MO branch and subsequent implantation of CRT–D in right subclavian region for persistence of left superior vena cava and complicated left sided implantation; hypertensive, dyslipidaemic, diabetic. Repeated subsequent surgery for shock channel malfunction with re–implantation of right ventricular lead. He came to our observation for infection of the CRT–D pocket by multiresistant Staphylococcus Aureus treated by intravenous antibiotic therapy and explantation of the infected device. We therefore proceeded to discharge the patient with Life–Vest as a bridging strategy until re–implantation and continued with long–acting antibiotic therapy administered every fortnight. After about 8 weeks, once the presence of infectious/inflammatory processes has been ruled out, CRT–D reimplantation is performed, after prophylaxis with Vancomycin, in the right subclavian region under sterile conditions and in the absence of complications. The management of cardiac device infections represents a challenge for the cardiologist especially in the complex patient with a history of re–interventions in which multi–resistant pathogens are often found. This clinical case demonstrates how collegial patient assessment and long–term protection strategies, such as the use of a Life–Vest, can achieve the diagnostic–therapeutic goal.

3-Tesla cardiac magnetic resonance imaging in primary dilated cardiomyopathy.

Cardiac magnetic resonance imaging (CMR) is an excellent non-invasive imaging tool in the assessment of patients with dilated cardiomyopathy (DCM). Few studies have analysed the findings in primary (idiopathic) DCM. To study the CMR features in primary DCM. We conducted a descriptive observational study on 20 adult patients with suspected or confirmed primary DCM. Each patient underwent a dedicated 3-Tesla CMR scan, and the findings were evaluated. Seventeen patients had systolic dysfunction with a reduced ejection fraction and elevated end-diastolic volume, 19 patients had contractile dysfunction in the form of global left ventricular hypokinesia, 13 patients showed no abnormal delayed contrast enhancement with gadolinium administration, and 7 patients showed abnormal late gadolinium enhancement patterns. In patients with primary DCM, CMR is a powerful diagnostic tool that can definitively establish the diagnosis, assess the severity of the disease, predict the risk of future adverse cardiovascular outcomes, check for complications, and assist in future follow-ups. What the study adds. Cardiac magnetic resonance imaging (CMR) is an excellent non-invasive imaging tool in the assessment of patients with primary dilated cardiomyopathy (DCM). Findings include global ventricular enlargement, systolic dysfunction (ejection fraction <40%), and elevated end-diastolic (≥140 mL) and end-systolic volumes. Global abnormal wall contractility is often seen. In DCM there is either no abnormal gadolinium enhancement or curvilinear mid-myocardial or subepicardial late gadolinium enhancement, unrelated to a coronary artery distribution.Implications of the findings. In patients with primary DCM, CMR provides powerful diagnostic and prognostic information. Enhanced awareness and understanding of this relatively uncommon condition among clinicians and radiologists would be of benefit in patient management and treatment.

DMD-Associated Dilated Cardiomyopathy: Genotypes, Phenotypes, and Phenocopies.

Variants in the DMD gene, that encodes the cytoskeletal protein, dystrophin, cause a severe form of dilated cardiomyopathy (DCM) associated with high rates of heart failure, heart transplantation, and ventricular arrhythmias. Improved early detection of individuals at risk is needed. Genetic testing of 40 male probands with a potential X-linked genetic cause of primary DCM was undertaken using multi-gene panel sequencing, multiplex polymerase chain reaction, and array comparative genomic hybridization. Variant location was assessed with respect to dystrophin isoform patterns and exon usage. Telomere length was evaluated as a marker of myocardial dysfunction in left ventricular tissue and blood. Four pathogenic/likely pathogenic DMD variants were found in 5 probands (5/40: 12.5%). Only one rare variant was identified by gene panel testing with 3 additional multi-exon deletion/duplications found following targeted assays for structural variants. All of the pathogenic/likely pathogenic DMD variants involved dystrophin exons that had percent spliced-in scores >90, indicating high levels of constitutive expression in the human adult heart. Fifteen DMD variant-negative probands (15/40: 37.5%) had variants in autosomal genes including TTN, BAG3, LMNA, and RBM20. Myocardial telomere length was reduced in patients with DCM irrespective of genotype. No differences in blood telomere length were observed between genotype-positive family members with/without DCM and controls. Primary genetic testing using multi-gene panels has a low yield and specific assays for structural variants are required if DMD-associated cardiomyopathy is suspected. Distinguishing X-linked causes of DCM from autosomal genes that show sex differences in clinical presentation is crucial for informed family management.

COVID-19 as a potential trigger for refractory arrhythmias and electrical storm in a patient with dilated cardiomyopathy: a case report

Arrhythmias occur both in the acute coronavirus disease 2019 (COVID-19) and in the post-acute period, which may be associated with the long-term SARS-CoV-2 persistence. In a case report, patient with primary dilated cardiomyopathy, an implanted cardioverter-defibrillator, recurrent ventricular arrhythmias, and an electrical storm are presented. The patient was repeatedly hospitalized in a city hospital, where electrical cardioversion, antiarrhythmic therapy, radiofrequency ablation of recurrent ventricular tachycardia regions, including emergency ("lifesaving") combined catheter radiofrequency destruction of the electrical storm substrate, was performed. Subsequently, against the background of ongoing postoperative therapy, massive pulmonary embolism (PE) suddenly developed, which led to the death. Autopsy established that the cause of the patient’s death was massive pulmonary embolism; SARS-CoV-2 and enterovirus was detected in the myocardium. Based on an autopsy study, the patient was diagnosed with primary dilated cardiomyopathy with secondary active chronic lymphocytic myocarditis.

Starting Pediatric VAD Program: Transforming Challenges into Opportunities; A Case Series of a Single Center

Background: The prevalence of heart failure is constantly increasing in both children and adults. End-stage heart failure in children unresponsive to medical therapy has limited treatment options. Surgical options include heart transplantation or implantation of durable ventricular assist devices (VADs). To start the VAD program, it was necessary to train core team members, invite experienced proctors and adjust the organizational approach. Methods: We present our first seven pediatric patients who underwent a VAD implantation with primary indication end-stage dilated cardiomyopathy. Results: The median age on implant was four and a half years and the median duration of VAD support was 39 days with long term survival achieved in three patients. The causes of death were multiorgan failure, thromboembolic events, sepsis, and low cardiac output syndrome. Ischemic stroke was the reason for successful neurointervention during VAD support in two patients. Conclusions: To establish a VAD program, numerous specialties must be included with adequate training and learning for all team members.

Clinical and genetic characteristics of children with primary dilated cardiomyopathy

To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.

GESTATIONAL HYPERTENSION AND PERIPARTUM CARDIOMYOPATHY: EPIDEMIOLOGICAL, CLINICAL AND EVOLUTIONARY PROFILE IN THE REFERENCE HOSPITALS OF YAOUNDE

Objective: peripartum objective (CMPP) is a primary dilated cardiomyopathy responsible for congestive heart failure that occurs during the last two months of pregnancy or during the first five months of postpartum. However, little is known about the data in Cameroon, justifying our descriptive study. Our main objective was therefore to describe the epidemiological, clinical and progressive symptoms of women with peripartum cardiomyopathy and the influence of gestational hypertension. Design and method: We conducted a prospective descriptive study over a six-month period. It was conducted in six referral hospitals in Yaoundé. The study population consisted of pregnant women with dyspnoea and women who had given birth with dyspnoea. All pregnant or postpartum women (from month 32 GA to month 5 postpartum) who had LVEF &lt;45% and/or FS &lt;30% with or without left ventricle dilatation were included. They were placed on treatment with a follow-up over 3 months, where they had a second cardiac ultrasound to highlight the evolutionary profile. Results: We recruited 10 patients from 26 women. The mean age was 25.9 years ± 4.9 years. The average parity was 1.6 ± 1.17 (extreme 0-3). Multiparas were the most represented. History of gestational hypertension was the main predisposing factor (50%); followed by multiparity (30%), twin pregnancy and advanced maternal age (20%). Heart failure was the clinical expression in 60% of cases. The echocardiographic regimen described hypokinetic dilated cardiomyopathy (mean LVEDD 61.2 ± 8.6 mm) with mean systolic function of 27.1 ± 10.6%. The main complications were acute pulmonary oedema (60%), thromboembolic events including pulmonary embolism (10%), ischemic stroke (10%) and death (10%). Treatment is mainly based on the use of diuretics, ACE inhibitors, beta-blockers, Aldactone (1/3 of patients) without forgetting anticoagulation performed with Rivaroxaban (n = 4) for some and aspirin (n = 6); and bromocriptine (initiated in 3 patients). Conclusions: MPPC is a serious disease because of its (significant morbidity and mortality rate) and its complications, both hemodynamic and thromboembolic.

PS-C30-13: GESTATIONAL HYPERTENSION AND PERIPARTUM CARDIOMYOPATHY: EPIDEMIOLOGICAL, CLINICAL AND EVOLUTIONARY PROFILE IN THE REFERENCE HOSPITALS OF YAOUNDE

Background: Peripartum cardiomyopathy (PPCM) is a primary dilated cardiomyopathy responsible for congestive heart failure that occurs in the last two months of pregnancy or during the first five months of postpartum. It is a rare pathology with unknown etiologies. Nevertheless, several etiopathogenic factors such as an history of gestational hypertension, black race, multiparity and poverty have been incriminated. However, the epidemiological and clinical data on peripartum cardiomyopathy are little known in Cameroon, thus justifying our descriptive study. Methodology: We carried out a prospective descriptive study over a period of six months. It was conducted in six reference hospitals in Yaounde. The study population was made of pregnant women with dyspnoea and women who had given birth with dyspnoea. Were included all pregnant or postpartum women (from the 32nd WA to the 5th months of postpartum) who had a LVEF &lt; 45% and/or a SF &lt; 30% associated or not with left ventricle dilation. They were placed on treatment with a follow-up over 3 months, where they had a second cardiac ultrasound to highlight the evolutionary profile. Results: We enrolled 10 patients from 26 women who were pregnant or had given birth and presented with dyspnoea within 6 months. The average age was 25.9 ± 4.9 years (range: 16–33 years). The average parity was 1.6 ± 1.17 (extreme 0–3). Multiparas were the most represented. The history of gestational hypertension was the main predisposing factor found (50%); followed by multiparity (30%), the notion of twin pregnancy and advanced maternal age (20%). Heart failure was the clinical expression in 60% of cases. Sinus tachycardia was constant; followed by signs of left ventricular hypertrophy and repolarization disorders on ECG assessment. The echocardiographic pattern depicted a hypokinetic dilated cardiomyopathy (mean LVEDD 61.2 ± 8.6 mm) with an average systolic function of 27.1 ± 10.6%. The main complications were acute pulmonary edema (60%), thromboembolic events including pulmonary embolism (10%), ischemic stroke (10%) and one death (10%). The treatment mostly based on the use of diuretics, ACE inhibitors, beta-blockers, Aldactone (1/3 of the patients) without forgetting the anticoagulation made with Rivaroxaban(n = 4) for some and aspirin (n = 6); and bromocriptine (initiated in 3 patients). Conclusion: PPCM is a cause of heart failure during pregnancy. It primarily arises during the postpartum period regardless of maternal age. It is a serious disease due to its (important morbi-mortality rate) and its complications, both hemodynamic and thromboembolic.\

Molecular Mechanisms of Mitochondrial Quality Control in Ischemic Cardiomyopathy.

Ischemic cardiomyopathy (ICM) is a special type of coronary heart disease or an advanced stage of the disease, which is related to the pathological mechanism of primary dilated cardiomyopathy. Ischemic cardiomyopathy mainly occurs in the long-term myocardial ischemia, resulting in diffuse myocardial fibrosis. This in turn affects the cardiac ejection function, resulting in a significant impact on myocardial systolic and diastolic function, resulting in a decrease in the cardiac ejection fraction. The pathogenesis of ICM is closely related to coronary heart disease. Mainly due to coronary atherosclerosis caused by coronary stenosis or vascular occlusion, causing vascular inflammatory lesions and thrombosis. As the disease progresses, it leads to long-term myocardial ischemia and eventually ICM. The pathological mechanism is mainly related to the mechanisms of inflammation, myocardial hypertrophy, fibrosis and vascular remodeling. Mitochondria are organelles with a double-membrane structure, so the composition of the mitochondrial outer compartment is basically similar to that of the cytoplasm. When ischemia-reperfusion induces a large influx of calcium into the cell, the concentration of calcium ions in the mitochondrial outer compartment also increases. The subsequent opening of the membrane permeability transition pore in the inner mitochondrial membrane and the resulting calcium overload induces the homeostasis of cardiomyocytes and activates the mitochondrial pathway of apoptosis. Mitochondrial Quality Control (MQC), as an important mechanism for regulating mitochondrial function in cardiomyocytes, affects the morphological structure/function and lifespan of mitochondria. In this review, we discuss the role of MQC (including mitophagy, mitochondrial dynamics, and mitochondrial biosynthesis) in the pathogenesis of ICM and provide important evidence for targeting MQC for ICM.

Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls

Dilated cardiomyopathy (DCM), caused by genetic and environmental factors, usually progresses to heart failure, a major cause of death in elderly people. A diet-associated form of DCM was recently identified in pet dogs eating non-traditional (NT) diets. To identify potential dietary causes, we analyzed metabolomic signatures and gene set/pathway enrichment in (1) all dogs based on disease, diet, and their interactions and (2) dogs with DCM based on diet. Metabolomic analysis was performed in 38 dogs with DCM eating NT diets (DCM-NT), 8 dogs with DCM eating traditional diets, 12 healthy controls eating NT diets, and 17 healthy controls eating traditional diets. Overall, 153 and 63 metabolites differed significantly between dogs with DCM versus healthy controls and dogs eating NT versus traditional diets, respectively, with 12 metabolites overlapping both analyses. Protein–protein interaction networks and gene set enrichment analysis identified 105 significant pathways and gene sets including aging-related pathways (e.g., nuclear factor-kappa B, oxidative damage, inflammation). Seventeen metabolites differed significantly in dogs with DCM eating NT versus traditional diets (e.g., fatty acids, amino acids, legume biomarkers), suggesting different mechanisms for primary versus diet-associated DCM. Our multifaceted metabolomic assessment of DCM in dogs highlighted diet’s role in some forms of DCM.

Clinical Profile and Risk Factors for Cardiac Death in Pediatric Patients With Primary Dilated Cardiomyopathy at a Tertiary Medical Center in China.

AimWe sought to identify the clinical characteristics and risk factors for cardiac mortality in pediatric patients with primary dilated cardiomyopathy (DCM) in China.MethodsA total of 138 pediatric patients who were consecutively diagnosed with primary DCM from January 2011 to December 2020 were included. We assessed patients’ clinical symptoms and performed laboratory examinations, electrocardiography, and echocardiography.ResultsOf these patients, 79 (57%) had severe systolic dysfunction (left ventricular ejection fraction of < 30%), 79 (57.2%) developed DCM before 12 months of age, 62 (45%) were male, 121 (87.7%) presented with advanced heart failure (cardiac functional class III/IV), and 54 (39.1%) presented with arrhythmia. At a median follow-up of 12 months, the overall cardiac mortality rate was 33%, and 40 of 46 deaths occurred within 6 months following DCM diagnosis. A multivariate Cox regression analysis identified several independent cardiac death predictors, including an age of 12 months to 5 years [hazard ratio (HR) 2.799; 95% confidence interval (CI) 1.160–6.758; P = 0.022] or 10–15 years (HR 3.617; 95% CI 1.336–9.788; P = 0.011) at diagnosis, an elevated serum alanine aminotransferase (ALT) concentration (≥ 51.5 U/L) (HR 2.219; 95% CI 1.06–4.574; P = 0.031), and use of mechanical ventilation (HR 4.223; 95% CI 1.763–10.114; P = 0.001).ConclusionThe mortality rate of primary DCM without transplantation is high. Age, an elevated serum ALT concentration, and the need for mechanical ventilation predict mortality in patients with primary DCM, providing new insights into DCM risk stratification.

Evaluation of Left Diastolic Function in Dilated Cardiomyopathy According to the 2016 ASE/EACVI Recommendations.

ObjectivesTo assess left ventricular diastolic function by using echocardiography in patients with dilated cardiomyopathy, and the relationship between left ventricular diastolic function and left ventricular dilatation, New York Heart Association (NYHA) heart failure index, left ventricular ejection fraction, and left ventricular fractional shortening.MethodsA descriptive cross-sectional study was conducted on patients with primary dilated cardiomyopathy hospitalized in Hue Central Hospital from April 2018 to August 2020.ResultsThe mean end-diastolic left ventricular volume was 133.57±31.58 mL and the mean end-systolic left ventricular volume was 99.9±26.03 mL. The mean left atrial volume was 61.63±27.13 mL. The mean end-diastolic and end-systolic left ventricular diameters were 66.11±7.3 mm and 57.7±8.02 mm, respectively. The mean left ventricular ejection fraction was 24.68±5.97%. The mean left ventricular fractional shortening was 12.91±4.55%. The highest rate was grade II diastolic dysfunction (44.6%), followed by grade III diastolic dysfunction (35.8%) and grade I diastolic dysfunction at 19.6%. There was a moderate positive correlation between the left ventricular diastolic dysfunction and the NYHA class of heart failure with r=0.445, p<0.001. All dilated cardiomyopathy patients in the study group had mainly grade II–III severe diastolic dysfunction.ConclusionsRoutine evaluation of diastolic function in patients with heart failure can help in elucidation of pathogenesis and management of patients. This dysfunction was clearly demonstrated by the change in the parameters of the evaluation of left ventricular diastolic function on echocardiography according to the 2016 ASE/EACVI recommendations, a new recommendation introduced to approach the assessment of diastolic function in a more convenient and easier way.

PACAP-38 and PAC1 Receptor Alterations in Plasma and Cardiac Tissue Samples of Heart Failure Patients.

Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) is a multifunctional neuropeptide, which may play a role in cardioprotection. However, little is known about the presence of PACAP-38 in heart failure (HF) patients. The aim of our study was to measure the alterations of PACAP-38 like immunoreactivity (LI) in acute (n = 13) and chronic HF (n = 33) and to examine potential correlations between PACAP-38 and HF predictors (cytokines, NT-proBNP). Tissue PACAP-38 LI and PAC1 receptor levels were also investigated in heart tissue samples of patients with HF. Significantly higher plasma PACAP-38 LI was detected in patients with acute HF, while in chronic HF patients, a lower level of immunoreactivity was observed compared to healthy controls (n = 13). Strong negative correlation was identified between plasma PACAP-38 and NT-proBNP levels in chronic HF, as opposed to the positive connection seen in the acute HF group. Plasma IL-1 β, IL-2 and IL-4 levels were significantly lower in chronic HF, and IL-10 was significantly higher in patients with acute HF. PACAP-38 levels of myocardial tissues were lower in all end-stage HF patients and lower PAC1 receptor levels were detected in the primary dilated cardiomyopathy group compared to the controls. We conclude that PACAP-38 and PAC1 expression correlates with some biomarkers of acute and chronic HF; therefore, further studies are necessary to explore whether PACAP could be a suitable prognostic biomarker in HF patients.

Midwall Fibrosis and Cardiac Mechanics: Rigid Body Rotation Is a Novel Marker of Disease Severity in Pediatric Primary Dilated Cardiomyopathy

BackgroundMidwall fibrosis (MWF) detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) predicts adverse outcome in adults with dilated cardiomyopathy (DCM). Its relevance in children and adolescents is relatively unknown. Left ventricular (LV) strain, rotation and twist are important parameters of cardiac function; yet, their role in pediatric heart failure is understudied. This study aimed to evaluate MWF and cardiac mechanics in pediatric DCM.MethodsPatients ≤21 years with primary DCM were prospectively enrolled and underwent standardized CMR including LGE. All participants were categorized according to the presence or absence of MWF (MWF+ vs. MWF–). Cardiac mechanics were assessed using CMR feature tracking. Impaired LV twist with apex and base rotating in the same direction was termed rigid body rotation (RBR).ResultsIn total, 17 patients (median age 11.2 years) were included. MWF was present in seven patients (41%). Median N-terminal pro brain natriuretic peptide (NT-proBNP) was higher (5,959 vs. 242 pg/ml, p = 0.887) and LV ejection fraction (LVEF) lower (28 vs. 39%, p = 0.536) in MWF+ vs. MWF– patients, yet differences were not statistically significant. MWF+ patients had reduced global longitudinal (GLS), circumferential (GCS) and radial strain (GRS), again without statistical significance (p = 0.713, 0.492 and 1.000, respectively). A relationship between MWF and adverse outcome was not seen (p = 0.637). RBR was more common in MWF+ (67 vs. 50%), and was associated with the occurrence of adverse events (p = 0.041). Patients with RBR more frequently were in higher New York Heart Association classes (p = 0.035), had elevated NT-proBNP levels (p = 0.002) and higher need for catecholamines (p = 0.001). RBR was related to reduced GLS (p = 0.008), GCS (p = 0.031), GRS (p = 0.012), LV twist (p = 0.008), peak apical rotation (p < 0.001), and LVEF (p = 0.001), elevated LV end-diastolic volume (p = 0.023) and LV end-systolic volume (p = 0.003), and lower right ventricular stroke volume (p = 0.023).ConclusionsMWF was common, but failed to predict heart failure. RBR was associated with clinical and biventricular functional signs of heart failure as well as the occurrence of adverse events. Our findings suggest that RBR may predict outcomes and may serve as a novel marker of disease severity in pediatric DCM.Clinical Trial Registration: https://clinicaltrials.gov/, identifier: NCT03572569.

Shared Genetic Etiology of Primary Dilated Cardiomyopathy and Ischemic Dilated Cardiomyopathy.

Background: Mutations in genes encoding sarcomere and cytoskeletal proteins are major causes of primary dilated cardiomyopathy (DCM). Likewise, ischemic myocardial injury is a major cause of secondary cardiac remodeling, which, in a subset, is severe and resembles DCM. The latter is referred to as ischemic dilated cardiomyopathy (IDCM). We postulated the presence of pathogenic and likely pathogenic variants (PVs and LPVs, respectively) in genes known to cause primary DCM might predispose the heart to severe cardiac dilatation and dysfunction post myocardial ischemic injury, i.e., IDCM. Methods: We performed whole-exome sequencing in 1,041 patients with primary DCM, 215 patients with IDCM, and 414 healthy controls. Indices of cardiac size and function were similar between those with primary and ischemic DCM. PVs and LPVs, including the truncating variants in 36 genes known to cause primary DCM were identified and compared among the three groups. Results: Pathogenic variants and LPVs were detected in 266 individuals, comprised of 215/1,041 (20.7%) patients with DCM, 27/215 (12.6%) patients with IDCM, and 24/414 (5.8%) control individuals. PVs and LPVs in the TTN gene were the most common and detected in 130/1,041 (12.5%) of patients with DCM, 15/215 (7.0%) of cases with IDCM, and 10/414 (2.4%) control individuals. Of 135 TTNtv, 118 involved exons that were >90% spliced in. These variants were found in 120/1,041 (11.5%) of DCM patients, 6/215 (2.8%) of IDCM cases, and only in 1/414 (0.2%) of the control population (p < 0.001 among the three groups). Conclusions: Pathogenic variants and LPVs in genes known to cause primary DCM are enriched in patients with IDCM, suggesting that such variants function as susceptibility alleles for cardiac dilatation and dysfunction in post myocardial ischemic injury. Thus, IDCM shares a partial genetic etiology with the primary DCM.

Long-Term Outcomes and Prognosticators of Pediatric Primary Dilated Cardiomyopathy in an Asian Cohort.

Background: Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy. The epidemiological profiles and prognosticators of clinical outcomes in Asian populations are not well elucidated.Methods: Data of 104 children aged <18 years with a diagnosis of primary DCM from January 1990 to December 2019 in our institutional database were retrospectively investigated. Relevant demographic, echocardiographic, and clinical variables were recorded for analysis. A P <0.05 was considered statistically significant.Results: The median age at diagnosis was 1.4 years (interquartile range = 0.3–9.1 years), and 52.9% were males. During a median follow-up duration of 4.8 years, 48 patients (46.2%) were placed on the transplantation waitlist, and 52.1% of them eventually received heart transplants. An exceptionally high overall waitlist mortality rate was noted (27.1%), which was even higher (43.5%) if the diagnostic age was <3 years. The 1-, 5-, and 10-year transplant-free were 61.1, 48.0, and 42.8%. Age at diagnosis >3 years and severe mitral regurgitation at initial diagnosis were independent risk factors for death or transplantation (hazard ratios = 2.93 and 3.31, respectively; for both, P <0.001). In total, 11 patients (10.6%) experienced ventricular function recovery after a median follow-up of 2.5 (interquartile range = 1.65–5) years. Younger age at diagnosis was associated a higher probability of ventricular function recovery.Conclusions: Despite donor shortage for heart transplantation and subsequently high waitlist mortality, our data from an Asian cohort indicated that transplant-free long-term survival was comparable with that noted in reports from Western populations. Although younger patients had exceptionally higher waitlist mortality, lower diagnostic age was associated with better long-term survival and higher likelihood of ventricular function recovery.

Molecular analysis of dilated and left ventricular noncompaction cardiomyopathies in Egyptian children.

Paediatric cardiomyopathy is a progressive, often lethal disorder and the most common cause of heart failure in children. Despite its severe outcomes, the genetic aetiology is still poorly characterised. High-throughput sequencing offers a great opportunity for a better understanding of the genetic causes of cardiomyopathy. The current study aimed to elucidate the genetic background of cardiomyopathy in Egyptian children. This hospital-based study involved 68 patients; 58 idiopathic primary dilated cardiomyopathy and 10 left ventricular noncompaction cardiomyopathy. Cardiomyopathy-associated genes were investigated using targeted next-generation sequencing. Consanguinity was positive in 53 and 70% of dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy patients, respectively. Positive family history of cardiomyopathy was present in 28% of dilated cardiomyopathy and 10% of the left ventricular noncompaction cardiomyopathy patients. In 25 patients, 29 rare variants were detected; 2 likely pathogenic variants in TNNI3 and TTN and 27 variants of uncertain significance explaining 2.9% of patients. The low genetic detection rate suggests that novel genes or variants might underlie paediatric cardiomyopathy in Egypt, especially with the high burden of consanguinity. Being the first national and regional report, our study could be a reference for future genetic testing in Egyptian cardiomyopathy children. Genome-wide tests (whole exome/genome sequencing) might be more suitable than the targeted sequencing to investigate the primary cardiomyopathy patients. Molecular characterisation of cardiomyopathies in different ethnicities will allow for global comparative studies that could result in understanding the pathophysiology and heterogeneity of cardiomyopathies.

Diet associated canine dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a common cause of heart failure in the dog. Primary DCM is often a disease of exclusion, but inherited genetic breed dispositions have been reported. Secondary causes of DCM include toxins, nutritional deficiency, systemic and infectious disease. The number of dogs diagnosed with DCM has increased significantly in the last 20 years, and has been linked to the rise in popularity of boutique, exotic and grain-free, legume-rich diets. Veterinary cardiologists raised concerns as DCM was being reported in atypical breeds. Subsequently, the United States Food and Drug Agency released a statement in 2018 warning pet owners of the risks of grain-free and novel protein diets. It is assumed that the problem also occurs in the UK because these diets are popular here also. Contrary to primary causes of DCM, dogs have improved clinically and on echocardiograph when their diet has been changed and/or supplemented. No clear cause has yet been identified between these diets and DCM, but the potential reasons seem to be multifactorial and limited by a lack of understanding of the bioavailability, digestibility and metabolism of the novel proteins and legume-rich diets.

Diffuse myocardial fibrosis by T1 mapping is associated with heart failure in pediatric primary dilated cardiomyopathy

BackgroundIn adult cardiomyopathy (CM), diffuse myocardial fibrosis is associated with adverse clinical outcome. However, its relevance in pediatric patients remains relatively unknown. The study aimed to evaluate myocardial extracellular volume (ECV) reflecting diffuse myocardial fibrosis with cardiovascular magnetic resonance (CMR) T1 mapping, and to analyze correlations with clinical and functional data in children and adolescents with different CM phenotypes. MethodsPatients with primary dilated (DCM), hypertrophic (HCM) or left ventricular non-compaction CM (LVNC) were prospectively enrolled and compared with healthy controls. Study participants underwent standardized CMR with modified Look-Locker Inversion recovery (MOLLI) T1 mapping. ResultsIn total, 33 patients (median age 12.0 years; DCM: n = 10, HCM: n = 13; LVNC: n = 10) and 7 controls (14.5 years) were included.DCM: ECV was higher than in controls (38.1 ± 7.5% vs. 27.2 ± 3.6%; p = 0.014). Patients with elevated ECV were younger than those with normal values (p = 0.044). ECV correlated with N-terminal pro brain natriuretic peptide (r = 0.66, p = 0.038), left ventricular ejection fraction (r = −0.63, p = 0.053), and stroke volume of left (r = −0.75, p = 0.013) and right ventricle (r = −0.67, p = 0.033). During a median follow-up of 25.3 months, 3 patients underwent heart transplantation (HTx), and 2 were listed for HTx. All 5 patients had elevated ECV.HCM/LVNC: ECV was within normal range in HCM (25.5 ± 4.5%) and LVNC (29.6 ± 4.2), and was not related with clinical and/or functional parameters. ConclusionsOur results indicate an increased burden of diffuse myocardial fibrosis in relation with younger age in pediatric DCM. ECV was associated with clinical and biventricular functional markers of heart failure in DCM.

A combinatorial oligogenic basis for the phenotypic plasticity between late-onset dilated and arrhythmogenic cardiomyopathy in a single family.

Introduction:Primary dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) are the two common and distinct forms of hereditary cardiomyopathies caused by defined pathogenic variants (PVs) typically in different sets of genes. DCM is characterized by left ventricular dilatation, dysfunction, and failure, whereas ARVC classically involves the right ventricle and is characterized by fibrofatty infiltration of the myocardium. DCM is caused primarily by the PVs in genes encoding sarcomere and cytoskeletal protein, while ARVC is mainly a disease of the desmosome proteins. DCM and ARVC exhibit partial phenotypic and genetic overlaps.Aim:To analyze the genetic basis of the phenotypic heterogeneity of cardiomyopathy in members of a single family.Methods and Results:We recruited, clinically characterized, and performed whole-exome sequencing in five affected, three probably affected, and two clinically unaffected members of a single family. The family members mainly exhibited late-onset DCM associated with conduction defects and arrhythmias. One family member who died suddenly was diagnosed with the classic ARVC at autopsy and another presented with isolated ventricular tachycardia. A novel splicing (truncating) and a rare missense variant in the TTN gene, likely in cis, co-segregated with the phenotype in all affected and probably affected family members and were likely the causal variants. Several PVs and LPVs in other genes involved in cardiomyopathies and arrhythmias were also identified that seem to modify the expression of the phenotype. Notably, LPVs in the DSP and PKP2 genes, which are known genes for ARVC, were identified in the family member who also carried the TTN variants but developed the classic ARVC.Conclusion:The findings indicate the causal role of the TTN variants, exhibiting an age-dependent penetrance in late-onset DCM, and highlight the potential modifying role of the concomitant LPVs in additional genes on the expression of the phenotype, including a phenotypic switch from the anticipated DCM to ARVC. The findings support an oligogenic basis of the cardiac phenotype in hereditary cardiomyopathies. A comprehensive genetic analysis involving all PVs and LPVs along with detailed phenotypic characterization is necessary to gain insights into the molecular pathogenesis of hereditary cardiomyopathies.