Dilated cardiomyopathy due to novel LMNA mutation: a case report.

A case of a 44-year-old man presenting with a family history of LMNA mutation and cardiac symptoms (dizziness, weakness, palpitations, and shortness of breath) congruent with dilated cardiomyopathy. Genetic testing revealed a novel likely pathogenic mutation of the LMNA gene (c.513G>A, exon 2) not previously associated with dilated cardiomyopathy, and the patient underwent guideline direct treatment for dilated cardiomyopathy. In patients with LMNA mutations, VTA risk should be calculated to determine the need for prophylactic ICD placement.

A statistical model to identify hereditary and epigenetic fusion genes associated with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a heart condition that causes enlarged and weakened left ventricles and affects the heart's ability to pump blood effectively. Most genetic etiology still needs to be understood. Previously, we have used the known germline hereditary fusion genes (HFGs) to identify HFGs associated with multiple myeloma and leukemia. In this study, we have developed a statistical model to study fusion transcripts discovered from the left ventricles of 122 DCM patients and 252 GTEx (Genotype Tissue Expression) healthy controls to discover novel HFGs, ranging from 4% to 87.7%, and EFGs, ranging from 4% to 99.2%, associated with DCM. This discovery of numerous novel HFGs and EFGs associated with DCM provides first-hand evidence that DCM results from interactive developmental consequences between germline genetic and environmental abnormalities and paves the way for future research and diagnostic and therapeutic applications, instilling hope for the future of DCM treatment.

The emerging role of clonal haematopoiesis in the pathogenesis of dilated cardiomyopathy.

The increased sensitivity of novel DNA sequencing techniques has made it possible to identify somatic mutations in small circulating clones of haematopoietic stem cells. When the mutation affects a 'driver' gene, the mutant clone gains a competitive advantage and has the potential to expand over time, a phenomenon referred to as clonal haematopoiesis (CH), which is emerging as a new risk factor for various non-haematological conditions, most notably cardiovascular disease (e.g. heart failure). Dilated cardiomyopathy (DCM) is a form of non-ischaemic heart failure that is characterized by a heterogeneous aetiology. The first evidence is arising that CH plays an important role in the disease course in patients with DCM, and a strong association of CH with multiple aetiologies of DCM has been described (e.g. inflammation, chemotherapy, and atrial fibrillation). The myocardial inflammation induced by CH may be an important trigger for DCM development for an already susceptible heart, e.g. in the presence of genetic variants, environmental triggers, and comorbidities. Studies investigating the role of CH in the pathogenesis of DCM are expected to increase rapidly. To move the field forward, it will be important to report the methodology and results in a standardized manner, so results can be combined and compared. The accurate measurement of CH in patients with DCM can provide guidance of specific (anti-inflammatory) therapies, as mutations in the CH driver genes prime the inflammasome pathway.

Validation of Left Ventricular High Frame Rate Echo-Particle Image Velocimetry against 4D Flow MRI in Patients.

OBJECTIVE: Accurately measuring intracardiac flow patterns could provide insights into cardiac disease pathophysiology, potentially enhancing diagnostic and prognostic capabilities. This study aims to validate Echo-Particle Image Velocimetry (echoPIV) for in vivo left ventricular intracardiac flow imaging against 4D flow MRI. METHODS: We acquired high frame rate contrast-enhanced ultrasound images from three standard apical views of 26 patients who required cardiac MRI. 4D flow MRI was obtained for each patient. Only echo image planes with sufficient quality and alignment with MRI were included for validation. Regional velocity, kinetic energy (KE) and viscous energy loss (EL˙) were compared between modalities using normalized mean absolute error (NMAE), cosine similarity and Bland-Altman analysis. RESULTS: Among 24 included apical view acquisitions, we observed good correspondence between echoPIV and MRI regarding spatial flow patterns and vortex traces. The velocity profile at base-level (mitral valve) cross-section had cosine similarity of 0.92 ± 0.06 and NMAE of (14 ± 5)%. Peak spatial mean velocity differed by (3 ± 6) cm/s in systole and (6 ± 10) cm/s in diastole. The KE and rate of EL˙ also revealed a high level of cosine similarity (0.89 ± 0.09 and 0.91 ± 0.06) with NMAE of (23 ± 7)% and (52 ± 16)%. CONCLUSION: Given good B-mode image quality, echoPIV provides a reliable estimation of left ventricular flow, exhibiting spatial-temporal velocity distributions comparable to 4D flow MRI. Both modalities present respective strengths and limitations: echoPIV captured inter-beat variability and had higher temporal resolution, while MRI was more robust to patient BMI and anatomy.

The emerging role of cardiopulmonary exercise testing and cardiac rehabilitation in dilated cardiomyopathy: A mini review.

Cardiovascular mortality is a major health burden worldwide and the number of patients with cardiac diseases is increasing. Dilated cardiomyopathy (DCM) is the most frequent cause for patient visits in cardiac care units and emergency departments. It is commonly misdiagnosed as ischaemic cardiac disease. Middle- and low-income countries rely on pharmacological management as the only treatment option. Most of the patients cannot afford heart transplants or advanced treatment strategies. Most health professionals also do not prescribe cardiac rehabilitation for DCM patients in their routine clinical practice. There is evidence that supervised cardiac rehabilitation is safe and beneficial for DCM patients. In addition to medications, cardiopulmonary exercise testing (CPET) and supervised cardiac rehabilitation, can provide more benefits to the affected population of cardiomyopathies. CPET and cardiac rehabilitation are still novel concepts in countries like Pakistan. The present review aims to provide clinicians with an overview of an evidence-based and innovative perspective. This perspective emphasizes the utilization of the additional benefits of cardiac rehabilitation in the holistic management of DCM patients and the prevention of chronic heart failure.

Cardiomyopathy characterizing and heart failure risk predicting by echocardiography and pathoanatomy in aged male mice.

Correlation between echocardiographic and pathoanatomic variables and their prognostic value in murine cardiomyopathy models remain unknown. Using echocardiography, morphometrics, and survival monitoring, we characterized transgenic (TG) mice with dilated cardiomyopathy due to cardiac overexpression of ß2-adrenoceptors focusing on predicting heart failure (HF) risk and HF mortality. In 12-month-old non-TG and TG mice, echocardiography was performed to determine left ventricular (LV) dimensions (d), wall thickness (h), and fractional shortening (FS). Animals were monitored for 3 months for survival. Organ weights and pathological events indicating left HF were determined. TG mice (n = 76) had reduced FS and enlarged LV, and 79% died of HF or likely arrhythmias during the follow-up period while all non-TG mice (n = 26) survived. These mice with left HF also had pulmonary congestion and hypertrophy/dilatation of the right ventricle (RV). Weights of lungs, RV, and atria were intercorrelated (r = 0.79-0.83) and also negatively correlated with FS × (h/d) index (r = -0.502 to -0.609). By FS × (h/d) tertiles, TG mice of low tertiles were identified with the highest mortality (96%) largely due to HF (76%). In conclusion, in aged cardiomyopathy mice a good correlation existed between echocardiographic and pathoanatomic variables. Echocardiography-derived LV function and remodeling were useful in identifying a subgroup of TG mice with a high risk of HF and HF fatality.

Unraveling the nexus of nesprin in dilated cardiomyopathy: From molecular insights to therapeutic prospects.

Dilated cardiomyopathy is a complex and debilitating heart disorder characterized by the enlargement and weakening of the cardiac chambers, leading to impaired contractility and heart failure. Nesprins, a family of nuclear envelope spectrin repeat proteins that include isoforms Nesprin-1/-2, are integral components of the LInker of Nucleoskeleton and Cytoskeleton complex. They facilitate the connection between the nuclear envelope and the cytoskeleton, crucial for maintaining nuclear architecture, migration and positioning, and mechanical transduction and signaling. Nesprin-1/-2 are abundantly expressed in cardiac and skeletal muscles.They have emerged as key players in the pathogenesis of dilated cardiomyopathy. Mutations in synaptic nuclear envelope-1/-2 genes encoding Nesprin-1/-2 are associated with dilated cardiomyopathy, underscoring their significance in cardiac health. This review highlights the all known cases of Nesprin-1/-2 related dilated cardiomyopathy, focusing on their interactions with the nuclear envelope, their role in mechanical transduction, and their influence on gene expression. Moreover, it delves into the underlying mechanisms through which Nesprin dysfunction disrupts nuclear-cytoskeletal coupling, leading to abnormal nuclear morphology, impaired mechanotransduction, and altered gene regulation. The exploration of Nesprin's impact on dilated cardiomyopathy offers a promising avenue for therapeutic interventions aimed at ameliorating the disease. This review provides a comprehensive overview of recent advancements in understanding the pivotal role of Nesprins in dilated cardiomyopathy research.

Progressive cardiomyopathy with intercalated disc disorganization in a rat model of Becker dystrophy.

Becker muscular dystrophy (BMD) is an X-linked disorder due to in-frame mutations in the DMD gene, leading to a less abundant and truncated dystrophin. BMD is less common and severe than Duchenne muscular dystrophy (DMD) as well as less investigated. To accelerate the search for innovative treatments, we developed a rat model of BMD by deleting the exons 45-47 of the Dmd gene. Here, we report a functional and histopathological evaluation of these rats during their first year of life, compared to DMD and control littermates. BMD rats exhibit moderate damage to locomotor and diaphragmatic muscles but suffer from a progressive cardiomyopathy. Single nuclei RNA-seq analysis of cardiac samples revealed shared transcriptomic abnormalities in BMD and DMD rats and highlighted an altered end-addressing of TMEM65 and Connexin-43 at the intercalated disc, along with electrocardiographic abnormalities. Our study documents the natural history of a translational preclinical model of BMD and reports a cellular mechanism for the cardiac dysfunction in BMD and DMD offering opportunities to further investigate the organization role of dystrophin in intercellular communication.

Multicentre, randomized, double-blind, prospective study on the effects of ImmunoAdSorptiOn on cardiac function in patients with Dilated CardioMyopathy (IASO-DCM): Rationale and design.

AIMS: Pilot studies indicate that immunoadsorption with subsequent IgG substitution (IA/IgG) induces beneficial effects in patients with dilated cardiomyopathy (DCM) and heart failure. This placebo-controlled study investigates whether IA/IgG treatment enhances left ventricular (LV) systolic function as compared to a control group receiving pseudo-treatment. METHODS: This multicentre, randomized, double-blind, parallel-group trial aims to include 200 patients with heart failure due to DCM (LV ejection fraction [LVEF] <40%) on optimized guideline-directed heart failure medication. Participants are randomly assigned in a 1:1 ratio to IA/IgG using protein-A columns, or to pseudo-immunoadsorption followed by an intravenous infusion without IgG. Follow-up visits take place by telephone after 1 and 3 months and at the study centres after 6, 12 and 24 months. The primary efficacy endpoint is the change in LVEF from baseline to 6 months determined by contrast echocardiography, analysed at a core lab. In addition, LV end-diastolic and end-systolic volumes will be analysed as secondary endpoints over the entire study period to assess whether IA/IgG affects LV remodelling. As main secondary outcome, a composite of all-cause death, cardiac resuscitation, hospitalization for heart failure, and need for cardiac surgery to improve myocardial pump function will be evaluated after 24 months. In addition, exploratory outcomes as well as safety endpoints related to the treatment will be assessed throughout the whole study period. CONCLUSION: IASO-DCM is a randomized study which will provide comprehensive insights into the effects of immunoadsorption with subsequent IgG substitution in patients with DCM.

Ischaemic Cardiomyopathy Secondary to Asymptomatic Coronary Artery Disease: A Case Report.

Ischaemic cardiomyopathy (ICM) represents a common complication of coronary artery disease (CAD). Ischaemia causes ventricular remodelling, leading to an irreversible loss of myocardial tissue and adequate contractility, primarily affecting the left ventricular ejection fraction (LVEF). We present the case of a 46-year-old male known as hypertensive presented to the hospital with a five-week history of progressive exertional dyspnoea, bilateral lower limb oedema subsequently involving his scrotum and penis. He reported reduced oral intake and occasional palpitations but denied chest pain, cough, fever, or haemoptysis. He had no personal history of cardiac disease, recent travels, or recreational drug use. Notably, he consumed approximately 12 units of alcohol weekly and was a non-smoker. On admission, he was treated for new-onset heart failure, and initial investigations showed acute kidney injury, raised troponin, and brain natriuretic peptide (BNP), and chest X-ray showed an enlarged heart size (cardiothoracic ratio (CTR), 0.56) with moderate right pleural effusion. Echocardiography revealed a severely dilated left ventricle with severely impaired systolic function (LVEF 16%), bi-atrial dilatation, borderline dilated right ventricle with impaired systolic function, and moderate tricuspid regurgitation. Cardiac MRI showed that the left ventricle was severely dilated with severely impaired systolic function with nonviable mid to apical inferior and inferoseptal transmural post-ischaemic scar with associated hypokinesia. Ischaemic cardiomyopathy may vary from asymptomatic to severely symptomatic, commonly when symptomatic patients will present with anginal chest pain and dyspnoea on exertion. In contrast, asymptomatic patients can sometimes have up to 80% of transient ischaemic events with no chest pain or associated symptoms. This case underscores the importance of considering asymptomatic coronary artery disease in clinical practice and highlights the need for novel interventions and markers for early ischemia detection.

Anaesthetic Management of Right Inguinal Hernioplasty With Hemiorchidectomy in a High-Risk Dilated Cardiomyopathy Patient.

This case report details the successful anaesthetic management of a 65-year-old male with severe dilated cardiomyopathy, coronary artery disease, and extensive cardiovascular risk factors scheduled for elective right inguinal hernioplasty with hemiorchidectomy. The anaesthetic approach, including regional nerve blocks (ilioinguinal, iliohypogastric, genital branch of genitofemoral) and transversus abdominis plane block, successfully minimised cardiac stress and maintained hemodynamic stability throughout the procedure.

Usefulness of tissue tracking to differentiate tachycardia-induced cardiomyopathy from dilated cardiomyopathy in patients admitted for heart failure.

INTRODUCTION: Differentiation of tachycardia-induced cardiomyopathy (TIC) from dilated cardiomyopathy (DCM) in patients admitted for heart failure (HF) with left ventricular dysfunction and supraventricular tachyarrhythmia (SVT) remains challenging. The role of tissue tracking (TT) in this setting remains unknown. METHODS: Forty-three consecutive patients admitted for HF due to SVT with left ventricular ejection fraction (LVEF) < 50% undergoing CMR were retrospectively included. Those eventually evolving to LVEF > 50% at follow-up were classified as TIC and those maintaining a LVEF < 50% were classified as DCM. Clinical, echocardiography, and CMR findings, including TT, were analyzed to predict LVEF recovery. RESULTS: Twenty-five (58%) patients were classified as TIC. Late gadolinium enhancement (LGE) was more frequent in DCM group (61% vs 16%, p = 0.004). Left ventricle (LV) peak systolic radial velocity and peak diastolic radial strain rate were lower in DCM group (7.24 ± 4.44 mm/s vs 10.8 ± 4.5 mm/s; p = 0.015 and -0.12 ± 0.33 1/s vs -0.48 ± 0.51 1/s; p = 0.016, respectively). Right ventricle (RV) peak circumferential displacement was lower in patients with TIC (0.2 ± 1.3 vs 1.3 ± 0.9°; p = 0.009). In the multivariate analysis, diabetes (p = 0.046), presence of LGE (p = 0.028), LV peak systolic radial velocity < 7.5 mm/s (p = 0.034), and RV peak circumferential displacement > 0.5° (p = 0.028) were independent predictors of lack of LVEF recovery. CONCLUSION: In the setting of acute HF with LV dysfunction related to SVT, diabetes, LGE, LV peak systolic velocity, and RV peak circumferential displacement are independent predictors of lack of LVEF recovery and, therefore, represent clinically useful parameters to differentiate TIC from DCM.

Alström syndrome-wide clinical variability within the same variant: a case report and literature review.

Background: Alström disease is a rare disorder caused by various variants in the ALMS1 gene. It is characterised by multiorgan involvement, namely neurosensory deficits, endocrine and metabolic disturbances, cardiomyopathy, and hepatic and renal dysfunction. The disease exhibits marked interindividual variability, both in clinical manifestations and age of onset. Several attempts have been made to establish a relationship between phenotype and genotype, with little success. Methods: We present the case of an infant who presented with dilated cardiomyopathy, above-average weight and neurosensory deficits, raising the suspicion for Alström syndrome, later confirmed through genetic testing. Moreover, we conducted an extensive literature search to identify all reported cases having the same variant as our patient, in order to evaluate whether specific mutated alleles have a role in determining phenotype-genotype associations. Results: A 4-month-old female infant with a recent history of bronchiolitis was referred to our centre due to a systolic murmur. In our service, the clinical exam was significant for above-average weight, dyspnea, wheezing and a grade II systolic murmur. Echocardiography revealed dilated cardiomyopathy with severe systolic dysfunction of the left ventricle. Laboratory investigations revealed elevated NT-proBNP and troponin levels, along with positive IgM antibodies for CMV and EBV. Dilated cardiomyopathy attributed to viral myocarditis was suspected. Treatment with ACE inhibitors and diuretics was started, with a favourable response initially. However, after a few months, the patient presented with vertical nystagmus and head bobbing. The ophthalmologic exam revealed cone-rode dystrophy. Considering the constellation of symptoms, Alström syndrome was suspected. Genetic testing revealed a homozygous variant [c.4156dup (p.Thr1386Asnfs*15)] in the ALMS1 gene, confirming the diagnosis. Conclusion: Our literature review revealed 8 additional cases harbouring the same variant as our patient, five in a heterozygous state, two in a homozygous state and one with only one allele identified. The identified patients presented high heterogeneity of clinical manifestations and age of onset. The heterogeneity persisted even in patients with homozygous variants, suggesting the involvement of factors beyond the specific disease-causing variant in determining disease manifestation. Therefore, genotype-phenotype correlations might not be supported by specific variants.

A case report of a rare genetic mutation (LMNA-C.185G>C, p.Arg62Pro) associated with dilated cardiomyopathy in a Han Chinese child.

Dilated cardiomyopathy (DCM) remains an enigmatic myocardial disorder characterized either by enlargement of either the left or right ventricle or both and reduced contractility, posing a significant burden on pediatric populations as a leading cause of cardiac-related mortality and morbidity. This paper presents a compelling case of DCM in a Han Chinese child whose genomic analysis unveiled a novel LMNA-C.185G>C (p.Arg62Pro) variant. Over a meticulous 3-year clinical follow-up, spanning ten outpatient consultations and hospital admissions since the initial diagnosis, the patient exhibited a progressive emergence of various cardiac conduction anomalies closely mirroring LMNA-associated phenotypes. Delving into a comprehensive review of the patient's 14-year medical journey and familial history, antecedent signs of muscular dystrophy (MD) predated DCM onset. Familial scrutiny revealed a lineage marred by muscular atrophy, with the patient's maternal grandmother having a history of muscular dystrophy and an episode of DCM, necessitating cardiac transplantation in the patient's uncle at age 37. This scenario illuminates the intricate interplay between LMNA-associated diseases and genetic predisposition. Timely identification of etiological triggers stands paramount in DCM management. Beyond conventional genetic scrutiny, leveraging novel serum biomarkers such as anti-heart muscle antibodies (AHA) remarkably enhanced diagnostic precision. Notably, personalized therapeutic interventions comprising prednisolone regimens and intravenous immunoglobulin infusions precipitated marked amelioration in heart failure symptoms and serum biomarker profiles. It is noteworthy to identify this novel genetic locus within the Han Chinese populace, underscoring the imperative of expanding the LMNA mutation repository within this demographic cohort. Early recognition of clinical manifestations and etiological cues in pediatric DCM heralds a paradigm shift in risk prognostication and individualized therapeutic interventions, underscoring the profound significance of precision medicine in combating rare familial cardiomyopathies.

Prognostic value of enhanced cine cardiac MRI-based radiomics in dilated cardiomyopathy.

BACKGROUND: Early precise identification of high-risk dilated cardiomyopathy (DCM) phenotype is essential for clinical decision-making and patient surveillance. The aim of the study was to assess the prognostic value of enhanced cine cardiac magnetic resonance (CMR)-based radiomics in DCM. METHODS: We prospectively enrolled 401 (training set: 281; test set: 120) DCM patients. Radiomic features were extracted from enhanced cine images of entire left ventricular wall and selected by the least absolute shrinkage and selection operator. Different predictive models were built using logistic regression classifier to predict all-cause mortality and heart transplantation. Model performances were compared with the area under the receiver operating characteristic curves (AUCs). Kaplan-Meier curves, log-rank test, and Cox regression were used for survival analysis. RESULTS: Endpoint events occurred in 65 patients over a median follow-up period of 25.4 months. 13 radiomic features were finally selected. The Rad_Combined model integrating clinical characteristics, CMR parameters and radiomics features achieved the best performance with an AUC of 0.836 and 0.835 in the training and test sets, respectively. High-risk groups with endpoint events defined by the Rad_Combined model had significantly shorter survival time than low-risk group in both the training [Hazard Ratio (HR) = 7.74, P < 0.001] and test sets (HR = 4.84, P < 0.001). CONCLUSION: The Rad_Combined model might serve as an effective tool to help risk stratification and clinical decision-making for patients with DCM. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017058 by the ethics committee of West China hospital,Sichuan University.

Exploring the predictive values of SERP4 and FRZB in dilated cardiomyopathy based on an integrated analysis.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate potential hub genes for dilated cardiomyopathy (DCM). METHODS: Five DCM-related microarray datasets were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were used for identification. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, disease ontology, gene ontology annotation and protein-protein interaction (PPI) network analysis were then performed, while a random forest was constructed to explore central genes. Artificial neural networks were used to compare with known genes and to develop new diagnostic models. 240 population blood samples were collected and expression of hub genes was verified in these samples using RT-PCR and demonstrated by Nomogram. RESULTS: After differential analysis, 33 genes were statistically significant (adjusted P < 0.05). Functional enrichment of these differential genes resulted in 85 Gene Ontology (GO) functions identified and 6 pathways enriched for the KEGG pathway. PPI networks and molecular complex assays identified 10 hub genes (adjusted P < 0.05). Random forest identified SMOC2 and SFRP4 as the most important, followed by FCER1G and FRZB. NeuraHF models (SMOC2, SFRP4, FCER1G and FRZB) were selected by artificial neural network model and had better diagnostic efficacy for the onset of DCM, compared with the traditional KG-DCM models (MYH7, ACTC1, TTN and LMNA). Finally, SFRP4 and FRZB were expressed higher in DCM verified by RT-PCR and as a factor for DCM identified by Nomogram. CONCLUSIONS: We performed an integrated analysis and identified SFRP4 and FRZB as a new factor for DCM. But the exact mechanism still needs further experimental verification.

The Influence of Arrhythmia on the Outcomes of Pediatric Patients with Idiopathic Dilated Cardiomyopathy.

Children diagnosed with dilated cardiomyopathy (DCM) are at an increased risk of developing arrhythmias, which can significantly affect their overall prognosis. However, the implantation and effectiveness of implantable cardioverter-defibrillators (ICDs) pose challenges in the pediatric population. Therefore, it is crucial to determine the prevalence of arrhythmia-related death in pediatric patients with DCM. This study investigated the correlation between arrhythmias and mortality in pediatric patients with DCM. This retrospective cohort study examined children with idiopathic DCM referred to Rajaie Cardiovascular, Medical, and Research Institute in Tehran, Iran, from 2017 to 2023. All patients underwent a standard 12-lead electrocardiogram, 24-h Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. Patient outcomes, including death, heart transplantation, and survival, were evaluated within one year of Holter monitoring. A total of 178 children (79 males) with a mean age of 83.06 ± 56.41 months were included in the study. Overall, 72 deaths (40.4%) and 46 heart transplants (25.8%) were recorded and 60 patients (33.7%) survived. There was no significant association between patients' outcomes with ventricular arrhythmias, late gadolinium enhancement, corrected QT interval, and QRS interval prolongation; however, a significantly higher proportion of dead patients had abnormal heart rate variability (P = 0.034). Heart failure was the leading cause of death, with ventricular arrhythmia accounting for two out of 72 deaths. Both cases of ventricular arrhythmia were associated with severe cardiac dysfunction. Arrhythmia-related mortality is rare in children with idiopathic DCM, with severe heart failure being the primary cause of death in this population. Life-threatening arrhythmias primarily occur in DCM children with more compromised cardiac function.

Genetic Landscape of Patients With Dilated Cardiomyopathy and a Systemic Immune-Mediated Disease.

BACKGROUND: Systemic immune-mediated diseases (SIDs) are a well-known cause of dilated cardiomyopathy (DCM), a cardiac phenotype influenced by genetic predispositions and environmental factors. OBJECTIVES: This study sought to examine if an underlying genetic predisposition is present in patients with DCM and SID. METHODS: Genotyped DCM-SID patients (n = 183) were enrolled at 3 European centers. Genetic variants were compared with healthy control subjects (n = 20,917), DCM patients without SID (n = 560), and individuals with a suspicion of an SID (n = 1,333). Clinical outcomes included all-cause mortality, heart failure hospitalization, and life-threatening arrhythmias. RESULTS: The SID diagnosis preceded the DCM diagnosis by 4.8 months (Q1-Q3: -68.4 to +2.4 months). The prevalence of pathogenic/likely pathogenic (P/LP) variants in DCM patients with an SID from the Maastricht cohort was 17.1%, compared with 1.9% in healthy control subjects (P < 0.001). In the Madrid/Trieste cohort, the prevalence was 20.5% (P < 0.001). Truncating variants showed the strongest enrichment (10.7% [OR: 24.5] (Maastricht) and 16% [OR: 116.6 (Madrid/Trieste); both P < 0.001), with truncating TTN (titin) variant (TTNtv) being the most prevalent. Left ventricular ejection fraction at presentation was reduced in TTNtv-SID patients compared with DCM patients with SID without a P/LP (P = 0.016). The presence of a P/LP variant in DCM-SID had no impact on clinical outcomes over a median follow-up of 8.4 years (Q1-Q3: 4.9-12.1 years). CONCLUSIONS: One in 6 DCM patients with an SID has an underlying P/LP variant in a DCM-associated gene. This highlights the role of genetic testing in those patients with immune-mediated DCM, and supports the concept that autoimmunity may play a role in unveiling a DCM phenotype in genotype-positive individuals.

Revived Role of Pulmonary Artery Band in Management of Heart Failure in Pediatric Dilated Cardiomyopathy.

Lack of appropriate durable Ventricular Assist Devices (VADs) that can be managed at home for very young children, and long wait times for transplant have led to search for alternate easily reproducible therapies. In the past decade or more, pulmonary artery banding (PAB), as a new indication of an old technology, has been gradually carried out worldwide as an alternative to mechanical circulatory support in children with end-stage left ventricular dilated cardiomyopathy (DCM) complicated with heart failure(HF), and has achieved encouraging early and mid-term outcomes. Technically, PAB is simple, safe, and effective. This is a promising therapeutic strategy, especially in developing countries where heart transplantation is difficult to implement. As a transition before transplantation, and even a potential treatment, PAB brings more options and hope for children with heart failure who are waiting for transplantation and are refractory to drug therapy. This article reviews the past and current situation, the mechanism, the surgical timing, and application prospect of PAB in the treatment of DCM complicated with heart failure.

Association Between Coronary Microvascular Dysfunction and Exercise Capacity in Dilated Cardiomyopathy.

BACKGROUND: Aerobic exercise capacity is an independent predictor of mortality in dilated cardiomyopathy (DCM), but the central mechanisms contributing to exercise intolerance in DCM are unknown. OBJECTIVES: Characterize coronary microvascular function in DCM and determine if cardiovascular magnetic resonance (CMR) measures are associated with aerobic exercise capacity. METHODS: Prospective case-control comparison of adults with DCM and matched controls. Adenosine-stress perfusion CMR to assess cardiac structure, function and automated inline myocardial blood flow quantification, and cardiopulmonary exercise testing (CPET) to determine peak VO2, were performed. Pre-specified multivariable linear regression, including key clinical and cardiac variables, was undertaken to identify independent associations with peak VO2. RESULTS: Sixty-six patients with DCM (mean age 61 years, 71% male) were propensity-matched to 66 controls (mean age 59 years, 71% male) based on age, sex, body mass index and diabetes. DCM patients had markedly lower peak VO2 (19.8±5.5 versus 25.2±7.3mL/kg/min; P<0.001). The DCM group had greater left ventricular (LV) volumes, lower systolic function, and had more fibrosis compared to controls. In the DCM group, there was similar rest but lower stress myocardial blood flow (1.53±0.49 versus 2.01±0.60mL/g/min; P<0.001) and lower MPR (2.69±0.84 versus 3.15±0.84; P=0.002). Multivariable linear regression demonstrated that LV ejection fraction, extracellular volume fraction and MPR, were independently associated with percentage predicted peak VO2 in DCM (R2=0.531, P<0.001). CONCLUSIONS: In comparison to controls, DCM patients have lower stress myocardial blood flow and MPR. In DCM, MPR, LV ejection fraction and fibrosis are independently associated with aerobic exercise capacity.