Primary Myocardial Disease Research Articles

Abstract 4145861: Systemic Sclerosis is Associated with Sub-Clinical Abnormalities in Myocardial Energetics, Perfusion and Increased Fibrosis

Background: Primary cardiac involvement in systemic sclerosis (SSc) is heterogenous, poorly defined and associated with significant cardiac morbidity and mortality. The underlying mechanism is not well understood but may include the impact of coronary microvascular dysfunction and myocardial inflammation. Myocardial cellular metabolic alterations in SSc are yet to be established. Aims: Using 31 Phosphorous magnetic resonance spectroscopy ( 31 P MRS) and cardiovascular magnetic resonance (CMR), we aimed to establish if myocardial energetics, measured as phosphocreatine (PCr) /ATP ratio, and quantitative myocardial perfusion were reduced in individuals with SSc compared to healthy volunteers (HV). Methods: A total of 35 age and sex matched participants were recruited (25 SSc, 10 HV). All subjects underwent 31 P MRS and comprehensive CMR protocol including volumetric analysis, quantitative myocardial perfusion and T1 mapping. Results: Table-1 shows clinical and CMR / 31 P MRS data. Bi-ventricular volumes, systolic function and left atrial function were similar in both groups. NT-Pro BNP and myocardial extra cellular volume (ECV) were significantly increased in SSc. Both PCr/ATP and myocardial perfusion reserve (MPR) were significantly reduced in SSc compared with controls. The disease activity as measured by the European Scleroderma Trials and Research group (EUSTAR) activity index did not correlate with either NTproBNP (P=0.79), PCr/ATP (P=0.35) or MPR (P=0.6). Conclusions: In addition to validating our previous observations of reduced perfusion and increased myocardial fibrosis in SSc, we have demonstrated for the first time significant reductions in myocardial energetics in patients with SSc. These findings provide further valuable insight into the pathogenesis of primary myocardial disease in SSc.

Targeting Canonical Wnt-signaling Through GSK-3β in Arrhythmogenic Cardiomyopathy: Conservative or Progressive?

Arrhythmogenic cardiomyopathy is a primary myocardial disease and a major cause of sudden death in all populations of the world. Canonical Wnt signalling is a critical pathway controlling numerous processes including cellular differentiation, hypertrophy and development. GSK3β is a ubiquitous serine/threonine kinase, which acts downstream of Wnt to promote protein ubiquitination and proteasomal degradation. Several studies now suggest that inhibiting GSK3β can prevent and reverse key pathognomonic features of ACM in a range of experimental models. However, varying concerns are reported throughout the literature including the risk of paradoxical arrhythmias, cancer and off-target effects in upstream or downstream pathways. CLINICAL RELEVANCE: In light of the start of the phase 2 TaRGET clinical trial, designed to evaluate the potential therapeutic efficacy of GSK3β inhibition in patients with arrhythmogenic cardiomyopathy, this report aims to review the advantages and disadvantages of this strategy.

Abstract We147: The Utility of Cardiopulmonary Exercise Testing (CPET) Amongst Male and Female athletes to Differentiate Between Physiological Left Ventricular Enlargement and Mildly Depressed Resting Systolic Function and Athletic Individuals with Dilated Cardiomyopathy.

Background: Athletes frequently reveal a dilated left ventricle (LV),some also demonstrate a co-existent mildly depressed LV ejection fraction, raising the possibility of mild dilated cardiomyopathy (DCM). The maximal oxygen consumption(VO2max) is a valuable tool for assessing fitness, largely determined by cardiac output. References ranges derived from the general population, may have limitations when assessing athletes with primary myocardial disease. This study investigated the role of VO2max and VO2max predicted (V02pred) to differentiate between physiological LV dilatation and athletic individuals with DCM in male and female athletes. Methods: 147 male and 35 female athletes with dilated LV(mean age 35.4years, 34.5 years respectively) underwent a 25watt cycle ergometer continuous ramp protocol. 75% males and 67% females participated in endurance sports, remaining participating in mixed sports. 52 had mild DCM, 62 defined as healthy control athletes(dilated LV) and 68 were Grey zone (dilated LV and mildly depressed LVEF) Results: DCM males (N=39) revealed a lower mean VO2max than male control (N=46), 34.9ml/kg/min and 48ml/kg/min respectively (p value <0.001). DCM females(N=13) showed lower VO2max of 29.9ml/min/kg than female control (N=16) who revealed similar values to male controls (48 ml/kg/min)(p value <0.001). 62 male Grey zones and 6 female Grey zone revealed lower VO2max than controls 43.1ml/min/kg and 34.1ml/min/kg respectively. DCM females had lower VO2pred than control females 119% and 161% respectively but significantly higher than their male counterparts, means of 106% and 123% respectively (p value <0.001). Male and female grey zones had lower mean VO2pred than controls, 121% and 106% respectively. Higher VO2max of ≥38ml/kg/min and VO2pred of ≥120% gave a sensitivity, specificity of 84.7% and 77%respectively to differentiate healthy athletes and athletic DCMs in males and females. Only41.1% Grey zone athletes were able to achieve above these thresholds. Conclusion: Female athletes with dilated LV may reveal supranormal VO2max which can equal their male counterparts. Furthermore, athletic females with physiological or pathological LV dilatation can reveal higher VO2pred than male athletes. Most athletic DCM individuals show lower CPET parameters than controls athletes but can still achieve greater than normal measurements seen in healthy general population. VO2 may have a role in assisting in differentiating healthy athletes from athletic DCM.

Additional factors associated with sudden cardiac death in HCM patients

Abstract Background Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by an increase in the thickness of the left ventricular (LV) wall, which is not explained only by abnormal loading conditions. Sudden cardiac death (SCD) is the most devastating complication of HCM occurring in asymptomatic or younger patients without warning. Purpose To evaluate additional SCD risk factors in Ukrainian population of HCM patients. Materials and methods We retrospectively evaluated 350 consecutive HCM patients that were followed from 2006 to 2021 in our Cardiological Department. General clinical examination, standard 12-lead ECG, transthoracic echocardiography and 24 hours Holter ECG monitoring data were estimated. The 5-year SCD risk was calculated according to the HCM Risk-SCD score. The endpoint of the study was SCD and its surrogates, including adequate performance of the implantable cardioverter-defibrillator and successful resuscitation. Results Follow-up time was 5.0 (1.5-9.5) years. During this time, 16 patients (4.6%) reached the end point, which was 0.9%/year. According to the HCM Risk-SCD score, 5 (31.3%) of this group had a high risk of SCD (≥ 6%) and 3 (18.8%) had an intermediate risk (≥ 4% and < 6%). In multivariable Cox regression analysis adjusted for conventional SCD risk factors it was found that independent predictors of SCD were unexplained syncope (HR 3.81, 95% CI 1.11-13.12, p=0.034), systolic blood pressure (SBP) (HR 0.97 , 95% CI 0.94- 0.99, p=0.026), "infarct-like" ST elevation on ECG (HR 6.81, 95% CI 2.09-22.16, p=0.001) and PQ interval duration (HR 1.03, 95% CI 1.01-1.05, p=0.002), Harrell's C-index 0.84, 95% CI 0.73-0.95, p < 0.0001). Conclusions In our study HCM Risk-SCD score predicted SCD or surrogates only in 50% of cases. In order to improve the risk stratification some additional independent predictors of SCD can be proposed. ECG parameters ("infarct-like" ST elevation and PQ interval duration) and level of SBP were found to have SCD predictive value.

Echocardiographic Evaluation of Left Ventricular Hypertrophy

Abstract Left ventricular hypertrophy (LVH) can occur as a result of increase in the left ventricular (LV) wall thickness or increase in the LV cavity size, thus leading to increase in the LV mass. Strength training and aerobic exercise lead to physiological LVH, whereas conditions such as hypertension and aortic stenosis (AS) cause pathological LVH. It is one aspect of ventricular remodeling. LVH can also occur because of some primary myocardial diseases as well as due to certain infiltrative disorders. LVH is not a disease in itself, but a manifestation of some other disease. LVH is a marker of adverse cardiovascular health and remodeling and is associated with a high risk of adverse cardiac outcomes. Besides this, LVH itself can lead to heart failure or sudden cardiac death. Hence, a thorough assessment of LVH is important for proper management of the underlying condition. Echocardiography and cardiac magnetic resonance imaging are the two most important imaging modalities used for the assessment of LVH. This review describes various echocardiography techniques for LVH assessment as well as echocardiographic recognition of the underlying etiological condition.

Genotype-Phenotype Insights of Inherited Cardiomyopathies-A Review.

Background: Cardiomyopathies (CMs) represent a heterogeneous group of primary myocardial diseases characterized by structural and functional abnormalities. They represent one of the leading causes of cardiac transplantations and cardiac death in young individuals. Clinically they vary from asymptomatic to symptomatic heart failure, with a high risk of sudden cardiac death due to malignant arrhythmias. With the increasing availability of genetic testing, a significant number of affected people are found to have an underlying genetic etiology. However, the awareness of the benefits of incorporating genetic test results into the care of these patients is relatively low. Aim: The focus of this review is to summarize the current basis of genetic CMs, including the most encountered genes associated with the main types of cardiomyopathies: hypertrophic, dilated, restrictive arrhythmogenic, and non-compaction. Materials and Methods: For this narrative review, we performed a search of multiple electronic databases, to select and evaluate relevant manuscripts. Results: Advances in genetic diagnosis led to better diagnosis precision and prognosis prediction, especially with regard to the risk of developing arrhythmias in certain subtypes of cardiomyopathies. Conclusions: Implementing the genomic information to benefit future patient care, better risk stratification and management, promises a better future for genotype-based treatment.

ECG changes and their prognostic value for the development of sudden cardiac death in HCM patients

Background. Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by an increase in the left ventricular (LV) wall thickness, which is not explained only by abnormal loading conditions. The development of sudden cardiac death (SCD) is one of the most dangerous complications of HCM. The aim of our study was to evaluate the prognostic value of electrocardiography (ECG) changes for the development of SCD in the Ukrainian population of patients with HCM. Materials and methods. We evaluated 350 patients with HCM who were examined in the City Clinical Hospital 8 (Kharkiv, Ukraine) from 2006 to 2021. The diagnosis of HCM was made in accordance with the current guidelines of the European Society of Cardiology. Clinical and instrumental data of patients with HCM were analyzed retrospectively, including general clinical data, 12-lead ECG, echocardiography, Holter monitoring, calculation of the 5-year risk of SCD according to the HCM Risk-SCD tool. The endpoint of the study was SCD and its surrogates, including adequate performance of the implantable cardioverter-defibrillator and the state after a successful resuscitation. Results. Follow-up was 5.0 (1.5–9.5) years. During this time, 16 patients (4.6 %) reached the endpoint, which was 0.9 %/year. According to the HCM Risk-SCD, 5 (31.3 %) patients in this group were at a high (≥ 6 %) and 3 (18.8 %) were at an intermediate risk of SCD (≥ 4 and < 6 %). A multivariable Cox regression analysis has shown that independent predictors of SCD are syncope (hazard ratio (HR) 3.81, 95% confidence interval (CI) 1.11–13.12, p = 0.034), systolic blood pressure (HR 0.97, 95% CI 0.94–0.99, p = 0.026), ECG with “infarction-like” ST elevation (HR 6.81, 95% CI 2.09–22.16, p = 0.001) and PQ interval value (HR 1.03, 95% CI 1.01–1.05, p = 0.002), Harrell’s C-index (HR 0.84, 95% CI 0.73–0.95, p < 0.0001). Conclusions. The proposed HCM Risk-SCD tool was not effective enough in predicting SCD in our study. In order to improve the risk stratification, ECG changes (“infarction-like” ST elevation and PQ interval prolongation) and systolic blood pressure lowering can be used, which were found to be independent predictors of SCD risk.

Comprehensive review on gene mutations contributing to dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the most common primary myocardial diseases. However, to this day, it remains an enigmatic cardiovascular disease (CVD) characterized by ventricular dilatation, which leads to myocardial contractile dysfunction. It is the most common cause of chronic congestive heart failure and the most frequent indication for heart transplantation in young individuals. Genetics and various other factors play significant roles in the progression of dilated cardiomyopathy, and variants in more than 50 genes have been associated with the disease. However, the etiology of a large number of cases remains elusive. Numerous studies have been conducted on the genetic causes of dilated cardiomyopathy. These genetic studies suggest that mutations in genes for fibronectin, cytoskeletal proteins, and myosin in cardiomyocytes play a key role in the development of DCM. In this review, we provide a comprehensive description of the genetic basis, mechanisms, and research advances in genes that have been strongly associated with DCM based on evidence-based medicine. We also emphasize the important role of gene sequencing in therapy for potential early diagnosis and improved clinical management of DCM.

Syncopes in adolescents in sport

The study analyzes current data on syncope in children and adolescents. The study presents the classification of syncope and briefly describes the clinical manifestations of neurally mediated syncope and the main methods of its diagnosis and treatment. Syncopes associated with organic cardiac pathologies and primary cardiac arrhythmias are caused by hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, coronary artery anomalies, primary long QT syndrome, WolffParkinsonWhite syndrome, and bradyarrhythmias. The diagnostic features of syncope in children and young athletes and modern approaches to treatment and prevention are discussed.
 Although most syncopes in athletes are not associated with physical activity and have a neurotransmitter genesis, a thorough medical examination is needed. Factors that induce the development of syncopes in athletes must be identified. A prerequisite for admission to sports is the exclusion of the cardiac and arrhythmogenic reasons of syncopes. The decision to expand the sports regime should be made only after a thorough collection of medical history, including family history, and a comprehensive examination. In addition, the degree of risk in view of injuries, provocation, or fatal events following the loss of consciousness during sports must be estimated. This is extremely relevant for sports such as swimming, complex coordination sports (gymnastics and acrobatics), auto and motor sports, and alpine skiing.
 Although syncopes are common problems in pediatric practice, with only a few cases with cardiac causes based on structural or primary electrical myocardial diseases, they pose the greatest danger in sports medicine. Thus, such conditions must be excluded in young athletes because sports load can aggravate cardiac pathologies, which cause syncopes, due to untimely diagnosis before the start of a sports career.

Associations between spirometric impairments and microvascular complications in type 2 diabetes: a cross-sectional study

ObjectiveEvidence shows that the conventional cardiometabolic risk factors do not fully explain the burden of microvascular complications in type 2 diabetes (T2D). One potential factor is the impact of pulmonary...

Anesthetic Management of Patients with Dilated Cardiomyopathy Undergoing Noncardiac Surgery.

Dilated cardiomyopathy (DCM), a primary myocardial disease, is characterized by dilation of the left or both ventricles and systolic dysfunction with or without congestive heart failure. DCM per se is a well-recognized risk factor for sudden cardiac death and poor surgical outcomes following noncardiac surgery. Surgical trauma/stress represents unique challenges for DCM patient management. Unfortunately, there is a big knowledge gap in managing DCM patients undergoing non-cardiac surgery. Therefore, the aim of our review is to provide basic facts and current advances in DCM, as well as a practical guideline to perioperative care providers, for the management of surgical patients with DCM, who are quite rare compared with the general surgical population. This review summarizes recent advances in the medical management of DCM as well as perioperative assessment and management strategies for DCM patients undergoing noncardiac surgery. Optimal surgical outcomes depend on multiple-disciplinary care to minimize perioperative cardiovascular disturbances.

Functional defects in hiPSCs-derived cardiomyocytes from patients with a PLEKHM2-mutation associated with dilated cardiomyopathy and left ventricular non-compaction

Dilated cardiomyopathy (DCM) is a primary myocardial disease, leading to heart failure and excessive risk of sudden cardiac death with rather poorly understood pathophysiology. In 2015, Parvari's group identified a recessive mutation in the autophagy regulator, PLEKHM2 gene, in a family with severe recessive DCM and left ventricular non-compaction (LVNC). Fibroblasts isolated from these patients exhibited abnormal subcellular distribution of endosomes, Golgi apparatus, lysosomes and had impaired autophagy flux. To better understand the effect of mutated PLEKHM2 on cardiac tissue, we generated and characterized induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs) from two patients and a healthy control from the same family. The patient iPSC-CMs showed low expression levels of genes encoding for contractile functional proteins (α and β-myosin heavy chains and 2v and 2a-myosin light chains), structural proteins integral to heart contraction (Troponin C, T and I) and proteins participating in Ca2+ pumping action (SERCA2 and Calsequestrin 2) compared to their levels in control iPSC-derived CMs. Furthermore, the sarcomeres of the patient iPSC-CMs were less oriented and aligned compared to control cells and generated slowly beating foci with lower intracellular calcium amplitude and abnormal calcium transient kinetics, measured by IonOptix system and MuscleMotion software. Autophagy in patient’s iPSC-CMs was impaired as determined from a decrease in the accumulation of autophagosomes in response to chloroquine and rapamycin treatment, compared to control iPSC-CMs. Impairment in autophagy together with the deficiency in the expression of NKX2.5, MHC, MLC, Troponins and CASQ2 genes, which are related to contraction-relaxation coupling and intracellular Ca2+ signaling, may contribute to the defective function of the patient CMs and possibly affect cell maturation and cardiac failure with time.

Is myocardial fibrosis in patients with non-ischemic dilated cardiomyopathy associated with the whole-heart myocardial mechanics?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Non-ischemic dilated cardiomyopathy (NIDCM) is a severe form of primary myocardial disease related with progressive heart failure (HF) and a poor prognosis. In patients with NIDCM, myocardial fibrosis (MF) is associated to adverse cardiovascular outcomes and should be evaluated quickly in each case of NIDCM [1,2]. Purpose To evaluate the relationships between the whole-heart myocardial strain parameters and presence of late gadolinium enhancement (LGE) in a prospective cohort of NIDCM patients. Methods The study group consisted of 101 patients with NIDCM who were referred for a cardiovascular magnetic resonance (CMR) and speckle tracking echocardiography examination. We analyzed MF by LGE, and the whole-heart (both ventricles and atria) myocardial mechanics were evaluated by speckle tracking. All patients underwent a comprehensive clinical evaluation, laboratory test assessment, electrocardiogram, Holter monitoring. The exclusion criteria were ischemic coronary disease, primary valvular heart disease, chronic kidney disease (eGFR <30 ml/min/1.73 m2), under the age of 18, a poor echocardiographic or CMR image quality, inflammatory myocardial disease, previous pulmonary embolism, peripartum cardiomyopathy and toxic damage. Results The study group was divided into two groups according to the presence of MF fibrosis. The presence of MF was associated to worse of the whole-heart myocardial strain parameters. Both ventricles or atria were more dilated in the group with MF. The strongest relationships were detected between presence of MF and mechanical strain parameters of the left side of the heart (left ventricle ejection fraction (LVEF) (r=0.662, 25 p<0.001), left ventricle global circumferential strain (LV GCS) (r=-0.609, p<0.001), left ventricle global longitudinal strain (LV GLS) (r=-0.586, p<0.001), left atrial reservoir strain (LASr) (r=0.588, p<0.001). Logistic regression analysis revealed that the last three mentioned strain parameters were independently associated with presence of MF. Conclusions In patients with NIDCM, the whole-heart myocardial mechanics are worse in patients‘ presence of MF. LV GLS, LV GCS, and LARs are the best 2D echocardiographic mechanical strain parameters to prognosticate the presence of MF.

Study design and rationale of EXPLORER-CN: a phase III, randomised, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of mavacamten in Chinese adults with symptomatic obstructive hypertrophic cardiomyopathy

IntroductionHypertrophic cardiomyopathy (HCM) is a primary myocardial disease commonly caused by pathogenic genetic variants encoding sarcomere proteins. Mavacamten, a first-in-class allosteric inhibitor of cardiac-specific myosin, has demonstrated efficacy and safety...

Personalized Management of Sudden Death Risk in Primary Cardiomyopathies: From Clinical Evaluation and Multimodality Imaging to Ablation and Cardioverter-Defibrillator Implant.

Sudden cardiac death represents the leading cause of death worldwide; although the majority of sudden deaths occur in an elderly population with coronary artery disease, some occur in young and otherwise healthy individuals, as is the case of cardiomyopathies. The aim of the present review is to provide a stepwise hierarchical approach for the global sudden death risk estimation in primary cardiomyopathies. Each individual risk factor is analyzed for its contribution to the overall risk of sudden death for each specific cardiomyopathy as well as across all primary myocardial diseases. This stepwise hierarchical and personalized approach starts from the clinical evaluation, subsequently passes through the role of electrocardiographic monitoring and multimodality imaging, and finally concludes with genetic evaluation and electro-anatomical mapping. In fact, the sudden cardiac death risk assessment in cardiomyopathies depends on a multiparametric approach. Moreover, current indications for ventricular arrhythmia ablation and defibrillator implantation are discussed.

Cardiac Resynchronization Therapy and Hypertrophic Cardiomyopathy: A Comprehensive Review.

Hypertrophic cardiomyopathy (HCM) is an inherited primary myocardial disease characterized by asymmetrical/symmetrical left ventricle (LV) hypertrophy, with or without LV outflow tract (LVOT) dynamic obstruction, and poor prognosis. Cardiac resynchronization therapy (CRT) has emerged as a minimally invasive tool for patients with heart failure (HF) with decreased LV ejection fraction (LVEF) and prolonged QRS duration of over 120 ms with or without left bundle branch block (LBBB). Several HCM patients are at risk of developing LBBB because of disease progression or secondary to septal myomectomy, while others might develop HF with decreased LVEF, alleged end-stage/dilated HCM, especially those with thin myofilament mutations. Several studies have shown that patients with myectomy-induced LBBB might benefit from left bundle branch pacing or CRT to relieve symptoms, improve exercise capacity, and increase LVEF. Otherwise, patients with end-stage/dilated HCM and prolonged QRS interval could gain from CRT in terms of NYHA class improvement, LV systolic performance increase and, to some degree, LV reverse remodeling. Moreover, several electrical and imaging parameters might aid proper selection and stratification of HCM patients to benefit from CRT. Nonetheless, current available data are scarce and further studies are still required to accurately clarify the view. This review reassesses the importance of CRT in patients with HCM based on current research by contrasting and contextualizing data from various published studies.

A Missense Variation in PHACTR2 Associates with Impaired Actin Dynamics, Dilated Cardiomyopathy, and Left Ventricular Non-Compaction in Humans.

Dilated cardiomyopathy (DCM) with left ventricular non-compaction (LVNC) is a primary myocardial disease leading to contractile dysfunction, progressive heart failure, and excessive risk of sudden cardiac death. Using whole-exome sequencing to investigate a possible genetic cause of DCM with LVNC in a consanguineous child, a homozygous nucleotide change c.1532G>A causing p.Arg511His in PHACTR2 was found. The missense change can affect the binding of PHACTR2 to actin by eliminating the hydrogen bonds between them. The amino acid change does not change PHACTR2 localization to the cytoplasm. The patient’s fibroblasts showed a decreased globular to fibrillary actin ratio compared to the control fibroblasts. The re-polymerization of fibrillary actin after treatment with cytochalasin D, which disrupts the actin filaments, was slower in the patient’s fibroblasts. Finally, the patient’s fibroblasts bridged a scar gap slower than the control fibroblasts because of slower and indirect movement. This is the first report of a human variation in this PHACTR family member. The knock-out mouse model presented no significant phenotype. Our data underscore the importance of PHACTR2 in regulating the monomeric actin pool, the kinetics of actin polymerization, and cell movement, emphasizing the importance of actin regulation for the normal function of the human heart.

Genetic Association between Polymorphisms of Interleukin-32 and Dilated Cardiomyopathy in Chinese Han Population.

Dilated cardiomyopathy is a primary myocardial disease and one of the critical causes of heart failure. It is the most common indication for heart transplantation worldwide, and most idiopathic dilated cardiomyopathies are sporadic and multifactorial. Evidence has supported that several inflammatory cytokines and immune responses are involved in its pathological process. Interleukin-32 is a proinflammatory cytokine and is elevated during the worsening cardiac function. Herein, we evaluated the correlation between interleukin-32 gene polymorphisms (rs12934561 and rs28372698) and the susceptibility to dilated cardiomyopathy. We enrolled 418 dilated cardiomyopathy patients and 437 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping the two single-nucleotide polymorphisms (SNPs), and SPSS software was used for statistical analyses. The C allele and CC genotype frequencies of rs12934561 were remarkably elevated in dilated cardiomyopathy patients compared to controls (both P < 0.001). The A allele and AA genotype frequencies of rs28372698 significantly decreased in dilated cardiomyopathy patients (P = 0.004 and P = 0.02, respectively). Compared to TT/TC genotype carriers of rs12934561, CC homozygotes presented an increased risk of dilated cardiomyopathy when the left ventricular ejection fraction no more than 30% (P = 0.02). The IL-32 gene polymorphisms might implicate in DCM risk in the Chinese Han population, and rs12934561 could be a potential forecasting factor for screening high-risk population for DCM.

The Dysfunctional Right Ventricle in Dilated Cardiomyopathies: Looking from the Right Point of View

Dilated cardiomyopathies (DCMs) are a heterogenous group of primary myocardial diseases, representing one of the leading causes of heart failure, and the main indication for heart transplantation. While the degree of left ventricular dilation and dysfunction are two key determinants of adverse outcomes in DCM patients, right ventricular (RV) remodeling and dysfunction further negatively influence patient prognosis. Consequently, RV functional assessment and diagnosing RV involvement by using an integrative approach based on multimodality imaging is of paramount importance in the evaluation of DCM patients and provides incremental prognostic and therapeutic information. Transthoracic echocardiography remains the first-line imaging modality used for the assessment of the RV, and newer techniques such as speckle-tracking and three-dimensional echocardiography significantly improve its diagnostic and prognostic accuracy. Nonetheless, cardiac magnetic resonance (CMR) is considered the gold standard imaging modality for the evaluation of RV size and function, and all DCM patients should be evaluated by CMR at least once. Accordingly, this review provides a comprehensive overview of the anatomy and function of the RV, and the pathophysiology, diagnosis, and prognostic value of RV dysfunction in DCM patients, based on traditional and novel imaging techniques.

Development and verification of the nomogram for dilated cardiomyopathy gene diagnosis

Dilated cardiomyopathy (DCM) is a primary myocardial disease of unclear mechanism and poor prevention. The purpose of this study is to explore the potential molecular mechanisms and targets of DCM via bioinformatics methods and try to diagnose and prevent disease progression early. We screened 333 genes differentially expressed between DCM and normal heart samples from GSE141910, and further used Weighted correlation network analysis to identify 197 DCM-related genes. By identifying the key modules in the protein–protein interaction network and Least Absolute Shrinkage and Selection Operator regression analysis, seven hub DCM genes (CX3CR1, AGTR2, ADORA3, CXCL10, CXCL11, CXCL9, SAA1) were identified. Calculating the area under the receiver’s operating curve revealed that these 7 genes have an excellent ability to diagnose and predict DCM. Based on this, we built a logistic regression model and drew a nomogram. The calibration curve showed that the actual incidence is basically the same as the predicted incidence; while the C-index values of the nomogram and the four external validation data sets are 0.95, 0.90, 0.96, and 0.737, respectively, showing excellent diagnostic and predictive ability; while the decision curve indicated the wide applicability of the nomogram is helpful for clinicians to make accurate decisions.