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ESC Heart Failure Oct 2022Chemotherapy-induced dilated cardiomyopathy (CI-DCM) is a well-recognized phenotype of non-ischemic dilated cardiomyopathy (DCM), characterized by poor outcomes....
AIMS
Chemotherapy-induced dilated cardiomyopathy (CI-DCM) is a well-recognized phenotype of non-ischemic dilated cardiomyopathy (DCM), characterized by poor outcomes. However, a detailed comparison between idiopathic DCM (iDCM) and CI-DCM is still lacking.
METHODS AND RESULTS
All consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry were analysed. CI-DCM and iDCM were defined according to current recommendations. The primary study outcome measure was all-mortality death and secondary outcomes were a) a composite of cardiovascular death/heart-transplantation/ventricular-assist-device implantation, and b) major ventricular arrhythmias. The study included 551 patients (499 iDCM and 52 CI-DCM). At enrolment, compared with iDCM, CI-DCM patients were older (51 ± 14 years vs. 58 ± 3 years, respectively, P < 0.001) and had a higher left ventricular ejection fraction (32% ± 9 vs. 35% ± 10, respectively, P = 0.03). Over a median follow-up of 90 months (IQR 54-140 months), CI-DCM patients had a higher incidence of all-cause mortality compared with iDCM (36.5% vs. 8.4% in CI-DCM and iDCM respectively, P < 0.001), while the incidence of major ventricular arrhythmias was higher in the iDCM group compared with CI-DCM (4% vs. 0%, in CI-DCM and iDCM respectively, P = 0.03). The risk of the composite outcome was comparable between the two groups (P = 0.91). At Cox multivariable analysis, the diagnosis of CI-DCM emerged as independently associated to primary outcome (HR 6.42, 95% C.I. 2.52-16.31, P < 0.001).
CONCLUSIONS
In a well-selected DCM cohort, patients with a chemotherapy-induced aetiology had a higher incidence of all-cause mortality compared with iDCM. Conversely, the incidence of life-threatening ventricular arrhythmic events was higher among patients with iDCM.
Topics: Humans; Cardiomyopathy, Dilated; Stroke Volume; Ventricular Function, Left; Heart Transplantation; Arrhythmias, Cardiac; Antineoplastic Agents
PubMed: 35735911
DOI: 10.1002/ehf2.14045 -
International Heart Journal 2022Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain... (Meta-Analysis)
Meta-Analysis
Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain controversial. The present meta-analysis aimed to investigate whether sex plays a role in the outcome of patients with DCM and to provide real-world information on these potential sex differences for physicians and patients.We searched the PubMed, Cochrane, and EMBASE databases for published cohort studies up to February 16, 2020 that reported sex-specific prognostic outcomes (e.g., all-cause mortality; sudden cardiac death (SCD) ) in patients with DCM.Finally, 5 clinical cohort studies with a total of 5,709 patients were included. The results showed that males with DCM had a higher risk of all-cause mortality than females (HR: 1.61, 95% CI: 1.36~1.90; P < 0.00001). Next, the included studies were divided into short-term (< 5 years) and long-term (≥ 5 years) outcome groups by follow-up duration. Males showed a higher risk of all-cause mortality in both subgroups (< 5 years, HR: 1.59, 95% CI: 1.13~2.23; P = 0.008; ≥ 5 years, HR: 1.65, 95% CI: 1.33~2.05; P < 0.00001). In addition, the risks of SCD (HR: 1.80, 95% CI: 1.63~2.61; P = 0.002) and cardiovascular mortality in males (HR: 1.67, 95% CI: 1.25~2.23; P = 0.0005) were higher than those in females.The evidence from the published studies suggested that compared with females, males with DCM had an increased risk of all-cause mortality, cardiovascular mortality, and SCD.
Topics: Cardiomyopathy, Dilated; Death, Sudden, Cardiac; Female; Humans; Male; Prognosis; Sex Factors
PubMed: 35095074
DOI: 10.1536/ihj.20-448 -
Journal of Cardiovascular Medicine... Oct 2023Hypoalbuminemia was extensively used to diagnose malnutrition in older adults. Malnutrition was associated with mortality in elderly patients with cardiovascular...
AIMS
Hypoalbuminemia was extensively used to diagnose malnutrition in older adults. Malnutrition was associated with mortality in elderly patients with cardiovascular diseases. The relationship between hypoalbuminemia and clinical outcomes in elderly patients with nonischemic dilated cardiomyopathy (NIDCM) remains unknown.
METHODS
A total of 1058 consecutive patients with NIDCM (age ≥60 years) were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to assess the association of hypoalbuminemia with clinical outcomes.
RESULTS
Patients with hypoalbuminemia were older (69.29 ± 6.67 vs. 67.61 ± 5.90 years, P < 0.001) and had higher prevalence of in-hospital and long-term death than those without (6.9 vs. 1.7%, 50.7 vs. 35.2%, P < 0.001). Logistic regression analysis showed that hypoalbuminemia was significantly related to in-hospital death [odds ratio (OR): 4.334, 95% confidence interval (CI): 2.185-8.597, P < 0.001]. Kaplan-Meier survival analysis showed that patients with hypoalbuminemia had worse prognosis than those with nonhypoalbuminemia (log-rank χ2 28.96, P < 0.001). After adjusting for age, serum creatinine, HDL-C, AST/ALT hypoalbuminemia, LVEF and diabetes, hypoalbuminemia remained an independent predictor for long-term death (hazard ratio 1.322, 95% CI 0.046-1.670, P = 0.019).
CONCLUSION
Hypoalbuminemia was associated with increased risk of in-hospital and long-term mortality in elderly patients with NIDCM.
Topics: Humans; Aged; Middle Aged; Cardiomyopathy, Dilated; Serum Albumin; Hypoalbuminemia; Retrospective Studies; Hospital Mortality; Prognosis; Risk Factors
PubMed: 37577864
DOI: 10.2459/JCM.0000000000001530 -
Journal of the American College of... Jun 2022
Topics: Cardiomyopathy, Dilated; Humans; Phenotype
PubMed: 35654494
DOI: 10.1016/j.jacc.2022.04.008 -
Archives of Cardiovascular Diseases 2023Genetic cardiomyopathy is a rare disease in childhood.
BACKGROUND
Genetic cardiomyopathy is a rare disease in childhood.
AIMS
To analyse clinical and genetic aspects of a paediatric cardiomyopathy population, and to establish genotype-phenotype correlations.
METHODS
We performed a retrospective study of all patients with idiopathic cardiomyopathy aged<18years in Southeast France. Secondary causes of cardiomyopathy were excluded. All data (clinical, echocardiography, genetic testing) were collected retrospectively. Patients were classified into six groups: hypertrophic cardiomyopathy; dilated cardiomyopathy; restrictive cardiomyopathy; left ventricular non-compaction; arrhythmogenic right ventricular dysplasia; and mixed cardiomyopathy. Patients who did not have a complete genetic test according to current scientific developments had another deoxyribonucleic acid blood sample during the study time. Genetic tests were considered positive if the variant found was classified as pathogenic, likely pathogenic or a variant of uncertain significance.
RESULTS
Eighty-three patients were included between 2005 and 2019. Most patients had hypertrophic cardiomyopathy (39.8%) or dilated cardiomyopathy (27.7%). The median age at diagnosis was 1.28years (interquartile range: 0.27-10.48years). Heart transplantation was performed in 30.1% of patients, and 10.8% died during follow-up. Among 64 patients with a complete genetic analysis, 64.1% had genetic anomalies, mostly in MYH7 (34.2%) and MYBPC3 (12.2%) genes. There were no differences in the whole cohort between genotype-positive and genotype-negative patients. In the hypertrophic cardiomyopathy group, 63.6% had a positive genetic test. Patients with a positive genetic test more often had extracardiac impact (38.1% vs. 8.3%; P=0.009), and more often required an implantable cardiac defibrillator (23.8% vs. 0%; P=0.025) or a heart transplant (19.1% vs. 0%; P=0.047).
CONCLUSIONS
In our population, children with cardiomyopathy had a high positive genetic test rate. Hypertrophic cardiomyopathy with a positive genetic test is associated with a worse outcome.
Topics: Child; Humans; Infant; Child, Preschool; Retrospective Studies; Mutation; Cardiomyopathy, Dilated; Genetic Profile; Genetic Association Studies; Cardiomyopathy, Hypertrophic; Phenotype; Genetic Testing
PubMed: 37246080
DOI: 10.1016/j.acvd.2023.04.008 -
Minerva Cardiology and Angiology Apr 2022Non-ischemic dilated cardiomyopathy (NI-DCM) represents a specific etiology of systolic heart failure that usually affect young individuals with a genetic background in... (Review)
Review
Non-ischemic dilated cardiomyopathy (NI-DCM) represents a specific etiology of systolic heart failure that usually affect young individuals with a genetic background in up to 40% of cases. Behind the term NI-DCM there is a spectrum of different diseases, and an accurate etiological classification appears pivotal for the clinical management and prognostic stratification of these patients. In the last years the prognosis of NI-DCM patients dramatically improved thanks to the progresses in medical treatment/ device therapy and earlier diagnosis especially in familial context. In this review we summarize the actual state of art in the management of these patients. In the era of precision medicine, a lot of progresses have been made to expand our knowledge on the management of NI-DCM patients. A complex interaction between genotype and external triggers is the main determinant of the clinical phenotype in NI-DCM, and a lot of efforts must be done by clinicians to systematically rule out all the possible causes involved in the pathogenesis. Progresses in cardiac imaging and familial screening led us to detect subtle abnormalities in the initial phase of the disease and also helped us to furtherly stratify the prognosis and arrhythmic risk of these patients. It is plausible that a more precise etiological classification will be needed in the near future. NI-DCM contains a spectrum of different diseases. Proper etiological classification, early diagnosis and strict follow-up are essential to tailor care of these patients.
Topics: Cardiomyopathy, Dilated; Early Diagnosis; Forecasting; Humans; Myocardial Ischemia; Prognosis
PubMed: 34338487
DOI: 10.23736/S2724-5683.21.05736-7 -
Molecular & Cellular Proteomics : MCP Dec 2023Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two primary etiologies of end-stage heart failure. However, there remains a dearth of...
Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two primary etiologies of end-stage heart failure. However, there remains a dearth of comprehensive understanding the global perspective and the dynamics of the proteome and phosphoproteome in ICM and DCM, which hinders the profound comprehension of pivotal biological characteristics as well as differences in signal transduction activation mechanisms between these two major types of heart failure. We conducted high-throughput quantification proteomics and phosphoproteomics analysis of clinical heart tissues with ICM or DCM, which provided us the system-wide molecular insights into pathogenesis of clinical heart failure in both ICM and DCM. Both protein and phosphorylation expression levels exhibit distinct separation between heart failure and normal control heart tissues, highlighting the prominent characteristics of ICM and DCM. By integrating with omics results, Western blots, phosphosite-specific mutation, chemical intervention, and immunofluorescence validation, we found a significant activation of the PRKACA-GSK3β signaling pathway in ICM. This signaling pathway influenced remolding of the microtubule network and regulated the critical actin filaments in cardiac construction. Additionally, DCM exhibited significantly elevated mitochondria energy supply injury compared to ICM, which induced the ROCK1-vimentin signaling pathway activation and promoted mitophagy. Our study not only delineated the major distinguishing features between ICM and DCM but also revealed the crucial discrepancy in the mechanisms between ICM and DCM. This study facilitates a more profound comprehension of pathophysiologic heterogeneity between ICM and DCM and provides a novel perspective to assist in the discovery of potential therapeutic targets for different types of heart failure.
Topics: Humans; Cardiomyopathy, Dilated; Proteomics; Mitophagy; Myocardial Ischemia; Heart Failure; Cytoskeleton; Microtubules; rho-Associated Kinases
PubMed: 37852321
DOI: 10.1016/j.mcpro.2023.100667 -
Genome Medicine Sep 2023Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular...
BACKGROUND
Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.
METHODS
We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.
RESULTS
Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.
CONCLUSIONS
Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.
Topics: Humans; Animals; Dogs; Cardiomyopathy, Dilated; Homeostasis; Models, Animal; Phenotype; Risk Factors
PubMed: 37723491
DOI: 10.1186/s13073-023-01221-3 -
Clinical and Applied... 2023Despite the emerging prevalence of left ventricular (LV) thrombus in dilated cardiomyopathy (DCM), clinical characteristics, management, and disease prognosis are poorly...
Despite the emerging prevalence of left ventricular (LV) thrombus in dilated cardiomyopathy (DCM), clinical characteristics, management, and disease prognosis are poorly studied. We aim to assess the efficacy/safety profile of direct oral anticoagulants (DOACs) compared to warfarin by evaluating thrombus evolution, risk for stroke and systemic embolism (SSE), heart failure (HF) rehospitalization, all-cause mortality, and major adverse cardiovascular events (MACEs), and determine the impact of thrombus evolution on adverse events. We performed a historical cohort study of patients with a primary diagnosis of DCM and LV thrombus. Relationships between anticoagulants and thrombus resolution were analyzed with the Kaplan-Meier method and Cox regression. Associations between longitudinal thrombus evolution and adverse event hazard were measured with joint modeling. Among 122 patients included, 58.0% were prescribed warfarin, and 42.0% DOACs. Complete thrombus resolution at 90-day-after-index and 180-day-after-index was observed in 93 and 111 patients, with no difference in cumulative resolution between DOACs and warfarin. During a median follow-up of 12.5 months, MACE, all-cause death, SSE, and HF rehospitalization occurred in 42.6%, 27.9%, 4.1%, and 13.9% of patients, comparable in warfarin and DOACs groups. Thrombus persistence was associated with a higher risk of HF rehospitalization. Thrombus progression was associated with poor prognosis, with per unit increment in square-root-transformed thrombus-area resulting in a 1.0691-fold increase in MACE risk and a 1.0546-fold increase in death risk. This study suggests that in DCM patients with LV thrombus, DOACs were comparable to warfarin in thrombus resolution and safety profile. Thrombus persistence or progression was associated with an increased risk of HF rehospitalization, MACE, and mortality.
Topics: Humans; Administration, Oral; Anticoagulants; Cardiomyopathy, Dilated; Cohort Studies; Heart Failure; Prognosis; Stroke; Thrombosis; Warfarin
PubMed: 37259522
DOI: 10.1177/10760296231179683 -
Hellenic Journal of Cardiology : HJC =... 2023Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is... (Review)
Review
Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is an essential protein for maintaining muscle integrity. The lack of dystrophin plays a pathophysiological role in the development of dilated cardiomyopathy in Duchenne muscular dystrophy. Currently, no consensus exists on specific pharmacological therapy guidelines for these patients; however, it centers around the guidelines for heart failure management. This systematic review investigated 12 randomized control trials dating back to 2005 in the pharmacotherapy of patients with dilated cardiomyopathy Duchenne muscular dystrophy. This review specifically included angiotensin-converting enzyme inhibitors, aldosterone receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. Despite their limitations, these studies have shown promising effects in improving the overall heart function and prognosis in patients with this condition. However, to attain higher statistical significance, future studies should investigate larger populations and for longer periods.
Topics: Humans; Cardiomyopathy, Dilated; Muscular Dystrophy, Duchenne; Dystrophin; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists
PubMed: 37406964
DOI: 10.1016/j.hjc.2023.06.007