-
BMC Cardiovascular Disorders Jun 2024Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome,...
BACKGROUND
Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation.
CASE PRESENTATION
Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation.
CONCLUSIONS
Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.
Topics: Humans; Cardiomyopathy, Dilated; Male; Carney Complex; Adult; Heart Transplantation; Myxoma; Heart Failure; Heart Neoplasms; Treatment Outcome; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
PubMed: 38886700
DOI: 10.1186/s12872-024-03946-4 -
Scientific Reports Jun 2024Dilated cardiomyopathy (DCM) is a common cause of heart failure, thromboembolism, arrhythmias, and sudden cardiac death. The quality of life and long-term survival rates...
Dilated cardiomyopathy (DCM) is a common cause of heart failure, thromboembolism, arrhythmias, and sudden cardiac death. The quality of life and long-term survival rates of patients with dilated DCM have greatly improved in recent decades. Nevertheless, the clinical prognosis for DCM patients remains unfavorable. The primary driving factors underlying the pathogenesis of DCM remain incompletely understood. The present study aimed to identify driving factors underlying the pathogenesis of DCM from the perspective of gene regulatory networks. Single-cell RNA sequencing data and bulk RNA data were obtained from the Gene Expression Omnibus (GEO) database. Differential gene analysis, single-cell genomics analysis, and functional enrichment analysis were conducted using R software. The construction of Gene Regulatory Networks was performed using Python. We used the pySCENIC method to analyze the single-cell data and identified 401 regulons. Through variance decomposition, we selected 19 regulons that showed significant responsiveness to DCM. Next, we employed the ssGSEA method to assess regulons in two bulk RNA datasets. Significant statistical differences were observed in 9 and 13 regulons in each dataset. By intersecting these differentiated regulons and identifying shared targets that appeared at least twice, we successfully pinpointed three differentially expressed targets across both datasets. In this study, we assessed and identified 19 gene regulatory networks that were responsive to the disease. Furthermore, we validated these networks using two bulk RNA datasets of DCM. The elucidation of dysregulated regulons and targets (CDKN1A, SAT1, ZFP36) enhances the molecular understanding of DCM, aiding in the development of tailored therapies for patients.
Topics: Cardiomyopathy, Dilated; Gene Regulatory Networks; Single-Cell Analysis; Humans; Sequence Analysis, RNA; Gene Expression Profiling; RNA; Computational Biology; Gene Expression Regulation
PubMed: 38886541
DOI: 10.1038/s41598-024-64693-2 -
Scientific Reports Jun 2024The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive....
The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2-12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72-0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84-0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74-0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.
Topics: Humans; Male; Female; Middle Aged; Leukocytes; Cross-Sectional Studies; Telomere; Phenotype; Aged; Death, Sudden, Cardiac; Heart Failure; White People; Telomere Homeostasis; Electrocardiography; Risk Factors; United Kingdom; Cardiovascular Diseases
PubMed: 38886520
DOI: 10.1038/s41598-024-64997-3 -
Frontiers in Cardiovascular Medicine 2024Lacosamide is frequently used as a mono- or adjunctive therapy for the treatment of adults with epilepsy. Although lacosamide is known to act on both neuronal and...
BACKGROUND
Lacosamide is frequently used as a mono- or adjunctive therapy for the treatment of adults with epilepsy. Although lacosamide is known to act on both neuronal and cardiac sodium channels, potentially leading to cardiac arrhythmias, including Brugada syndrome (BrS), its adverse effects in individuals with genetic susceptibility are less understood.
CASE
We report a 33-year-old female with underlying epilepsy who presented to the emergency department with a four-day history of seizure clusters, and was initially treated with lacosamide therapy. During the intravenous lacosamide infusion, the patient developed sudden cardiac arrest caused by ventricular arrhythmias necessitating resuscitation. Of note, the patient had a family history of sudden cardiac death. Workup including routine laboratory results, 12-lead electrocardiogram (ECG), echocardiogram, and coronary angiogram was non-specific. However, a characteristic type 1 Brugada ECG pattern was identified by ajmaline provocation testing; thus, confirming the diagnosis of BrS. Subsequently, the genotypic diagnosis was confirmed by Sanger sequencing, which revealed a heterozygous mutation (c.2893C>T, p.Arg965Cys) in the gene. Eventually, the patient underwent implantable cardioverter-defibrillator implantation and was discharged with full neurological recovery.
CONCLUSION
This case highlights a rare but lethal adverse event associated with lacosamide treatment in patients with genetic susceptibility. Further research is warranted to investigate the interactions between lacosamide and variants.
PubMed: 38883985
DOI: 10.3389/fcvm.2024.1406614 -
Journal of Thoracic Disease May 2024Hypertrophic cardiomyopathy (HCM), identified as a primary cause of sudden cardiac death (SCD), intertwines with pulmonary hypertension (PH) to amplify cardiovascular...
Integrative bioinformatics approach for identifying key genes and potential therapeutic targets in the concurrent manifestation of hypertrophic cardiomyopathy and pulmonary hypertension.
BACKGROUND
Hypertrophic cardiomyopathy (HCM), identified as a primary cause of sudden cardiac death (SCD), intertwines with pulmonary hypertension (PH) to amplify cardiovascular morbidity. This complex synergy poses significant therapeutic challenges due to the absence of drugs specifically targeting their concurrent manifestation. This study seeks to unravel the molecular intricacies linking HCM and PH, aiming to lay the groundwork for targeted therapeutic interventions.
METHODS
Through the analysis of gene expression profiles from datasets GSE36961 (HCM) and GSE113439 (PH) within the public data repository of Gene Expression Omnibus (GEO), this research systematically identified differentially expressed genes (DEGs), conducted extensive functional annotations, and constructed detailed protein-protein interaction (PPI) networks to uncover crucial hub genes. Further, co-expression analyses, alongside drug prediction and molecular docking simulations, were employed to pinpoint potential therapeutic agents that could ameliorate the combined pathology of HCM and PH.
RESULTS
Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub genes. Validation across three additional datasets (GSE35229, GSE32453, and GSE53408) from GEO accentuated secreted phosphoprotein 1 () as a key gene of interest. Remarkably, the study identified tacrolimus, ponatinib, bosutinib, dasatinib, doxorubicin, and zanubrutinib as promising drugs for addressing the dual challenge of HCM and PH.
CONCLUSIONS
The findings of this investigation shed light on the genetic underpinnings of HCM and PH's simultaneous occurrence, emphasizing the central role of in their pathogenesis. The identification of six candidate drugs offers a hopeful vista for future therapeutic strategies targeting this complex cardiovascular interplay, marking a significant stride towards mitigating the compounded morbidity of HCM and PH. Future mechanistic and clinical studies are warranted for the investigation of this potential target and therapeutics.
PubMed: 38883633
DOI: 10.21037/jtd-23-1822 -
Cureus May 2024Introduction The World Health Organization has drawn attention to the fact that coronary artery disease (CAD) is our modern "epidemic." Nowadays, sudden death during...
Examining the Pre- and Post-percutaneous Coronary Intervention Blood Pressure Variability Using Ambulatory Blood Pressure Monitoring in Patients With Stable and Unstable Coronary Artery Disease.
Introduction The World Health Organization has drawn attention to the fact that coronary artery disease (CAD) is our modern "epidemic." Nowadays, sudden death during sleep has become prevalent due to a lack of oxygen supply to the heart. CAD causes more deaths and disabilities and incurs greater economic costs than any other illness in the developed world. The prevalence of cardiovascular disorders and heart disease is on the rise in India. Hypertension is one of the leading risk factors for all cardiovascular diseases. This study aims to compare blood pressure variability before and after percutaneous coronary intervention (PCI), using ambulatory blood pressure monitoring (ABPM) in patients with stable and unstable CAD. Materials and methods This prospective observational study was conducted among 52 patients with stable and unstable CAD, admitted to the medicine department, who required PCI at a tertiary care hospital. Before and after PCI, the same antihypertensive drugs were orally administered. ABPM was performed before PCI and one day after PCI. ABPM was conducted every 30 minutes during the day and every 60 minutes during the night over a 24-hour period using a mobil-o-graph (IEM, Germany). The results of the observed parameters were analyzed using the HMS Client-Server 4.0 system (Informer Technologies, Inc., Los Angeles, USA). The collected data were analyzed using SPSS Statistics version 21.0 software (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). Results Out of 52 patients, 28 (53.8%) had stable CAD and 24 (46.2%) had unstable CAD. The mean age of patients with stable and unstable CAD was 56.64±9.44 and 57.04±12.36 years, respectively. The majority of patients with stable (67.9%) and unstable CAD (62.5%) were males. Various other variables were considered, such as lipid profile, blood sugar, cardiac troponin-I, and medical history, including hypertension and type 2 diabetes mellitus. Among stable CAD patients, a comparison between pre- and post-PCI systolic blood pressure (SBP) did not show a significant difference in all SBP measurements (p>0.05). However, the mean diurnal index was significantly lower following PCI compared to before PCI (p=0.019). Among unstable CAD patients, a comparison between pre- and post-PCI SBP showed a significant change in peak daytime, average daytime, and diurnal index (p<0.05). For all other SBP measurements, the difference between pre- and post-PCI measurements was not statistically significant (p>0.05). In patients with stable CAD, a statistically significant change in diastolic blood pressure (DBP) following PCI was observed for peak daytime, peak nighttime, and average nighttime values. In contrast, for patients with unstable CAD, a statistically significant change in DBP following PCI was observed for peak daytime, peak nighttime, and minimum daytime values (p<0.05). Statistically, post-PCI, there was no significant difference between the two groups for SBP and DBP measurements (p>0.05). Additionally, there was no significant difference between the two groups pre- and post-PCI in the pattern of dipping. Conclusion A comparison of the ABPM before and after PCI showed that, within 48 hours post-PCI, the ambulatory blood pressure indicators did not differ statistically from those before PCI.
PubMed: 38882951
DOI: 10.7759/cureus.60465 -
ARYA Atherosclerosis 2023Cerebral ischemia and coronary artery disease (CAD), the major leading causes of mortality and morbidity worldwide, are pathophysiologically interrelated. Cerebral...
INTRODUCTION
Cerebral ischemia and coronary artery disease (CAD), the major leading causes of mortality and morbidity worldwide, are pathophysiologically interrelated. Cerebral ischemic events are categorized as large or small vessels disease. The current study compares the factors related to CAD events incidence following ischemic large versus small disease CVA.
METHOD
The current cohort study was conducted on 225 patients with ischemic stroke in two groups of large (n=75) and small (n=150) vessel disease during 2018-19. The patients' demographic, medical, and clinical characteristics were recruited. They were followed for three years regarding the incidence of CAD events, including ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), unstable angina (UA), and sudden cardiac death (SCD). Data about the coronary angiography, computed tomography angiography (CTA), Single Photon Emission Computed Tomography (SPECT), and the therapeutic approach were gathered.
RESULTS
There were insignificant differences between the patients with small versus large vessels CVA in terms of ACS incidence (P-value=0.105), type of the events (P-value=0.836), angiographic (P-value=0.671), SPECT (P-value=0.99) and CTA findings (P-value>0.99) and approached CAD (P-value=0.728). Cox regression assessments revealed an increased risk of CAD events due to large versus small vessels disease after adjustments for hypertension, diabetes mellitus, dyslipidemia, re-stroke, and the previous history of IHD (HR=2.005, 95%CI: 1.093-2.988, P-value=0.021).
CONCLUSION
According to the findings of this study, large-vessel involvement in an ischemic stroke was associated with more than a two-fold increase in the three-year probability of ischemic heart disease incidencet.
PubMed: 38882650
DOI: 10.48305/arya.2023.26660.2820 -
Heart Rhythm Jun 2024The electromechanical window (EMW) is calculated by subtracting the repolarization duration from a mechanical reference representing contraction duration in the same... (Review)
Review
The electromechanical window (EMW) is calculated by subtracting the repolarization duration from a mechanical reference representing contraction duration in the same heartbeat (e.g., aortic-valve closure during echocardiography with simultaneous ECG). Here, we review the current knowledge on the role of the EMW as an independent parameter for ventricular arrhythmia-risk stratification. We (1) provide a standardized approach to echocardiographic EMW assessment, (2) define relevant cut-off values for both abnormal EMW negativity and positivity, (3) discuss pathophysiologic underpinnings of EMW negativity, and (4) outline the potential future role of cardiac electromechanical relations in patients with proarrhythmic conditions.
PubMed: 38878938
DOI: 10.1016/j.hrthm.2024.06.012 -
JACC. Clinical Electrophysiology May 2024Conventional measures of heart rate variability (HRV) have shown only modest associations with sudden cardiac death (SCD). Detrended fluctuation analysis (DFA), with...
BACKGROUND
Conventional measures of heart rate variability (HRV) have shown only modest associations with sudden cardiac death (SCD). Detrended fluctuation analysis (DFA), with novel methodological developments to evaluate the short-term scaling exponent, is a potentially superior method compared to conventional HRV tools.
OBJECTIVES
In this study, the authors studied the analysis of the association between DFA and SCD.
METHODS
The investigators studied the predictive value of ultra-short-term heart rate fluctuations (1-minute electrocardiogram samples) with DFA at rest and during different stages of physical exertion for incident SCD among 2,794 participants undergoing clinical exercise testing in the prospective FINCAVAS (Finnish Cardiovascular Study). The novel key DFA measure, the short-scale scaling exponent computed with second-order detrending (DFA2 α), was the main exposure variable. SCDs were defined by American Heart Association/European Society of Cardiology criteria using death certificates with written accounts of the events.
RESULTS
During a median follow-up of 8.3 years (Q1-Q3: 6.4-10.5), 83 SCDs occurred. DFA2 α measured at rest (but not in exercise) associated highly significantly with the risk of SCD, with 1-SD lower values associating with a 2.4-fold (Q1-Q3: 2.0-3.0) risk (P < 0.001). The results persisted when adjusting for other major risk factors for SCD, including age, cardiovascular morbidities, cardiorespiratory fitness, heart rate reduction, and left ventricular ejection fraction. Associations between conventional HRV parameters (measured at any stage of exercise or at rest) and SCD were substantially weaker and statistically nonsignificant after adjusting for other risk factors.
CONCLUSIONS
Ultra-short-term DFA2 α, when measured at rest, is a powerful and independent predictor of SCD. The association between DFA2 α and SCD is modified by physical exertion.
PubMed: 38878016
DOI: 10.1016/j.jacep.2024.04.018 -
ESC Heart Failure Jun 2024Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic cardiac disorder characterized by unexplained left ventricular hypertrophy. It can cause a wide...
AIMS
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic cardiac disorder characterized by unexplained left ventricular hypertrophy. It can cause a wide spectrum of clinical manifestations, ranging from asymptomatic to heart failure and sudden cardiac death (SCD). Approximately half of HCM cases are caused by variants in sarcomeric proteins, including α-tropomyosin (TPM1). In this study, we aimed to characterize the clinical and molecular phenotype of HCM in an Iranian pedigree with SCD.
METHODS AND RESULTS
The proband and available family members underwent comprehensive clinical evaluations, including echocardiography, cardiac magnetic resonance (CMR) imaging and electrocardiography (ECG). Whole-exome sequencing (WES) was performed in all available family members to identify the causal variant, which was validated, and segregation analysis was conducted via Sanger sequencing. WES identified a novel missense variant, c.761A>G:p.D254G (NM_001018005.2), in the TPM1 gene, in the proband, his father and one of his sisters. Bioinformatic analysis predicted it to be likely pathogenic. Clinical features in affected individuals were consistent with HCM.
CONCLUSIONS
The identification of a novel TPM1 variant in a family with HCM and SCD underscores the critical role of genetic screening in at-risk families. Early detection of pathogenic variants can facilitate timely intervention and management, potentially reducing the risk of SCD in individuals with HCM.
PubMed: 38874371
DOI: 10.1002/ehf2.14906