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Circulation Jun 2024Low plasma levels of eicosapentaenoic acid (EPA) are associated with cardiovascular events. This trial aimed to assess the clinical benefits of icosapent ethyl in...
BACKGROUND
Low plasma levels of eicosapentaenoic acid (EPA) are associated with cardiovascular events. This trial aimed to assess the clinical benefits of icosapent ethyl in patients with coronary artery disease, a low EPA/arachidonic acid (AA) ratio, and statin treatment.
METHODS
In this prospective, multicenter, randomized, open-label, blinded end-point study, patients with stable coronary artery disease and a low EPA/AA ratio (<0.4) were randomized to EPA (1800 of icosapent ethyl administered daily) or control group. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina pectoris, and coronary revascularization. The secondary composite end points of coronary events included sudden cardiac death, fatal and nonfatal myocardial infarction, unstable angina requiring emergency hospitalization and coronary revascularization, or coronary revascularization.
RESULTS
Overall, 3884 patients were enrolled at 95 sites in Japan. Among them, 2506 patients had a low EPA/AA ratio, and 1249 and 1257 patients were randomized to the EPA and control group, respectively. The median EPA/AA ratio was 0.243 (interquartile range, 0.180-0.314) and 0.235 (interquartile range, 0.163-0.310) in the EPA and control group, respectively. Over a median period of 5 years, the primary end point occurred in 112 of 1225 patients (9.1%) and 155 of 1235 patients (12.6%) in the EPA and control group, respectively (hazard ratio, 0.79 [95% CI, 0.62-1.00]; =0.055). Meanwhile, the secondary composite end point of coronary events in the EPA group was significantly lower (81/1225 [6.6%] versus 120/1235 [9.7%] patients; hazard ratio, 0.73 [95% CI, 0.55-0.97]). Adverse events did not differ between the groups, but the rate of new-onset atrial fibrillation was significantly higher in the EPA group (3.1% versus 1.6%; =0.017).
CONCLUSIONS
Icosapent ethyl treatment resulted in a numerically lower risk of cardiovascular events that did not reach statistical significance in patients with chronic coronary artery disease, a low EPA/AA ratio, and statin treatment.
REGISTRATION
URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012069.
PubMed: 38873793
DOI: 10.1161/CIRCULATIONAHA.123.065520 -
Frontiers in Immunology 2024The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can... (Review)
Review
The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can contribute to the development of chronic inflammatory diseases. Important among these diseases is atherosclerosis, which refers to focal lesions in the arterial intima driven by elevated apolipoprotein B-containing lipoproteins, notably low-density lipoprotein (LDL), and characterized by the formation of a plaque composed of inflammatory immune cells, a collection of dead cells and lipids called the necrotic core, and a fibrous cap. As the disease progresses, the necrotic core expands, and the fibrous cap becomes thin, which increases the risk of plaque rupture or erosion. Plaque rupture leads to a rapid thrombotic response that can give rise to heart attack, stroke, or sudden death. With marked lowering of circulating LDL, however, plaques become more stable and cardiac risk is lowered-a process known as atherosclerosis regression. A critical aspect of both atherosclerosis progression and regression is the crosstalk between innate (myeloid cells) and adaptive (T-lymphocytes) immune cells. Myeloid cells are specialized at clearing apoptotic cells by a process called efferocytosis, which is necessary for inflammation resolution. In advanced disease, efferocytosis is impaired, leading to secondary necrosis of apoptotic cells, inflammation, and, most importantly, defective tissue resolution. In regression, efferocytosis is reawakened aiding in inflammation resolution and plaque stabilization. Here, we will explore how efferocytosing myeloid cells could affect T-cell function and vice versa through antigen presentation, secreted factors, and cell-cell contacts and how this cellular crosstalk may contribute to the progression or regression of atherosclerosis.
Topics: Humans; Atherosclerosis; T-Lymphocytes; Myeloid Cells; Animals; Cell Communication; Phagocytosis; Apoptosis; Plaque, Atherosclerotic
PubMed: 38873597
DOI: 10.3389/fimmu.2024.1403150 -
Current Treatment Options in... Dec 2023Sudden cardiac arrest is associated with high morbidity and mortality. Despite having a disproportionate burden of sudden cardiac death (SCD), rates of primary and...
PURPOSE OF REVIEW
Sudden cardiac arrest is associated with high morbidity and mortality. Despite having a disproportionate burden of sudden cardiac death (SCD), rates of primary and secondary prevention of SCD with implantable cardioverter-defibrillator (ICD) therapy are lower among eligible racially minoritized patients. This review highlights the racial and ethnic disparities in ICD utilization, associated barriers to ICD care, and proposed interventions to improve equitable ICD uptake.
RECENT FINDINGS
Racially minoritized populations are disproportionately eligible for ICD therapy but are less likely to see cardiac specialists, be counseled on ICD therapy, and ultimately undergo ICD implantation, fueling disparate outcomes. Racial disparities in ICD utilization are multifactorial, with contributions at the patient, provider, health system, and structural/societal level.
SUMMARY
Racial and ethnic disparities have been demonstrated in preventing SCD with ICD use. Proposed strategies to mitigate these disparities must prioritize care delivery and access to care for racially minoritized patients, increase the diversification of clinical and implementation trial participants and the healthcare workforce, and center reparative justice frameworks to rectify a long history of racial injustice.
PubMed: 38873495
DOI: 10.1007/s11936-023-01025-z -
Frontiers in Genetics 2024Long QT syndrome (LQTS) is an inherited malignant arrhythmia syndrome that poses a risk of sudden death. Variants in the Potassium Voltage-Gated Channel Subfamily H...
BACKGROUND
Long QT syndrome (LQTS) is an inherited malignant arrhythmia syndrome that poses a risk of sudden death. Variants in the Potassium Voltage-Gated Channel Subfamily H Member 2 () gene are known to cause Long QT syndrome through an autosomal dominant inheritance pattern. However, as of now, there have been no reports of any variant leading to Long QT syndrome exhibiting incomplete penetrance that is influenced by gender.
METHODS
Whole-exome sequencing (WES) was conducted on the proband to identify pathogenic variants. Subsequently, Sanger sequencing was employed to validate the identified likely pathogenic variants in all family members.
RESULTS
We analyzed a pedigree spanning three-generations afflicted by Long QT syndrome. WES revealed a novel missense variant (p.Val630Gly, c.1889 T>G) as the causative factor for the family's phenotype. Within this family, all three male carriers of the variant carriers exhibited the Long QT syndrome phenotype: one experienced sudden death during sleep, another received an implantable cardioverter defibrillator (ICD), and a younger man displayed a prolonged QTc interval without any instances of syncope or malignant arrhythmia to date. Interestingly, the middle-aged female carrier showed no Long QT Syndrome phenotype. However, her offspring, diagnosed with Turner syndrome (45, X) and also a carrier of this variant, experienced frequent syncope starting at 12 years old and was diagnosed with Long QT syndrome, leading to an ICD implantation when she was 15 years old. These observations suggest that the manifestation of Long QT syndrome associated with this KCNH2 variant exhibits incomplete penetrance influenced by gender within this family, indicating potential protective mechanisms against the syndrome in females affected by this variant.
CONCLUSION
Our investigation has led to the identification of a novel pathogenic variant responsible for Long QT syndrome within a familial context characterized by gender-selective, incomplete penetrance. This discovery highlights a unique pathogenic inheritance pattern for the gene associated with Long QT syndrome, and could potentially shed light on the distinct penetrance behaviors and patterns of the gene. This discovery broadens our exploration of the KCNH2 gene in cardiac arrhythmias, highlighting the intricate genetic dynamics behind Long QT syndrome.
PubMed: 38873110
DOI: 10.3389/fgene.2024.1409459 -
Journal of Medical Economics Jun 2024Patients with obstructive hypertrophic cardiomyopathy (oHCM) experience significant clinical burden which is associated with a high economic burden. Peak oxygen uptake... (Review)
Review
Patients with obstructive hypertrophic cardiomyopathy (oHCM) experience significant clinical burden which is associated with a high economic burden. Peak oxygen uptake (pVO2), measured by cardiopulmonary exercise testing, is used to quantify functional capacity, and has been studied as a primary endpoint in recent clinical trials. This study aimed to gather evidence to consolidate the prognostic value of pVO2 in oHCM and to assess whether it is feasible to predict health outcomes in an economic model based on changes in pVO2. A targeted literature review was conducted in MEDLINE (via PubMed) and Embase databases to identify evidence on the prognostic value of pVO2 as a surrogate health outcome to support future oHCM economic model development. Following screening, study characteristics, population characteristics and pVO2 prognostic association data were extracted. A total of 4,687 studies were identified. 3,531 and 538 studies underwent title/abstract and full-text screening, respectively, of which 151 were included and 9 of these were in hypertrophic cardiomyopathy (HCM); only 3 studies focused on oHCM. The 9 HCM studies consisted of 1 systematic literature review and 8 primary studies reporting on 27 potentially predictive relationships from a pVO2-based metric with clinical outcomes including all-cause mortality, cardiovascular mortality, sudden cardiac death, transplant, paroxysmal and permanent atrial fibrillation. pVO2 was described as a predictor of single and composite endpoints, in 3 and 6 studies respectively, with 1 study reporting on both. This study primarily uses systemic literature review methods but does not qualify as one due to not entailing parallel reviewers during title-abstract and full-text stages of review. The findings of this study suggest pVO2 is predictive of multiple health outcomes, providing rationale to use pVO2 in the development of an economic model.
PubMed: 38868944
DOI: 10.1080/13696998.2024.2367920 -
Noro Psikiyatri Arsivi 2024Electroconvulsive therapy (ECT) is one of the biological therapies that is well tolerated and has a low risk of complications. Acute cardiovascular complications related...
INTRODUCTION
Electroconvulsive therapy (ECT) is one of the biological therapies that is well tolerated and has a low risk of complications. Acute cardiovascular complications related to ECT such as ventricular arrhythmia, myocardial infarction and cardiac arrest have been recorded. Increased frontal QRS-T (fQRS-T) angle was associated with ventricular arrhythmia, sudden cardiac death and total mortality. In this study, we aimed to evaluate the effect of ECT on the myocardium using electrocardiography (ECG) parameters such as fQRS-T angle, QRS duration, QT and QTc interval.
METHODS
A total of 108 patients diagnosed with bipolar disorder (n=36), depressive disorder (n=70) and schizophrenia (n=2) who underwent ECT were included in this study. 12-lead surface ECG of all patients were taken before the ECT, 15 min. after ECT and 24 hour after ECT.
RESULTS
QRS duration, QT interval and corrected QT (QTc) interval were not changed significantly during the follow-up period. However, we found that, fQRS-T angle was significantly increased 15 minutes after ECT compared to baseline angle (p<0.001). We also detected that this increase in fQRS-T angle 15 minutes after ECT was significantly reduced 24 hours after ECT (p=0.031). Meanwhile, there was no significant difference between baseline and 24th hour fQRS-T angle (p=0.154).
CONCLUSIONS
In our study, a significant increase in fQRS-T angle was observed 15 min after ECT. However, the fQRS-T angle was found to return to normal after 24 hours. Our findings may indicate that ECT does not have a permanent side effect on the risk of cardiovascular events according to the fQRS-T angle.
PubMed: 38868850
DOI: 10.29399/npa.28443 -
European Heart Journal Supplements :... Apr 2024The identification of ventricular premature complexes during a cardiological evaluation necessitates the implementation of diagnostic processes aimed at discerning the...
The identification of ventricular premature complexes during a cardiological evaluation necessitates the implementation of diagnostic processes aimed at discerning the clinical context that may predispose individuals to a high risk of sudden cardiac death. Epidemiological studies reveal that ventricular premature beats occur in approximately 75% of healthy (or seemingly healthy) individuals, as long as there is no evidence of underlying structural heart disease, such as benign idiopathic ventricular extrasystole originating from the right and left ventricular outflow tracts. In the real world, however, ventricular ectopic beats with morphologies very similar to seemingly benign occurrences are not uncommon. They are notable in subjects exhibiting rapid and complex repetitive forms during exercise testing and Holter electrocardiogram. Additionally, these subjects may display more or less extensive scarring signs on cardiac magnetic resonance and may have a family history of cardiomyopathy and/or sudden cardiac death. Therefore, the purpose of this review is to critically analyse the process of evaluating premature ventricular complexes, which is crucial for accurate risk stratification. The latter cannot overlook some inevitable elements, including morphology, origin, complexity, and the associated clinical setting (absence or presence of structural heart disease).
PubMed: 38867874
DOI: 10.1093/eurheartjsupp/suae006 -
European Heart Journal Supplements :... Apr 2024Brugada syndrome mainly affects young subjects with structurally normal heart and can cause x syncope or sudden death due to ventricular arrhythmias, even as the first...
Brugada syndrome mainly affects young subjects with structurally normal heart and can cause x syncope or sudden death due to ventricular arrhythmias, even as the first manifestation, in approximately 5-10% of cases. To date, two questions remain open: how to recognize subjects who will experience arrhythmic events and how to treat them. The guidelines suggest treating subjects with a previous history of cardiac arrest or arrhythmogenic syncope, while they are unconclusive about the management of asymptomatic patients, who represent ∼90% of Brugada patients. We recently demonstrated that in asymptomatic patients, the presence of spontaneous Brugada type 1 electrocardiogram (ECG) pattern and inducibility of ventricular arrhythmias at electrophysiological study allows us to identify a group of patients at greater risk who deserve treatment. Regarding treatment, there are three options: implantable cardioverter defibrillator, drugs, and epicardial transcatheter ablation. Recent studies have shown that the latter is effective and free from serious side effects, thus opening a new scenario in the treatment of Brugada patients at risk. Subjects who present drug-induced-only type 1 Brugada ECG pattern, in whom a spontaneous type 1 pattern has been ruled out with repeated ECGs and 12-lead 24-h Holter monitoring, represent a very low-risk group, provided they adhere to behavioural recommendations and undergo regular follow-up.
PubMed: 38867864
DOI: 10.1093/eurheartjsupp/suae021 -
European Heart Journal Supplements :... Apr 2024Sudden cardiac death remains a critical public health concern globally, affecting millions annually. Recent advances in cardiac arrhythmia mapping have demonstrated that...
Sudden cardiac death remains a critical public health concern globally, affecting millions annually. Recent advances in cardiac arrhythmia mapping have demonstrated that the ventricular epicardial region has a critical arrhythmogenic role in some inherited cardiogenetic diseases. Among these, long-QT syndrome (LQTS) exposes patients to the risk of life-threatening arrhythmic events. Despite advancements, there is a need for more effective therapeutic strategies. A recent study has uncovered a noteworthy connection between LQTS and epicardial structural abnormalities, challenging the traditional view of LQTS as purely an electrical disorder. High-density mapping revealed electroanatomic abnormalities in the right ventricular epicardium, presenting a potential target for catheter ablation, to finally suppress ventricular fibrillation recurrences in high-risk LQTS patients.
PubMed: 38867856
DOI: 10.1093/eurheartjsupp/suae009 -
Stem Cell Research Aug 2024Dilated cardiomyopathy (DCM) is one of the main causes of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation worldwide....
Dilated cardiomyopathy (DCM) is one of the main causes of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation worldwide. Mutations in dozens of cardiac genes have been connected to the development of DCM including the Troponin T2 gene (TNNT2). Here, we generated a human induced pluripotent stem cells (hiPSCs) from a DCM patient with a familial history that carries a missense mutation in TNNT2. The hiPSCs show typical morphology of pluripotent stem cells, expression of pluripotency markers, normal karyotype, and in vitro capacity to differentiate into all three germ layers.
Topics: Humans; Cardiomyopathy, Dilated; Induced Pluripotent Stem Cells; Troponin T; Cell Differentiation; Cell Line; Male; Karyotype
PubMed: 38861774
DOI: 10.1016/j.scr.2024.103467