Promise and Peril of a Genotype-First Approach to Mendelian Cardiovascular Disease.

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard-of-care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in-depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype-first screening of asymptomatic individuals for Mendelian CVD.

Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial.

Background: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics.

Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery: Design and Rationale of the REPAIR MR Trial.

Background The current standard of care for the treatment of patients with primary mitral regurgitation (MR) is surgical mitral valve repair. Transcatheter edge-to-edge repair with the MitraClip device provides a less invasive treatment option for patients with both primary and secondary MR. Worldwide, >150 000 patients have been treated with the MitraClip device.

Automated Quantification of Abnormal QRS Peaks From High-Resolution ECGs Predicts Late Ventricular Arrhythmias in Hypertrophic Cardiomyopathy: A 5-Year Prospective Multicenter Study.

Background Patients with hypertrophic cardiomyopathy (HCM) are at risk of ventricular arrhythmia (VA) attributed to abnormal electrical activation arising from myocardial fibrosis and myocyte disarray. We sought to quantify intra-QRS peaks (QRSp) in high-resolution ECGs as a measure of abnormal activation to predict late VA in patients with HCM. Methods and Results Prospectively enrolled patients with HCM (n=143, age 53±14 years) with prophylactic implantable cardioverter-defibrillators had 3-minute, high-resolution (1024 Hz), digital 12-lead ECGs recorded during intrinsic rhythm.

Atrial Electrical Remodeling in Mice With Cardiac-Specific Overexpression of Angiotensin II Type 1 Receptor.

Background Elevated angiotensin II levels are thought to play an important role in atrial electrical and structural remodeling associated with atrial fibrillation. However, the mechanisms by which this remodeling occurs are still unclear. Accordingly, we explored the effects of angiotensin II on atrial remodeling using transgenic mice overexpressing angiotensin II type 1 receptor (AT1R) specifically in cardiomyocytes.

Redo-Transcatheter Aortic Valve Replacement: Strategies When the First Transcatheter Aortic Valve Replacement Fails.

Transcatheter aortic valve replacement (TAVR) is the standard of care for patients with symptomatic severe aortic stenosis at high or prohibitive surgical risk. The 2020 valvular heart disease guidelines from the American College of Cardiology and American Heart Association now include TAVR as a class I indication for patients aged 65-80 years and not at high or prohibitive risk. The longer life expectancy of this patient population raises the issue of TAVR valve durability and the management of bioprosthetic valve failure of TAVR valves.

Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non-hypertensive Alzheimer's patients.

Introduction: Acetylcholinesterase inhibitors (AChEIs) are commonly used to treat mild to moderate cases of Alzheimer disease (AD). To the best of our knowledge, there has been no study estimating the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Therefore, this study aimed to estimate the association between AChEIs and the risk of bleeding and cardiovascular ischemic events in patients with non-hypertensive AD.

Repurposing colchicine's journey in view of drug-to-drug interactions. A review.

Colchicine's medical evolution is historically bound to the Mediterranean basin, since remarkable researchers from this region underscored its valuable properties. With the passing of years colchicine became an essential pharmaceutical substance for the treatment of rheumatologic and cardiovascular diseases. In light of recent findings, the therapeutic value of colchicine has grown.

Assessing cardiovascular infection and inflammation with FDG-PET.

FDG-PET has been shown to be a useful imaging modality for the assessment of cardiovascular infection and inflammatory pathologies. However, interpretation of these studies can be challenging in light of the variability of physiological myocardial uptake and, occasionally, interpreter's lack of familiarity with the typical findings present in cardiac pathologies. In this article, we review established and emerging applications for cardiovascular infection and inflammation imaging with FDG-PET and present typical examples of representative pathologies.

Platelet Quiescence in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Bypass Graft Surgery.

Background The optimal antiplatelet strategy for patients with acute coronary syndromes who require coronary artery bypass surgery remains unclear. While a more potent antiplatelet regimen will predispose to perioperative bleeding, it is hypothesized that through "platelet quiescence," ischemic protection conferred by such therapy may provide a net clinical benefit. Methods and Results We compared patients undergoing coronary artery bypass surgery who were treated with a more potent antiplatelet inhibition strategy with those with a less potent inhibition through a meta-analysis.

Post-operative pain following cardiac implantable electronic device implantation: insights from the BRUISE CONTROL trials.

Aims: Post-operative pain following cardiac implantable electronic device (CIED) insertion is associated with patient dissatisfaction, emotional distress, and emergency department visits. We sought to identify factors associated with post-operative pain and develop a prediction score for post-operative pain.

Methods And Results: All patients from the BRUISE CONTROL-1 and 2 trials were included in this analysis.

Aspirin Reduces the Potentiating Effect of CD40L on Platelet Aggregation via Inhibition of Myosin Light Chain.

Background Antiplatelet therapy with aspirin (acetylsalicylic acid [ASA]) is less efficient in some coronary patients, which increases their risk of developing thrombosis. Elevated blood levels of thromboinflammatory mediators, like soluble CD40L (sCD40L), may explain such variabilities. We hypothesized that in the presence of elevated levels of sCD40L, the efficacy of ASA may vary and aimed to determine the effects of ASA on CD40L signaling and aggregation of platelets.

SPECT and PET imaging of adrenomedullin receptors: a promising strategy for studying pulmonary vascular diseases.

Circulating adrenomedullin (AM) levels are elevated in several cardiovascular diseases, including pulmonary vascular diseases causing pulmonary hypertension. To date the perfusion agent Tc-albumin macroaggregates (MAA) is the only approved radiopharmaceutical used for imaging of pulmonary circulation. Unlike Tc-MAA, imaging the AM receptors involves a molecular process dependent on the density of the receptors and the affinity of specific radioligands.

Metabolic Response to Stress by the Immature Right Ventricle Exposed to Chronic Pressure Overload.

Background The right ventricle exposed to chronic pressure overload exhibits hypertrophy and decompensates when exposed to stress. We hypothesize that impaired ability to increase myocardial oxidative flux through pyruvate dehydrogenase leads to hypertrophied right ventricular (RV) dysfunction when exposed to hemodynamic stress, and pyruvate dehydrogenase stimulation can improve RV function. Methods and Results Infant male Yorkshire piglets (13.

Variants at the APOE /C1/C2/C4 Locus Modulate Cholesterol Efflux Capacity Independently of High-Density Lipoprotein Cholesterol.

Background Macrophage cholesterol efflux to high-density lipoproteins ( HDLs ) is the first step of reverse cholesterol transport. The cholesterol efflux capacity ( CEC ) of HDL particles is a protective risk factor for coronary artery disease independent of HDL cholesterol levels. Using a genome-wide association study approach, we aimed to identify pathways that regulate CEC in humans.

Simultaneous inference of haplotypes and alleles at a causal gene.

We present a methodology which jointly infers haplotypes and the causal alleles at a gene influencing a given trait. Often in human genetic studies, the available data consists of genotypes (series of genetic markers along the chromosomes) and a phenotype. However, for many genetic analyses, one needs haplotypes instead of genotypes.

The Canadian STOP-PAIN project: the burden of chronic pain-does sex really matter?

Objectives: The Canadian STOP-PAIN Project assessed the human and economic burden of chronic pain (CP) in individuals on waitlists of Canadian multidisciplinary pain treatment facilities. This article focuses on sex differences. Objectives were to (1) determine the pain characteristics and related biopsychosocial factors that best differentiated women and men with CP; and (2) examine whether public and private costs associated with CP differed according to sex.

Reproducibility of near-infrared spectroscopy parameters measured during brachial artery occlusion and reactive hyperemia in healthy men.

Near-infrared spectroscopy (NIRS) is a noninvasive technique evaluating microvascular function. The aim of this study was to assess the reproducibility of NIRS parameters during reactive hyperemia induced by a 5 min brachial artery occlusion. Twenty-four healthy young males (mean 34 ± 8 years old) had two microvascular function evaluations by NIRS over a 7 to 30-day period (mean 16 ± 10 days).

Brugada syndrome.

First described in 1992, Brugada syndrome is characterized by a specific electrocardiographic pattern in the right precordial leads and susceptibility to ventricular arrhythmias and sudden death. Brugada syndrome is included among the channelopathies, primary electrical disorders that, characteristically, are not associated with concomitant structural cardiac abnormalities. In recent years, substantial preclinical and clinical research has led to the identification of multiple causative mutations and to understanding of the mechanisms underlying the development of the characteristic phenotype and of the factors that determine clinical prognosis in patients.

Left ventricular end-diastolic pressure is a predictor of mortality in cardiac surgery independently of left ventricular ejection fraction.

Background: Several risk factors have been shown to increase mortality in cardiac surgery. However, the importance of left ventricular end-diastolic pressure (LVEDP) as an independent risk factor before cardiac surgery is unclear. Method.