ABCD-GENE Score and Clinical Outcomes Following Percutaneous Coronary Intervention: Insights from the TAILOR-PCI Trial.

Background In TAILOR-PCI, genotype-guided selection of P2Y inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD-GENE score for tailoring P2Y inhibitor selection after percutaneous coronary intervention.

Disseminated Blastomycosis Presenting with Spontaneous Coronary Artery Dissection.

Unlabelled: Spontaneous coronary artery dissection (SCAD) is increasingly recognized as an important cause of acute coronary syndrome (ACS) and myocardial infarction (MI) in individuals with few or no known atherosclerotic risk factors. While systemic autoimmune inflammatory disorders are associated with precipitating SCAD, the role of infection-induced systemic inflammation in SCAD is not well defined. We present the case of a 49-year-old Caucasian woman with ST-elevation myocardial infarction (STEMI) diagnosed as SCAD from a severe systemic inflammatory response related to disseminated blastomycosis.

International survey of patients undergoing percutaneous coronary intervention and their attitudes toward pharmacogenetic testing.

Objective: To evaluate perceptions toward pharmacogenetic testing of patients undergoing percutaneous coronary intervention (PCI) who are prescribed dual antiplatelet therapy (DAPT) and whether geographical differences in these perceptions exist.

Participants And Methods: TAILOR-PCI is the largest genotype-based cardiovascular clinical trial randomizing participants to conventional DAPT or prospective genotyping-guided DAPT. Enrolled patients completed surveys before and 6 months after randomization.

Platypnea-Orthodeoxia Syndrome: Diagnostic Challenge and the Importance of Heightened Clinical Suspicion.

Platypnea-orthodeoxia syndrome is an uncommon condition of positional dyspnea and hypoxemia; symptoms occur when the patient is upright and resolve with recumbency. Causes can be broadly categorized into 4 groups: intracardiac shunting, pulmonary shunting, ventilation-perfusion mismatch, or a combination of these. Platypnea-orthodeoxia syndrome should be suspected when normal arterial oxygen saturations are recorded while an individual is supine, followed by abrupt declines in those saturations when upright.

Ergotamine-associated valvulopathy with recurrent chylous pleural effusion.

We report a rare case of ergotamine-associated mitral stenosis in a 55-year-old woman who presented with recurrent chylous pleural effusion. Echocardiographic, gross, and microscopic features of the mitral valve were consistent with chronic ergotamine-induced valvulopathy. We conclude that medication-induced valvulopathy should be included in the differential diagnosis of valvular heart disease.

KATP channel knockout worsens myocardial calcium stress load in vivo and impairs recovery in stunned heart.

Gene knockout of the KCNJ11-encoded Kir6.2 ATP-sensitive K(+) (K(ATP)) channel implicates this stress-response element in the safeguard of cardiac homeostasis under imposed demand. K(ATP) channels are abundant in ventricular sarcolemma, where subunit expression appears to vary between the sexes.

Gene knockout of the KCNJ8-encoded Kir6.1 K(ATP) channel imparts fatal susceptibility to endotoxemia.

Sepsis, the systemic inflammatory response to infection, imposes a high demand for bodily adaptation, with the cardiovascular response a key determinant of outcome. The homeostatic elements that secure cardiac tolerance in the setting of the sepsis syndrome are poorly understood. Here, in a model of acute septic shock induced by endotoxin challenge with Escherichia coli lipopolysaccharide (LPS), knockout of the KCNJ8 gene encoding the vascular Kir6.

KCNJ11 gene knockout of the Kir6.2 KATP channel causes maladaptive remodeling and heart failure in hypertension.

Heart failure is a growing epidemic, with systemic hypertension a major risk factor for development of disease. However, the molecular determinants that prevent the transition from a state of hypertensive load to that of overt cardiac failure remain largely unknown. Here in experimental hypertension, knockout of the KCNJ11 gene, encoding the Kir6.

ATP-sensitive K+ channel knockout compromises the metabolic benefit of exercise training, resulting in cardiac deficits.

Exercise training elicits a metabolic and cardiovascular response that underlies fitness. The molecular mechanisms that orchestrate this adaptive response and secure the wide-ranging gains of a regimented exercise program are poorly understood. Formed through association of the Kir6.

Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+ channel, predisposes to catecholamine-induced ventricular dysrhythmia.

Metabolic-sensing ATP-sensitive K+ channels (KATP channels) adjust membrane excitability to match cellular energetic demand. In the heart, KATP channel activity has been linked to homeostatic shortening of the action potential under stress, yet the requirement of channel function in securing cardiac electrical stability is only partially understood. Here, upon catecholamine challenge, disruption of KATP channels, by genetic deletion of the pore-forming Kir6.

Transgenic overexpression of human DMPK accumulates into hypertrophic cardiomyopathy, myotonic myopathy and hypotension traits of myotonic dystrophy.

Abnormal expression of human myotonic dystrophy protein kinase (hDMPK) gene products has been implicated in myotonic dystrophy type 1 (DM1), yet the impact of distress accumulation produced by persistent overexpression of this poorly understood member of the Rho kinase-related protein kinase gene-family remains unknown. Here, in the aged transgenic murine line carrying approximately 25 extra copies of a complete hDMPK gene with all exons and an intact promoter region (Tg26-hDMPK), overexpression of mRNA and protein transgene products in cardiac, skeletal and smooth muscles resulted in deficient exercise endurance, an integrative index of muscle systems underperformance. In contrast to age-matched (11-15 months) wild-type controls, hearts from Tg26-hDMPK developed cardiomyopathic remodeling with myocardial hypertrophy, myocyte disarray and interstitial fibrosis.

ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating.

Stress tolerance of the heart requires high-fidelity metabolic sensing by ATP-sensitive potassium (K(ATP)) channels that adjust membrane potential-dependent functions to match cellular energetic demand. Scanning of genomic DNA from individuals with heart failure and rhythm disturbances due to idiopathic dilated cardiomyopathy identified two mutations in ABCC9, which encodes the regulatory SUR2A subunit of the cardiac K(ATP) channel. These missense and frameshift mutations mapped to evolutionarily conserved domains adjacent to the catalytic ATPase pocket within SUR2A.