Prevalence of Microvascular and Endothelial Dysfunction in the Nonculprit Territory in Patients With Acute Myocardial Infarction.

BACKGROUND: Approximately half of the patients presenting with ST-segment-elevation myocardial infarction (STEMI) have multivessel disease. The physiology of the nonculprit artery has not been thoroughly studied to date. We sought to characterize the coronary physiology of the nonculprit artery in the early phase after STEMI and determine the real prevalence of microvascular and endothelial dysfunction. METHODS AND RESULTS: Patients with STEMI and another coronary artery lesion in a different territory were prospectively included in an observational single-center study. The protocol took place after revascularization of the culprit artery and comprised 3 phases: first, epicardial endothelial functional assessment using intracoronary acetylcholine; second, epicardial severity quantification based on fractional flow reserve, and nonendothelial microvascular function with coronary flow reserve and the index of microvascular resistance; third, endothelium-dependent microvascular function assessment based on the endothelial coronary flow reserve. Eighty-four patients were included. Mean age was 62±10 years, and 86.9% were men. Only 6 subjects had a nonpathological study: macrovascular endothelial dysfunction was present in 60% of the patients; fractional flow reserve ≤0.8, coronary flow reserve <2, and index of microvascular resistance >25 were evident in 34%, 37%, and 28% of the subjects respectively; and microvascular endothelial dysfunction (endothelial coronary flow reserve <1.5) was observed in 44%. In hospital-mortality was 0%, and no major complications occurred. At 6-month follow-up, there were no events related to the nonculprit artery. CONCLUSIONS: Microvascular and endothelial dysfunction in the nonculprit artery territory in patients with STEMI are very common. In 93% of the patients, we found functional abnormalities. Acetylcholine administration in the early phase post-STEMI in patients with multivessel disease is safe.

Clinical Characteristics and Electrophysiological Mechanisms Underlying Brugada ECG in Patients With Severe Hyperkalemia.

Background Several metabolic conditions can cause the Brugada ECG pattern, also called Brugada phenotype (BrPh). We aimed to define the clinical characteristics and outcome of BrPh patients and elucidate the mechanisms underlying BrPh attributed to hyperkalemia. Methods and Results We prospectively identified patients hospitalized with severe hyperkalemia and ECG diagnosis of BrPh and compared their clinical characteristics and outcome with patients with hyperkalemia but no BrPh ECG. Computer simulations investigated the roles of extracellular potassium increase, fibrosis at the right ventricular outflow tract, and epicardial/endocardial gradients in transient outward current. Over a 6-year period, 15 patients presented severe hyperkalemia with BrPh ECG that was transient and disappeared after normalization of their serum potassium. Most patients were admitted because of various severe medical conditions causing hyperkalemia. Six (40%) patients presented malignant arrhythmias and 6 died during admission. Multiple logistic regression analysis revealed that higher serum potassium levels (odds ratio, 15.8; 95% CI, 3.1-79; P=0.001) and male sex (odds ratio, 17; 95% CI, 1.05-286; P=0.045) were risk factors for developing BrPh ECG in patients with severe hyperkalemia. In simulations, hyperkalemia yielded BrPh by promoting delayed and heterogeneous right ventricular outflow tract activation attributed to elevation of resting potential, reduced availability of inward sodium channel conductance, and increased right ventricular outflow tract fibrosis. An elevated transient outward current gradient contributed to, but was not essential for, the BrPh phenotype. Conclusions In patients with severe hyperkalemia, a BrPh ECG is associated with malignant arrhythmias and all-cause mortality secondary to resting potential depolarization, reduced sodium current availability, and fibrosis at the right ventricular outflow tract.