Aims The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. Methods and results  In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.01, 95% confidence interval (CI) 7.89–29.74, P < 8.36e−11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31–24.87, P < 2.2e−16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP−), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP− and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP− and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. Conclusions  Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.

No abstract

Background: Recent trials suggest that complete revascularization in patients with acute ST-segment–elevation myocardial infarction and multivessel disease is associated with better outcomes than infarct-related artery (IRA)–only revascularization. There are different methods to select non-IRA lesions for revascularization procedures. We assessed the clinical outcomes of complete angiographically guided revascularization versus stress echocardiography–guided revascularization in patients with ST-segment–elevation myocardial infarction. Methods: We performed a randomized clinical trial in patients with multivessel disease who underwent a successful percutaneous coronary intervention of the IRA to test differences in prognosis (composite end point included cardiovascular mortality, nonfatal reinfarction, coronary revascularization, and readmission for heart failure after 12 months of follow-up) between complete angiographically guided revascularization (n=154) or stress echocardiography–guided revascularization (n=152) of the non-IRA lesions in an elective procedure before hospital discharge. Results: The trial was prematurely stopped after the inclusion of 77% of the planned study population. As many as 152 (99%) patients in the complete revascularization group and 44 (29%) patients in the selective revascularization group required a percutaneous coronary intervention procedure of a non-IRA lesion before discharge. The primary end point occurred in 21 (14%) patients of the stress echocardiography–guided revascularization group and 22 (14%) patients of the complete angiographically guided revascularization group (hazard ratio, 0.95; 95% CI, 0.52–1.72; P =0.85). Conclusions: In patients with ST-segment–elevation myocardial infarction and multivessel disease, stress echocardiography–guided revascularization may not be significantly different to complete angiographically guided revascularization, thereby reducing the need for elective revascularization before hospital discharge. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01179126.

IntroductionThe exercise treadmill test is widely used in the evaluation of patients with suspected or known coronary artery disease. The typical ischemic response used to be ST-segment depression.Case presentationWe describe a case of a 51-year-old Caucasian man with an unusual ischemic response during the exercise treadmill test: a "giant R wave" electrocardiogram pattern as a manifestation of hyperacute ischemia that resolved with sublingual nitroglycerin. Coronary catheterization showed a severe stenosis in a proximal dominant circumflex coronary artery. We hypothesize that, in this case, the "giant R wave" pattern was related to severe hyperacute ischemia due to coronary spasm superimposed on the atherosclerotic lesion, which probably caused complete occlusion of the artery. The patient was successfully treated with coronary percutaneous revascularization.ConclusionsThis is a dramatic and rare ischemic response during the exercise treadmill test, in which, a rapid administration of nitroglycerin can prevent life-threatening events.

No abstract