To date, hundreds of variants in 13 genes have been associated with long QT syndrome (LQTS). The prevalence of LQTS is estimated to be between 1:2000 and 1:5000. The knowledge of genetic variation in the general population has until recently been limited, but newly published data from NHLBI GO Exome Sequencing Project (ESP) has provided important knowledge on this topic. We aimed to investigate the prevalence of previously LQTS-associated variants in ESP (5400 individuals), in order to identify possible false-positive LQTS variants. With this aim, we performed a search for previously published LQTS-associated variants in ESP. In addition, a PolyPhen-2 prediction was conducted, and the four most prevalent LQTS-associated variants with significant functional effects present in ESP were genotyped in a second control population. We identified 33 missense variants previously associated with LQTS in ESP. These 33 variants affected 173 alleles and this corresponded to a LQTS prevalence of 1:31 in the ESP population. PolyPhen-2 predicted 30% of the 33 variants present in ESP to be benign compared with 13% among LQTS-associated variants not present in ESP (P=0.019). Genotyping of the four variants KCNH2 P347S; SCN5A: S216L, V1951L; and CAV3 T78M in the control population (n=704) revealed prevalences comparable to those of ESP. Thus, we identified a much higher prevalence of previously LQTS-associated variants than expected in exome data from population studies. Great caution regarding the possible disease causation of some of these variants has to be taken, especially when used for risk stratification in family members.

From a nationwide study of all deaths in a 7-year period more than half of all victims of SCDc experienced antecedent and/or prodromal symptoms prior to death. The incidence rate of sudden death and SCDc was 1.5 and 1.1 per 100 000 person-years, respectively. Cardiac symptoms in young persons should warrant clinical work-up and an autopsy should be performed in all cases of sudden unexpected death in which the deceased was not known with congenital heart disease prior to death. This is pivotal, in the subsequent familial cascade screening, to diagnose and treat potential inherited cardiac diseases in family members.

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Objectives To ascertain the effect of age on outcomes after culprit‐only and complete revascularization after Primary PCI (PPCI) for ST‐elevation myocardial infarction (STEMI). Background The numbers of older patients being treated with PPCI are increasing. The optimal management of nonculprit stenoses in such patients is unclear. Methods We conducted an analysis of patients aged ≥75 years randomized in the DANAMI‐3‐PRIMULTI study to either culprit‐only or complete FFR‐guided revascularization. The primary endpoint was a composite of all‐cause mortality, nonfatal reinfarction, and ischaemia‐driven revascularization of lesions in noninfarct‐related arteries after a median of 27 months of follow‐up. Results One hundred and ten of six hundred and twenty seven patients in the DANAMI‐3‐PRIMULTI trial were aged ≥75 years. These patients were more likely female (p < .001), hypertensive (p < .001), had lower hemoglobin levels (p < .001), and higher serum creatinine levels (p < .001) than the younger patients in the trial. Other than less use of drug‐eluting stents (96.6 versus 88.0%: p = .02), there were no significant differences in procedural technique and success between patients aged <75 years and those ≥75 years of age. There was no significant difference in the incidence of the primary endpoint in patients ≥75 years randomized to culprit‐only or FFR‐guided complete revascularization (HR 1.49 [95% CI 0.57–4.65]; log‐rank p = .19; p for interaction versus patients <75 years <.001). There was a significant interaction between age as a continuous variable, treatment assignment, and the primary outcome (p < .001); beyond the age of about 75 years, there may be no prognostic advantage to complete revascularization. Conclusions In patients ≥75 years, after treatment of the culprit lesion in STEMI, there is no significant prognostic benefit to prophylactic complete revascularization of nonculprit stenoses. Pending further study, data would support a symptom‐guided approach to further invasive treatment.

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Ticagrelor, administered as crushed tablets through a nasogastric tube, leads to sufficient platelet inhibition after 12 hours, and in many cases earlier, in the vast majority of patients undergoing pPCI and subsequent intensive care management after an OHCA.

Aims Quantitative computed tomography (QCT) allows assessment of morphological features of coronary atherosclerosis. We aimed to test the hypothesis that clinical patient presentation is associated with distinct morphological features of coronary atherosclerosis. Methods and results A total of 1652 participants, representing a spectrum of clinical risk profiles [787 asymptomatic individuals from the general population, 468 patients with acute chest pain without acute coronary syndrome (ACS), and 397 patients with acute chest pain and ACS], underwent multidetector computed tomography. Of these, 274 asymptomatic individuals, 254 patients with acute chest pain without ACS, and 327 patients with acute chest pain and ACS underwent QCT to assess coronary plaque volumes and proportions of dense calcium (DC), fibrous, fibro fatty (FF), and necrotic core (NC) tissue. Furthermore, the presence of vulnerable plaques, defined by plaque volume and tissue composition, was examined. Coronary plaque volume increased significantly with worsening clinical risk profile [geometric mean (95% confidence interval): 148 (129–166) mm3, 257 (224–295) mm3, and 407 (363–457) mm3, respectively, P < 0.001]. Plaque composition differed significantly across cohorts, P < 0.0001. The proportion of DC decreased, whereas FF and NC increased with worsening clinical risk profile (mean proportions DC: 33%, 23%, 23%; FF: 50%, 61%, 57%; and NC: 17%, 17%, 20%, respectively). Significant differences in plaque composition persisted after multivariable adjustment for age, gender, body surface area, hypertension, statin use at baseline, diabetes, smoking, family history of ischaemic heart disease, total plaque volume, and tube voltage, P < 0.01. Conclusion Coronary atherosclerotic plaque volume and composition are strongly associated to clinical presentation.

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