Haymcintyre5569

Background Genomic variations have shown an ethnic-specific pattern within various cohorts. selleck chemicals Genetic variants of KCNQ1, KCNH2, SCN5A and KCNE1 causing LQT syndrome have been described in many populations. In this article the spectrum of variants of these genes is presented in Iranian patients. Methods 102 unrelated individuals diagnosed with LQT were enrolled in this study. Clinical and electrocardiogram (ECG) data of 95 patients were documented, and analyzed by expert pediatric cardiologists. Coding regions and exon-intron boundaries were amplified and sequenced. Segregation analysis was done for novel variants as well as in silico analyses. Results Sixty nine of 95 cases (73%) had Schwartz score of ≥3.5. The causal variants were found in 31 cases (9 novel variants). 21 patients had KCNQ1 (LQTS1) of which15 patients were homozygous for KCNQ1 variants, 9 of these patients (29%) had a Jervell and Lange-Nielsen phenotype. 4 patients had KCNH2 (LQTS2) variants, 7 cases had SCN5A had heterozygous variants, and 2 cases had heterozygous variants in KCNE1 (LQTS5). 19 variants were missense, 3 were nonsense, and 3 were frameshifts. There was one large deletion and 3 intronic variants. Conclusion The yield of genetic testing and the genotype profile of LQTS patients in Iran is different from reports elsewhere, with lower overall yield and with 48% having homozygous states.The advent of tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. However, cardiotoxicity associated with these targeted therapies puts the cancer survivors at higher risk. Ponatinib is a third-generation TKI for the treatment of CML patients having gatekeeper mutation T315I, which is resistant to the first and second generation of TKIs, namely, imatinib, nilotinib, dasatinib, and bosutinib. Multiple unbiased screening from our lab and others have identified ponatinib as most cardiotoxic FDA approved TKI among the entire FDA approved TKI family (total 50+). Indeed, ponatinib is the only treatment option for CML patients with T315I mutation. This review focusses on the cardiovascular risks and mechanism/s associated with CML TKIs with a particular focus on ponatinib cardiotoxicity. We have summarized our recent findings with transgenic zebrafish line harboring BNP luciferase activity to demonstrate the cardiotoxic potential of ponatinib. Additionally, we will review the recent discoveries reported by our and other laboratories that ponatinib primarily exerts its cardiotoxicity via an off-target effect on cardiomyocyte prosurvival signaling pathways, AKT and ERK. Finally, we will shed light on future directions for minimizing the adverse sequelae associated with CML-TKIs.Background The long-term effect of tricuspid regurgitation (TR) after device implantation on long-term mortality remains unknown. In the present study, we sought to examine whether patients undergoing an implantable cardiac device procedure (pacemaker, cardiac defibrillator or cardiac resynchronisation therapy) have an increased risk of TR and to determine the effect of this on long-term survival. Methods A total of 304 patients who underwent device implant and had pre- and post-implant transthoracic echocardiogram were included in the analysis. All-cause mortality was the study endpoint over a follow-up period of median 11.6 years. Results New ≥ moderate tricuspid regurgitation post-device implantation developed in 66/304 (21.7%) patients. New right ventricular dysfunction post-device implantation occurred in 59/304 (19.4%) patients. Independent predictors of new RV dysfunction were ischaemic heart disease (OR 4.23, 95% CI 1.58 - 11.33, p = 0.004), left ventricular impairment (OR 2.74, 95% CI 5.41 - 30.00, p 10 years) survival.Background Current European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias have further reduced low density lipoprotein-cholesterol (LDL-C) targets, as compared to the guidelines released in 2016. These targets are particularly restraining for patients at very high risk (VHR). Methods Using the data from a nationwide, prospective registry on patients with established atherosclerotic cardiovascular disease (ASCVD), we sought to assess 1) the contemporary use of conventional cholesterol-lowering therapies and the achievement of LDL-C goals according to previous and current ESC guidelines in subjects at VHR; 2) the proportion of VHR patients potentially eligible for proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) treatment. Results Among the 5053 patients with data available, 4751 (94.0%) were deemed as VHR. Among these patients, the mean LDL-C levels were 62.4 ± 47.7 mg/dl at enrollment. A high dose of statin was used in 54.9%, while the association of high dose statin and ezetimibe was prescribed in 4.8% of VHR patients. A target level of LDL-C less then 70 mg/dl recommended by 2016 ESC guidelines was reached by 58.1%, while a target of less then 55 mg/dl and LDL-C reduction ≥50% recommended by 2019 ESC guidelines, would be reached by 3.2% of patients at VHR. Accordingly, 9.4% and 1.4% of VHR patients would be eligible for PCSK9i according to ESC guidelines and Italian regulations, respectively. Conclusions In VHR patients enrolled in this large cohort of established ASCVD managed by cardiologists, the lipid management and LDL-C targets attainment is largely suboptimal.Background Useful tools for risk assessment in patients with STEMI are needed. We evaluated the prognostic impact of the evolving myocardial infarction (EMI) and the preinfarction syndrome (PIS) ECG patterns and determined their correlation with angiographic findings and treatment strategy. Methods This substudy of the randomized Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI (TOTAL) included 7860 patients with STEMI and either the EMI or the PIS ECG pattern. The primary outcome was a composite of death from cardiovascular causes, recurrent MI, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within one year. Results The primary outcome occurred in 271 of 2618 patients (10.4%) in the EMI group vs. 322 of 5242 patients (6.1%) in the PIS group [AdjustedHR, 1.54; 95% CI, 1.30 to 1.82; p less then .001]. The primary outcome occurred in the thrombectomy and PCI alone groups in 131 of 1306 (10.0%) and 140 of 1312 (10.7%) patients with EMI [HR 0.