Ribosomal protein S6 kinase beta-1 gene variants cause hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM. METHODS AND RESULTS: Here, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 (RPS6KB1 or S6K1) gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect. CONCLUSIONS: Our study demonstrates for the first time that the variants in the S6K1 gene are associated with HCM, and early detection of the S6K1 variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of S6K1 gene variants.

Percutaneous Coronary Interventions in Chronic Total Occlusion - Profile, Technique and Outcome - The Malabar Experience.

INTRODUCTION: Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) remains a challenge. The reasons being that these procedures may be lengthy and complex, with elevated radiation exposure, increased contrast load, lower procedural success rate, and a higher risk of complication when compared with non-CTO elective PCI.Clarifying the long-term clinical outcomes of CTO-PCI is very important to justify potential investments in training and technology. However, there is a paucity of data from Indian subcontinent. Hence we decided to report the outcomes from a real-life cohort of consecutive patients undergoing elective PCI for CTO at our institution. MATERIALS AND METHODS: Single-center, prospective observational study. A total of 339 consecutive patients who underwent elective PCI for chronic total occlusion between Feb 2016 to Feb 2018 were included in the study. Procedural techniques, complications and clinical outcomes {all-cause death, cardiac death, major adverse cardiac events (MACE) and target vessel revascularization (TVR)} were assessed in our study population. RESULTS: 339 patients were prospectively followed up for a duration that ranged from 3 months to 36 months, with a median follow up of 24 months. Overall procedural success was achieved in 85.5% (n = 290) cases. No significant differences were noted in In-Hospital adverse events (5.5% vs. 4.1%; p 0.998). MACE rate was significantly higher in unsuccessful CTO group (36.7% vs. 8.9%, p 0.001) and was predominantly driven by Ischemia Driven (ID) - Revascularization (16.3% vs. 3.1%, p < 0.001). Cardiac death and All-cause death was not significantly different between the groups. Residual angina (26.5% vs. 10%, p 0.003) and residual dyspnoea (34.7% vs. 12.4%, p < 0.001) were significantly worse in unsuccessful CTO group. CONCLUSIONS: Procedural success in the present drug-eluting stent (DES) era is more than 80% and newer techniques and hardwares have improved the procedural success rate, especially in younger age groups. MACE rates were significantly higher in the unsuccessful CTO group. Residual angina and dyspnoea were significantly worse in the unsuccessful CTO group.

Balloon embedded bifurcation stenting with single stent for side branch protection - Preliminary results from an Indian population.

BACKGROUND: Intervention for bifurcation lesions is associated with increased risk of adverse events and includes acute side branch (SB) occlusion during main branch (MB) stenting. This acute occlusion of side branch can often be catastrophic for the patient. We here in describe our experience in Indian population with a technique which can be incorporated into bifurcation stenting to reduce or almost eliminate the incidence of side branch occlusion. METHOD AND RESULTS: 70 patients with bifurcation lesion were included in the study and underwent a balloon embedded bifurcation stenting with a semi inflated balloon placed across the SB ostium. Angiographic and procedural success were achieved in all the patients. TIMI 3 flow was achieved in both the MB and SB in all cases and there was no incidence of dissection or acute occlusion of SB. Mean fluoroscopy time and contrast volume was similar to that of conventional bifurcation stenting. CONCLUSION: The present study suggests that balloon embedded bifurcation stenting with a semi inflated balloon to protect the SB is feasible, not associated with procedural adverse events and successful in minimising or almost eliminating the incidence of acute side branch occlusion.