Heart rate manipulation in dilated cardiomyopathy: Assessing the role of Ivabradine

Background: Heart rate (HR) reduction is of benefit in chronic heart failure (HF). The effect of heart rate reduction using Ivabradine on various echocardiographic parameters in dilated cardiomyopathy has been less investigated. Methods: Of 187 patients with HF (DCM, NYHA II–IV, baseline HR > 70/min), 125 patients were randomized to standard therapy (beta blockers, ACEI, diuretics, n = 62) or add-on Ivabradine (titrated to maximum 7.5 mg BD, n = 63). Beta-blockers were titrated in both the groups. Results: At 3 months both groups had improvement in NYHA class, 6 min walk test, Minnesota Living With Heart Failure (MLWHF) scores and fall in BNP, however the magnitude of change was greater in Ivabradine group. Those on Ivabradine also had lower LV volumes, higher LVEF (28.8 ± 3.6 vs 27.2 ± 0.5, p = 0.01) and more favorable LV global strain (11 ± 1.7vs 12.2 ± 1.1, p = <0.001), MPI (0.72 ± 0.1 vs 0.6 ± 0.1, p = <0.001), LV mass (115.2 ± 30 vs 131.4 ± 35, p = 0.007), LV wall stress (219.8 ± 46 vs 238 ± 54) and calculated LV work (366 ± 101 vs 401 ± 102, p = 0.05). The benefit of Ivabradine was sustained at 6 months follow up. The % change in HR was significantly higher in Ivabradine group (−32.2% vs −19.3%, p = 0.001) with no difference in blood pressure. Resting HR < 70/min was achieved in 96.8% vs 27.9%, respectively in the two groups. Conclusion: Addition of Ivabradine to standard therapy in patients with DCM and symptomatic HF and targeting a heart rate < 70/min improves symptoms, quality of life and various echocardiographic parameters. Keywords: Heart failure, Dilated cardiomyopathy, Heart rate, Ivabradine, Beta blocke

HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy

People living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading causes of heart failure in PLWH. However, the molecular mechanism of antiretroviral drugs (ARVs) induced heart failure is unclear. To determine the mechanism of ARVs induced cardiac dysfunction, we performed global transcriptomic profiling of ARVs treated neonatal rat ventricular cardiomyocytes in culture. Differentially expressed genes were identified by RNA-sequencing. Our data show that ARVs treatment causes upregulation of several biological functions associated with cardiotoxicity, hypertrophy, and heart failure. Global gene expression data were validated in cardiac tissue isolated from HIV patients having a history of ART. Interestingly, we found that homeodomain-only protein homeobox (HOPX) expression was significantly increased in cardiomyocytes treated with ARVs and in the heart tissue of HIV patients. Furthermore, we found that HOPX plays a crucial role in ARVs mediated cellular hypertrophy. Mechanistically, we found that HOPX plays a critical role in epigenetic regulation, through deacetylation of histone, while the HDAC inhibitor, Trichostatin A, can restore the acetylation level of histone 3 in the presence of ARVs

Role of metabolic manipulator trimetazidine in limiting percutaneous coronary intervention–induced myocardial injury

Background: Trimetazidine (TMZ) is a metabolic modulator that shifts substrate utilization from fatty acid to carbohydrates, thereby, increasing myocardial glucose oxidation and improving myocardial ischemia. We evaluated whether TMZ is effective in reducing myocardial injury after percutaneous coronary intervention (PCI). Methods: Patients with stable angina undergoing elective PCI were divided into two groups, one who received oral TMZ (35 mg BD) started 7 days before PCI (n = 48) and second who did not receive any TMZ (in addition to the standard therapy (n = 52)). Troponin-I (cTnI) and creatine kinase–MB (CK-MB) were measured before, 8, and 24 h after PCI. The primary end point was a difference in post-PCI cTnI and CK-MB levels (vs baseline). Frequency of cTnI release in the two groups, total amount of cTnI release, and difference in TIMI flow grade before and after the procedure were also assessed. Results: Baseline demographics in the groups were comparable. Despite similar baseline levels, post-procedural cTnI was lower at 8 h (0.13 vs 0.56 ng/ml, p = 0.03) and 24 h (0.2 vs 1.13 ng/ml, p = 0.004) in the TMZ group. Decline or no change in cTnI was significantly more common in the TMZ group (26% vs 2%, p < 0.01). Total cTnI released after PCI, as assessed by area under curve was significantly lower in the TMZ group (15.84 vs 3.32 ng h/ml, p = 0.005). Although CK-MB levels were also lower in the TMZ group, the difference was not statistically significant. Incidence of post-PCI TIMI 1 or 2 flow was significantly lesser in the TMZ group. Conclusions: Oral TMZ started 7 days before PCI was effective in limiting PCI-induced myocardial injury with lower cTnI levels and higher prevalence of TIMI-3 flow. Keywords: Metabolic modulation, Trimetazidine, PCI, Peri-procedural myocardial injury, Troponin, TIMI flo