The genetics of cardiac failure: Role of a G protein-coupled receptor polymorphism in therapeutic response in an Indian population.

BACKGROUND AND AIM: The incidence of heart failure (HF) is rising to epidemic proportions in developing countries like India. A lack of adequate Indian studies underscores the importance of pursuing research into HF in an Indian population. G protein-coupled receptor kinase 5 (GRK5) Gln41>Leu (rs2230345) polymorphism was reported as a genetic modifier associated with survival in HF patients. A prospective study was conducted to investigate the association of GRK5 Gln41>Leu polymorphism with response to ß-blocker therapy in Indian HF patients. METHODS: HF patients (n=584) were recruited for the study. The patients were genotyped by tetra-primer based allele specific polymerase chain reaction and confirmed with Sanger sequencing. The HF patients were evaluated for GRK5 gene expression and followed up for ~3 years. Drug dosages, cardiac output and hospitalization-free survival were evaluated as study outcomes. HF subgroups (i.e. systolic or diastolic dysfunction, biventricular dysfunction and pulmonary artery hypertension) were also analyzed in association with hospital-free survival. RESULTS: HF patients showed genotype frequencies of AT (15%) and TT (1%). AT/TT genotype carriers showed downregulated GRK5 gene expression and significant reduction in carvedilol drug dosage (p=0.0001). Moreover, AT/TT genotype carriers on ß-blockers showed improved ejection fraction from 27% to 36% (p=0.0007) and increased hospitalization-free survival in comparison to other HF patients. HF patients with AA genotype showed an increased rate of hospital admission in comparison with patients with the AT/TT genotype. HF subgroups with the AT/TT genotype showed an increased hospitalization-free survival versus subgroups with the AA genotype. CONCLUSIONS: GRK5 Gln41>Leu polymorphism in response to ß-blocker therapy improved cardiac function in HF patients. RELEVANCE FOR PATIENTS: This study presents a comprehensive clinicofunctional pharmacogenetic characterization of GRK5 Gln41>Leu polymorphism in a cohort of Indian HF patients. GRK5 Gln41>Leu polymorphism can confer improved cardiac function and reduce hospitalization, thus improving the quality of life in HF patients.

Clinical characteristics and outcomes of patients admitted with acute heart failure: insights from a single-center heart failure registry in South India.

BACKGROUND: The epidemiology of HF in India is largely unexplored. Current resources are based on a few hospital-based and a community-based registry from North India. Thus, we present the data from a single hospital-based registry in South India. Patients admitted with acute heart failure over a period of 1 year were enrolled in the registry and were characterized based on their ejection fraction (EF) measured by echocardiogram. The clinical profile of the patients was assessed, including their in-hospital outcomes. One-way ANOVA and univariate analysis were performed for comparison between three EF-based groups and for the assessment of in-hospital outcomes. RESULTS: A total of 449 patients were enrolled in the registry, of which 296, 90, and 63 patients were categorized as, HFrEF, HFmrEF, and HFpEF, respectively. The prevalence of HFrEF was higher (65.99%). The mean age (SD) of the study cohort was 59.9±13.3. The majority of the patients presented with acute denovo HF (67%) and were more likely to be males (65.9%). The majority of patients presented with warm and wet clinical phenotype (86.4%). In hospital mortality was higher in HFmrEF (3.3%). CONCLUSION: Patients with HFrEF had high adherence to guideline-directed medical therapy (GDMT). HFrEF patients were also likely to have longer hospital stay along with a worsening of renal function. The in-hospital mortality was comparable between the EF-based groups. Additionally, the association of clinical phenotypes with outcome highlighted that patients in warm and wet phenotype had a longer length of hospital stay, whereas the mortality and worsening renal function rates were found to be significantly higher in the cold and wet group.

Impact of Clinical Audit on Adherence to the Guidelines Directed Medical Therapy in Patients Admitted with Heart Failure.

BACKGROUND: The adoption of guideline recommendations of pharmacotherapy to improve the clinical course of Heart Failure (HF) remains below par. Our objective is to evaluate the impact of clinical audit on adherence to the Guideline-Directed Medical Therapy (GDMT) in patients admitted with acute heart failure with reduced ejection fraction (EF). METHODS: A prospective interventional study was conducted over a period of 12 months from June 2018 to May 2019 in all patients admitted with acute heart failure with reduced ejection fraction. The discharge prescriptions of patients who met the inclusion criteria were audited for appropriateness in the usage of neurohormonal blockers and Ivabradine, by a clinical pharmacist on a monthly basis. Audit results were presented to the practicing physicians every month and feedback was given. RESULTS: Discharge prescriptions of 716 patients who presented with HF were audited for the reasonable or unreasonable omission of neurohormonal blocking drugs. The first-month audit revealed that the unreasonable omission of Angiotensin-Converting Enzyme Inhibitors/ Angiotensin Receptor Blockers/ Angiotensin Receptor Neprilisin Inhibitors ( ACEI/ARB/ARNI), Betablockers and Mineralocorticoid Receptor Antagonists (MRA) were 24.5%, 13.1%, and 9.09% respectively, which reduced to nil at the end of the study period (p=0.00). Initiation of Ivabradine before prescribing or achieving the target dose of Betablocker was noted in 38.18% of patients in the first month, which was also reduced to nil (p=0.00) at the end of the study. CONCLUSION: This study reveals that periodic clinical audit improves adherence to GDMT in patients admitted with heart failure with reduced ejection fraction.

Corsair microcatheter for retrograde coronary chronic total occlusion recanalization: early experience outside the realm of dedicated recanalization specialists.

OBJECTIVE: To determine the extent to which use of the Corsair microcatheter (CM, Asahi Intecc Co., Japan) improves procedural outcomes when an experienced operator who is not a dedicated recanalization specialist attempts retrograde chronic total occlusion (CTO) recanalization through collateral channels during percutaneous coronary intervention. BACKGROUND: The recently introduced CM has improved success rates of retrograde CTO recanalization to nearly 100% in the hands of dedicated coronary recanalization specialists; however, the impact the CM has on the results of non-specialist operators attempting retrograde CTO recanalization is not known. METHODS: A non-specialist operator attempted CM-assisted recanalization in seven consecutive CTO cases requiring retrograde recanalization. The results obtained were compared with those achieved by the same operator in eleven consecutive retrograde CTO recanalization procedures during the last 2 years before the CM became available. RESULTS: CM-assisted retrograde CTO recanalization was successful in 6 of 7 cases (86%), but failed in one case attempted through a tortuous epicardial collateral; there were no complications. In contrast, during the 2 years before the CM became available, retrograde CTO recanalization was successful in only 3 of 11 attempted cases (27%), and was associated with significant morbidity. Lesions in the two groups were comparable in terms of technical difficulty and procedural risk. CONCLUSIONS: The non-specialist operator's retrograde CTO recanalization results improve significantly when using the CM. Given the effectiveness and safety of CM-assisted retrograde CTO recanalization, operators should be less aggressive with anterograde recanalization attempts, and should switch to the retrograde approach earlier and more often.