Indian Consensus on the Role and Position of Angiotensin Receptor-neprilysin Inhibitors in the Management of Heart Failure.

The incidence of heart failure (HF) in India is estimated to be 0.5-1.7 cases per 1,000 people per year, and approximately 4,92,000-1.8 million new cases are detected every year. Despite the high rate of mortality associated with HF, most patients do not receive maximal guideline-directed medical therapy (GDMT). Current guidelines advocate early multidrug combination therapy with four classes of drugs, namely, beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose transport protein 2 inhibitors (SGLT-2is), particularly in patients with heart failure with reduced ejection fraction (HFrEF). ARNIs reduce cardiac morbidity and mortality in patients with HFrEF. However, recent data indicated that only 4.8% of patients with HFrEF receive ARNI in India. Hence, at a national consensus on HF meeting, cardiology experts from India formulated a national consensus on the use of ARNI in HF based on current evidence and guidelines. The consensus states that ARNI should be used early in HF, particularly in de novo patients with HFrEF, and those with acute decompensated heart failure (ADHF), irrespective of the presence of low systolic blood pressure (SBP) or diabetes. Moreover, those with HFrEF on renin-angiotensin-aldosterone system (RAAS) inhibitors should be switched to ARNI to reduce the risk of repeated hospitalization for HF, worsening HF, and cardiac death, and to improve the quality of life (QoL). Starting ARNI during the first hospitalization is preferable, and it is safe and effective across all doses. ARNIs can also be used for secondary benefits in patients with preserved ejection fraction [heart failure with preserved ejection fraction (HFpEF)] and HF with mildly reduced EF [heart failure with mildly reduced ejection fraction (HFmrEF)].

Physical map of QTL for eleven agronomic traits across fifteen environments, identification of related candidate genes, and development of KASP markers with emphasis on terminal heat stress tolerance in common wheat.

KEY MESSAGE: Key message This study identified stable QTL, promising candidate genes and developed novel KASP markers for heat tolerance, providing genomic resources to assist breeding for the development of high-yielding and heat-tolerant wheat germplasm and varieties. To understand the genetic architecture of eleven agronomic traits under heat stress, we used a doubled-haploid population (177 lines) derived from a heat-sensitive cultivar (PBW343) and a heat-tolerant genotype (KSG1203). This population was evaluated under timely, late and very late sown conditions over locations and years comprising fifteen environments. Best linear unbiased estimates and a genetic map (5,710 SNPs) developed using sequencing-based genotyping were used for QTL mapping. The identified 66 QTL (20 novel) were integrated into wheat physical map (14,263.4 Mb). These QTL explained 5.3% (QDth.ccsu-4A for days to heading and QDtm.ccsu-5B for days to maturity) to 24.9% (QGfd.ccsu-7D for grain filling duration) phenotypic variation. Thirteen stable QTL explaining high phenotypic variation were recommended for marker-assisted recurrent selection (MARS) for optimum/heat stress environments. Selected QTL were validated by their presence in high-yielding doubled-haploid lines. Some QTL for 1000-grain weight (TaERF3-3B, TaFER-5B, and TaZIM-A1), grain yield (TaCol-B5), and developmental traits (TaVRT-2) were co-localized with known genes. Specific known genes for traits like abiotic/biotic stress, grain quality and yield were co-located with 26 other QTL. Furthermore, 209 differentially expressed candidate genes for heat tolerance in plants that encode 28 different proteins were identified. KASP markers for three major/stable QTL, namely QGfd.ccsu-7A for grain filling duration on chromosome 7A (timely sown), QNgs.ccsu-3A for number of grains per spike on 3A, and QDth.ccsu-7A for days to heading on 7A (late and very late sown) environments were developed for MARS focusing on the development of heat-tolerant wheat varieties/germplasm.

Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Myval: A Novel Transcatheter Heart Valve for the Treatment of Severe Aortic Stenosis.

Transcatheter aortic valve implantation (TAVI) performed using femoral arterial access is now a guideline recommended treatment for severe calcific aortic stenosis (AS) in elderly patients. Technological advancements and procedural refinements have focused on making TAVI simpler, safer, more effective and durable. Myval (Meril Lifesciences) is a new generation balloon-expandable transcatheter heart valve (THV) developed in India that possesses novel features to improve deliverability and aid precise deployment. Following the first-in-human study, Myval was approved in India for commercial implantation in October 2018 and was subsequently given a CE mark in April 2019. This article reviews the science, technology and up-to-date clinical evidence for the Myval THV.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

WheatQTLdb V2.0: a supplement to the database for wheat QTL.

We recently developed a database for hexaploid wheat QTL (WheatQTLdb; www.wheatqtldb.net), which included 11,552 QTL affecting various traits of economic importance. However, that database did not include valuable QTL from other wheat species and/or progenitors of hexaploid wheat. Therefore, an updated and improved version of wheat QTL database (WheatQTLdb V2.0) was developed, which now includes information on hexaploid wheat (Triticum aestivum) and the following seven other related species: T. durum, T. turgidum, T. dicoccoides, T. dicoccum, T. monococcum, T. boeoticum, and Aegilops tauschii. WheatQTLdb V2.0 includes a much-improved list of QTL, including 27,518 main effect QTL, 202 epistatic QTL, and 1321 metaQTL. This newly released WheatQTLdb V2.0 also has additional valuable options to search and choose the QTL, category-wise, and trait-wise data for their use in research or breeding programs.

WheatQTLdb: a QTL database for wheat.

During the last three decades, QTL analysis in wheat has been conducted for a variety of individual traits, so that thousands of QTL along with the linked markers, their genetic positions and contribution to phenotypic variation (PV) for concerned traits are now known. However, no exhaustive database for wheat QTL is currently available at a single platform. Therefore, the present database was prepared which is an exhaustive information resource for wheat QTL data from the published literature till May, 2020. QTL data from both interval mapping and genome-wide association studies (GWAS) have been included for the following classes of traits: (i) morphological traits, (ii) N and P use efficiency, (iii) traits for biofortification (Fe, K, Se, and Zn contents), (iv) tolerance to abiotic stresses including drought, water logging, heat stress, pre-harvest sprouting and salinity, (v) resistance to biotic stresses including those due to bacterial, fungal, nematode and insects, (vi) quality traits, and (vii) a variety of physiological traits, (viii) developmental traits, and (ix) yield and its related traits. For the preparation of the database, literature was searched for data on QTL/marker-trait associations (MTAs), curated and then assembled in the form of WheatQTLdb. The available information on metaQTL, epistatic QTL and candidate genes, wherever available, is also included in the database. Information on QTL in this WheatQTLdb includes QTL names, traits, associated markers, parental genotypes, crosses/mapping populations, association mapping panels and other useful information. To our knowledge, WheatQTLdb prepared by us is the largest collection of QTL (11,552), epistatic QTL (107) and metaQTL (330) data for hexaploid wheat to be used by geneticists and plant breeders for further studies involving fine mapping, cloning, and marker-assisted selection (MAS) during wheat breeding.

Meta-QTLs, ortho-MQTLs, and candidate genes for thermotolerance in wheat (Triticum aestivum L.).

Meta-QTL analysis for thermotolerance in wheat was conducted to identify robust meta-QTLs (MQTLs). In this study, 441 QTLs related to 31 heat-responsive traits were projected on the consensus map with 50,310 markers. This exercise resulted in the identification of 85 MQTLs with confidence interval (CI) ranging from 0.11 to 34.9 cM with an average of 5.6 cM. This amounted to a 2.96-fold reduction relative to the mean CI (16.5 cM) of the QTLs used. Seventy-seven (77) of these MQTLs were also compared and verified with the results of recent genome-wide association studies (GWAS). The 85 MQTLs included seven MQTLs that are particularly useful for breeding purposes (we called them breeders' MQTLs). Seven ortho-MQTLs between wheat and rice genomes were also identified using synteny and collinearity. The MQTLs were used for the identification of 1,704 candidate genes (CGs). In silico expression analysis of these CGs permitted identification of 182 differentially expressed genes (DEGs), which included 36 high confidence CGs with known functions previously reported to be important for thermotolerance. These high confidence CGs encoded proteins belonging to the following families: protein kinase, WD40 repeat, glycosyltransferase, ribosomal protein, SNARE associated Golgi protein, GDSL lipase/esterase, SANT/Myb domain, K homology domain, etc. Thus, the present study resulted in the identification of MQTLs (including breeders' MQTLs), ortho-MQTLs, and underlying CGs, which could prove useful not only for molecular breeding for the development of thermotolerant wheat cultivars but also for future studies focused on understanding the molecular basis of thermotolerance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01264-7.

Intervention in coronary bifurcation lesions: Staying on top of the proximal optimization technique (POT).

Proximal optimization technique (POT) restores the stent to the fractal geometry of coronary bifurcations and is the final step when using two-stent strategy. Optimal positioning of balloon during final POT is vital to achieve best results without side branch compromise. In vitro studies provide valuable insights to define procedural strategies and help achieve best outcomes for coronary bifurcation lesions.

Office blood pressure measurement practices among community health providers (medical and paramedical) in northern district of India.

INTRODUCTION: Hypertension is directly responsible for 57% of all stroke deaths and 24% of all coronary heart disease deaths in India. Appropriate blood pressure measurement techniques are the cornerstone of clinical acumen. Despite the clear guidelines on BP measurement technique, there seems to be large inter-observer variations. AIM & METHODS: A prospective, observational study was done to assess the knowledge and to study the current practices of office BP measurement among the 400 medical and paramedical staff working in various hospitals of a northern district of India. A single observer under the supervision of investigators observed all the participants and a proforma was filled based on AHA guidelines. After observing BP measurement technique scoring was done (≤ 8 question correct = inaccurate practices, >9 questions correct = accurate practices). Similarly, the knowledge was assessed by giving a pretested questionnaire. RESULTS: 5.85 % of the medical staff had excellent knowledge and 80% of the doctors and 62% of the paramedical staff had good knowledge about BPM. Only 1.47% (3 doctors) and 0.5% (1 nurse) had accurate practices. There was no correlation between knowledge and practices. CONCLUSIONS: We conclude that the right technique and knowledge of blood pressure measurement among community health providers is inadequate and warrants further interventions to improve.