Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ?-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

Prevalence of Health Problems, Professional and Financial Satisfaction among Doctors Working Across Vadodara City: A Cross-sectional Study

Background: The present study was conducted to know the distribution of various health problems among doctors and to assess professional and financial satisfaction levels among doctors. Methods: A Google Form questionnaire-based cross-sectional study was conducted among 122 doctors in Vadodara selected purposively after taking consent. Google form was circulated by email and WhatsApp groups. The form consisted of questions related to demographic details, health problems, financial and job satisfaction. All the responses were recorded and analyzed in MS Excel 2019. Results: Among the 122 doctors, 89 (72.95%) were male and 33 (27.04%) were female and 101 (82.78%) doctors were taking treatment for some ailment. Around 86.9% of doctors regularly opt for a health check-up. Among the health problems reported by doctors, the most common were musculoskeletal ailments (72.13%) followed by hypertension (28.9%), diabetes (17.2), cardiac (12.3%), endocrinal (10.65%), eye (9.01), mental (6.55) problems. Approximately 37.70% of doctors answered that health problems temporarily affect their work; 5.73% of doctors felt the need to modify their work pattern. About 91.80% of doctors were satisfied by their profession, while 108 (88.52%) doctors were financially satisfied with their work. Conclusion: More than half of the professionals complained of musculoskeletal problems. The majority of health care professionals were professionally and financially satisfied.

Role of Iron Therapy in Heart Failure: A Consensus Statement from India

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

The Power and Promise of Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure Management: National Consensus Statement

Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril–Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril–Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril–Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril–Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40–50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.

Suspecting and diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM) in India: An Indian expert consensus

Transthyretin cardiac amyloidosis (ATTR-CM) is a rare and under-recognized disorder characterized by the aggregation of transthyretin-derived insoluble amyloid fibrils in the myocardium. Heterogeneity of symptoms at presentation, makes its diagnosis often delayed. An expert panel gathered on a virtual platform across India to conduct a meeting for developing a guiding tool for ATTR-CM diagnosis. The panel recommended younger age (40 years) for suspecting ATTR-CM and thick-walled non-dilated hypokinetic ventricle was considered as one of the important red flags. Electrocardiogram (ECG) and echocardiography (ECHO) findings were recommended as primary tests to raise the suspicion while nuclear scintigraphy and hematological tests were recommended to confirm the diagnosis and rule out amyloid light-chain (AL) amyloidosis. Cardiac magnetic resonance (CMR) and biopsy were recommended in case of ambiguity in the presence of red flags. Considering the lack of expert guidelines in the Indian scenario, a standardized diagnostic algorithm was also proposed.

Experts’ Consensus on Use of Long-Acting Nitroglycerine in the Management of Angina and Chronic Coronary Syndrome in India

Aim: To address the existing gaps in knowledge about long-acting nitroglycerine (LA-NTG) and provide recommendations to address these issues. Methodology: Approved LA-NTG questionnaire that included 17 questions related to the role of LA-NTG in the management of angina and chronic coronary syndrome (CCS) was shared with 150 expert cardiologists from different regions from India. Results of these survey questionnaires were further discussed in 12 regional level meetings. The opinions and suggestions from all the meetings were compiled and analyzed. Further, recommendations were made with the help of attending national cardiology experts and a consensus statement was derived. Results: This is the first consensus on LA-NTG, summarizing the clinical evidence from India and suggesting recommendations based on these data. The experts recommended early use of LA-NTG as a first-line antianginal therapy in combination with beta-blocker since it improves exercise tolerance in patients with CCS. A strong consensus was observed for using LA-NTG in patients with co-morbid hypertension, diabetes, chronic kidney disease and post-percutaneous coronary intervention angina. As a part of cardiac rehabilitation, LA-NTG allows patients with angina to exercise to a greater functional capacity. Conclusions: A national consensus was observed for several aspects of LA-NTG in the management of angina and CCS. The clinical experience of the experts confirmed an extremely satisfied patient perception about the efficacy of LA-NTG.

A rare clinical entity of asymptomatic adult bochdalek hernia

Bochdalek hernia (BH) is the commonest congenital diaphragmatic hernia, caused by the failure of the posterolateral diaphragmatic foramina to fuse properly. It is extremely rare in adults and accounts for 5-10%. Presenting a case of 48 years female with complaints of dry cough and left chest pain for 1 week. Diminished breath sounds and abnormal gurgling sounds heard on auscultation of left chest wall. X-ray chest showed elevated left hemi diaphragm and gastric bubble. Computed tomography (CT) chest revealed left diaphragmatic hernia with splenic flexure, transverse colon, mesocolon, spleen and upper pole of left kidney as content and atelectasis of left lung lower lobe. Patient underwent laparoscopic repair of hernia with mesh plasty. Intraoperatively, the contents were reduced into the abdominal cavity and left lung expansion noted. The defect of size 6×10 cm in the left diaphragm was sutured and composite mesh placed. Post-operative chest x-ray showed expanded left lung. On follow up of patient after 2 weeks and 1 month, patient was asymptomatic. BH in adults is an uncommon. The contents can be reduced via thoracic or abdominal approach, with abdominal approach having easier access. With the advent of minimal access techniques, delineating clear anatomy, more working space, early recovery, and early return to home and work is possible. Thus, laparoscopic repair of adult diaphragmatic hernia is a safe and effective modality of surgical treatment.

Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility

Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal andoropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2aclade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were alsodetected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz.G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutationsreside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain,which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observedbetween these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations ofmiRNA binding and structure were also predicted for these mutations. More importantly, the possibleimplications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of Sprotein have also been discussed. Results report for the first time a bird’s eye view on the accumulation ofmutations in SARS-CoV-2 genome in Eastern India.

Outcome of Transforaminal Lumbar Interbody Fusion (TLIF) For Spondylolisthesis of Lumbar Spine

Background: This retrospective study was performed toassess the radiological and clinical outcome of patients whounderwent transforaminal lumbar interbody fusion (TLIF) withan interbody cage for spondylolisthesis.Methods: Forty five consecutive patients of spondylolisthesiswho underwent transforaminal lumbar interbody fusion (TLIF)during the period from July 2016 to June 2018 were reviewedretrospectively. Clinical data and radiological data werecollected and analysed. Twenty seven male and eighteenfemale patients underwent the TLIF procedure with a meanage of 48.6 years (24–66 years). The primary pathology was alytic listhesis in 28 patients and degenerative listhesis in 17.There was no multilevel fixation. Two cases were revisionsurgery. The mean blood loss was 290 ml and mean operativetime 160 minutes. No patient need to stay in ICU or HDU.Hospital stay was 4-5 days. Radiological outcome wasassessed by observing the presence of fusion mass at biplanarradiography whereas clinical outcomes were assessed bymeans of the Parker Visual Analog scale (VAS).Results wereclassified into three categories (excellent and good, fair, andpoor) using the Parker criteria. Pain was recorded by usingVisual Analog Scale.Results: There were no intra-operative complications. Twopatients developed neurological deficit in the form of partial footdrop. There were statistically significant improvements frompreoperative VAS to post-operative VAS. Fusion couldbe assessed in all patients. Anterior interbody fusion wasachieved in 78.3% of cases and posterior lateral fusion wasachieved in 69.6%.Four patients showed no fusion at the endof 6 months post operatively.Conclusions: Transforaminal lumbar interbody fusion is a safeand effective method to achieve circumferential fusion. It istechnically challenging and needs to be proficient in thetechnique to avoid catastrophic complications. Clinical scoringconfirmed that satisfactory overall outcome. Complicationsresulting from the procedure is uncommon and generally minorand transient.

Adaptation of 2016 European Society of Cardiology/European Atherosclerosis Society guideline for lipid management to Indian patients – A consensus document

In the year 2016, European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines provided recommendations on dyslipidemia management. The recommendation from these guidelines are restricted to European subcontinent. To adapt the updated recommendations for Indian subset of dyslipidemia, a panel of experts in management of dyslipidemia provided their expert opinions. This document provides expert consensus on adapting 2016 ESC dyslipidemia guidelines recommendations in Indian setting. The document also discussed India-specific relevant literature to support the consensus opinions provided in management of dyslipidemia.

Contrast-induced nephropathy.

Contrast-induced nephropathy (CIN) is a fairly common yet under-recognized clinical condition in the interventional cardiological practice. A 25% or more than 0.5 mg/dl rise of serum creatinine is generally accepted as defining CIN. The most important risk factors for CIN are pre-existing renal disease, volume of contrast media, nature of contrast media, and diabetes mellitus. Among the various postulated pathophysiological mechanisms for the precipitation of CIN, intra-renal vasoconstriction, and oxidative tubular injury are the best documented. Effective strategies to prevent CIN include adequate peri-procedural hydration with normal saline, use of N-acetylcysteine, keeping the volume of contrast media as low as feasible, and avoiding high-osmolal ionic contrast media. However, more efficient and cost-effective strategies are being developed and the search for the ideal contrast media is still on.

Immature teratoma with choriocarcinoma-like lesion of testis: case report of an unusual presentation.

An eighteen year old male presented with hemoptysis and superior vena caval syndrome. History and clinical examination revealed a testicular mass which was previously diagnosed as hematocele. Chest x-ray showed a four cm diameter shadow and several smaller shadows. Histological examination of the testicular mass established it as immature teratoma with choriocarcinoma-like lesion (CCLL)--a rare association in testicular tumours. Focal positivity for betaHCG was noted in the testicular tumour. Guided aspiration of the lung showed features of a metastatic non seminomatous germ cell tumour.

Small cell carcinoma of ovary: a rare pathology.

A 15-year-old girl presented with rapidly developing ascites and bilateral tender pelvic masses, diagnosed as small cell carcinoma of the ovary, based on histopathological and immunohistochemical features. The case is being presented because of its rare occurrence.

Clear cell carcinoid tumour of lung--a case report.

An unusual case of pulmonary clear cell carcinoid tumour in a fifteen year old boy is being described. The differential diagnoses considered in this case are described. This is one of the uncommon varieties of carcinoid of lung reported in the world literature.

Thymolipoma--a case report.

A 28 year old male presented with a 8 months history of chest pain, cough and breathlessness. CT scan revealed a large mass in right anterior mediastinum showing fat and soft tissue attenuation. Histopathology of the resected mass revealed a tumour showing extensive areas of mature fat and relatively less interspersed thymic tissue confirming thymolipoma. Because of its rarity, we are presenting this case with a brief review of literature.

Pleuropulmonary blastoma--a rare pathology.

Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy in children. The clinical features, radiologic, cytologic, gross and histopathological features of one such case in a 9 year old girl is discussed along with a short review of literature.

Primary breast sarcomas--report of two cases.

Two (2) primary breast sarcomas out of 110 primary breast malignancies from N.R.S. Medical College, Kolkata are being reported. Primary Breast Sarcomas are classified into five (5) broad groups with their representative features. Our two cases are classified as fibrosarcoma and malignant haemangioendothelioma and their features are documented. Because of its rarity, we are presenting this case with brief review of literature.

A new 85 kDa, breast tumour associated antigen — A potential diagnostic and prognostic agent.

In an attempt to develop measures for early diagnosis and prognosis of the disease and to explore association of murine mammary tumour virus (MuMTV) or related virus in breast cancer, we purified a breast tumour associated antigen (BTAA) from the breast tumour tissues of untreated female cancer patients. The BTAA purified by DEAE discontinuous column chromatography followed by SE-HPLC was an 85 kDa glycoprotein. A high level of circulating antibodies against this antigen was observed, using ELISA, in all the untreated female breast cancer patients. The BTAA was not immunologically related to MuMTV antigens but strongly resembled an 83 kDa glycoprotein tumour associated antigen, purified from MuMTV induced mouse mammary tumour. In patients after surgical removal of the breast tumour, the circulating antibodies to the BTAA decreased gradually, but reappeared in the patients with secondary metastasis. In healthy age matched women or in female patients with carcinoma of tissues other than breast, no significant titre of the BTAA antibodies was observed.

Mini-exon derived RNA gene of Leishmania donovani: structure, organization and expression.

Mini-exon derived RNA is a small nuclear RNA of trypanosomatid protozoa such as Leishmania which donates its 5'-terminal 39 nucleotides to the 5'-ends of cellular messenger RNAs by trans-splicing. We have cloned a mini-exon derived RNA gene from Leishmania donovani and studied its organization and expression. About 200 copies of the gene per haploid genome are organized as a tandem repeat on a single chromosome. The gene is transcribed as a 95-nucleotide RNA. The first 39 nucleotides of mini-exon derived RNA is also found at the 5'-terminus of a cellular mRNA (β-tubulin), thus confirming its identity. Sequence analysis of the gene and its flanking regions showed that while classical RNA polymerase II promoter elements such as TATA and CAAT are absent from the 5'- upstream region, intragenic sequence motifs resembling RNA polymerase III promoter elements are present. The implications of this finding for mini-exon derived RNA expression are discussed.