Publications by authors named "Sandeep Seth"

87 Publications

Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial.

Anaesth Intensive Care 2021 Sep 18;49(5):366-378. Epub 2021 Aug 18.

Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India.

Persistent tachycardia in patients with septic shock predicts poor outcome. This study sought to investigate the effect of the cardiac pacemaker current inhibitor ivabradine on heart rate and cardio-circulatory function in patients with septic shock. After informed consent, 60 patients with septic shock and persistent tachycardia (heart rate >95 /minute) were prospectively randomly assigned to receive either standard therapy for septic shock (group S) or standard therapy along with enteral ivabradine (group I) for the initial 96 hours after enrolment. Primary outcome was the difference in heart rate between the two groups during the first 96 hours. Secondary outcomes included the effect of ivabradine on haemodynamic, oxygenation, myocardial function and organ function parameters, incidence of adverse events and 30-day overall survival. Heart rate was lower in group I compared to group S (median difference in area under the curve -25.6 (95% confidence intervals -31.4 to -15.9) /minute; <0.001). Vasopressor requirements, blood lactate levels, Sequential Organ Failure Assessment scores and E/e' ratio were lower in group I compared to group S. Stroke volume index and ejection fraction were higher in group I while cardiac index and oxygen delivery parameters were maintained similar to group S. There was no difference in 30-day mortality or in the incidence of serious adverse events. Enteral ivabradine is effective in reducing heart rate, and improving haemodynamic parameters and cardiac function in patients with septic shock and persistent tachycardia, without increasing the incidence of adverse events.
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http://dx.doi.org/10.1177/0310057X211009913DOI Listing
September 2021

Comparison of Ga-DOTANOC PET/CT with cardiac MRI in patients with clinical suspicion of cardiac sarcoidosis.

Ann Nucl Med 2021 Sep 14;35(9):1058-1065. Epub 2021 Jun 14.

Department of Nuclear Medicine, Cardiothoracic centre, All India Institute of Medical Sciences, Room. No. 36, New Delhi, 110029, India.

Background: Ga-DOTA-NaI-octreotide (DOTANOC) is a promising new alternative to F-fluorodeoxyglucose (FDG) for imaging inflammation in cardiac sarcoidosis. The aim of the study was to compare Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) with cardiac magnetic resonance imaging (CMR) in patients with clinical suspicion of cardiac sarcoidosis.

Methods And Results: Patients with extracardiac sarcoidosis and clinical suspicion of cardiac involvement underwent Ga-DOTANOC cardiac PET/CT, myocardial perfusion single photon emission computed tomography (MPS) and CMR (T2-weighted and delayed gadolinium-enhanced T1-weighted images). The patients were screened using revised criteria of Japanese circulation society. Presence of perfusion defects on MPS, abnormal myocardial uptake on Ga-DOTANOC PET/CT and characteristic pattern of late gadolinium enhancement (LGE) with or without T2 hyperintensity on CMR was considered positive.

Results: Seventeen patients (13 male and 4 female) were included in the study. Out of the 17 patients, both CMR and PET were positive in 11 and both were negative in 2. In the remaining 4 patients, CMR was positive but PET was normal. Thus, PET and CMR were concordant in 13 (76.5%) patients and discordant in 4 (23.5%). Intermodality agreement was fair (Cohen's kappa = 0.39).

Conclusion: LGE on CMR is superior to Ga-DOTANOC PET/CT for detecting cardiac involvement in sarcoidosis and there is fair concordance between the two. However, since LGE does not specifically differentiate between inflammation and fibrosis, Ga-DOTANOC PET/CT may be better than CMR in identifying patients with active inflammation, since it directly targets inflammatory cells and can have a complementary role to CMR.
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http://dx.doi.org/10.1007/s12149-021-01641-4DOI Listing
September 2021

An unusual case of Shone's complex in an adult depicted on computed tomography angiography.

J Card Surg 2021 Aug 1;36(8):2956-2957. Epub 2021 Jun 1.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.

We present a case of a 22-year-old male with dyspnea on exertion where computed tomography revealed complete Shone's complex. This case highlights the complementary role of computed tomography in the anatomical evaluation of patients with complex heart diseases.
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http://dx.doi.org/10.1111/jocs.15635DOI Listing
August 2021

Familial dilated cardiomyopathy with RBM20 mutation in an Indian patient: a case report.

Egypt Heart J 2021 May 22;73(1):47. Epub 2021 May 22.

Department of Cardiology, All India Institute of Medical Science, New Delhi, India.

Background: Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by ventricular dilation and a left ventricular ejection fraction of less than 40%. Unlike hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC), DCM-causing mutations are present in a large number of genes. In the present study, we report a case of the early age of onset of DCM associated with a pathogenic variant in the RBM20 gene in a patient from India.

Case Presentation: A 19-year-old Indian male diagnosed with DCM was suggested for heart transplantation. His ECG showed LBBB and echocardiography showed an ejection fraction of 14%. He had a sudden cardiac death. A detailed family history revealed it to be a case of familial DCM. Genetic screening identified the c.1900C>T variant in the RBM20 gene which led to a missense variant of amino acid 634 (p.Arg634Trp).

Conclusion: To the best of our knowledge, the variant p.Arg634Trp has been earlier reported in the Western population, but this is the first case of p.Arg634Trp in an Indian patient. The variant has been reported to be pathogenic at an early age of onset; therefore, close clinical follow-up should be done for the family members caring for the variant.
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http://dx.doi.org/10.1186/s43044-021-00165-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140951PMC
May 2021

Dual Tachycardia in a Middle-aged Woman: Occam's Razor vs Hickam's Dictum.

JAMA Intern Med 2021 Jul;181(7):980-982

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1001/jamainternmed.2021.1434DOI Listing
July 2021

Reversible complete heart block due to hypercalcaemia.

BMJ Case Rep 2021 Jan 18;14(1). Epub 2021 Jan 18.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.

A 65-year-old woman presented to the emergency room with a syncope. An ECG done revealed complete heart block with a narrow QRS escape rhythm and a normal QT interval. Further investigation revealed severe hypercalcaemia and elevated parathormone levels. Her heart block disappeared on correction of the hypercalcaemia. A right inferior parathyroid adenoma was found and surgically removed. Thus, hypercalcaemia may lead to reversible complete heart block without QT interval shortening.
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http://dx.doi.org/10.1136/bcr-2020-238537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813424PMC
January 2021

Experience of endomyocardial biopsy from a tertiary care center in India.

Asian Cardiovasc Thorac Ann 2021 Jul 20;29(6):498-507. Epub 2020 Dec 20.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Background: Endomyocardial biopsy is the gold standard and has a definite role in the surveillance of cardiac allograft rejection. Its role in other cardiac diseases is limited. However, it is required for conclusive diagnosis of a few entities in which it can influence patient management. There is no reported data regarding the utility of endomyocardial biopsy in the Indian population. Thus, this study was undertaken in a tertiary care center in India to assess the utility of endomyocardial biopsy in various cardiac diseases in the context of clinical diagnoses.

Methods: All endomyocardial biopsies conducted over a 27-year period were evaluated. Clinical details including indication for biopsy were collected. Histopathological findings were recorded and classified as definitive diagnosis, probable diagnosis with features consistent with the clinical diagnosis, and nonspecific morphological findings.

Results: A total of 927 endomyocardial biopsies from 719 patients were reviewed. Endomyocardial biopsy was diagnostic in 12.5% of native cardiac biopsies and 52.1% showed nondiagnostic findings. The most frequent diagnoses were amyloidosis (58.7%) and myocarditis (8.6%). Endomyocardial biopsy had a diagnostic role in evaluation of restrictive cardiac diseases. Endomyocardial fibrosis and tubercular myocarditis, relatively more prevalent in the Indian population, were also identified. Cases of rheumatic heart disease, desmin cardiomyopathy, and microfibrillar cardiomyopathy were surprise findings, proving the usefulness of endomyocardial biopsy in detecting some rare cardiac conditions.

Conclusion: Endomyocardial biopsy is an important tool for the diagnosis of specific cardiac diseases including some rare entities, and for conditions which are more prevalent in our country, requiring biopsy confirmation.
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http://dx.doi.org/10.1177/0218492320981503DOI Listing
July 2021

Somatostatin analogue scintigraphy in myocardial inflammation: An interesting image.

J Nucl Cardiol 2020 12 13;27(6):2436-2437. Epub 2020 Jan 13.

Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1007/s12350-019-02023-0DOI Listing
December 2020

Investigating Coronary Artery Disease methylome through targeted bisulfite sequencing.

Gene 2019 Dec 6;721:144107. Epub 2019 Sep 6.

CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

Background: Gene environment interactions leading to epigenetic alterations play pivotal role in the pathogenesis of Coronary Artery Disease (CAD). Altered DNA methylation is one such epigenetic factor that could lead to altered disease etiology. In this study, we comprehensively identified methylation sites in several genes that have been previously associated with young CAD patients.

Methods: The study population consisted of 42 healthy controls and 33 young CAD patients (age group <50 years). We performed targeted bisulfite sequencing of promoter as well as gene body regions of several genes in various pathways like cholesterol synthesis and metabolism, endothelial dysfunction, apoptosis, which are implicated in the development of CAD.

Results: We observed that the genes like GALNT2, HMGCR were hypermethylated in the promoter whereas LDLR gene promoter was hypomethylated indicating that intracellular LDL uptake was higher in CAD patients. Although APOA1 did not show significant change in methylation but APOC3 and APOA5 showed variation in methylation in promoter and exonic regions. Glucokinase (GCK) and endothelial nitric oxide synthase 3 (NOS3) were hyper methylated in the promoter. Genes involved in apoptosis (BAX/BCL2/AKT2) and inflammation (PHACTR1/LCK) also showed differential methylation between controls and CAD patients. A combined analysis of the methylated CpG sites using machine learning tool revealed 14 CpGs in 11 genes that could discriminate CAD cases from controls with over 93% accuracy.

Conclusions: This study is unique because it highlights important gene methylation alterations which might predict the risk of young CAD in Indian population. Large scale studies in different populations would be important for validating our findings and understanding the epigenetic events associated with CAD.
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http://dx.doi.org/10.1016/j.gene.2019.144107DOI Listing
December 2019

Loss of function mutation in the P2X7, a ligand-gated ion channel gene associated with hypertrophic cardiomyopathy.

Purinergic Signal 2019 06 31;15(2):205-210. Epub 2019 May 31.

Department of Anthropology, University of Delhi, New Delhi, India.

Hypertrophic cardiomyopathy (HCM) is an inherited heart failure condition, mostly found to have genetic abnormalities, and is a leading cause of sudden death in young adults. Whole exome sequencing should be given consideration as a molecular diagnostic tool to identify disease-causing mutation/s. In this study, a HCM family with multiple affected members having history of sudden death were subjected to exome sequencing along with unaffected members. Quality passed variants obtained were filtered for rarity (MAF > 0.5%), evolutionary conservation, pathogenic prediction, and segregation in affected members after removing shared variants present in unaffected members. Only one non-synonymous mutation (p. Glu186Lys or E186K) in exon 6 of P2X7 gene segregated in HCM-affected individuals which was absent in unaffected family members and 100 clinically evaluated controls. The site of the mutation is highly conserved and led to complete loss of function which is in close vicinity to ATP-binding site-forming residues, affecting ATP binding, channel gating, or both. Mutations in candidate genes which were not segregated define clinical heterogeneity within affected members. P2X7 gene is highly expressed in the heart and shows direct interaction with major candidate genes for HCM. Our results reveal a significant putative HCM causative gene, P2X7, for the first time and show that germ-line mutations in P2X7 may cause a defective phenotype, suggesting purinergic receptor involvement in heart failure mediated through arrhythmias which need further investigations to be targeted for therapeutic interventions.
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http://dx.doi.org/10.1007/s11302-019-09660-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635509PMC
June 2019

Equilibrium Radionuclide Angiography in Evaluation of Left Ventricular Mechanical Dyssynchrony in Patients with Dilated Cardiomyopathy: Comparison with Electrocardiographic Parameters and Speckle-Tracking Echocardiography.

Indian J Nucl Med 2019 Apr-Jun;34(2):88-95

Department of Nuclear Medicine, Cardiothoracic Centre, All India Institute of Medical Sciences, New Delhi, India.

Purpose Of The Study: The purpose of this study was to study the role of equilibrium radionuclide angiography (ERNA) in the assessment of left ventricular (LV) mechanical dyssynchrony in patients with dilated cardiomyopathy (DCM), by correlating the findings with electrocardiographic parameters and speckle-tracking echocardiography (STE).

Methods: This was a prospective observational study. A total of 55 patients with a mean age 42.5 ± 11 years (range: 19-61 years) diagnosed with DCM underwent ERNA and echocardiography sequentially. On ERNA, phase images of LV were obtained, and standard deviation of LV mean phase angle (SD LVmPA) was derived to quantify intra-LV mechanical dyssynchrony (ILVD). Similarly, on STE, "dyssynchrony index" was calculated as the standard deviation of time-to-peak systolic circumferential strain (SDCS) of the six mid-LV segments. The cutoff values used to define mechanical dyssynchrony were SD LVmPA >13.2° (or >27.1 ms) and SDCS >74 ms on ERNA and STE, respectively. The results obtained from the two modalities were then compared.

Results: Speckle-tracking analysis could be done on the echocardiographic data of only 42 patients. Paired data from ERNA and STE studies of these 42 patients (26 males and 16 females) were compared, which showed no significant difference in the detection of ILVD ( = 0.125). The two modalities showed good agreement with Cohen's kappa value of 0.78 ( < 0.0001). SD LVmPA and SDCS values showed moderately strong linear correlation (ρ = 0.69; < 0.0001). No significant association of mechanical dyssynchrony on ERNA or STE was found with QRS duration and with the presence or absence of left bundle branch block. ILVD was also found to be negatively correlated with LV ejection fraction.

Conclusion: ERNA is comparable to STE for the assessment of LV mechanical dyssynchrony.
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http://dx.doi.org/10.4103/ijnm.IJNM_165_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481198PMC
May 2019

Beneficial effects of fenofibrate in pulmonary hypertension in rats.

Mol Cell Biochem 2018 Dec 14;449(1-2):185-194. Epub 2018 May 14.

Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Room No. 4017, Ansari Nagar, New Delhi, 110029, India.

Pulmonary hypertension (PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats. FF, because of its pleiotropic property, could be helpful in reducing inflammation, oxidative stress, and reactive oxygen species. On day 1, MCT (50 mg/kg, s.c.) was given to all the rats in MCT, sildenafil, and FF group except normal control rats. After 3 days of giving MCT, sildenafil (175 µg/kg, orally) and FF (120 mg/kg, orally) were given for 25 days. Echocardiography, hemodynamic parameters, fulton's index, histopathology, oxidative stress parameters, inflammatory markers, Bcl2/Bax gene expression ratio in the right ventricle, and protein expression for NOX-1 in lungs were studied in all the groups. FF has shown to prevent decrease in ratio of pulmonary artery acceleration time to ejection time, increase in ratio of right ventricular outflow tract dimension to aortic outflow dimension, rise in right ventricular systolic pressure, right ventricular hypertrophy, increase in the percentage medial wall thickness (%MWT), increase in oxidative stress and inflammation, increase in NADPH oxidase-1 (NOX-1) expression, and decrease in mRNA expression of Bcl2/Bax ratio caused by MCT. To conclude, FF prevented MCT-induced PH in rats by various mechanisms. It might be helpful in preventing PH in patients who are likely to develop PH.
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http://dx.doi.org/10.1007/s11010-018-3355-3DOI Listing
December 2018

Beneficial Effect of (Linn) against Monocrotaline-Induced Pulmonary Hypertension in Rats.

Medicines (Basel) 2018 Apr 17;5(2). Epub 2018 Apr 17.

Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.

Background: The study was designed to explore any beneficial effect of Ocimum sanctum (Linn) (OS) in experimental pulmonary hypertension (PH) in rats. OS is commonly known as “holy basil” and “Tulsi” and is used in the Indian System of Medicine as antidiabetic, antioxidant, hepatoprotective, adaptogenic, and cardioprotective.

Methods: Monocrotaline (MCT) administration caused development of PH in rats after 28 days and rats were observed for 42 days. Treatments (sildenafil; 175 µg/kg, OS; 200 mg/kg) were started from day 29 after the development of PH and continued for 14 days. Parameters to assess the disease development and effectiveness of interventions were echocardiography, right and left ventricular systolic pressures, and right ventricular end diastolic pressure, percentage medial wall thickness (%MWT) of pulmonary artery, oxidative stress markers in lung tissue, NADPH oxidase (Nox-1) protein expression in lung, and mRNA expression of Bcl2 and Bax in right ventricular tissue.

Results: OS (200 mg/kg) treatment ameliorated increased lung weight to body weight ratio, right ventricular hypertrophy, increased RVSP, and RVoTD/AoD ratio. Moreover, OS treatment decreases Nox-1 expression and increases expression of Bcl2/Bax ratio caused by MCT.

Conclusion: The present study demonstrates that OS has therapeutic ability against MCT-induced PH in rat which are attributed to its antioxidant effect. The effect of OS was comparable with sildenafil.
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http://dx.doi.org/10.3390/medicines5020034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023537PMC
April 2018

Familial Hypertrophic Cardiomyopathy - Identification of cause and risk stratification through exome sequencing.

Gene 2018 Jun 21;660:151-156. Epub 2018 Mar 21.

Dept. of Anthropology, Delhi University, Delhi, India; Genome Foundation, Hyderabad, India; Dept. of Genetics, Osmania University, Hyderabad, India. Electronic address:

Background: Hypertrophic Cardiomyopathy (HCM) with variable clinical presentations and heterogeneity is the common cause of sudden cardiac death. Genetic diagnosis is challenging in these complex diseases but exome sequencing as a genetic diagnostic tool provides explainable results.

Methods: In a familial Hypertrophic Cardiomyopathy with multigenerational inheritance with apparent phenotype, had a history of sudden death and severe arrhythmia followed by implantation of Implantable cardioverter defibrillator (ICD). Exome sequencing (100×) trailed by effective filtering steps for exome variants on the basis of different parameters, segregated variants are prioritized for the disease and further clinical relevance are evaluated for the variants.

Results: A rare causal variant in troponin-T gene (TNNT2, NM_000364.3;c.274C > T;p.Arg92Trp) is identified, shared by only affected members, absent in unaffected members and also in 200 unrelated control chromosomes. TNNT2 mutation act as a driver mutation but mutations in other disease-related genes, KCNMB1, LPL, APOE and other biochemical factors provides risk stratification within affected family members.

Conclusion: This study contributes to the role of "rare variants" in complex disease phenotypes and heterogeneity within family and the necessity of whole exome targeted approaches in complex cardiomyopathy, which are known to harbor private mutations.
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http://dx.doi.org/10.1016/j.gene.2018.03.062DOI Listing
June 2018

Histological and morphometric analysis of dilated cardiomyopathy with special reference to collagen IV expression.

Indian J Pathol Microbiol 2017 Oct-Dec;60(4):481-486

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Collagen distribution alterations are well known in dilated cardiomyopathy. There are also changes in microvasculature along with other histomorphorphological features.

Aims And Objectives: To study the histomorphological features of DCM along with their quantitative correlation with LVEF. Alterations in collagen IV distribution pattern and microvasculature in DCM were also evaluated.

Materials And Methods: The present study includes 34 right ventricular endomyocardial biopsies, 7 explanted native hearts and 41 autopsy control hearts. Sections were taken from lower half of right interventricular septum and stained for H and E, Masson trichrome and immunohistochemistry for CD34, SMA and Collagen IV to study the histological features, pattern of fibrosis, capillary and arteriolar distribution and collagen IV expression respectively. Morphometric analysis was carried out in all cases and controls using Image analysis software Image pro plus 7 and correlated with left ventricular ejection fraction.

Results: The histomorphological changes of DCM include myocyte hypertrophy, nucleomegaly, and interstitial fibrosis. Interfiber fibrosis was the commonest. There was evidence of myocarditis, ischemic change and vessel wall alterations. Considerable alteration in Collagen IV distribution was observed with reduction in intensity and proportion of staining around myocytes quantified using Allred scoring against uniform pericellular staining in controls. Morphometric analysis revealed significant increase in nuclear area, myocyte width, percentage of fibrosis and reduction in capillary myocyte ratio in cases as compared to controls. There was no significant difference in arteriolar density. No significant association was observed between morphometric parameters and LVEF.

Conclusion: Histomorphological changes in DCM are non-specific. Quantitation of histological parameters cannot be used to predict the disease progression as there was no significant correlation with LVEF. There is appreciable alteration in Collagen IV distribution in DCM owing to extracellular matrix alterations.
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http://dx.doi.org/10.4103/IJPM.IJPM_213_16DOI Listing
July 2018

Late effects of treatment in survivors of childhood cancers: A single-centre experience.

Indian J Med Res 2017 Aug;146(2):216-223

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Background & Objectives: With improved survival of childhood cancer patients, the number of long-term cancer survivors is increasing. Some studies have assessed the long-term morbidity after childhood cancer treatment in the developing countries. This study was conducted to assess the spectrum of late effects of cancer treatment in paediatric cancer survivors.

Methods: Evaluation of the first 300 patients who completed five years of follow up in the after treatment completion clinic was done. Details of primary diagnosis, treatment received and current clinical status were noted. The spectrum of late effects was ascertained by appropriate investigations.

Results: Haematological malignancies comprised 25 per cent of total cases. Most common primary diagnosis comprised acute lymphoblastic leukaemia, retinoblastoma and Hodgkin's lymphoma. The median age at evaluation and follow up was 14 and 8.5 yr, respectively. Twenty three per cent (69) of the survivors had a minimal disability (growth retardation or underweight), 13 per cent (39) had moderate disabilities needing medical attention (hepatitis B surface antigen positive, myocardial dysfunction, azoospermia and hypothyroidism), while two per cent had major/life-threatening disabilities (mental retardation, liver disease and mortality). Eleven patients relapsed on follow up, of those five patients expired. Two second malignancies were recorded during the period of follow up.

Interpretation & Conclusions: Late effects were of concern; however, severe disability (Grade 3-5) was seen in only two per cent survivors. Lifelong follow up of childhood cancer survivors is required to assess cancer-related morbidity, occurrence of a secondary neoplasm, to facilitate timely diagnosis and to implement remedial or preventive interventions to optimize health outcomes. Awareness towards the existence of late effects of cancer therapy is required among parents, patients and health professionals.
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http://dx.doi.org/10.4103/ijmr.IJMR_196_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761031PMC
August 2017

Mitral Valve Replacement Using Carpentier-Edwards Pericardial Bioprosthesis in Patients With Rheumatic Heart Disease Aged Below 40 Years: 17-Year Results.

Heart Lung Circ 2018 Jul 1;27(7):864-871. Epub 2017 Aug 1.

Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, New Delhi, India.

Background: This study was designed to evaluate patients aged less than 40 years implanted with tissue heart valves with respect to survival, thromboembolism, structural degeneration and quality of life.

Methods: Between January, 2000 and December, 2016, 132 patients (51 males) with rheumatic heart disease underwent mitral valve replacement using Carpentier-Edwards, perimount, pericardial bioprostheses. The patients' ages ranged between 12 and 39 years (mean±SD 30.12±5.51 years).

Results: The hospital and late mortality were 1.5% and 1.5% respectively. The total cumulative follow-up period was 1330.98 patient-years with a mean of 124.78±50.3 months (range, 1-204 months). The actuarial survival and actuarial event-free survival at 204 months was 96.9% (±0.01%) and 93.4%(±0.03%) respectively. There was one episode of thromboembolism (0.32 events per 100 patient years). Six (4.7%) patients underwent redo mitral valve replacement for severe bioprosthetic degeneration with stiffening and calcification using a Medtronic mechanical prosthesis (Medtronic Open Pivot, MN, USA).

Conclusions: We conclude that Carpentier-Edwards perimount pericardial prosthesis provides satisfactory clinical performance in a young population with a low risk of degeneration and other valve-related events.
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http://dx.doi.org/10.1016/j.hlc.2017.05.147DOI Listing
July 2018

Longitudinal ventricular systolic dysfunction in patients with very severe obstructive sleep apnea: A case control study using speckle tracking imaging.

Indian Heart J 2017 May - Jun;69(3):305-310. Epub 2016 Dec 21.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.

Objective: Obstructive sleep apnea (OSA) is a prevalent condition that is increasingly recognized to be associated with cardiovascular disease. We aimed to investigate the subclinical systolic ventricular dysfunction of patients with OSA using novel speckle tracking echocardiographic (STE) techniques.

Methods: This study included 31 patients of polysomnography proven very severe OSA [Apnea Hypopnea Index(AHI) >40] and an equal number of matched population with no OSA as controls. All the study participants underwent a detailed conventional and tissue Doppler strain echocardiogram in addition to STE.

Results: There was no significant difference in conventional ventricular systolic function parameters including left ventricular (LV) ejection fraction, and myocardial performance index of left ventricle. Diastolic function was significantly reduced in patients with OSA as compared to controls. There was no difference in global circumferential strain or time to its peak between the two groups. However global longitudinal LV strain (GLS) was significantly reduced in patients with OSA (p<0.01). Similarly time to peak longitudinal strain was prolonged in the OSA group as compared to controls. Segmental analysis revealed that the longitudinal strain abnormalities were more pronounced in the apical and mid segments of LV. AHI remained the only significant predictor of GLS in these patients.

Conclusion: Very severe OSA is associated with significant diastolic dysfunction as well as early systolic abnormalities as evidenced by abnormal global longitudinal strain. Sleep apnea severity as measured by AHI was the only significant predictor of abnormal longitudinal strain in these patients.
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http://dx.doi.org/10.1016/j.ihj.2016.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485386PMC
April 2018

Serial semi-invasive hemodynamic assessment following pericardiectomy for chronic constrictive pericarditis.

Ann Card Anaesth 2017 Apr-Jun;20(2):169-177

Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, New Delhi, India.

Objectives: This study was designed to prospectively investigate the effects of pericardiectomy via median sternotomy on intra- and postoperative hemodynamics by a new semi-invasive device (Flotrac/VigileoTM monitor) using arterial pressure waveform analysis.

Patients And Methods: Thirty consecutive patients aged 15 to 55 years (mean+SD, 31.73 + 13.53 years), who had undergone total pericardiectomy via median sternotomy underwent serial hemodynamic evaluation. FlotracTM Sensor - derived stroke volume, stroke volume variation, systemic vascular resistance index (SVRI), cardiac index and right atrial pressure were measured just before and after pericardiectomy, at 12 hours, 24 hours, 48 hours, 72 hours and at discharge postoperatively.

Results: Majority of patients (73.33%) exhibited statistically significant reduction of right atrial pressure and SVRI along with improvement in cardiac index and oxygen delivery in the immediate and late postoperative period. However, the stroke volume and stroke volume variation did not increase proportionately on completion of surgery. Patients with low cardiac output syndrome exhibited persistently high central venous pressure with reduced cardiac index and echocardiographically abnormal diastolic filling characteristics.

Conclusions: We conclude that there is early normalization of hemodynamics following pericardiectomy via median sternotomy and the adequacy of pericardiectomy can be accurately assessed by the new semi-invasive arterial pressure waveform analysis device. Stroke volume variation is a non-predictor of fluid requirement during and after pericardiectomy.
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http://dx.doi.org/10.4103/aca.ACA_98_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408521PMC
November 2017

Development of macaronic Hindi-English 'Hinglish' text message content for a coronary heart disease secondary prevention programme.

Heart Asia 2016 30;8(2):32-38. Epub 2016 Sep 30.

The George Institute for Global Health, Sydney, Australia; Sydney Medical School, The University of Sydney, Sydney, Australia.

Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in India. Text message based prevention programs have demonstrated reduction in cardiovascular risk factors among patients with CHD in selected populations. Customisation is important as behaviour change is influenced by culture and linguistic context.

Objectives: To customise a mobile phone text message program supporting behaviour and treatment adherence in CHD for delivery in North India.

Methods: We used an iterative process with mixed methods involving three phases: (1) Initial translation, (2) Review and incorporation of feedback including review by cardiologists in India to assess alignment with local guidelines and by consumers on perceived utility and clarity and (3) Pilot testing of message management software.

Results: Messages were translated in three ways: symmetrical translation, asymmetrical translation and substitution. Feedback from cardiologists and 25 patients was incorporated to develop the final bank. Patients reported Hinglish messages were easy to understand (93%) and useful (78%). The software located in Australia successfully delivered messages to participants based in Delhi-surrounds (India).

Conclusions: Our process for customisation of a text message program considered cultural, linguistic and the medical context of potential participants. This is important in optimising intervention fidelity across populations enabling examination of the generalisability of text message programs across populations. We also demonstrated the customised program was acceptable to patients in India and that a centralised cross-country delivery model was feasible. This process could be used as a guide for other groups seeking to customise their programs.

Trial Registration Number: TEXTMEDS Australia (Parent study)-ACTRN 12613000793718.
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http://dx.doi.org/10.1136/heartasia-2016-010789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051379PMC
September 2016

Evaluation of early direct current cardioversion for maintenance of sinus rhythm in rheumatic atrial fibrillation following successful balloon mitral valvotomy.

Indian Heart J 2016 Jul-Aug;68(4):486-92. Epub 2016 Mar 2.

Professor & Head, Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India.

Background: Patients with rheumatic mitral stenosis (MS) and atrial fibrillation (AF) are at risk for thromboembolism and restoration of sinus rhythm (SR) may be the preferred strategy. Percutaneous balloon mitral valvotomy (PBMV) improves hemodynamics, but may not be enough to restore SR.

Methods: Prospective randomized study aimed at evaluating efficacy of early direct current cardioversion (DCCV) following successful PBMV in patients with long-standing AF. Group 1 (n=20) had patients of rheumatic MS with AF who underwent successful PBMV. Group 2 (n=15) patients were DC cardioverted and administered oral Amiodarone for 6 weeks. Primary endpoint was maintenance of SR after 6 months. Secondary endpoints were functional capacity, number of embolic episodes, adverse drug effects, and all-cause mortality.

Results: In Group 2, all patients underwent successful cardioversion. At a mean follow-up of 7.6 months, 95% in Group 1 were in AF. In Group 2, 87% patients were in SR and 13% had reverted to AF. Difference in rate of SR was 0.82 (95% CI 0.2, 1.01) (p=0.001), with relative risk of 7.1 (1.95, 25.9, 95% CI, p=0.001) for patients to be in AF who underwent only successful PBMV, i.e. Group 1. There was significant improvement in quality of life (SF36) score in Group 2 (p=0.001), with no deaths, stroke, or adverse drug effects in either group.

Conclusion: In patients with rheumatic MS and AF, early DCCV and a short-duration oral Amiodarone, following successful PBMV, may be a reasonable strategy to attain long-term SR.
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http://dx.doi.org/10.1016/j.ihj.2015.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990730PMC
May 2017

Beneficial effects of aqueous extract of stem bark of Terminalia arjuna (Roxb.), An ayurvedic drug in experimental pulmonary hypertension.

J Ethnopharmacol 2017 Feb 9;197:184-194. Epub 2016 Jul 9.

Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India. Electronic address:

Ethnopharmacological Relevance: The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH.

Aim Of The Study: The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated.

Materials And Methods: The study was approved by Institutional Animal Ethics Committe. Male Wistar rats (150-200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively.

Results: MCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil.

Conclusions: Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening.
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http://dx.doi.org/10.1016/j.jep.2016.07.029DOI Listing
February 2017

Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway.

Sci Rep 2016 06 28;6:28042. Epub 2016 Jun 28.

Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.

Coronary artery disease (CAD) is one of the largest causes of death worldwide yet the traditional risk factors, although useful in identifying people at high risk, lack the desired predictive accuracy. Techniques like quantitative plasma proteomics holds immense potential to identify newer markers and this study (conducted in three phases) was aimed to identify differentially expressed proteins in stable CAD patients. In the first (discovery) phase, plasma from CAD cases (angiographically proven) and controls were subjected to iTRAQ based proteomic analysis. Proteins found to be differentially expressed were then validated in the second and third (verification and validation) phases in larger number of (n = 546) samples. After multivariate logistic regression adjusting for confounding factors (age, diet, etc.), four proteins involved in the reverse cholesterol pathway (Apo A1, ApoA4, Apo C1 and albumin) along with diabetes and hypertension were found to be significantly associated with CAD and could account for approximately 88% of the cases as revealed by ROC analysis. The maximum odds ratio was found to be 6.70 for albumin (p < 0.0001), followed by Apo AI (5.07, p < 0.0001), Apo CI (4.03, p = 0.001), and Apo AIV (2.63, p = 0.003). Down-regulation of apolipoproteins and albumin implicates the impairment of reverse cholesterol pathway in CAD.
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http://dx.doi.org/10.1038/srep28042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923873PMC
June 2016

Low holo-transcobalamin levels are prevalent in vegetarians and is associated with coronary artery disease in Indian population.

Biomarkers 2016 Jul 21;21(5):436-40. Epub 2016 Mar 21.

a Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology , Sukhdev Vihar , New Delhi , India ;

Coronary artery disease (CAD) has been increasing alarmingly in India. We had earlier shown that vitamin B12 deficiency is associated with CAD in Indian population. However, only about a quarter of the total vitamin B12 is internalised in the cells by the proteins transcobalamin II. Vitamin B12-bound transcobalamin II (holotranscobalamin, holoTC) is thus referred to as biologically active B12. In this study, we ascertained the levels of holoTC in 501 CAD cases and 1253 healthy controls and for the first time show that holoTC levels are significantly lower (p = 2.57E-4) in CAD (26.81 pmol/l) cases as compared to controls (29.97 pmol/l).
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http://dx.doi.org/10.3109/1354750X.2016.1153718DOI Listing
July 2016

Clinical efficacy of water extract of stem bark of Terminalia arjuna (Roxb. ex DC.) Wight & Arn. in patients of chronic heart failure: a double-blind, randomized controlled trial.

Phytomedicine 2016 Oct 23;23(11):1211-9. Epub 2016 Feb 23.

Dabur India Limited, Ghaziabad, 201010 Uttar Pradesh, India.; Emami Limited, Kolkata, 700107 West Bengal, India.

Background: The stem bark of Terminalia arjuna (Roxb. ex DC.) Wight and Arn. (Arjuna) is used in Indian system of medicine (Ayurveda) for treatment of various cardiac diseases, including heart failure. However, well designed clinical trials exploring its efficacy and safety in chronic heart failure (CHF) are lacking.

Purpose: To ascertain the add-on efficacy and safety of a standardized water extract of stem bark of Arjuna (Arjuna extract) in CHF patients on standard pharmacotherapy.

Study Design: Double-blind, parallel, randomized, placebo-controlled add-on clinical trial.

Methods: After approval of institutional ethics committee, 100 patients of CHF of New York Heart Association (NYHA) functional class II on standard pharmacotherapy having an echocardiographic left ventricular ejection fraction (LVEF) ≤ 40% were consecutively recruited with informed consent and randomized 1:1 to Arjuna extract 750 mg or matching placebo twice daily. The primary outcome measure was change in LVEF at 12 weeks. Secondary outcome measures included changes in (i) NYHA functional class, (ii) distance covered in 6 min walk test (6MWT), (iii) quality of life (QoL), as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ), (iv) plasma brain natriuretic peptide, (v) plasma cytokines (interleukin-6, high sensitivity C-reactive protein and tumour necrosis factor-α) and (vi) oxidative stress markers [serum thiobarbituric acid reactive substances (TBARS), red blood cell (RBC) superoxide dismutase (SOD), RBC catalase and RBC glutathione (GSH)] at 6 and 12 weeks. Safety assessment was done by adverse event monitoring and laboratory investigations. Results were expressed as mean ± SD or median (interquartile range) and analysed with intention-to- treat principle using appropriate two-sided statistical tests. A p-value < 0.05 was considered significant.

Results: Arjuna extract was well-tolerated, but did not change LVEF (24.3 ± 7.1 versus 25.5 ± 7.7%; p = 0.4) or secondary outcome measures except preservation of RBC catalase activity [1275(104, 10350) versus 1243.5(104, 10350) U/g haemoglobin; p = 0.01] compared to placebo. Significantly greater percentage increases occurred in distance covered in 6 MWT, RBC-SOD, RBC catalase, RBC GSH and in symptom severity and stability domains of KCCQ in patients on Arjuna extract versus those on placebo, on a post-hoc analysis, between subgroups of patients who improved in these outcomes.

Conclusion: Arjuna extract did not improve LVEF in CHF patients over 12 weeks, although there was improvement in functional capacity, antioxidant reserves and symptom-related QoL domains in some patients.
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http://dx.doi.org/10.1016/j.phymed.2016.02.007DOI Listing
October 2016
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