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   Table of Contents - Current issue
September-December 2020
Volume 6 | Issue 3
Page Nos. 207-303

Online since Wednesday, December 23, 2020

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Conceptual Framework on Conducting Two-Way Analysis of Variance Highly accessed article p. 207
Onchiri Sureiman, Callen Moraa Mangera
The two-way analysis of variance (ANOVA) is perceived to many researchers as being complex and tedious. The perception is partly caused by not understanding the application procedures. To give solution to the problem, this paper made an overview of the independent t-test and one-way ANOVA before highlighting the procedure of two-way ANOVA by the use of examples and simplified methods. The authors also developed a simplified conceptual framework that can be applied. To ensure ease in the interpretation of results, the researchers must understand the concept of two-way ANOVA manually before using the online calculator.
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Left Ventricle Can't Stay Alone – A Review of Right Ventricular Failure Post-Left Ventricular Assist Device Implantation Highly accessed article p. 216
Manoj Kumar Sahu, Prateek Vaswani
Background: Increasing incidence of heart failure with end-stage heart disease and limited availability of donor heart for transplantation made mechanical assist devices a lucrative option. Left ventricular assist device (LVAD) is used increasingly in recent years as a bridge to transplant and also as destination therapy with significantly improved outcomes. Implantation of LVAD improves the left heart systolic dysfunction, but its reliance on adequate right ventricular (RV) function with proposed risk of aggravating RV dysfunction may result in dismal outcomes if not intervened timely. Methodology: MeSH database was searched for LVAD, RV failure (RVF), RV anatomy and physiology, assessment for RV functions from 1990 till current year and was included in the narrative review. Results: The above searched English Medical Literature revealed that RVF contributed to dismal outcomes post-LVAD implantation. The absence of consistent defining criteria makes it hard to determine RVF. RVF leads to impaired LVAD flows, difficulty in weaning from cardio-pulmonary bypass, decreased tissue perfusion, and multi-organ failure, increasing the morbidity and mortality. Ideal durable mechanical assist devices to support the RV are still not available. Conclusion: This review highlights the details about perioperative assessment for RV dysfunction, criteria for RVF, investigational modalities to assess RV function, and management of RVF following LVAD implantation. Early identification, treatment, and prevention of RVF are of paramount importance and understanding this is a pivotal first step in successfully managing RVF post-LVAD implantation. The development of durable right-sided mechanical support would improve the scope of care of LVAD patients developing persistent RVF.
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PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9): A Narrative Review p. 226
Pamila Dua, KH Reeta
Coronary artery disease (CAD), the most common type of heart disease, is the leading reason for mortality in both developing and developed countries. Increased cholesterol and fatty deposits (called plaques) may cause hardening or narrowing of the arteries which supply blood to heart muscles. Triglycerides, low density lipoproteins (LDL), high density lipoproteins (HDL) are different types of cholesterols found in the blood and LDL is the main target for lipid modifying therapy, with the aim of improving long term CAD prognosis. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is one of the candidate genes with expression of PCSK9 protein and PCSK9 inhibitors are coming up as newer lipid lowering therapy. This narrative review highlights the journey of drug development from recognition of PCSK9 gene to the recent approvals of PCSK9 targeting LDL lowering pharmacotherapy. A bibliographic survey was made with titles PCSK9, PCSK9 inhibitors and coronary artery disease in different search engines from year 2000 to 2019 and filtered with review, preclinical and clinical studies. Retrieved articles were revisited and it was observed that PCSK9 is expressed mainly in hepatocytes and to some extent in mesenchymal cells of kidney, intestinal ileum, colon epithelia and in telencephalon neurons of embryonic brain. In hepatocytes, loss-of function mutations of PCSK9 leads to higher levels of LDL receptors. These receptors make LDL receptor-LDL cholesterol complex, which is directed to the lysosome for degradation of LDL in hepatocytes and lowers LDL cholesterol levels, ultimately resulting in protection from CAD. Gain-of-function mutations hamper LDL degradation. PCSK9 research has proposed an exciting new area for cholesterol management and CAD risk reduction. Different PCSK9 inhibitors with different therapeutic targets for CAD are evolving day by day from bench to bedside. This review could be valuable for helping researchers acquire a deeper insight for PCSK9 and its Inhibitors.
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History and Origin of Coronaviruses p. 234
Pooja Bhardwaj
Objective: The coronavirus disease 2019 (COVID-19) also known as COVID-19 or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a viral infection caused by severe acute respiratory syndrome coronavirus 2, emerged first in Wuhan, China, and spread all over the world. The World Health Organization on January 30, 2020, officially declared the COVID-19 epidemic as a public health emergency of international concern. There is speculation as to the origin of the infection and the objective of this narrative review is to scan the available literature to create a cohesive review. Methodology: This review article is based on a literature search of PubMed, Google, and Google Scholar using the keywords “ Corona virus,” “COVID-19,” “COVID” “Origins,” “Review,” and “classification.” Articles providing new information were selected. Results: The coronavirus which has caused a pandemic has a genomic structure which closely resembles that of a bat coronavirus. The region that binds angiotensin-converting enzyme 2 (ACE2), i.e., the region of the spike proteins, resembles a coronavirus found in the pangolin (a scaly anteater found in the Chinese market and used in Chinese medicine). It is possible that the coronavirus was existing initially in its natural hosts, the bat, or pangolin. It is likely that the spike proteins mutated to bind to molecules similar to the human ACE2 protein therefore allowing it to infect humans. Another possibility is that it jumped species from bat to human and then became capable of causing pathogenic disease. The mutations in the receptor-binding domain portion of the spike protein and its distinct backbone, rules out laboratory manipulation as a potential origin for SARS-CoV-2. It is not certain if the necessary mutations for causing the pandemic occurred before or after SARS-CoV-2 made the jump to humans. Conclusions: The current corona pandemic is due to the SARS-CoV-2 and there is evidence that it has spread to humans from bats. Pangolins, civet cats may be reservoirs for the virus, but as of now, there is no evidence of a laboratory origin of the virus. It is not clear whether the virus jumped species recently or was preexisting in humans and became pathogenic because of a recent mutation.
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Acute Myocarditis Associated with Coronavirus Disease 2019: Systematic Review and Pooled Analysis of Reported Cases p. 239
Lucrecia Maria Burgos, Andreina Gil Ramírez, Mirta Diez
Context: Coronavirus disease (COVID-19) clinical manifestations are mainly respiratory, although cardiac complications are being reported. However, specific information about the clinical characteristics and in-hospital outcomes of patients with myocarditis associated with COVID-2019 is limited. Aim: The aim is to describe the clinical characteristics and outcomes of patients with acute myocarditis associated with COVID-19. Methods: The study consisted of a systematic review of all available case reports. Systematic searches were conducted using MEDLINE (PubMed interface) LILACS and Scielo to identify studies from December 2019 to 11 July 2020 involving adult patients with acute myocarditis associated with COVID-19. Results: Twenty patients were included. The median age was 49 years (interquartile range [IQR] 32.25–69), and 60% were male. Ten patients presented ST-segment elevation on the ECG. All patients had elevated serum levels of troponin T or I, N-terminal pro-brain natriuretic peptide (median 3436 ng/L, IQR 1315-12054) and C-reactive protein (median 33 mg/L, IQR 18–94). Interleukin-6 was measured in three patients, presenting elevated values as well. Left ventricular ejection fraction (LVEF) was severely impaired in 60% of the patients. Half of the patients received corticosteroids, 43.7% antivirals and 31.3% hydroxychloroquine. Moreover, 15.8% of patients underwent mechanical circulatory support. Most patients (90.9%) recovered heart function with LVEF above 40%. In-hospital mortality rate was 15.8%, the main cause of death being bacterial septic shock (75%). Conclusion: Several cases of coronavirus-related myocarditis have been reported. The clinical presentation was heterogeneous. The vast majority of patients were treated with steroids and antivirals. Most patients recovered cardiac function; however, mortality was relatively high.
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A Neonatal Echocardiographic Z-Score Nomogram for a Developing Country p. 244

Background: Currently used pediatric Echocardiographic Z scores are mostly founded on western data and have restricted applicability for newborns in developing nations. Since biological parameters may vary in different populations the data from those studies cannot be applied to the Indian neonates directly. Aims & Objectives: This study was directed to obtain echocardiographic data of various routinely measured cardiovascular structures using 2D and M mode echocardiography in Indian newborns up to 24 hours after birth and to derive Z-Score graphs for those parameters. Materials and Methods: This was a prospective observational study of a cohort of normal newborns conducted at a tertiary care hospital in western India. Neonates with congenital heart disease on screening echo were excluded and 100 normal neonates were included in the study with the intention of obtaining echocardiographic data of various routinely assessed cardiac parameters and to obtain a Z - score graph for each parameter. Echocardiographic evaluation was done utilizing a GE vivid S6 system. For the assessment of the relationship of an individual parameter with respect to BSA, regression equation was applied. Results: 22 parameters were assessed and using polynomial regression model relation to Body surface area was assessed and Z score charts were derived. Conclusion: Majority of the Z score values and reference ranges in our study were lower compared to the western standards thus it emphasizes the need for such a Z score in a developing country and hence these Z score values obtained from our study could be useful as compared to western charts for use in developing countries for planning the appropriate cardiac intervention and surgery in the neonatal population. However, large-scale studies with heterogenicity of age groups will be needed before they can become clinically applicable in the general population.
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Cost Needed to Treat and Number Needed to Treat Analysis of Drugs for the Treatment of Heart Failure in India p. 253
Varghese George, Krishnamohan Mullavelil, Ancy Thannikkal Joseph, Rajeev Aravindakshan, Denny John, Cheriyan Koshy, Krishnan Nair Venugopal
Introduction: Our aim was to review the cost-effectiveness of guideline-directed medical therapy of heart failure in India and identify drugs that can be made available free of cost or at subsidized rates to the patient population. Methods: Data extracted from ten landmark trials in heart failure was used to compute the number needed to treat (NNT) and cost needed to treat (CNT) of drugs used in heart failure, to prevent cardiovascular mortality and heart failure re-hospitalization using the HDS Plotter-Incremental Cost Effectiveness Calculator. Since various brands (i.e., trade names) with a wide cost range are available in the Indian market, the average retail price in Indian Rupees for the year 2019 was used for the analysis. NNT and CNT of each drug were computed, and the cost-effectiveness was analyzed. The CNT of these drugs was compared with India's per capita Gross Domestic Product (GDP). The WHO recommendation of three times per capita GDP was used as the cost-effectiveness threshold. Results: Medications that were labeled as Class I for the treatment of heart failure were included in our analysis. Ivabradine, valsartan, and angiotensin receptor neprilysin inhibitor (ARNi) did not meet the cost-effectiveness criteria for preventing cardiovascular mortality. For the prevention of heart failure re-hospitalization, all drugs except ARNi met the cost-effectiveness threshold. Conclusion: Any future research would need to consider the compliance factor along with Willingness to Pay to understand the real acceptance of these drugs on the ground in India.
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Clinical and Angiographic Profile of Young Patients Presenting with Spontaneous Electrocardiogram Resolution of ST-Segment Elevation (Spontaneous Aborted) Myocardial Infarction: A Substudy of the Premature Coronary Artery Disease Registry (Registered Under [CTRI/2018/03/012544]) p. 259
Rahul S Patil, Laxmi H Shetty, Aman Sinha, JR Vijay Kumar, Manidipa Majumdar, Suvradip Dutta, TR Raghu, CN Manjunath
Background: There are very few data regarding clinically defined spontaneous resolution (SR) in ST-segment elevation (STE) acute coronary syndrome (ACS) patients. Most recent European and American practice guidelines fail to give specific recommendations for these patients. Specifically, the timing of intervention in patients with SR remains unclear. Aim and Study: The aim of the study was to study the clinical, social, biochemical, and angiographic profile of Indian youth presenting with spontaneous resolution (SR) of ST-segment elevation (STE). Subjects and Methods: The premature coronary artery disease (PCAD) registry is a prospective, descriptive, observational study of Indians aged below 40 years with coronary artery disease (CAD) conducted between April 2017 and April 2020. Of 3450 patients registered in PCAD registry, a total of 41 (1.2%) out of these 3450 patients presented with STE myocardial infarction (MI), which resolved spontaneously, and hence these patients satisfied entry criteria. Entire clinical and angiographic profile of these patients was documented. Conventional lipids were estimated using commercially available kits. The data were analyzed by statistical software R version 3.5.0 (R Core Team (2018). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria). Results: The mean age of all patients under PCAD registry was 30.49 years. A majority of 38 (92.68%) of the patients were males, 30 (73.17%) were smokers. Of total, four patients (9.75%) were diabetic. Twenty-five out of 41 patients (60.97%) were coming under the below poverty line category. Five patients (12.19%) were Muslims by religion, whereas the remaining were Hindus. The majority (38 patients, 92.68%) were nonvegetarians. The most common index presentation of the transient STE was with anterior wall MI (27 patients, 65.85%). The mean total cholesterol of the entire study population was 172.947 ± 47.11. Thirty-nine out of 41 patients (95.12%) underwent diagnostic coronary angiogram. Ultimately, 32 out of 41 patients (78.05%) were discharged and continued on optimal medical therapy and follow-up and nine patients (21.95%) underwent percutaneous coronary revascularization. Conclusions: Patients with ACS and SR of ST-elevation on electrocardiogram (ECG) exhibit a characteristic profile that differentiates them from the rest of patients with STEMI: younger age, a greater prevalence of males and smokers, and a lesser elevation of the necrosis markers, a greater ejection fraction, and a higher prevalence of single-vessel disease. Contrary to popular belief, coronary angiogram showed a significant proportion of them to be having underlying organic CAD. Our study highlights the need for early intervention in such patients.
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A Survey of the Practices of Storage and Transport for Donor Heart in India p. 264
Sarvesh Pal Singh, Milind Padmakar Hote, Sandeep Seth, Manoj Durairaj, Anvay Mulay, KG Suresh Rao, Kewal Krishan, Julius Punnen, KR Balakrishnan, Alla Gopala Krishan Gokhale
Background: Heart transplant remains the gold standard for the treatment of end-stage heart failure. The most common method of donor heart preservation, during transport, is “triple-bag technique” with static cold storage (SCS). The safe duration of storage (ischemic time) for a donor heart with SCS is 4 h shortest among all the transplantable solid organs. One of the factors determining the donor heart's quality is the storage and transport of the donor organ. This study identified the centers which perform heart transplants routinely (≥7 per year) for the past 3 years and compared the differences between their donor heart storage and transport practices. Methodology: After obtaining ethical clearance from the Institutional Ethics Committee, this survey was done among the centers performing heart transplants in India. Centers performing an average of ≥7 heart transplants per year for the past consecutive 3 years were identified and included in the study. Centers that refused to participate or did not respond to a maximum of 3 reminders to send the filled questionnaire were excluded from the survey. A total of 11 transplant teams fulfilled the inclusion criteria, but only eight units responded to the request. The authors identified the team leaders in all the transplant teams and obtained concurrence before sharing an indigenous questionnaire about the practice of storage and transport of donor heart followed in their centers. Teams were contacted by digital platforms and telephone. Results: The analysis of current practices for donor heart preservation reveals that the triple-bag technique is the most commonly used method for SCS of donor heart, and Custodiol HTK is the most commonly used solution for cardioplegia. The dose of Custodiol varies between 25 and 50 ml/kg in different centers. It is also a common practice to immerse the heart in cold Custodiol solution in the first bag. Although any donor retrieval team does not measure the temperature, every team claims the temperature of the preservative solution used for flushing is 0°C–4°C. All the participating teams use ice cubes or slush in the transport box around the heart encased in 3 plastic bags. Conclusions: The authors of this survey conclude that the triple bag technique use may not be essential and can be converted to a two-bag technique as practiced by a couple of units. The use of cold Custodiol solution in the first bag probably has no rationale, and the use of 0.9% saline is a non-inferior cost-effective option. Ice slush may be avoided in the first bag because of the theoretical possibility of triggering a freeze in the donor heart.
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Frailty in Elderly Patients with Acute Coronary Syndrome in India p. 270
Amit Kumar, Praveen Singh, Aarti Gupta, Saurabh Sharma
Background: Association of frailty in Indian elderly patients with acute coronary syndrome (ACS) has not been investigated. Our objective was to estimate the prevalence of frailty due to the severity of ACS in elderly patients in India. The study also aimed to find out the association between the number of health deficits with ACS severity among elderly patients and to explore the association of frailty with conventional risk factors for coronary artery disease among the patients. Materials and Methods: A cross-sectional study was performed for a period of 18 months where 100 elderly patients ≥60 years age, having ACS, regardless of gender, were recruited from the Department of Medicine, Guru Teg Bahadur Hospital, Delhi. Frailty was assessed with the help of Fried index along with a number of deficits in health. Assessment of ACS was done on the basis of the ECHO findings that took into account the left ventricular ejection fraction. Results: The occurrence of frailty was 44% among elderly patients presenting with ACS. The association between the number of health deficits with the severity of ACS at presentation among elderly patients was found to be statistically significant (P < 0.001), with ACS severity increases as health deficit increases. No significant association was observed on co-relating each conventional factor with frailty, while a strong association between depression and frailty was observed (P < 0.001). Conclusion: This study concludes that in Indian elderly patients, there is an important association between frailty and ACS in terms of incidence, diagnosis, and prognosis.
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Lung Transplantation: The Indian Experience and Suggested Guidelines Part II A: The Technique of Lung Transplantation p. 278
Thirugnanasambandan Sunder, Paul Thangaraj Ramesh, Madhan Kumar Kuppuswamy, Shiv Kumar Choudhary, Milind P Hote, V Devagourou, Palleti Rajashekar, Sarvesh Pal Singh, Sandeep Seth
Background: A series of lectures and workshop on lung and heart–lung transplantation were organized by the Departments of Cardiology and Cardiothoracic Surgery at All India Institute of Medical Sciences, New Delhi, and the Department of Heart and Lung Transplantation at Apollo Hospitals, Chennai. The 1st day workshop on preoperative workup part was published as Part-I in this journal in August 2018. The hands-on cadaveric workshop conducted on May 20, 2018, forms the basis of the first section of the second part (Part II a) which deals with the technique of lung transplantation. The techniques of lung transplantation and Indian scenario are also reviewed. Methodology: The technique practiced by the transplant team at Apollo Hospitals, Chennai, was used for the demonstration of donor lung, heart–lung block harvest and implanting lungs, heart–lung block, while also discussing other possible techniques. Human cadavers were used, and live high-definition audio–video transmission to the lecture hall was made. Results: Accurate figures regarding lung transplantation in India are still not available. However, as per the Indian Society for Heart and Lung Transplantation, current data suggest that overall, about 1050 heart transplants and 310 lung transplants have been done in India. Of these, it is anticipated that national data regarding number of single-lung transplants, double-lung transplants, and heart–lung transplants will be available soon. The Department of Heart and Lung Transplantation at Apollo Hospitals, Chennai, has performed a total of 69 hearts and 149 lungs in 119 patients in various combinations: isolated heart transplants (40 patients), double-lung transplantation (DLT) (43 patients), single-lung transplantation (7 patients), heart and DLT (27 patients), en bloc heart and liver transplantation (1 patient), and combined heart–lung and kidney transplantation (1 patient). While the survival data for India are not currently available, our 3-year survival for DLT is 76.2%. Conclusions: While the surgical technique demonstrated is used in most of our cases, at times, different techniques have had to be adopted based on challenges confronted on the operating table. However, we have found that developing surgical protocols and maintaining consistency in the operative techniques translates into good surgical outcomes.
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Renal artery Chronic Total occlusion Angioplasty in a Patient with Bilateral Renal Artery Occlusion and Hypertensive Emergency p. 292
S Srinivas Chowdary Parvathaneni, Raghuram Palaparti, Gopala Krishna Koduru, Sudarshan Palaparthi, Purnachandra Rao Kondru, Harikrishna Marri
Atherosclerotic bilateral renal artery chronic total occlusions (CTOs) as a cause of hypertensive emergency is rare, and other causes such as vasculitis should be ruled out before definitive diagnosis. Successful CTO intervention in such a scenario has only been sparsely reported. A 53-year-old-male smoker with severe resistant hypertension required multiple emergency admissions for flash pulmonary edema and aggressive blood pressure control. He was found to have deranged renal parameters with a serum creatinine of 2.4 mg/dL and an estimated glomerular filtration rate of 25 mL/min. His complete blood picture, metabolic panel, and inflammatory markers were within normal limits. Renal Doppler ultrasonography revealed bilateral severe renal artery stenosis and a contracted left kidney. Renal angiography showed total occlusion of both renal arteries with well-collateralized right kidney. He underwent right renal artery CTO angioplasty with stenting. Left renal artery occlusion was managed conservatively because of the contracted kidney size and poor function. He is doing well for the last 30 months with good hypertension control, well-perfusing and preserved right kidney volume, stable renal function, and significantly fewer medications from baseline. Renal artery stenting is lifesaving in patients with bilateral renal artery occlusion and should be expeditiously performed, particularly in patients with and hypertensive emergency or recurrent unexplained heart failure. Kidney size, function, presence of collateralization, and viable renal parenchymal tissue guide in planning the intervention.
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Unicuspid Aortic Valve with Bilateral Superior Vena Cavae, Abnormal Coronary Anatomy, and Right Ventricular Clot: A Rare Case Report p. 296
Anish Gupta, Palleti Rajashekar
A teenager presented with congestive heart failure due to severe aortic stenosis. She had also developed ventricular clots due to ventricular dysfunction, therefore, was taken up for emergency aortic valve replacement. To our surprise, she had bilateral superior vena cava, which has not been reported with unicuspid aortic valve and ventricular clots, to the best of our knowledge. She also had an abnormal location of coronary ostia making them susceptible to injury during routine aortotomy, but it was picked up during transesophageal echocardiography and a careful aortic incision was planned. This report emphasizes the importance of careful aortotomy in congenital aortic pathologies, where coronary ostia may be located in abnormal positions. The role of transesophageal echocardiography is paramount in this situation to find the location of coronary ostia before incising the aorta.
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The Tale of Kantrowitz Brothers: A Dream to Support the Failing Heart! p. 299
Jes Jose, Rohan Magoon, Jasvinder Kaur Kohli, Ramesh Kashav
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Cardiology Practice in India: Need for a Paradigm Shift p. 301
Rakesh Agarwal
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Retraction p. 303

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