Association of Physicians of India: Position Statement on Role of Chirally Pure Molecules in Clinical Practice.

Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas. However, since there is a low level of awareness on the advantages of chirally pure molecules among clinicians, pharmacists and patients in India, the Association of Physicians of India (API) developed this position statement to increase awareness on the concept of chirality and the associated advantages of using chirally pure drugs in certain therapeutic areas to maximize patient outcomes. This includes the clinical evidence associated with single enantiomers such as S-metoprolol, S-amlodipine, esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac, dexketoprofen, levofloxacin in terms of efficacy and safety as compared with their racemates. In addition, the API also provides some tactical recommendations for clinicians, pharmacists, patients, regulatory body and pharmaceutical companies to increase awareness on chirally pure drugs and puts forth the need for expedited availability of chirally pure drugs in the Indian market.

Cardiac Biomarkers for Better Management of Acute Coronary Syndromes.

Acute myocardial infarction (AMI) causes significant mortality and morbidity. Timely diagnosis allows clinicians to risk stratify their patients and select appropriate treatment. Biomarkers have been used to diagnose or rule out AMI. An increasing number of novel biomarkers have been identified to predict the outcome following AMI or acute coronary syndrome (ACS). This may facilitate tailoring of appropriate therapy to high-risk patients. This review focuses on a variety of promising biomarkers which provide diagnostic and prognostic information.

Dual antiplatelet therapy in acute coronary syndromes and coronary artery interventions.

Optimization of platelet inhibition in patients with acute coronary syndromes reduces the risk for ischemic events, but at the same time increases the risk for bleeding. There are several predictors of bleeding risk in patients with acute coronary syndromes. These include demographic variables such as advanced age, female gender, low body weight, concomitant diseases such as diabetes,renal insufficiency, noncardiac vascular disease such as cerebral vascular disease and a history of bleeding. It also includes the type of acute coronary syndromes such as patients presenting with ST segment elevation myocardial infarction, high killip class and low blood pressure. The diabetic population contains a higher proportion of patients who do not respond to antiplatelet drugs as expected and who also have more activated platelets that deserve very vigorous inhibition. The importance of dual antiplatelet therapy in patients undergoing balloon angioplasty and stenting is much discussed. Yet there are some questions which are to be answered clearly such as the following:- 1) In the need to balance the benefit of clot prevention with bleeding risk, is it better to continue dual antiplatelet therapy for longer than one year? 2) If so, is this benefit specific to drug eluting stents or to a more general population of stent patients? 3) Is the benefit mediated by prevention of stent thrombosis or is there a global reduction in cardiovascular risk? This review is to understand all these aspects and help a physician use antiplatelet drugs appropriately in day to day clinical practice for better patient outcomes.

Renal artery stenting: one year outcome on BP control and antihypertensive medication.

AIM: There is lot of controversy regarding the efficacy of renal artery stenting in atherosclerotic renal artery stenosis. The aim of this retrospective study is to evaluate blood pressure control and requirement of antihypertensive drugs after renal artery stenting. METHODS AND RESULTS: Eighty patients who have undergone renal artery stenting for atherosclerotic renal artery stenosis with hypertension were evaluated and followed up for one year. Those with procedural complications were excluded. The systolic and diastolic BP control, number of medications, their dosage and serum creatinine levels were assessed at 3 months and at one year. At the end of one year 3 patients had total cure (all 3 had bilateral renal artery stenting). In 30 patients, there was reduction in number of drugs and in 11 patients there was reduction in dosage of antihypertensive drugs. In 16 patients there was a need to change the class of drugs. In 16 patients same drugs and dosage were continued. In 4 patients, the dose was increased. CONCLUSIONS: At the end of one year, 3 patients had cure, 44 patients improved and there was no change in 33 patients. Our results are comparable to other reported series. Renal artery stenting is a cost effective approach in properly selected patients of renal artery stenosis with hypertension.

18F- FDG PET/CT in reclassifying the probable diagnosis of IE - A review.

In the diagnosis of infective endocarditis (IE), Modified Duke's criteria, coupled with clinical suspicion, serve as the guiding framework. For cases involving prosthetic valve endocarditis and infections affecting implantable devices, the use of metabolic imaging with 18 F-FDG PET/CT scans has gained prominence, as per the recommendations of the European Society of Cardiology guidelines. This imaging modality enhances sensitivity and specificity by identifying infective foci within the heart and extracardiac locations. Early utilization of these scans is crucial for confirming or ruling out IE, although caution is required to mitigate false positive responses, especially in the presence of ongoing inflammatory activity. A standardized ratio of ≥2.0 between FDG uptake around infected tissues and the blood pool has demonstrated a sensitivity of 100 % and specificity of 91 %. It is noteworthy that the sensitivity of FDG PET/CT varies, being lower for native valve and lead infections but considerably higher for prosthetic valve and pulse generator infections. This review provides a comprehensive overview of the advantages offered by FDG PET/CT in achieving a definitive diagnosis of IE.

Pharmacologic reperfusion therapy with indigenous tenecteplase in 15,222 patients with ST elevation myocardial infarction - the Indian Registry.

OBJECTIVE: To study the efficacy and safety of single intravenous bolus administration of indigenously developed tenecteplase (TNK-tPA) in the management of patients with ST-elevation myocardial infarction (STEMI) in clinical practice. METHODS: Observational, prescription-event monitoring study. RESULTS: Data of 15,222 patients who had STEMI and received weight adjusted TNK injection was analyzed. Overall 95.43% patients had clinically successful thrombolysis (CST). In the different subgroups, hypertensives, diabetics, smokers and hyperlipidemic patients had CST rates comparable to the general patient data. CST rates were significantly lower in the elderly patients (>70 years; 92.11%; p < 0.0001), in patients with history of Ischemic Heart Disease (IHD, 93.86%; p = 0.0004) and in patients receiving delayed treatment (>6 h after onset of chest pain; 85.38%; p < 0.0001). CST was significantly higher in patients who received an early thrombolysis (<3 h after onset of chest pain; 96.54%; p = 0.006). Overall mortality was 1.69%, while it was significantly higher in the elderly (4.42%), patients with history of IHD (2.67%), females (2.93%) and in those who received delayed treatment (4.98%). The overall incidences of intracranial hemorrhage (ICH), bleeding excluding ICH, stroke and ventricular tachyarrhythmia were 0.39%, 2.01%, 0.16% and 2.35% respectively. Age >70 years, diabetes, hyperlipidemia and history of IHD were associated with a higher incidence of heart failure, myocardial re-infarction or ventricular tachyarrhythmias. However, incidence of ICH and bleeding other than ICH was comparable amongst all patient subgroups. CONCLUSION: This study confirms the safety and efficacy of indigenous tenecteplase in Indian patients with STEMI, including high risk subgroups. It also highlights the fact that delayed treatment denotes denial of benefits of pharmacologic reperfusion therapy.

SPECT in asymptomatic diabetics with and without microalbuminuria.

OBJECTIVE: To identify coronary artery disease (CAD) in asymptomatic diabetics with the help of myocardial perfusion single photon emission computed tomography (MPS), a non-invasive imaging modality and its correlation in diabetics with or without microalbuminuria. METHODS: This study included 99 patients in the age group of 30 to 80 years who were asymptomatic but possessed one or more risk factors for CAD. These patients were divided into two groups, diabetics with and without microalbuminuria (Micral). Thirty eight patients were Micral positive and 61 were Micral negative. Ischemia was detected by MPS and compared with coronary angiographic findings in both the groups. RESULTS: Amongst the 99 diabetic patients, MPS was positive in 39 patients. Out of 39 MPS positive patients, 31(79.5%) were micral positive and 8 (20.5%) were micral negative. Out of 38 micral positive patients, 31 patients were positive on MPS and 27 had significant angiographic (CAG) findings. Those with micral positive and MPS positive had multivessel CAD by CAG. It was seen that MPS status was 91.4% sensitive, 74.1% specific and had 82.1% positive predictive values (PPV) and 87.0% negative predictive value (NPV) for detection of significant CAD. CONCLUSION: Microalbuminuria is an inexpensive screening tool and a powerful independent predictor for major cardiovascular events in patients with type 2 diabetes mellitus. MPS is a sensitive, non invasive diagnostic test for identification of CAD in asymptomatic diabetic patients.

Expert Consensus on Ivabradine-based Therapy for Heart Rate Management in Chronic Coronary Syndrome and Heart Failure with Reduced Ejection Fraction in India.

Heart rate is an important indicator of health and disease and the modulation of heart rate can help to improve cardiovascular outcomes. Besides ß-blockers, Ivabradine is a wellestablished heart rate modulating drug that reduces heart rate without any hemodynamic effects. This consensus document was developed with the help of expert opinions from cardiologists across India on effective heart rate management in routine clinical practice and choosing an appropriate Ivabradine-based therapy considering the available scientific data and guideline recommendations. Based on the discussion during the meetings, increased heart rate was recognized as a significant predictor of adverse cardiovascular outcomes among patients with chronic coronary syndromes and heart failure with reduced ejection fraction making heart rate modulation important in these subsets. Ivabradine is indicated in the management of chronic coronary syndromes and heart failure with reduced ejection fraction for patients in whom heart rate targets cannot be achieved despite guideline-directed ß-blocker dosing or having contraindication/intolerance to ß-blockers. A prolonged release once-daily dosage of Ivabradine can be considered in patients already stabilized on Ivabradine twice-daily. Ivabradine/ß-blocker fixed-dose combination can also be considered to reduce pill burden. Two consensus algorithms have been developed for further guidance on the appropriate usage of Ivabradine-based therapies. Ivabradine and ß-blockers can provide more pronounced clinical improvement in most chronic coronary syndromes and heart failure with reduced ejection fraction patients with a fixed-dose combination providing an opportunity to improve adherence.

Systemic lupus erythematosus presenting as cardiac tamponade-a case report.

Although pericarditis and pericardial effusion (PE) are some of the common manifestations of systemic lupus erythematosus (SLE), the occurrence of cardiac tamponade is quite rare. We present herewith a young girl with cardiac tamponade presenting as initial manifestation of SLE.

Correlation of myocardial perfusion SPECT with invasive and computed tomography coronary angiogram.

BACKGROUND: The consequences of atherosclerosis can be detected by multislice computed tomography (MSCT), invasive coronary angiogram (CAG) and the resultant myocardial ischaemia by myocardial perfusion single photon emission computed tomography (MPS). In this study an attempt is made to compare MSCT with MPS and also to compare the MSCT findings with that of invasive CAG in patients suspected to have coronary artery disease (CAD). MATERIALS AND METHODS: A total of 99 patients suspected to have CAD underwent both MSCT and MPS with (99m)Tc sestamibi. The MSCT studies were classified as having no CAD, significant CAD (>50% diameter stenosis), and insignificant CAD (<50% diameter stenosis). Myocardial perfusion single photon emission computed tomography was reported as normal and reversible ischaemia. In a subgroup of 33 patient invasive CAG was done. RESULTS: In 99 patients, 396 coronaries were evaluated with MSCT and MPS. Coronary artery calcium scoring (CACS) in these patient ranged from 0 to 2200. No CAD was noted in 128 (32%) coronaries but MPS was found abnormal in 9 (7%) coronaries. Insignificant CAD was noted in 169 (43%) coronaries amongst which reversible ischaemia was noted in 23 (14%). Significant CAD was noted in 99 (25%) coronaries of which only 54 (55%) were MPS positive for reversible ischaemia. The MSCT has a negative predictive value (NPV) of 97%. When MSCT was normal, MPS was almost normal, but the reverse was not true. That is when MPS was normal MSCT was not always normal but showed lesion of insignificant obstruction. In the subset of 33 patients, who underwent invasive angiogram, 132 coronaries were evaluated. Coronary angiogram showed 48 coronaries (36%) to have significant CAD (>50% diameter stenosis). Multislice computed tomography correlated well in 46 (84%) with P value of <0.001 (χ(2)-test) but for 9 (16%) showing overestimation due to increased CACS (>800). Myocardial perfusion single photon emission computed tomography was normal in 15 (27%) coronaries. CONCLUSION: Myocardial perfusion single photon emission computed tomography provides functional information of the anatomical lesions and MSCT provides anatomical information. Both are two different diagnostic modalities. The MSCT has high NPV in patients with less likelihood for CAD. When compared with CAG, the correlation with MSCT was good and is useful where the calcium score is low.

Role of omega-3 ethyl ester concentrate in reducing sudden cardiac death following myocardial infarction and in management of hypertriglyceridemia: an Indian consensus statement.

INTRODUCTION: Sudden cardiac death (SCD) is the most lethal manifestation of heart disease. In an Indian study the SCDs contribute about 10% of the total mortality and SCD post ST elevation myocardial infarction (MI) constitutes for about half of total deaths. OBJECTIVE: Given the limitations of existing therapy there is a need for an effective, easy to use, broadly applicable and affordable intervention to prevent SCD post MI. Leading cardiologists from all over India came together to discuss the potential role of n-3 acid ethyl esters (90%) of eicosapentaenoic acid (EPA) 460 mg & docosahexaenoic acid (DHA) 380 mg in the management of post MI patients and those with hypertriglyceridemia. RECOMMENDATIONS: Highly purified & concentrated omega-3 ethyl esters (90%) of EPA (460 mg) & DHA (380 mg) has clinically proven benefits in improving post MI outcomes (significant 15% risk reduction for all-cause mortality, 20% risk reduction for CVD and 45% risk reduction in SCD in GISSI-Prevenzione trial) and in reducing hypertriglyceridemia, and hence, represent an interesting option adding to the treatment armamentarium in the secondary prevention after MI based on its anti-arrhythmogenic effects and also in reducing hypertriglyceridemia.

Efficacy and safety of tenecteplase in Indian elderly STEMI patients from the Elaxim Indian Registry.

OBJECTIVE: To analyze the efficacy and safety of indigenous Tenecteplase in Indian elderly STEMI patients in a clinical setting. METHODS: Post-licensure, observational, prescription event monitoring (PEM) study. RESULTS: 2162 patients received weight-adjusted Tenecteplase injection. The data for elderly (> 60 years) and non-elderly (< or = 60 years) was identified, segregated and compared. Out of 2162 patients, 805 were elderly patients and 1357 were non-elderly. Clinically successful thromolysis was seen in 83.98% of elderly and 86% of non-elderly group (p = 0.22). There was no significant difference in percentage of patients reporting bleeding, stroke, intracranial hemorrhage, myocardial reinfraction, ventricular tachyarrhythmia between the groups. Mortality was significantly (p = < 0.0001) more in elderly (6.21%) than non-elderly (2.06%) patients. CONCLUSION: The indigenously developed Tenecteplase shows high efficacy and safety in its in-hospital use in Indian elderly patients with STEMI.

Efficacy & safety of tenecteplase in 6000 patients with ST-elevation myocardial infarction from the Elaxim Indian Registry.

OBJECTIVE: To study the efficacy and safety of single intravenous bolus administration of indigenously developed tenecteplase in the management of patients presenting with ST-elevation myocardial infarction in clinical practice. METHODS: Post-licensure, observational, prescription-event monitoring study. RESULTS: Data of 6000 patients who had ST-elevation myocardial infarction and received weight-adjusted tenecteplase injection was analyzed. Overall 90.93% patients had clinically successful thrombolysis, with highest success rate (93.2%) in patients treated within 3 hours. Overall mortality was 3.23%. The elderly (< or = 65 yrs; 24.58%) and diabetics (38.2%) had clinically successful thrombolysis of 87.73% and 90.49% respectively. Female patients (16.38%) had success rates comparable to males but with higher (6.41%) mortality. The overall incidences of intracranial hemorrhage (ICH), severe bleeding, stroke and ventricular tachyarrhythmia were 0.62%, 3.18%, 0.12% and 3.07% respectively and were not significantly different in females, diabetics and elderly patients. Delay in treatment beyond 6 hours was associated with increased incidence of heart failure, ventricular tachyarrhythmia and mortality. CONCLUSION: This study confirms the efficacy and safety of indigenous tenecteplase in the management of patients with ST-elevation myocardial infarction.

Can OCT change the therapeutic strategy in ACS due to plaque erosion?

The pathophysiology of acute coronary syndromes was thought to be coronary thrombosis over a plaque rupture. Autopsy studies revealed that not all cases were due to plaque rupture, even denuded endothelium or calcific nodule can beget a thrombus. Introduction of OCT made, in vivo recognition of lesion morphology clear. Plaque ruptures are most common and need primary angioplasty. Recent studies established plaque erosion is responsible for ACS in one third of the cases and majority of them present as Non ST elevation myocardial infarction and commonly found in young patients without major risk factors. Evidence from recent studies suggested that stenting can be deferred and they can be managed conservatively with good long term outcomes. More randomized trials are needed comparing plaque rupture and plaque erosion as regards conservative versus invasive management. If these studies substantiate the concept of conservative management, it will lead to a paradigm shift in their management.

Myocardial perfusion single photon emission computed tomography in asymptomatic diabetics.

BACKGROUND: Coronary artery disease (CAD) is the most important cause of mortality in diabetic patients. Diabetes mellitus (DM) due to autonomic neuropathy leads to asymptomatic CAD. Hence, it is important to screen the patients with DM for CAD. AIM: To study the prevalence of asymptomatic CAD by Myocardial Perfuision SPECT (Single Photon Emission Computed Tomography) (MPS) in diabetics. METHODS: This prospective study included 88 asymptomatic patients (58 males and 30 females) of Type 2 DM of more than 5 years duration in the age group of 40-65 years. Risk factors like hypertension, dyslipidemia, smoking, family history of CAD and Body Mass Index > or = 25 kg/sq.m were assessed. All these patients underwent MPS study as two day standard protocol. Thirty eight patients underwent invasive Coronary Angiography (CAG) and stenosis greater than 50% was considered significant. RESULTS: Abnormal perfusion was detected in 38 (43%) diabetics and 4 (11%) controls. A total of 81 perfusion defects were identified (19 fired and 62 reversible). CAG showed significant coronary stenosis in 26 (68.4%), insignificant in 8 (21%) and no stenosis in 4 (10.6%) patients. A total of 114 coronaries were analysed, significant stenosis in 67 (58.8%) coronaries, 21 (18.4%) had insignificant lesions and 26(22.8%) were normal. In comparison to CAG, MPS had sensitivity of 86.6% and specificity of 51%. CONCLUSION: The Myocardial Perfusion SPECT is a sensitive diagnostic tool to identify ischemia in asymptomatic diabetics. MPS can be used as screening test for risk stratification. It has a prognostic value in predicting the outcome of CAD and can be useful for long-term follow up too.

Life threatening protamine reaction during bypass surgery--a case report.

An anaphylactic reaction to protamine sulphate during cardiac surgery is a rare but known entity. Preoperative prediction and outcome of such a reaction is still unclear. We report a case of severe anaphylactic reaction to protamine sulphate in a diabetic while performing beating heart bypass surgery. We also reviewed the literature and discussed the management of such cases.

Left ventricular non compaction a tertiary care centre experience.

AIM: To analyse the clinical profile of consecutive cases of Left Ventricular Non Compaction (LVNC), a condition characterized by excessive and prominent Left Ventricular (LV) trabeculations which may be associated with LV systolic dysfunction. METHODS: Twenty six consecutive cases from January 2003 to December 2008 with echocardiographic evidence of hypertrabeculation of LV were evaluated by clinical examination, electrocardiographic (ECG) and echocardiographic features. Diagnosis was based on 3 published definitions. RESULTS: Out of 26 cases of LVNC (18 Males: 8 Females) aged between 1 day and 63 years, isolated LVNC was seen in 16 cases and rest of the cases were associated with congenital heart disease (CHD), Rheumatic Heart Disease (RHD) and Coronary Artery Disease (CAD). All patients were previously undiagnosed cases of LVNC. Left ventricular ejection Fraction ranged from 20-60% in these cases. CONCLUSIONS: This study demonstrates the increased detection of patients fulfilling echocardiographic criteria of LVNC and its association with other disorders. It also shows that milder phenotypes exist and the disease is detected incidentally in some cases.

Efficacy and safety of tenecteplase in ST elevation myocardial infarction patients from the Elaxim Indian Registry.

OBJECTIVE: to study the efficacy and safety of indigenously developed tenecteplase injection in the management of Indian STEMI patients in clinical practice. METHODS: post-licensure, observational, prescription event monitoring study. RESULTS: 2100 patients received weight-adjusted tenecteplase injection. More than 90% patients received aspirin, clopidogrel, and enoxaparin/heparin. Clinically successful thrombolysis was reported in 86.71%, in-hospital mortality was 3.48%. The adverse events recorded were comparable with previously published data. Any bleeding (excluding intra-cranial hemorrhage) was seen in 4.62% patients which was reported in 0.90% patients of which 47.34% patients had also received GpIIb/IIIa inhibitors. CONCLUSION: This study confirms the efficacy and safety of indigenous tenecteplase in Indian STEMI patients.

Long QT syndrome in children with congenital deafness.

The Jervell and Lange Nielson syndrome(JLN) is an infrequent form of long QT syndrome (LQTS) in which prolonged QT interval and congenital deafness exist together. We attempted to identify patients with LQTS among 127 children (age 1.2 to 10 years) with congenital hearing loss. The corrected QT interval was measured from 12 lead electrocardiogram(ECG) , using Bazettes and Friedricia formulae.The QT interval was considered prolonged when it exceeded the upper limit of 440ms and 450ms, respectively. Ten children with congenital deafness had a corrected QT interval longer than 440ms. Although these children did not meet the definite criteria according to Schwartz parameters, all the 10 children could be defined as having intermediate probability of LQTS according to revised criteria. We advise that children with congenital deafness be screened for long QT syndrome.

Salmonella myocarditis presenting as acute myocardial infarction: a case report.

Cardiac involvement with Salmonella infection is well known and electrocardiographic changes bear a direct relationship to prognosis. We present here a case with ECG changes mimicking an acute myocardial infarction in salmonella infection.