Management of Acute Pulmonary Embolism: Consensus Statement for Indian Patients.

Pulmonary embolism (PE) is an important cause of morbidity and mortality among hospitalized patients. Although the exact epidemiology of PE is not known in India, Some of the studies show that more frequently it is missed and not managed appropriately leading to significant cardiovascular morbidity and mortality. Justification and purpose: Indian guidelines for the diagnosis and treatment of acute PE are not yet formulated. The objective of this consensus statement is to propose a diagnostic and management approach for acute PE in India. PROCESS: A working group of 15 experts in the management of acute PE (cardiologists, pulmonologist, haematologist, emergency specialist and intensivists). This consensus statement makes recommendations for diagnosis and management for PE based on literature review, including Indian data.

2013 consensus statement for early reperfusion and pharmaco-invasive approach in patients presenting with chest pain diagnosed as STEMI (ST elevation myocardial infarction) in an Indian setting.

UNLABELLED: In India, the prevalence of ST elevation myocardial infarction (STEMI) is rising exponentially leading to cardiovascular morbidity and mortality. Despite advancement in reperfusion therapy (pharmacologic and interventional), the overall utilization, system of care and timely reperfusion remains suboptimal. JUSTIFICATION AND PURPOSE: Alarming treatment delays exist in patients presenting with chest pain observed in real-world and published evidences. Time to diagnose STEMI and initiation of reperfusion therapy at various first medical contacts in India is variable mandating immediate attention. We intend to provide evidence based explicit recommendations for practicing clinicians about time-dependent early management and the concept of pharmaco-invasive (PI) approach, contextualized to the situation in India. PROCESS: Pre-prepared guidance document by expert steering committee was discussed and commented by over 150 experts representing from 16 states in India at regional level. The moderators of these meetings arrived at a consensus on the evaluation and management of STEMI patients by PI approach to improve clinical outcomes. RECOMMENDATIONS: In addition to patient awareness and education for early symptom identification, education is required for general practitioners and physicians/intensivists to implement early time dependent STEMI management. Percutaneous Coronary Intervention (PCI) is the gold standard, yet it remains inaccessible to majority of patients, hence early reperfusion by initial use of fibrinolytics is recommended followed by coronary intervention. Fibrinolytics are easily available, economical and evaluated in several clinical studies and hence we recommend a PI approach (early fibrinolysis followed by PCI 3-24 hours later). We recommend a time guided 'Protocol/Plan of Action' for early fibrinolysis and implementing a PI approach at the level of general practitioners, non-PCI hospitals/nursing homes with intensive care facility and in PCI capable centers. For STEMI patients with symptom duration < 6 hours, we suggest administration of fibrinolytics either tenecteplase (Grade1A), reteplase (Grade1B), alteplase (Grade1C) or streptokinase (Grade 2B) alongside contemporary adjunctive medical therapy for PI approach. The aim of this Consensus Statement is * To provide explicit recommendations for practicing clinicians about the early management of STEMI and concept of pharmaco-invasive approach * To provide recommendations based on the best available evidences, contextualized to the situation in India. It must be recognized that even when randomized clinical trials have been undertaken, treatment options may be limited by resources. The Cardiocare STEMI experts realize that the recommended diagnostic examinations and treatment options may not be available or affordable in all parts of India. Cost-effectiveness is becoming an increasingly important issue when deciding upon therapeutic strategies. As always with guidelines/consensus statement, they are not prescriptive. Clinical scenario and patients vary so much from one another that individual care is paramount, and there is still an important place for clinical judgment, experience, and common sense. The mandate of the Cardiocare STEMI expert consensus is to recommend evidence-based standards of care, related targets and strategies for implementation of standards in the management of STEMI. CONTEXT AND USE: This document should be taken as consensus recommendations by qualified experts, not as rigid rules. It comprises of published evidence and may not cover every eventuality; new evidence is published every day. Furthermore, this should not be used as a legal resource, as the general nature cannot provide individualized guidance for all patients under all clinical circumstances.

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.

The role of ß-blockers in the management of hypertension: an Asian perspective.

Following publication of the National Institute of Clinical Excellence (NICE) Guidelines in 2006, the use of ß-blockers as first-line therapy in hypertension has been somewhat controversial. However, a recent reappraisal of the European Society of Hypertension guidelines highlights that these agents exhibit similar BP lowering efficacy to other classes of agents, prompting a re-examination of the utility of these agents in various patient populations. The authors felt that it is important to address this controversy and provide an Asian perspective on the place of ß-blockers in current clinical practice and the benefits of ß-blockade in selected patient populations. In addition to their use as a potential first-line therapy in uncomplicated hypertension, ß-blockers have a particular role in patients with hypertension and comorbidities such as heart failure or coronary artery disease, including those who had a myocardial infarction. One advantage which ß-blockers offer is the additional protective effects in patients with prior cardiovascular events. Some of the disadvantages attributed to ß-blockers appear more related to the older drugs in this class and further appraisal of the efficacy and safety profile of newer ß-blockers will lend support to the current guideline recommendations in Asian countries and encourage increased appropriate use of ß-blockade in current clinical practice within Asia.

Biodegradable-polymer-based, paclitaxel-elutingInfinnium™ stent: 9-Month clinical and angiographic follow-up results from the SIMPLE II prospectivemulti-centre registry study

Background: SIMPLE II was a multi-centre, prospective registry study aimed at investigating the safety andefficacy of the Infinnium™ (Sahajanand Medical Technologies Pvt. Ltd, India) paclitaxel-eluting stent forthe treatment of single de novo lesions in the native coronary arteries.Methods: One hundred and three patients with symptomatic coronary artery disease were treated for singlede novo native coronary artery lesions using the Infinnium™ stent (paclitaxel concentration1.4 mcg/mm2 released over 48 days) in a multi-centre, prospective study performed on 3 continents (Asia,Europe and South America). The primary safety endpoint was major adverse cardiac events at 30 days(MACE 30d) and efficacy was assessed by in-stent binary restenosis as measured by quantitative coronaryangiography (QCA) at six-month follow-up. A clinical follow-up was scheduled at nine months.Results: The mean patient age was 58.5 years; 70.9% were males; 43.7% had unstable angina and 38.8%previous myocardial infarction. Risk factors included hypertension in 62.1%, hypercholesterolemia in52.4%, current smoking in 32.0% and diabetes in 28.2%. Stent implantation was successful in all patients,with more than one stent being implanted in 9 patients (8.7%). Hierarchical MACE 30d was 2.9%. At ninemonths, 101 patients had clinical follow-up (1 patient had died and 1 refused). There was one death(1.0%), one Q-wave myocardial infarction (Q MI) (1.0%), three non-Q MIs (2.9%), one clinically-driven targetlesion Coronary Artery Bypass Grafting (CABG) (1.0%), and one clinically-driven target lesion repeatpercutaneous coronary intervention (re-PCI) (1.0%). The overall event-free rate at nine months was 93.2%.QCA revealed in-stent and in-segment late loss of 0.38±0.49 mm and 0.18±0.46 mm, resulting in binaryrestenosis rates of 7.3% and 8.3%, respectively. There was one case of late stent thrombosis in the patientexperiencing the Q MI and subsequent re-PCI...

Biodegradable-polymer-based, paclitaxel-eluting Infinnium stent: 9-Month clinical and angiographic follow-up results from the SIMPLE II prospective multi-centre registry study.

BACKGROUND: SIMPLE II was a multi-centre, prospective registry study aimed at investigating the safety and efficacy of the Infinnium (Sahajanand Medical Technologies Pvt. Ltd, India) paclitaxel-eluting stent for the treatment of single de novo lesions in the native coronary arteries. METHODS: One hundred and three patients with symptomatic coronary artery disease were treated for single de novo native coronary artery lesions using the Infinnium stent (paclitaxel concentration 1.4 mcg/mm2 released over 48 days) in a multi-centre, prospective study performed on 3 continents (Asia, Europe and South America). The primary safety endpoint was major adverse cardiac events at 30 days (MACE 30d) and efficacy was assessed by in-stent binary restenosis as measured by quantitative coronary angiography (QCA) at six-month follow-up. A clinical follow-up was scheduled at nine months. RESULTS: The mean patient age was 58.5 years; 70.9% were males; 43.7% had unstable angina and 38.8% previous myocardial infarction. Risk factors included hypertension in 62.1%, hypercholesterolemia in 52.4%, current smoking in 32.0% and diabetes in 28.2%. Stent implantation was successful in all patients, with more than one stent being implanted in 9 patients (8.7%). Hierarchical MACE 30d was 2.9%. At nine months, 101 patients had clinical follow-up (1 patient had died and 1 refused). There was one death (1.0%), one Q-wave myocardial infarction (Q MI) (1.0%), three non-Q MIs (2.9%), one clinically-driven target lesion Coronary Artery Bypass Grafting (CABG) (1.0%), and one clinically-driven target lesion repeat percutaneous coronary intervention (re-PCI) (1.0%). The overall event-free rate at nine months was 93.2%. QCA revealed in-stent and in-segment late loss of 0.38+/-0.49 mm and 0.18+/-0.46 mm, resulting in binary restenosis rates of 7.3% and 8.3%, respectively. There was one case of late stent thrombosis in the patient experiencing the Q MI and subsequent re-PCI. CONCLUSIONS: The Infinnium paclitaxel-eluting stent appears to be safe and efficacious for the treatment of single de novo lesions in coronary arteries in a patient population with symptomatic coronary artery disease (CAD).

Coronary heart disease, hypertension, and angiotensinogen gene variants in Indian population.

Gene encoding components of the renin angiotensin system (RAS) have been implicated with the increased risk of cardiovascular disease (CVD). Two variants of the angiotensinogen (AGT) gene, M235T and T174M, have been shown to be associated with increased risk of hypertension. In the present study, we examined the association of these two polymorphisms and their synergistic interaction with the angiotensin I-converting enzyme (ACE) deletion homozygote genotype (D/D) on subjects with coronary heart disease (CHD) and hypertension. We studied 131 healthy individuals, 141 angiographically verified CHD patients, and 159 hypertensive subjects. The identification of the ACE and AGT gene polymorphisms was carried out using a PCR-based restriction endonuclease digestion method. There was no significant difference in the distribution of the M235T and T174M variants between the two test groups and the control group. Association was also not seen when analysis was carried out in patients when subgrouped according to the extent of the severity of the disease. In addition, the risk was not restricted to subjects carrying the D allele of the ACE gene and T235T of AGT. M235T and T174M variants do not contribute to the increased risk of CHD or hypertension in the Indian population.

Methylenetetrahydrofolate reductase gene mutation and hyperhomocysteinemia as a risk factor for coronary heart disease in the Indian population.

OBJECTIVE: The screening and therapeutic guidelines for the management of lipid abnormalities are reasonably well established. However, other risk factors like hyperhomocysteinemia (HCA) and single nucleotide polymorphisms involving the angiotensin converting enzyme (ACE) and angiotensinogen genes, various clotting factors etc., have yet to be established firmly as other causative factors of atherothrombotic disease. Our study was aimed at finding the relationship between HCA, folate, vitamins B12 levels, and mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes. METHODS: We studied 230 subjects, which included patients with angiographically documented coronary heart disease (CHD) (n=115) and controls (n=115) with no history of CHD. RESULTS: Elevated levels of plasma homocysteine, above 18 nmoles/ml, were detected in 19.13% and 18.26% of our patients and controls, respectively. Homocysteine was significantly correlated to Apo A1 (r=0.51, p < 0.05) and Apo B (r=0.49, p < 0.05). The heterozygous MTHFR mutation was found to be 54.5% (12/22) in our patients with HCA. Of these, 31.8% (7/22) were deficient for plasma folate. Heterozygosity for T833C mutation in the CBS gene was observed in 9.99% (2/22) of our patients with HCA. Both these patients were also deficient for plasma folate and vitamin B12. CONCLUSION: In our study, heterozygosity for the thermolabile MTHFR mutation was found to be associated with hyperhomocysteinemia (HCA). This genetic predisposition to HCA could be risk factor for CHD and can be correlated with vitamin supplementation. To the best of our knowledge this is the first report from India on plasma homocysteine levels and its genetic aspect in patients with CHD.

ACE and AT1R gene polymorphisms and hypertension in Indian population.

The renin angiotensin system (RAS) controls intrarenal blood pressure and sodium balance, and is an important target for antihypertensive therapy. Several polymorphisms have been identified within genes encoding RAS that may contribute to the development of elevated blood pressure. The relevance of these polymorphisms in hypertension remains controversial. In this study we have examined 105 hypertensive subjects and 192 controls from the Indian population for I/D polymorphism of angiotensin I converting enzyme (ACE) and A(1166)C polymorphism of angiotensin II type I receptor (AT1R) genes by polymerase chain reaction (PCR) and PCR-based restriction enzyme analysis method, respectively. There was no significant difference in the distribution of ACE (I/I, I/D, and D/D) and AT1R (A/A and A/C) genotypes between controls and hypertensive subjects. D allele was significantly associated with an early onset of hypertension and although nonsignificant, the frequency was high in subjects with family history of cardiovascular disorders. C(1166) allele of AT1R did not correlate with the age of onset of hypertension and the frequency was low in subjects with family history. Thus no association was found between ACE and AT1R genotypes and hypertension. However the D allele can be used as a predictor of risk of hypertension in the Indian population.

Genes of renin angiotensin system and coronary heart disease.

Coronary constriction, proliferation of smooth muscle cells and arrhythmia are involved in the pathophysiology of coronary heart disease and its complications such as myocardial infarction and sudden death. All these effects are favoured by high angiotensin II levels. Angiotensin II is the main effector molecule of the renin angiotensin system and it acts through angiotensin II type receptors. Genetically determined differences in the expression of the components of this system could adversely affect angiotensin II concentration and subsequently heart. Consequently each component of this system represents a potential candidate in the etiology of cardiovascular disease. In this article we review the variation of the angiotensin I converting enzyme, angiotensin II type I receptor and angiotensinogen genes and their association with cardiovascular disease.

Nitrate cross-tolerance: effect of sublingual isosorbide dinitrate and nitroglycerin during sustained nitrate therapy.

In a randomized, single-blind, crossover study, 10 patients with stable, exercise-induced angina pectoris were studied during sustained therapy with oral isosorbide dinitrate (ISDN). Circulatory changes and exercise performance were evaluated before and 6 hours after therapy with oral ISDN. One-half hour after this therapy, sublingual ISDN or nitroglycerin (NTG) was administered and exercise testing repeated. Treadmill walking time 6 hours after oral ISDN was similar to the control value. Subsequent administration of sublingual ISDN improved walking time from 429 +/- 156 to 513 +/- 166 seconds (p less than 0.005), whereas after NTG improved from 411 +/- 159 to 480 +/- 158 second (p less than 0.005). The improvement in walking time with ISDN (23%) and NTG (18%) and the absolute walking times were not different. The standing systolic blood pressure decreased from 124 +/- 23 to 112 +/- 22 mm Hg (p less than 0.02) after therapy with sublingual ISDN and 122 +/- 23 to 110 +/- 24 mm Hg (p less than 0.005) after administration of NTG. This study demonstrates that (1) during sustained ISDN therapy, walking time returns to control values by 6 hours; (2) administration of either sublingual ISDN or NTG results in significant circulatory changes and improvement in walking time; and (3) the changes in circulatory and exercise variables after administration of NTG in patients taking sustained ISDN therapy cannot be taken as evidence of an absence of cross-tolerance between these agents.

Haemodynamics and plasma concentrations following sublingual GTN and intravenous, or inhaled, isosorbide dinitrate.

We measured plasma nitrate levels and haemodynamics following sublingual glyceryl trinitrate (GTN) (0.5 mg), or isosorbide dinitrate (ISDN) administered intravenously (0.5 mg) or by inhalation (1.25 mg) in 23 patients undergoing cardiac catheterisation for investigation of chest pain. Peak levels were detected at 90 s and 5 min following intravenous and inhaled ISDN respectively and at 3 min following sublingual GTN. Intravenous and inhaled ISDN produced similar plasma levels at 30 s and both were significantly greater than following sublingual GTN. Plasma levels were maintained for longer following inhaled ISDN than intravenous ISDN or sublingual GTN. Haemodynamic responses were qualitatively similar following each treatment; reduction in pulmonary vascular resistance and pressure and left ventricular end diastolic pressure occurred in each group. Heart rate, cardiac output and LV dP/dt.P-1 remained unchanged. Maximal haemodynamic responses were greater following ISDN than GTN, with little difference between the two preparations of ISDN. Haemodynamic responses were more sustained following inhaled ISDN than following sublingual GTN or intravenous ISDN, the latter two being similar in this respect. These findings suggest that inhaled ISDN may provide more rapid and sustained relief from angina than sublingual GTN.

Isolated anomaly of the left anterior descending coronary artery.

An isolated anomaly of the left anterior descending coronary artery arising from the right sinus of Valsalva is described. A review of the literature shows that isolated anomalies of this vessel are very rare. However, the inability to visualize this vessel from the left sinus of Valsalva warrants careful search of the right sinus.

Nitroglycerin-induced coronary vasoconstriction.

Nitroglycerin is routinely used during coronary angiography for its vasodilating effects. An unusual case is described in which nitroglycerin induced severe coronary artery spasm. Interpretation of coronary angiograms after nitroglycerin should be made with caution.