A study of platelet aggregation in patients with acute myocardial infarction at presentation and after 48 hrs of initiating standard anti platelet therapy.

AIMS & OBJECTIVES: Platelet aggregation is a key factor behind coronary artery disease. Various complications after an attack of acute coronary syndrome are often related to the platelet hyperactivity in the early hours following the event. There is a growing concern regarding aspirin & clopidogrel resistance, which has put the time-tested therapies under scrutiny. Time has come to address the issue of platelet hyperactivity in the early hours & whether to individualize therapy and drug doses in different patients. MATERIALS & METHODS: We prospectively enrolled 41 patients with a diagnosis of acute myocardial infarction (AMI) between July 2009 and July 2010 admitted to the cardiology ward and ICCU of Medical College, Kolkata, after fulfillment of inclusion & exclusion criteria. The study was reviewed and approved by the Institutional Ethical Committee. Platelet Aggregation (PA) with 10 microM epinephrine, 2 microg/ml collagen and 10 microM ADP was performed with light transmittance aggregometry in all patients according to the standard protocol. Tests were done within 3 hours of sampling with platelet-rich plasma (PRP) by the turbidometric method in a 2-channel aggregometer (Chrono-Log 490 Model, Chrono-Log Corp, Havertown, Pa). Aspirin & clopidogrel resistance were defined as per ACC/AHA guidelines. Platelet aggregation studies were done at presentation (zero hour) and 48 hours after instituting dual antiplatelet therapy in standard doses. RESULTS: Patients with first attack of AMI showed a high mean platelet aggregation at 0 hours of 77.4% +/- 18.8% with ADP, 77.5% +/- 26% with Epinephrine & 73.5% +/- 24.9% with Collagen. With all three agonists, the initial hyperactivity of platelets at 0 hours was significantly higher among diabetics & obese. Though reduced, significant platelet hyperactivity remained at 48 hours after initiating standard antiplatelet therapy; 50.3% +/- 14.3% with ADP, 56.5% +/- 21.6% with epinephrine & 38.4% +/- 22% with collagen. CONCLUSION: In the early hours after AMI there is a fairly high degree of platelet aggregation. Even after 48 hours of standard antiplatelet therapy the platelet aggregation though reduced, still remains significantly high. Since recurrent ischemic episodes frequently occur in this vulnerable period, time has come to assess platelet aggregation status in high risk groups, if not in all patients of acute coronary syndrome during this period so that therapy may be individualized. Further researches are required in this area.

Lipid modifying action of atorvastatin in comparison to combination of atorvastatin and nicotinic acid in patients with ischaemic heart disease.

AIMS AND OBJECTIVES: The current study is a prospective, randomized controlled study with two parallel treatment groups done to assess the tolerability and efficacy of a combination of atorvastatin (10 mg) and extended release nicotinic acid (1G) in comparison to atorvastatin (20 mg) alone in modulating the lipid profile in patients of Ischemic Heart Disease in our population. METHODS AND RESULTS: Patients were randomly allocated into two equal groups (n = 216) as per selection criteria. Group A received Atorvastatin 20 mg while Group B received combination of Atorvastatin -10 mg and extended release nicotinic acid (1G), both once daily at bed time, for a period of 24 weeks. Final end-of-study assessment and evaluation of tolerability and efficacy was done after 24 weeks. Comparison between the groups was performed with paired t-test. A p value < 0.05 was considered to be statistically significant. There was significant reduction in cholesterol, LDL & triglycerides in both the groups. Mean values of cholesterol and LDL were comparable in both groups where as there was increased reduction of triglycerides in Group B. Mean value of HDL cholesterol significantly increased only in group B thus the total cholesterol: HDL ratio was decreased more favorably. SGPT level was not significantly altered in either of the groups. CONCLUSION: In the Indian perspective, where HDL is low and the LDL values are not very high, a combination of low dose atorvastatin with nicotinic acid may influence the lipid profile more favorably and reduce the cholesterol/HDL ratio in comparison to atorvastatin alone and is also fairly well tolerated.

Left atrial extension of lung malignancy with ECG changes resembling STEMI.

Lung malignancy extending into left atrium is seen very infrequently. We had a patient with a fast growing symptomatic lung mass and electrocardiogram showing persistent coving ST elevation without any biomarker change. Transthoracic echocardiography showed a large left atrial mass which was fixed to the free walls and extended into the appendage. There was also a large lung mass that was compressing the heart from its lateral aspect. CT-scan of chest corroborated the lung mass & CT-guided FNAC showed small cell carcinoma.

Echocardiographic profile of ART naïve human immunodeficiency virus (HIV) infected patients in a tertiary care hospital in Kolkata.

AIMS AND OBJECTIVE: Cardiac affection in human iummunodeficiency virus (HIV) infection is a recognized entity. Some form of heart disease is demonstrable at autopsy in approximately 40 percent of cases and by echocardiography in approximately 25 percent of patients with HIV. the studies indicate that cardiac involvements associated with HIV are mainly characterized by cardiomyopathy and pericardial disease. HIV infection is a global pandemic which is also rapidly spreading in india. We conducted the study to have some insight into the profile oflndian patients. MATERIAL & METHODS: In this cross sectional hospital based study, we evaluated immunological (CD4 count) and echocardiographic status of 45 asymptomatic HIV seropositive patients who did not receive anti-retroviral therapy. The results were compared with age and sex matched controls. Statistical analysis was done using appropriate statistical methods. RESULTS: Most common cardiovascular abnormalities were diastolic dysfunction (18%) followed by pericardial effusion (13%) and systolic dysfunction (7%). When compared with controls the study population had statistically higher number of diastolic dysfunction (p value = 0.035) but not systolic dysfunction (p value = 0.61); none of the control population was having pericardial effusion. Low CD4 count was significantly associated with pericardial effusion (p value 0.048) but the association with diastolic dysfunction (p value = 0.46) or systolic dysfunction (p value = 0.84) was not statistically significant. CONCLUSION: Cardiovascular complications are common among HIV infected patients in india, most common being diastolic dysfunction and pericardial effusion. Low CD4 counts are associated significantly with pericardial effusion. These abnormalities are likely to be found with greater frequency in clinical practice as management of opportunistic infections continues to improve.

Antiplatelet drug resistance in patients with recurrent acute coronary syndrome undergoing conservative management.

AIMS AND OBJECTIVES: Recurrent ischemic events continue to occur despite combination anti-platelet therapy. Currently aspirin, clopidogrel and dual resistance are increasingly recognized entities. The relationship of such resistance to recurrent ischemic events is largely unknown. In this study, we tried to gain an insight into the role of antiplatelet drug resistance with recurrent Acute Coronary Syndrome (ACS). MATERIALS AND METHODS: The antiplatelet effect of aspirin and clopidogrel was studied in 40 recurrent ACS patients and 170 patients with first episode of ACS, after > or = 7 days of dual antiplatelet therapy. Platelet aggregation study was done with optical aggregometer. Resistance to aspirin and clopidogrel was defined as > or = 50% aggregation with collagen and ADP respectively. RESULTS: Aspirin, clopidogrel and dual drug resistance were encountered respectively in 35%, 72.5% and 32.5% patients with recurrent ACS. The corresponding figures for the patients with first episode of ACS were 25.3%, 42.3% and 18.8% respectively. P values for the comparisons were 0.237 for aspirin, 0.0007 for clopidogrel and 0.084 for dual drugs. Patients with recurrent ACS were relatively younger and had a higher prevalence of conventional risk factors like hypertension, diabetes and elevated LDL. CONCLUSION: Antiplatelet drug resistance is likely to play an important role in recurrent ACS alongside other conventional risk factors. Further research is required in this field to have a definitive conclusion.

Dual antiplatelet therapy in ACS: time-dependent variability in platelet aggregation during the first week.

AIMS AND OBJECTIVES: Platelets play an important role in the pathogenesis of Acute Coronary Syndrome (ACS). Most of the complications of ACS occur during the initial hours of presentation. We tried to gain an insight into the platelet function during the initial phase of ACS in patients on dual antiplatelet therapy. MATERIALS AND METHODS: Platelet aggregation study was performed by light transmittance aggregometry in 64 ACS patients 48 hour and 7 days after initiation of dual antiplatelet therapy with aspirin and clopidogrel. RESULTS: Epinephrine, ADP and collagen induced platelet aggregation was significantly higher at 48 hours, following initiation of dual antiplatelet therapy, in comparison to the profile observed on the 7th day. Diabetics demonstrated a significantly higher aggregation at both the time points and aggregation was also somewhat higher in smokers though it did not reach statistical significance. CONCLUSION: This study conceptualizes the hypothetical role of alpha-2 adrenoreceptor blockers during the early hours following ACS and also warrants further investigations exploring the optimum loading dose of antiplatelet agents, especially clopidogrel in patients with ACS.

Dual antiplatelet drug resistance in patients with acute coronary syndrome.

AIMS AND OBJECTIVES: Antiplatelet therapy is a cornerstone in the management of the atherosclerotic vascular disease. Aspirin and clopidogrel are the two most commonly used antiplatelet drugs in its management. Recently, there has been a concern about the development of resistance to one or both antiplatelet agents with potentially devastating consequences. In this study we tried to assess the in vitro resistance to antiplatelet agents in patients presenting with acute coronary syndrome (ACS). MATERIALS AND METHODS: 144 patients presenting with ACS, who were not on any antiplatelet therapy prior to hospital admission were evaluated in this study. Baseline clinical data was obtained before giving the oral loading dose of aspirin and clopidogrel. Patients received a loading dose of 325 mg of aspirin and 300 mg of clopidogrel followed by a daily dose of 150 mg. of aspirin and 75 mg.of clopidogrel. After 7 days of dual antiplatelet therapy, platelet aggregation pattern was analyzed using optical aggregometer (chrono-log). Response to aspirin and clopidogrel was assessed by interaction with collagen (2microg/ml) and Adenosine diphosphate (ADP) (10micro/ml) respectively. The results were analyzed. Response to doubling the dose of antiplatelet agents was also observed in 6 aspirin resistant patients, 12 clopidogrel resistant patients and in 6 patients resistant to the effect of dual antiplatelet agents. RESULTS: There were 22 patients (15.27%) who showed poor response to aspirin, 28 patients (19.44%) to clopidogrel (primary non-responder) and 18 patients (12.5%) showed a primary non-responsiveness to both the antiplatelet agents in the usual doses. After dose doubling, all 6 aspirin resistant patients showed adequate response but 4 out of 12 clopidogrel resistant patients showed inadequate response. CONCLUSIONS: This pilot study brings out a disquieting picture of 12.5% patients suffering from ACS showing resistance to the antiplatelet effects of both aspirin and clopidogrel in the conventional dose. A long-term prospective randomized controlled trial is required to give an insight into this problem and its clinical consequences.

Heart Rate in Hypertension: Review and Expert Opinion.

Heart rate (HR) is strongly associated with both peripheral and central blood pressures. This association has implications in hypertension (HTN) prognosis and management. Elevated HR in HTN further elevates the risk of adverse outcomes. Evidence suggests that HR is an independent risk factor for cardiovascular (CV) and total mortality in patients with HTN. With objective to engage physicians and researchers in India to identify and discuss the implications related to HR management in HTN, experts in the HTN management provided consensus recommendations. The key expert recommendations included the following. (i) Heart rate (HR) has inverse relationship with the central aortic pressure, whereby reduction in HR is associated with an increase in central aortic pressure. This counter-balances the benefit of HR reduction with the harmful effects of rising central aortic pressure. (ii) Increase in the resting HR is associated with increased risk of incident HTN. A linear association between the two is observed especially in individuals with HR >80 bpm. (iii) A reduced HR variability further adds to the propensity for the development of HTN, especially in men. (iv) Each 10 beats per minute increase in the resting HR can substantially increase the risk of adverse CV and mortality outcomes. On treatment HR provides a better prognostic guide. (v) Ambulatory HR with day-time and night-time HR evaluation may also suggest different impact on outcomes. (vi) Target HR in patients with HTN remains unclear. Generally, HR<70 bpm on beta blocker (BB) treatment is advised which may be further lowered in patients with comorbidities like heart failure and coronary artery disease. (vii) Adopting healthy lifestyle approaches to keep check on BP and HR is essential. (viii) Use selective beta-1 blocker in symptomatic cases with elevated HR beyond 80-85 mmHg. BBs are expected to benefit by lowering HR by nearly 10 bpm. Preference should be given to newer beta-blockers which reduce HR and both peripheral and central blood pressure to derive comprehensive advantage of this dual action. (ix) It still remains unclear whether reducing HR in HTN without comorbidities alters the CV and mortality outcomes.

Evaluation of sustained blood pressure elevation in children.

OBJECTIVES: To document the prevalence and etiology of sustained blood pressure elevation in children. METHODS & RESULTS: It is a school-based prospective cross-sectional study involving healthy school children in age group of 5-15 years (both sexes). Children with any acute or chronic illnesses and the intersexes were excluded from the study group. Total number of hypertensive children were 37. Of these 37 cases, 23 hypertensive cases were boys and 14 were girls. All these hypertensive children maintained their blood pressure above +2SD for the corresponding age and sex. Male and female ratio of hypertensive cases was 62:38. All were primary hypertensives as per working definition. Majority belonged to Class II socio-economic status. CONCLUSION: Hypertension in children is very rare with a prevalence of 0.38% and majority had primary hypertension.

A multicentric double blind randomised controlled trial of atenolol versus losartan as first line drug for mild to moderate essential hypertension.

Ambulatory blood pressure monitoring provides a more reliable assessment of actual BP than office BP and is a more sensitive risk predictor of clinical cardiovascular outcomes. Recent international guidelines for hypertension have emphasised the usefulness of ambulatory BP for diagnosis and management of hypertension. We used ambulatory blood pressure monitoring to monitor the effect of the pharmacological treatment in patients with stage 1 or 2 hypertension. This was a multicentric randomised controlled trial having 360 subjects with 180 in each treatment arm. The duration of study was 6 months. The patients were randomly selected to receive atenolol or losartan as initial therapy. The dose of atenolol or losartan was 50 mg once daily at 8 am in the morning. Ambulatory BP assessment was done in a subgroup of subjects using Schiller BR-102 plus machine. One hundred and thirty patients were recruited for the study using ambulatory blood pressure monitoring. There were 66 patients in atenolol arm and 64 patients in the losartan arm. A significant white coat hypertension was noticed in both the arms. Out of 130 subjects in the ambulatory group, 41.53% had a white coat hypertension. Statistically significant reduction of office BP was observed with both atenolol and losartan; however, no significant difference in efficacy of the two drugs was found in reducing office BP. However, when using ambulatory blood pressure monitoring, the reduction with either drug was not significant. The dipper status was better in the atenolol group than the losartan group. Neither of the drugs prevent morning surge of BP when administered once daily in the morning. There was high prevalence of white coat hypertension in patients with stage 1 and stage 2 hypertension. There was similar reduction of systolic blood pressure and diastolic blood pressure by the 2 study drugs. Atenolol scores over losartan in converting non-dipper to dipper but its' impact on clinical outcome is not known. Morning surge of BP was unaffected by either of the study drugs.

Left atrial extension of lung carcinoma simulating myocardial infarction, unusual presentation: case report and literature review.

Lung malignancy invading the left atrium is rarely seen. We present a patient with a fast growing symptomatic lung mass. Electrocardiogram showed persistent coving ST elevation with no biomarker change. Transthoracic echocardiography showed a large left atrial mass attached to the free walls and extended into its appendage. An apparent continuity with a large lung mass compressing left ventricular lateral wall was observed which was better evident in computed tomography of the chest.