Effect of Ivabradine on Heart Rate and Duration of Exercise in Patients With Mild-to-Moderate Mitral Stenosis: A Randomized Comparison With Metoprolol.

BACKGROUND: Symptoms in mitral stenosis (MS) are heart rate (HR) dependent. Increase in HR reduces diastolic filling period with rise in transmitral gradient. By reducing HR, beta-blockers improve hemodynamics and relieve symptoms, but the use may be limited by side effects. The present randomized crossover study looked at comparative efficacy of ivabradine and metoprolol on symptoms, hemodynamics, and exercise parameters in patients with mild-to-moderate MS (mitral valve area, 1-2 cm) in normal sinus rhythm. MATERIAL AND METHODS: Baseline clinical assessment, treadmill stress testing, and an echocardiographic Doppler evaluation were performed to determine resting HR, total exercise duration, mean gradient across mitral valve, and mean pulmonary artery systolic pressure (PASP). Patients were then allocated to either metoprolol or ivabradine to maximal tolerated doses over 6 weeks (metoprolol: 100 mg twice a day, ivabradine: 10 mg twice a day). Reevaluation was done at the end of this period, and all drugs stopped for washout over 2 weeks. Thereafter, the 2 groups were crossed over to the other drug that was continued for another 6 weeks. Assessment was again performed at the end of this period. RESULTS: Thirty-three patients of 34 completed the protocol. Fifteen were male, mean age was 28.9 ± 6.6 years, all were in New York Heart Association class 2, and mean resting HR was 103.5 ± 7.2/min. Mean mitral valve area was 1.56 ± 0.16 cm, mean PASP was 38.1 ± 5.1 mm Hg, and mean gradient across mitral valve was 10.6 ± 1.6 mm Hg. Significant decrease in baseline and peak exercise HR was observed at the end of follow-up with both drugs. Reduction in mitral valve gradient after ivabradine (42%) and metoprolol (37%) and reduction in PASP after both ivabradine (23%) and metoprolol (27%) were to a similar extent. Significant reduction in total exercise duration after both ivabradine and metoprolol therapy was observed. One patient developed blurring of vision with ivabradine therapy but did not require discontinuation of drug. An improvement in dyspnea of one grade was observed in all the patients by treatment with both ivabradine and metoprolol. CONCLUSIONS: Both metoprolol and ivabradine reduced symptoms and improved hemodynamics significantly from baseline to a similar extent. Ivabradine thus can be used effectively and safely in patients with MS in normal sinus rhythm who are intolerant or contraindicated for beta-blocker therapy.

Optimal fluid amount for haemodynamic benefit in cardiac tamponade.

OBJECTIVES: The present study was undertaken to assess the effect of volume expansion on cardiac haemodynamics in patients with cardiac tamponade and to ascertain an optimum amount of fluid that can produce the maximum benefit in tamponade patients. BACKGROUND: In patients of tamponade, interim measures may occasionally be needed when facilities for pericardial fluid drainage are not immediately available. Intravascular volume expansion is the most commonly advocated measure but with limited scientific data. METHODS: Patients ≥16 years of age with large circumferential pericardial effusion and showing echocardiographic evidence of cardiac tamponade were included. Haemodynamically unstable patients, those with structural heart diseases, pregnant females, and those undergoing haemodialysis were excluded. The various haemodynamic parameters were measured using Edwards Life Sciences Vigilance II monitor, Swan Ganz CCO catheter, intrapericardial access, and arterial access at baseline and after each 250 ml fluid over 5 min (total 1000 ml in 20 min). The entire fluid was drained at the end of the procedure. RESULTS: A total of 28 patients constituted the study group, all of whom exhibited an improvement in haemodynamic parameters (systolic blood pressure, cardiac output) and a rise of the intracardiac pressures with volume expansion. Significant (p<0.05 ) increase in systolic and diastolic blood pressure, cardiac output, and cardiac index occurred up to 250-500 ml bracket; above which the significance was lost. A higher resting heart rate, a lower SBP at presentation, a higher initial intrapericardial pressure, and a lower cardiac index were the statistically significant predictors of a >15% increase in cardiac index. CONCLUSIONS: Rapid infusion of as little as 250 ml intravenous normal saline may improve the cardiac haemodynamics in a significant proportion of tamponade patients.

Profile and prevalence of clopidogrel resistance in patients of acute coronary syndrome.

UNLABELLED: Recently reports of a variable platelet response to aspirin and potential resistance to therapy have emerged with thienopyridines group of drugs. However the data available on clopidogrel resistance is scarce. The present study was initiated to prospectively evaluate the prevalence of clopidogrel resistance in patients of acute coronary syndrome(ACS) presently on dual anti platelet therapy by using an established method of optical platelet aggregation. We studied 39 patients of ACS, who were on clopidogrel 300 mg bolus followed by 75 mg per day for 3 days along with aspirin 325 mg per day. Fasting blood samples were assessed using optical platelet aggregation (Chronolog Corp, USA). Clopidogrel resistance was defined as <10% decrease from baseline in platelet aggregation. Clopidogrel semi-responders were defined as 10-29% ( <30%) decrease from baseline in platelet aggregation. Clopidogrel non-responders were defined as a composite of resistant and semi-responders. A baseline mean platelet aggregation obtained from 18 healthy subjects was 63.8 +/- 14.75% with 5 mu and 68.8 +/-13.91% with 10 mu of Adenosine Diphosphate. Hence, the definition of clopidogrel resistance was set as aggregation of >57% with 5 mu ADP and >61.9% with 10 mu ADP (< 10% decrease from baseline). The definition of clopidogrel semi-responder was set as aggregation of >or=45% with 5 mu ADP and >or=48% with 10 mu ADP (10-29% decrease from baseline). The mean platelet aggregation with 5 mu and 10 mu of Adenosine Diphosphate in the patient group was 30.77 +/- 17.19% and 35.71 +/- 17.0% respectively. Based on these criteria, 2.54% patients were found to be clopidogrel resistant, 12.7% were clopidogrel semi-responders and 84.7% were clopidogrel responders. On comparison of clopidogrel responders with non-responders, females ( p=0.07) and patients with higher serum triglyceride levels (p=0.08), had a trend to be more inclined towards clopidogrel non-responders. All other parameters tested namely age, smoking, diabetes, hypertension, obesity, cholesterol, hemoglobin, platelet count, ejection fraction and concurrent drug intake did not show any statistically significant difference among the groups. CONCLUSIONS: This study shows that clopidogrel resistant and clopidogrel semi-responders do occur in Indian patients with ACS and there are no reliable clinical predictors for this condition. The diagnosis therefore relies primarily on laboratory tests.

N-terminal probrain natriuretic peptide predicts adverse outcomes in acute-myocardial infarction even with preserved left ventricular ejection fraction.

BACKGROUND: Risk stratification of patients with acute myocardial infarction is based on various clinical, biochemical or electrocardiographic parameters. There is emerging evidence that N-terminal probrain natriuretic peptides (NT-proBNP) possess characteristics of an ideal biomarker. In this study we looked into the role of NT-proBNP in risk stratification and prediction of short-term events in patients presenting with acute myocardial infarction (MI) and having preserved left ventricular functions as assessed by ejection fraction (EF) on echocardiography. METHODS AND RESULTS: Of a total of 250 consecutive patients admitted with a diagnosis of acute ST segment elevation myocardial infarction, 84 patients were found to have ejection fraction greater than 50% (44 with anterior MI, 40 with inferior MI. Serum NT-proBNP was measured using electrochemiluminiscence assay (Roche). On two-dimensional echocardiography, modified Simpson's technique was used to measure the EF. Follow-up at day 30 included a two-dimensional echocardiography and assessment for worsening heart failure, recurrent ischemia, and repeat hospitalization. Death due to cardiovascular cause by 30 days was also noted. The mean value of NT-proBNP for those having EF over 50% was 1542.38 + 4649.12 pg/ml. For the purpose of a dichotomous analysis, the median value was determined (907.5 pg/ml). In patients having NT-proBNP above median, the Killip class was expectedly higher 1.62 + 0.21 vs 1.0 + 0.12 ( p< 0.05) and the thrombolysis in myocardial infarction scores were worse (4.77 + 1.56 vs 2.71 + 1.11, p < 0.05). The ejection fraction was similar (59.72 + 8.8 vs 58.76 + 6.9, p= NS) in the two groups. At 30 days followup, patients having NT-proBNP above median showed a further decline in the Killip class and EF. The clinical outcomes (composite of recurrent ischemia, worsening heart failure and repeat hospitalization) were also worse in this group ( p< 0.05). CONCLUSION: In patients with apparently normal ejection fraction and without left ventricular dysfunction, a higher NT-proBNP level would suggest poorer short-term clinical outcomes and would require a more aggressive treatment strategy.

N-terminal probrain natriuretic peptide as a predictor of short-term outcomes in acute myocardial infarction.

BACKGROUND: Risk stratification and prediction of high risk for mortality in patients with acute coronary syndromes is based on clinical evaluation, electrocardiogram, biochemical markers and various risk assessment scores. There is emerging evidence that N-terminal probrain natriuretic peptide possesses several characteristics of an ideal biomarker. In this study we looked into the role of N-terminal probrain natriuretic peptide in risk stratification and prediction of short-term events including mortality in patients presenting with acute coronary syndrome. METHODS AND RESULTS: A total of 120 consecutive patients admitted with a diagnosis of acute myocardial infarction, including both ST elevation myocardial infarction (n=80) and non-ST elevation myocardial infarction (n=40) were enrolled. Serum N-terminal probrain natriuretic peptide was measured using electrochemiluminiscence assay (Roche Diagnostics), on the Elecsys 2010 system. On two-dimentional echocardiography, modified Simpson's technique was used to measure the ejection fraction along with end-systolic volume. Various other demographic variables, echocardiographic parameters and risk scores were also assessed. Follow-up at day 30 included a two-dimentional echocardiographic evaluation and assessment for worsening heart failure, recurrent ischemia, and repeat hospitalization. Death due to cardiovascular cause by 30 days was also noted. The mean value of N-terminal probrain natriuretic peptide for the whole cohort was 2307 +/- 2287 pg/ml (271.4 +/- 269.1 pmol/L). For the purpose of comparative analysis, the median value was determined [1403 pg/ml (165 pmol/L)]. In patients having N-terminal probrain natriuretic peptide above median, the end-systolic volume was higher while ejection fraction was significantly lower at baseline (p<0.05). At 30 days follow-up, there was a further decline in ejection fraction from 47.7 +/- 11.4 to 43.9 +/- 9.9 (p<0.05), and clinical outcomes were worse in this group. There was a 5% mortality in the entire study group and all patients who died had N-terminal probrain natriuretic peptide above median. On multivariate logistic regression analysis, N-terminal probrain natriuretic peptide above median (OR=32.79, 95% CI 8.74-123.1, p<0.001) emerged as the strongest predictors of adverse outcomes, including 30-day mortality (p<0.001). CONCLUSIONS: N-terminal probrain natriuretic peptide emerged as a strong prognostic tool across the spectrum of acute myocardial infarction and had the strongest predictive value for short-term adverse outcomes including death.

Third heart sound revisited: a correlation with N-terminal pro brain natriuretic peptide and echocardiography to detect left ventricular dysfunction.

BACKGROUND: Auscultation of the third heart sound is an age-old sign for predicting ventricular dysfunction. New technology and biomarkers like two-dimensional echocardiography and N-terminal pro brain natriuretic peptide, respectively, have sidelined the utility of this sign, which does not involve any cost and is readily accessible. We sought to find the predictive accuracy of third heart sound and its correlation with N-terminal pro brain natriuretic peptide and ejection fraction using two-dimensional echocardiography to detect left ventricular dysfunction in patients of acute coronary syndrome. METHODS AND RESULTS: One hundred and ten patients presenting with acute coronary syndrome [acute ST elevation myocardial infarction (n=74) and non-ST elevation myocardial infarction (n=36)] were prospectively studied. A senior cardiologist, blinded to N-terminal pro brain natriuretic peptide and ejection fraction results auscultated for a left ventricular third heart sound in each patient. Ejection fraction was measured using modified Simpson's technique on two-dimensional echocardiography and N-terminal pro brain natriuretic peptide was measured using electrochemiluminiscence assay. Median levels of N-terminal pro brain natriuretic peptide were used to provide a dichotomous approach for analysis of the data. Third heart sound was present in 40 patients (acute ST elevation myocardial infarction: n=27, non-ST elevation myocardial infarction: n=13) and absent in 70 patients (acute ST elevation myocardial infarction: n=47, non-ST elevation myocardial infarction: n=23). The sensitivity and specificity of third heart sound for predicting N-terminal pro brain natriuretic peptide above median was 65.5% and 92.7%, respectively. The positive and negative predictive value was 90% and 73%, respectively. The N-terminal pro brain natriuretic peptide of those having third heart sound was 4081 +/- 2705 pg/ml compared to 1239.3 +/- 1169 pg/ml in those without third heart sound (p < 0.001). The sensitivity of third heart sound to detect ejection fraction <45% was 67.9% while the specificity was 74.4%. The positive and the negative predictive values were 47.5% and 87.1%, respectively. The ejection fraction of patients having third heart sound was 47.5 +/- 11.3% compared to 56 +/- 10.4% without third heart sound (p < 0.001). CONCLUSIONS: Auscultation of third heart sound has a good specificity and predictive value for predicting elevated N-terminal pro brain natriuretic peptide and left ventricular dysfunction. Thus age-old clinical cardiology still holds its forte in this new era of technology-driven cardiology.

Profile and prevalence of aspirin resistance in Indian patients with coronary artery disease.

BACKGROUND: Aspirin resistance is considered to be an enigma and the data available on aspirin resistance is scarce. This study was initiated to prospectively evaluate the prevalence of aspirin resistance in patients with stable coronary artery disease by using an established method of optical platelet aggregation. METHODS AND RESULTS: We studied 50 patients who were on 150 mg of aspirin for the previous 7 days. Fasting blood samples were assessed using optical platelet aggregation (Chronolog Corp, USA). The mean platelet aggregation with 10 microm of adenosine diphosphate in our patient group was 49.42 +/- 23.29% and with 0.5 mg/ ml of arachidonic acid it was 13.58 +/- 21.40%. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microm of adenosine diphosphate and a mean aggregation of > or =20% with 0.5 mg/ml of arachidonic acid. Aspirin semi responders were defined as those meeting only one of the criteria. Based on these criteria, 2.08% patients were found to be aspirin-resistant, 39.58% were aspirin semi responders and 58.33% were aspirin responders. Females tended to be more aspirin semi responsive (p = 0.08). All other parameters tested, namely, age, smoking, diabetes mellitus, hypertension, obesity, lipids, hemoglobin, platelet count, ejection fraction and drug intake did not show any statistically significant difference among the groups. Thus, in our group 41.66% patients showed inadequate response to aspirin. CONCLUSIONS: This study shows that aspirin resistance and aspirin semi responsiveness do occur in the Indian patients and there are no reliable clinical predictors for this condition. The diagnosis therefore relies primarily on laboratory tests.