Reliability of Fractional Flow Reserve in Non-Infarct-Related Arteries in ST-Segment Elevation Myocardial Infarction Patients Undergoing a Pharmaco-Invasive Approach.

Objectives We investigated the reproducibility of fractional flow reserve (FFR) of significant stenoses (≥70% narrowing) in the non-infarct related artery (NIRA) during the pharmaco-invasive percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) within 24 hours of thrombolysis and at a follow up of 2-3 weeks. Background STEMI with multivessel disease has worse outcomes. The benefits of FFR-directed PCI of NIRA at the time of primary PCI are yet controversial. Assessing the hemodynamic severity of the NIRA may help in deciding the management strategy of these lesions, save time, and avoid complications. Methods Thirty-one patients undergoing PCI for STEMI under a pharmaco-invasive approach were prospectively recruited. The FFR measurements in 34 stenoses (≥70% diameter stenosis) were obtained immediately after PCI of the culprit stenosis and were repeated at a mean follow-up of 17.6 ± 3.55 (14-21) days. In addition, time to thrombolysis, time from symptom onset to PCI, left ventricular ejection fraction (LVEF), quantitative coronary angiographic measurements of the non-culprit stenoses, and thrombolysis in myocardial infarction (TIMI) flow were recorded. Results There was a significant change in FFR values at follow-up as compared to baseline (0.78 ± 0.08 (0.68-0.93) to 0.77 ± 0.08 (0.67-0.93)) (p = 0.014). In four of the lesions, the FFR values differed by >0.05 at follow-up. The follow-up FFR values led to a change in the management strategy in 5 out of 31 patients (15%) of the lesions. The TIMI flow, percentage diameter stenosis, minimum lumen diameter, and LVEF did not change. There were no predictors of this change in FFR values. Conclusions During the acute phase of STEMI, the severity of non-culprit coronary artery stenoses can not be reliably assessed by FFR. The prolonged jeopardized state of myocardium in pharmaco-invasive PCI as compared to primary PCI seems to be responsible.

Optical Coherence Tomography Findings in Patients Presenting With In-Stent Restenosis: A Prospective Observational Study of Patterns of Neointimal Hyperplasia and Associated Risk Factors.

Introduction Morphological features of neointimal tissue play a pivotal role in the pathophysiology of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). This study was designed to qualitatively and quantitatively assess neointimal characteristics of lesions using optical coherence tomography (OCT) in patients presenting with ISR.  Methods This was a single-center, prospective, observational study performed at a tertiary-care center in India. Patients diagnosed with stable angina and acute coronary syndrome with post-procedural angiographically documented restenosis (>50%) were included. Results A total of 34 patients with ISR were studied. Neointimal hyperplasia was classified as (i) homogenous group (n = 18) and (ii) non-homogenous group (n = 16). Fourteen (77.8%) diabetics belonged to the homogenous group. Predominant plaque characteristics such as neoatherosclerosis, cholesterol crystals, and calcium were documented in 14 (77.8%), 12 (66.7%), and 11 (61.1%) patients in the homogenous group and 10 (62.5%), 10 (62.5%), and 9 (56.2%) patients in the non-homogenous group, respectively. Unexpanded stent struts were identified in 11 (61.1%) and 11 (68.8%) patients in the homogenous and non-homogenous groups, respectively. Mean strut thickness was 93.73 ± 31.03 µm and 83.54 ± 18.0 µm, ISR was 72.50 ± 15.93% and 65.37 ± 21.69%, the neointimal thickness was 588.06 ± 167.82 µm and 666.25 ± 218.05 µm, and neointimal hyperplasia was 54.54 ± 11.23% and 59.26 ± 8.86% in the homogenous and non-homogenous groups, respectively. Conclusion Neoatherosclerosis and stent underexpansion were predominantly observed in our study and only diabetes was found to be significantly associated with homogenous neointimal hyperplasia.

Impact of Complete Revascularization in the ISCHEMIA Trial.

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Impact of complete revascularization in the IschemiaTrial

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Ischemia With Nonobstructive Coronary Arteries: Insights From the ISCHEMIA Trial.

BACKGROUND: Ischemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown. OBJECTIVES: The authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA. METHODS: Core laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia. RESULTS: Among 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2]). CONCLUSIONS: Among participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity.

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy. METHODS: In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). RESULTS: Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61-1.30]; severe ischemia HR, 0.83 [95% CI, 0.57-1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86-1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98-1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06-6.98]) and MI (HR, 3.78 [95% CI, 1.63-8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar. CONCLUSIONS: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522.

Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy. METHODS: In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory­interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). RESULTS: Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61­1.30]; severe ischemia HR, 0.83 [95% CI, 0.57­1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86­1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98­1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06­6.98]) and MI (HR, 3.78 [95% CI, 1.63­8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%­12.4%]), but 4-year all-cause mortality was similar. CONCLUSIONS: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup.

To study the usefulness and comparison of myocardial strain imaging by 2D and 3D echocardiography for early detection of cardiotoxicity in patients undergoing cardiotoxic chemotherapy.

BACKGROUND: Chemotherapy-induced cardiotoxicity constitutes subclinical myocardial dysfunction, arrhythmias, pericarditis, coronary vasospasm, and significant symptomatic heart failure. Anthracyclines pose higher risk for long-term cardiac dysfunction, with increased incidences of morbidity and mortality. Hence, early detection of chemotherapy-induced cardiac dysfunction may prompt an earlier treatment modification. AIM: To evaluate global, longitudinal, radial, and circumferential strain changes in adult patients undergoing anthracycline chemotherapy along with the usefulness of three-dimensional (3D) echocardiography as the new modality over two-dimensional (2D) echocardiography. METHODS: This was a single centre, prospective, observational study that included asymptomatic patients free from any cardiac signs and symptoms attributable to heart failure, who underwent potentially cardiotoxic chemotherapy for malignancy from December 2017 to November 2018 at a tertiary care centre in India. Baseline demographics were recorded, and 2D and 3D echocardiography was performed at baseline and after completion of four cycles of chemotherapy. RESULTS: All the 55 patients received a cumulative dose of doxorubicin of less than 550 mg/m2. Follow-up period from the beginning of doxorubicin therapy was 108 ± 14 days. 9 patients were excluded from the study due to poor 3D images, so data analysis was done only for 46 patients. In 2D echocardiography, only global longitudinal strain (GLS) was observed to be significantly reduced (Δ18.33%; P < 0.001). 2D ejection fraction (EF) did not show significant change (Δ0.67%; P = 0.176), while by 3D echo, EF reduced significantly (Δ3.55%; P < 0.001). 3D global longitudinal (Δ29.19%; P < 0.001), circumferential (Δ30.65%; P < 0.001), area (Δ21.61%; P < 0.001), and radial (Δ29.66%; P < 0.001) strains were observed to be significantly reduced at follow-up. CONCLUSION: Myocardial dysfunction induced by cardiotoxic chemotherapy can be detected earlier by using 2D GLS, 3D volumetric analysis, and 3D strain analysis by calculating global, longitudinal, radial, and circumferential strain changes. 3D echocardiographic assessment seems to be more accurate in picking out small changes in left ventricular functions, but at the cost of slightly poor image quality as compared to the 2D echocardiography. These newer techniques could potentially improve the ability for early detection of subclinical abnormalities of LV function in patients undergoing cardiotoxic chemotherapy and thus early initiation of treatment could be possible.

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.

Isolated left ventricular diastolic collapse in pericardial tamponade: an uncommon echocardiographic finding.

A case of circumferential moderate pericardial effusion causing isolated collapse of left ventricular cavity on two-dimensional echocardiography is reported. Pericardial effusion, mostly of infective etiology, is relatively common in this part of the world. When large enough to cause tamponade, collapse of right atrium, right ventricle, and uncommonly left atrium can be seen. Left ventricular collapse is rare, both due to the larger muscle mass and higher chamber pressure.

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.