J. Elliott

Plasma N-Terminal Pro–Brain Natriuretic Peptide and Adrenomedullin New Neurohormonal Predictors of Left Ventricular Function and Prognosis After Myocardial Infarction

BACKGROUND Newly discovered circulating peptides, N-terminal pro-brain natriuretic peptide (N-BNP) and adrenomedullin (ADM), were examined for prediction of cardiac function and prognosis and compared with previously reported markers in 121 patients with myocardial infarction. METHODS AND RESULTS The association between radionuclide left ventricular ejection fraction (LVEF) and N-BNP at 2 to 4 days (r=-.63, P<.0001) and 3 to 5 months (r=-.58, P<.0001) after infarction was comparable to that for C-terminal BNP and far stronger than for ADM (r=-.26, P<.01), N-terminal atrial natriuretic peptide (N-ANP), C-terminal ANP, cGMP, or plasma catecholamine concentrations. For prediction of death over 24 months of follow-up, an early postinfarction N-BNP level > or = 160 pmol/L had sensitivity, specificity, positive predictive value, and negative predictive values of 91%, 72%, 39%, and 97%, respectively, and was superior to any other neurohormone measured and to LVEF. Only 1 of 21 deaths occurred in a patient with an N-BNP level below the group median (Kaplan-Meier survival analysis, P<.00001). For prediction of heart failure (left ventricular failure), plasma N-BNP > or = 145 pmol/L had sensitivity (85%) and negative predictive value (91%) comparable to the other cardiac peptides and was superior to ADM, plasma catecholamines, and LVEF. By multivariate analysis, N-BNP but not ADM provided predictive information for death and left ventricular failure independent of patient age, sex, LVEF, levels of other hormones, and previous history of heart failure, myocardial infarction, hypertension, or diabetes. CONCLUSIONS Plasma N-BNP measured 2 to 4 days after myocardial infarction independently predicted left ventricular function and 2-year survival. Stratification of patients into low- and high-risk groups can be facilitated by plasma N-BNP or BNP measurements, and one of these could reasonably be included in the routine clinical workup of patients after myocardial infarction.

B-Type Natriuretic Peptides and Ejection Fraction for Prognosis After Myocardial Infarction

Background—A recent landmark report has demonstrated that plasma B-type natriuretic peptide (BNP) measured in acute coronary syndromes independently predicts mortality, heart failure, and new myocardial infarction. After acute cardiac injury, left ventricular ejection fraction (LVEF) is also of prognostic significance and plays a major role in determining the therapeutic response. Methods and Results—The present report is the first from a substantial (n=666) cohort of patients with acute myocardial infarction to test the prognostic utility of concurrent measurements of BNP, amino-terminal BNP (N-BNP), norepinephrine, and radionuclide LVEF. The B-type peptides and LVEF were predictors of death, heart failure, and new myocardial infarction (all P <0.001) independent of patient age, gender, previous myocardial infarction, antecedent hypertension or diabetes, previous heart failure, plasma norepinephrine, creatinine, cholesterol, drug therapy, and coronary revascularization procedures. The combination of N-BNP (or BNP) with LVEF substantially improved risk stratification beyond that provided by either alone. Elevated N-BNP (or BNP) predicted new myocardial infarction only in patients with LVEF <40%. LVEF <40% coupled to N-BNP over the group median conferred substantial 3-year risks of death, heart failure, and new myocardial infarction of 37%, 18%, and 26%, respectively. N-BNP and BNP were equivalent prognostic markers for these clinical outcomes. Conclusions—Plasma N-BNP (or BNP) and LVEF are complementary independent predictors of major adverse events on follow-up after myocardial infarction. Combined measurement provides risk stratification substantially better than that provided by either alone.

Long-term prognostic importance of patency of the infarct-related coronary artery after thrombolytic therapy for acute myocardial infarction.

BACKGROUND After thrombolytic therapy, long-term patency of the infarct-related artery may reduce arrhythmias, limit ventricular dilatation, and provide collaterals to another infarct zone if further infarction occurs. However, independent long-term prognostic value of infarct artery patency has not been shown. METHODS AND RESULTS We followed 312 patients with first myocardial infarction treated < 4 hours after pain onset with thrombolysis (streptokinase [n = 188] or recombinant tissue-type plasminogen activator [n = 124]). At 28 +/- 11 days, cardiac catheterization was performed. Flow of the infarct-related artery was assessed by the TIMI scoring system, and a scoring system relating coronary stenoses and flow to the amount of myocardium supplied was also used. Follow-up was for 39 +/- 13 months. Cardiac death occurred in 5.8% of patients, and there were two noncardiac deaths. Revascularization was performed in 11.5% of patients. On univariate and multivariate analysis, ventricular function (ejection fraction, P = .006 and .02, or end-systolic volume index, P = .01 and .06) was the most important prognostic factor. Patency of the infarct-related artery measured as TIMI 3 flow was marginally significant on univariate analysis (P = .08) but not on multivariate analysis (P = .2). Patency was an independent prognostic factor in univariate and multivariate analysis when measured as an occlusion score (amount of myocardium supplied by an occluded artery, P = .01 and < .05). When the ejection fraction was > or = 50%, only occluded arteries supplying > 25% of the left ventricle affected prognosis adversely. If the ejection fraction was < 50%, occluded arteries supplying < 25% of myocardium also adversely affected prognosis. Treadmill exercise duration 4 weeks after infarction was the only other prognostic factor identified. CONCLUSIONS Ventricular function and infarct-related artery patency are independent prognostic factors after thrombolytic therapy for acute myocardial infarction.

Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction

Objective To determine the relations of plasma levels of brain natriuretic peptide (BNP), atrial natriuretic factor (ANF), N-terminal ANF (N-ANF), cyclic guanosine monophosphate (cGMP; the cardiac peptide second messenger), and plasma catecholamines to left ventricular function and to prognosis in patients admitted with acute myocardial infarction. Design Plasma hormones and ventricular function (radionuclide ventriculography) were measured 1–4 days after myocardial infarction in 220 patients admitted to a single coronary care unit. Radionuclide scanning was repeated 3–5 months after infarction. Clinical events were recorded over a mean period of 14 months. Results Both early and late left ventricular ejection fraction (LVEF) were most closely related to plasma BNP (r = −0.60, n = 220, p < 0.001; andr = −0.53, n = 192, p < 0.001, respectively), followed by ANF, N-ANF, cGMP, and the plasma catecholamines. Early plasma BNP concentrations less than twofold the upper limit of normal (20 pmol/l) had 100% negative predictive value for LVEF < 40% at 3–5 months after infarction. In multivariate analysis incorporating all the neurohormonal factors, only BNP remained independently predictive of LVEF < 40% (p < 0.005). Survival analysis by median levels of candidate predictors identified BNP as the most powerful discriminator for death (p < 0.0001). No early deaths (within 4 months) occurred in patients with plasma BNP concentrations below the group median (27 pmol/l), and over follow up only three of 26 deaths occurred in this subgroup. Of all episodes of left ventricular failure, 85% occurred in patients with plasma BNP above the median (p < 0.001). In multivariate analyses, BNP alone gave additional predictive information beyond sex, age, clinical history, LVEF, and plasma noradrenaline for both subsequent onset of LVF and death. Conclusions Plasma BNP measured within 1–4 days of acute myocardial infarction is a powerful independent predictor of left ventricular function, heart failure, or death over the subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma catecholamines.

Low-Normal or Excessive Body Mass Index: Newly Identified and Powerful Risk Factors for Death and Other Complications With Percutaneous Coronary Intervention

Recognized risk factors account for only a small portion of the variance in the 4% to 10% incidence of major ischemic events associated with percutaneous coronary intervention. Body mass index (BMI) (body weight in kg/[height in m]2) is a clinically useful estimate of body fat and has been shown to correlate with mortality from several causes. We sought to evaluate the effect of BMI as a potential risk factor for the complications of percutaneous coronary intervention in 3,571 consecutive percutaneous coronary intervention patients treated at a single referral center. Patients were prospectively divided into the nonobese (BMI < or = 25), mildly obese (BMI 26-35), and very obese (BMI > 35), based on accepted definitions. Multiple logistic regression analyses were used to determine the correlates of major complications from 25 candidate variables, including BMI < or = 25 (n = 614 patients) and BMI > 35 (n = 275 patients), recorded prospectively in a relational database. Death occurred in 2.8% of the BMI < or = 25 group, in 3.7% of the BMI > 35 group, and in 0.9% of the BMI 26-34 group (p < 0.001), but there was no difference in the incidence of other ischemic events. Blood product transfusion was required in 12% of the BMI < or = 25 group, in 7% of the BMI 25-34 group, and in 8% of the BMI > 35% group (p = 0.003). Multivariate analysis, after adjustment for other significant correlates, demonstrated that both BMI < or = 25 (odds ratio [OR] = 2.7, p = 0.005) and BMI > 35 (OR = 7.4, p < 0.001) were independent correlates of death. Low-normal or high BMI is a newly described and powerful risk factor for in-hospital death after percutaneous coronary intervention.

Management and 6-month outcomes in elderly and very elderly patients with high-risk non-ST-elevation acute coronary syndromes: The Global Registry of Acute Coronary Events

AIMS To test the hypothesis that increasing age in patients presenting with high-risk non-ST-segment elevation acute coronary syndromes (NSTE-ACS) does not adversely influence the benefit of an early invasive strategy on major adverse events at 6 months. METHODS AND RESULTS We report clinical outcomes in young (<70), elderly (70-80), and very elderly (>80 years) patients with high-risk NSTE-ACS enrolled in GRACE between 1999 and 2006. Six month data were available in 18 466 patients (27% elderly, 16% very elderly). Elderly and very elderly patients were less likely to receive evidence-based treatments at discharge and had a longer hospital stay (6 vs. 5 days). Angiography was performed more frequently in younger patients (67 vs. 33% in very elderly, 55% in elderly; P < 0.0001). Multiple logistic regression analysis confirmed the benefit of revascularization on the primary study endpoint (6-month stroke, death, myocardial infarction) in young [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.56-0.86], elderly (0.60, 0.47-0.76), and very elderly (0.72, 0.54-0.95) patients. Revascularization was associated with reductions in 6-month mortality (OR 0.52, 95% CI 0.37-0.72 in young; 0.38, 0.26-0.54 in elderly; 0.68, 0.49-0.95 in very elderly). Stroke risk in hospital or at 6 months was not increased by revascularization. CONCLUSION Following presentation with high-risk NSTE-ACS, an evidence-based approach to management was noted less frequently with advancing patient age. Angiography, in particular, was less likely to be undertaken. Revascularization, however, when performed, was associated with significant benefits at 6 months, independent of age, and did not increase risk of stroke.

One-Year Follow-up in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT I)

BACKGROUND Directional atherectomy is a frequently used percutaneous revascularization strategy, but its long-term outcomes have not previously been compared with those of balloon angioplasty in a prospective trial. METHODS AND RESULTS The 1012 patients enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT I) were followed for at least 1 year after randomization. Analyses of predetermined end points were performed, including a detailed analysis of the 14 patients who died. At 1 year, 11 patients had died in the atherectomy group compared with 3 in the angioplasty group (2.2% versus 0.6%, P = .035), with an excess of out-of-hospital deaths (2.2% versus 0.2%, P = .01) and late cardiac deaths (1.6% versus 0%, P = .01). Univariate predictors of death included age, abrupt closure, periprocedural enzyme elevation, and peripheral vascular complications. There was no evidence that the excess of deaths after atherectomy was linked to perforation, ectasia, or deep resection. Cumulative rates of myocardial infarction were higher in those who had been randomized to atherectomy than in those randomized to angioplasty (8.9% versus 4.4%, P = .005) with a trend toward excess Q-wave and non-Q-wave infarctions. By multivariate analysis, atherectomy was the only variable predictive of the combined end point of death or myocardial infarction. No clinical or angiographic characteristics added to this index. Rates of repeat percutaneous intervention at the target site (24.4% after atherectomy versus 25.9% after angioplasty), coronary artery bypass surgery (9.3% versus 9.1%), hospitalization (50% versus 47.1%), and stroke (1% in both groups) were not significantly different. CONCLUSIONS Long-term follow-up of the 1012 patients randomized to atherectomy or angioplasty has revealed a statistically significant excess of deaths after directional atherectomy that was not evident at 6 months. This difference could be due to the chance occurrence of a low mortality rate in those randomized to angioplasty. The excess of myocardial infarctions after atherectomy remains statistically significant at 1 year. Further investigation is warranted to improve the safety of atherectomy.

Antecedent hypertension and heart failure after myocardial infarction

OBJECTIVES We sought to assess the relationship of antecedent hypertension to neurohormones, ventricular remodeling and clinical heart failure (HF) after myocardial infarction (MI). BACKGROUND Heart failure is a probable contributor to the increased mortality observed after MI in those with antecedent hypertension. Hence, neurohormonal activation, adverse ventricular remodeling and a higher incidence of clinical HF may be expected in this group. However, no previous report has documented serial postinfarction neurohumoral status, serial left ventricular imaging and clinical outcomes over prolonged follow-up in a broad spectrum of patients with and without antecedent hypertension. METHODS Inpatient events were documented in 1,093 consecutive patients (436 hypertensive and 657 normotensive) with acute MI. In 68% (282 hypertensive, 465 normotensive) serial neurohormonal sampling and radionuclide ventriculography were performed one to four days and three to five months after infarction. Clinical outcomes were recorded over a mean follow-up of two years. RESULTS Plasma neurohormones were significantly higher in hypertensives than in normotensives one to four days and three to five months after infarction. From similar initial values, left ventricular volumes increased significantly in hypertensives, compared with normotensives. Left ventricular ejection fraction rose significantly in normotensive but not hypertensive patients. Together with higher inpatient (8.1% vs. 4.4%, p < 0.002) and post-discharge mortality (9.5% vs. 5.5%, p = 0.043), hypertensive patients incurred more inpatient HF (33% vs. 24%, p < 0.001) and more late HF requiring readmission to hospital (12.4% vs. 5.5%, p < 0.001). Antecedent hypertension predicted late HF in patients >64 years of age with neurohormonal activation and early left ventricular dilation. CONCLUSIONS Antecedent hypertension interacts with age, neurohumoral activation and early ventricular remodeling to confer greater risk of HF after MI.

Comparison of high sensitivity and contemporary troponin assays for the early detection of acute myocardial infarction in the emergency department

Background Current guidelines define acute myocardial infarction (AMI) by the rise and/or fall of cardiac troponin with ≥1 value above the 99th percentile. Past troponin assays have been unreliable at the lower end of the range. Highly sensitive assays have therefore been developed to increase the clinical sensitivity for detection of myocardial injury. Methods Three hundred and thirty-two patients with chest pain suggestive of AMI were prospectively recruited between November 2006 and April 2007. Serial blood samples were analysed to compare Roche Elecsys high sensitivity troponin T (hsTnT), Abbott Architect troponin I 3rd generation (TnI 3) and Roche Elecsys troponin T (TnT) for the diagnosis of AMI. Results One hundred and ten (33.1%) patients were diagnosed with AMI. Test performance for the diagnosis of AMI, as quantified by receiver operating characteristic area under the curve (95% confidence intervals) for baseline/follow-up troponins were as follows: hsTnT 0.90 (0.87–0.94)/0.94 (0.91–0.97), TnI 3 0.88 (0.84–0.92)/0.93 (0.90–0.96) and TnT 0.80 (0.74–0.85)/0.89 (0.85–0.94). hsTnT was superior to TnT (P < 0.001/0.013 at baseline/follow-up) but equivalent to TnI 3. For patients with a final diagnosis of AMI, baseline troponins were raised in more patients for hsTnT (83.6%) than TnI 3 (74.5%) and TnT (62.7%). A delta troponin of ≥20% increased the specificity of hsTnT from 80.6% to 93.7% but reduced sensitivity from 90.9% to 71.8%. Conclusion hsTnT was superior to TnT but equivalent to TnI 3 for the diagnosis of AMI. Serial troponin measurement increased test performance. hsTnT was the most likely to be raised at baseline in those with AMI. A delta troponin increases specificity but reduces sensitivity.

A randomized study of direct coronary stent delivery compared with stenting after predilatation: The NIR future trial

This randomized trial compared a strategy of direct stenting without predilatation (n = 39) with conventional stenting with predilatation (n = 42) in patients with suitable lesions in native vessels ≥ 2.5‐mm diameter to be covered by either a 9‐ or 16‐mm‐length NIR Primo stent. Equipment cost [mean (median) ± SD] was less in those with direct stenting [