Asim A. Mohammed

Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction.

OBJECTIVES The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management. BACKGROUND It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. METHODS In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. RESULTS Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP-guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects. Compared with SOC, NT-proBNP-guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. CONCLUSIONS In patients with HF due to LV systolic dysfunction, NT-proBNP-guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390).

Red blood cell distribution width and 1-year mortality in acute heart failure.

Red blood cell distribution width (RDW) predicts mortality in chronic heart failure (HF) and stable coronary artery disease. The prognostic value of RDW in more acute settings such as acute HF, and its relative prognostic value compared with more established measures such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), remains unknown.

High-Sensitivity Troponin T Concentrations in Acute Chest Pain Patients Evaluated With Cardiac Computed Tomography

Background— For evaluation of patients with chest pain and suspected acute coronary syndrome (ACS), consensus guidelines recommend use of a cardiac troponin cut point that corresponds to the 99th percentile of a healthy population. Most conventional troponin methods lack sufficient precision at this low level. Methods and Results— In a cross-sectional study, 377 patients (mean age 53.7 years, 64.2% male) with chest pain and low to intermediate likelihood for ACS were enrolled in the emergency department. Blood was tested with a precommercial high-sensitivity troponin T assay (hsTnT) and compared with a conventional cardiac troponin T method. Patients underwent a 64-slice coronary computed tomography coronary angiogram at the time of phlebotomy, on average 4 hours from initial presentation. Among patients with acute chest pain, 37 (9.8%) had an ACS. Using the 99th percentile cut point for a healthy population (13 pg/mL), hsTnT had 62% sensitivity, 89% specificity, 38% positive predictive value, and 96% negative predictive value for ACS. Compared with the cardiac troponin T method, hsTnT detected 27% more ACS cases (P=.001), and an hsTnT above the 99th percentile strongly predicted ACS (odds ratio 9.0, 95% confidence interval 3.9 to 20.9, P<0.001). Independent of ACS diagnosis, computed tomography angiography demonstrated that concentrations of hsTnT were determined by numerous factors, including the presence and severity of coronary artery disease, left ventricular mass, left ventricular ejection fraction, and regional left ventricular dysfunction. Conclusions— Among low- to intermediate-risk patients with chest pain, hsTnT provides good sensitivity and specificity for ACS. Elevation of hsTnT identifies patients with myocardial injury and significant structural heart disease, irrespective of the diagnosis of ACS.

Prospective, Comprehensive Assessment of Cardiac Troponin T Testing After Coronary Artery Bypass Graft Surgery

Background— The significance and clinical role of cardiac troponin testing after coronary artery bypass grafting remain unclear. Methods and Results— Cardiac troponin T (cTnT) was measured during the first 24 hours after coronary artery bypass graft surgery in 847 consecutive patients. Only 17 patients (2.0%) had new Q waves or left bundle-branch block after surgery; however, cTnT elevation was observed in nearly all subjects, with a median cTnT concentration of 1.08 ng/mL overall. Direct predictors of postoperative cTnT values included preoperative myocardial infarction (P<0.001), preoperative intraaortic balloon pump (P<0.001), intraoperative/postoperative intraaortic balloon pump (P<0.001), number of distal anastomoses (P=0.005), bypass time (P<0.001), and number of intraoperative defibrillations (P=0.009), whereas glomerular filtration rate (P<0.001), off-pump coronary artery bypass grafting (P=0.003), and use of warm cardioplegia (P=0.02) were inversely associated with cTnT values. A linear association was seen between cTnT levels and length of stay and ventilator hours, and in an analysis adjusted for the Society for Thoracic Surgery Risk Model, cTnT remained independently prognostic for death (odds ratio, 3.20; P=0.003), death or heart failure (odds ratio, 2.04; P=0.008), death or need for vasopressors (odds ratio, 2.70; P<0.001), and the composite of all 3 (odds ratio, 2.57; P<0.001). In contrast to consensus-endorsed cTnT cut points for postoperative evaluation, a cTnT <1.60 ng/mL had a negative predictive value of 93% to 99% for excluding various post–coronary artery bypass graft surgery complications. Conclusions— cTnT concentrations after coronary artery bypass graft surgery are nearly universally elevated, are determined by numerous factors, and are independently prognostic for impending postoperative complications when used at appropriate cut points.

Heart failure outcomes and benefits of NT-proBNP-guided management in the elderly: results from the prospective, randomized ProBNP outpatient tailored chronic heart failure therapy (PROTECT) study.

BACKGROUND Elderly patients with heart failure (HF) have a worse prognosis than younger patients. We wished to study whether elders benefit from natriuretic peptide-guided HF care in this single-center study. METHODS AND RESULTS A total of 151 patients with HF resulting from left ventricular systolic dysfunction (LVSD) were treated with HF treatment by standard-of-care (SOC) management or guided by N-terminal pro-B type natriuretic peptide (NT-proBNP) values (with a goal to lower NT-proBNP ≤1000 pg/mL) over 10 months. The primary end point for this post-hoc analysis was total cardiovascular events in 2 age categories (<75 and ≥75 years). In those ≥75 years of age (n = 38), NT-proBNP values increased in the SOC arm (2570 to 3523 pg/mL, P = .01), but decreased in the NT-proBNP-guided arm (2664 to 1418 pg/mL, P = .001). Elderly patients treated with SOC management had the highest rate of cardiovascular events, whereas the elderly with NT-proBNP management had the lowest rate of cardiovascular events (1.76 events per patient versus 0.71 events per patient, P = .03); the adjusted logistic odds for cardiovascular events related to NT-proBNP-guided care for elders was 0.24 (P = .008), whereas in those <75 years (n = 113), the adjusted logistic odds for events following NT-proBNP-guided care was 0.61 (P = .10). CONCLUSIONS Natriuretic peptide-guided HF care was well tolerated and resulted in substantial improvement in cardiovascular event rates in elders (ClinicalTrials.Gov #00351390).

Hyponatremia, natriuretic peptides, and outcomes in acutely decompensated heart failure: results from the International Collaborative of NT-proBNP Study

Background— Hyponatremia is a well-known predictor of mortality in patients with acutely decompensated heart failure. Associations between hyponatremia and other prognostic variables in acutely decompensated heart failure, such as amino-terminal pro-B type natriuretic peptide remain unclear. Methods and Results— Six hundred twenty-eight patients presenting to the emergency department with acutely decompensated heart failure were studied. All were hospitalized. Serum sodium (Na) concentration at presentation was examined as a function of mortality at 1 year, alone and relative to other predictors of death. Hyponatremia (Na ≤135 mmol/L) was diagnosed in 24%(n=149) patients. Compared with those without hyponatremia, those affected were less likely to be male or to have hypertension or coronary artery disease but were more likely to have severe symptoms, to be anemic, and to have higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations (all P ≤0.05). When examined as a function of Na deciles (ranging from Na <132 mmol/L to Na ≤142 mmol/L), a U-shaped association was found between Na level and 1-year mortality. In multivariate Cox proportional hazards analysis, hyponatremia was an independent predictor of 1-year mortality (hazards ratio=1.72; 95% CI=1.22 to 2.37; P =0.001) as was an NT-proBNP concentration above the median value of 4690 pg/mL (hazards ratio=1.49; 95% CI=1.10 to 2.00; P =0.009). Those with hyponatremia and more elevated NT-proBNP were more likely to develop worsening renal function during their hospitalization and had highest rates of 1-year death. Notably, however, hyponatremia predicted only 1-year mortality in those with an elevated NT-proBNP. Conclusion— Hyponatremia is associated with adverse outcome in patients with acutely decompensated heart failure; however, the prognostic value of low Na is mainly evident in those with more pronounced elevation of NT-proBNP concentrations.Background—Hyponatremia is a well-known predictor of mortality in patients with acutely decompensated heart failure. Associations between hyponatremia and other prognostic variables in acutely decompensated heart failure, such as amino-terminal pro-B type natriuretic peptide remain unclear. Methods and Results—Six hundred twenty-eight patients presenting to the emergency department with acutely decompensated heart failure were studied. All were hospitalized. Serum sodium (Na) concentration at presentation was examined as a function of mortality at 1 year, alone and relative to other predictors of death. Hyponatremia (Na ≤135 mmol/L) was diagnosed in 24% (n=149) patients. Compared with those without hyponatremia, those affected were less likely to be male or to have hypertension or coronary artery disease but were more likely to have severe symptoms, to be anemic, and to have higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations (all P≤0.05). When examined as a function of Na deciles (ranging from Na <132 mmol/L to Na ≤142 mmol/L), a U-shaped association was found between Na level and 1-year mortality. In multivariate Cox proportional hazards analysis, hyponatremia was an independent predictor of 1-year mortality (hazards ratio=1.72; 95% CI=1.22 to 2.37; P=0.001) as was an NT-proBNP concentration above the median value of 4690 pg/mL (hazards ratio=1.49; 95% CI=1.10 to 2.00; P=0.009). Those with hyponatremia and more elevated NT-proBNP were more likely to develop worsening renal function during their hospitalization and had highest rates of 1-year death. Notably, however, hyponatremia predicted only 1-year mortality in those with an elevated NT-proBNP. Conclusion—Hyponatremia is associated with adverse outcome in patients with acutely decompensated heart failure; however, the prognostic value of low Na is mainly evident in those with more pronounced elevation of NT-proBNP concentrations.

Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study

We sought to determine if heart failure (HF) care with a goal to lower N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) concentrations, compared with standard of care (SOC) management, is associated with improvement in echocardiographic parameters of cardiac structure and function.

Clinical applications of highly sensitive troponin assays.

Cardiac troponin is the biomarker of choice for the diagnosis of acute myocardial infarction. Recent consensus recommendations have adopted a concentration of troponin above the 99th percentile of a healthy population to diagnose myocardial infarction. Until recently, there was no assay capable of achieving recommended precision; however, with the development of “highly sensitive” troponin assays, it is now possible to accurately measure troponin concentrations at and below the current 99th percentile of a healthy population. These assays have enormous potential in not only identifying more patients with acute myocardial infarction, and providing superior risk prediction in those so afflicted, in addition highly sensitive troponins assays may be useful for long-term risk assessment of the patient with coronary disease. In this article, we will review the clinical applications, novel concepts, challenges, and limitations of using highly sensitive troponins assays.

Quality of life and chronic heart failure therapy guided by natriuretic peptides: Results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study

BACKGROUND Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown. METHODS One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome. RESULTS Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001). CONCLUSIONS We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.govNCT00351390).

Evaluation of First-Draw Whole Blood, Point-of-Care Cardiac Markers in the Context of the Universal Definition of Myocardial Infarction: A Comparison of a Multimarker Panel to Troponin Alone and to Testing in the Central Laboratory

CONTEXT Previous studies evaluating point-of-care testing (POCT) for cardiac biomarkers did not use current recommendations for troponin cutoff values or recognize the recent universal definition of acute myocardial infarction. Traditionally, achieving optimal sensitivity for the detection of myocardial injury on initial presentation required combining cardiac troponin and/or creatine kinase isoenzyme MB with an early marker, usually myoglobin. In recent years, the performance of central laboratory combining cardiac troponin assays has improved significantly, potentially obviating the need for a multimarker panel to achieve optimum sensitivity. OBJECTIVE To compare 2 commonly used POCT strategies to a fourth generation, central laboratory cardiac troponin T assay on first-draw specimens from patients being evaluated for acute myocardial infarction in the emergency department. The 2 strategies included a traditional POCT multimarker panel and a newer POCT method using cardiac troponin I alone. DESIGN Blood specimens from 204 patients presenting to the emergency department with signs and/or symptoms of myocardial ischemia were measured on the 2 POCT systems and by a central laboratory method. The diagnosis for each patient was determined by retrospective chart review. RESULTS The cardiac troponin T assasy alone was more sensitive for acute myocardial infarction than the multimarker POCT panel with equal or better specificity. When compared with a POCT troponin I, the cardiac troponin T was also more sensitive, but this difference was not significant. The POCT troponin I alone also had the same sensitivity as the multimarker panel. CONCLUSIONS Testing for combining cardiac troponin alone using newer, commercially available, central laboratory or POCT assays performed with equal or greater sensitivity to acute myocardial infarction as the older, traditional, multimarker panel. In the near future, high-sensitivity, central laboratory troponins will be available for routine clinical use. As a result, the quality gap between central laboratories and older POCT methods will continue to widen, unless the performance of the POCT methods is improved.