Shanmugam Uthamalingam

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.

Utility of the Neutrophil to Lymphocyte Ratio in Predicting Long-Term Outcomes in Acute Decompensated Heart Failure

Neutrophil-to-lymphocyte ratio (NLR) has been associated with poor outcomes in patients with acute coronary syndromes. However, its role for risk stratification in acute decompensated heart failure (ADHF) has not been well described. In this study, 1,212 consecutive patients admitted with ADHF who had total white blood cell and differential counts measured at admission were analyzed. The patients were divided into tertiles according to NLR. The association between NLR and white blood cell types with all-cause mortality was assessed using Cox regression analysis. During a median follow-up period of 26 months, a total of 284 patients (23.4%) had died, and a positive trend between death and NLR was observed; 32.8%, 23.2%, and 14.2% of deaths occurred in the higher, middle, and lower tertiles, respectively (p <0.001). After adjusting for confounding factors, multivariate analysis demonstrated that patients in the higher NLR tertile had the highest mortality (adjusted hazard ratio 2.23, 95% confidence interval (CI) 1.63 to 3.02, p <0.001), followed by those in the middle tertile (adjusted hazard ratio 1.62, 95% CI 1.16 to 2.23, p = 0.001). Furthermore, tertiles of NLR were superior in predicting long-term mortality compared with white blood cell, neutrophil, and relative lymphocyte counts. Patients in the higher NLR tertile (adjusted odds ratio 3.46, 95% CI 2.11 to 5.68, p <0.001) had a significantly higher 30-day readmission rate. In conclusion, higher NLR, an emerging marker of inflammation, is associated with an increased risk for long-term mortality in patients admitted with ADHF. NLR is a readily available inexpensive marker to aid in the risk stratification of patients with ADHF.

Usefulness of Acute Delirium as a Predictor of Adverse Outcomes in Patients >65 Years of Age With Acute Decompensated Heart Failure

Delirium is an acute confusional state that is very prevalent in older patients hospitalized with acute decompensated heart failure (ADHF). The association between delirium and ADHF outcome has not been well described. We analyzed 883 consecutive patients >65 years of age admitted with ADHF. Acute delirium was diagnosed based on the Confusion Assessment Method. Delirious patients (total n = 151) had an increased in-hospital all-cause death compared to nondelirious patients (n = 17, 11%, vs n = 45, 6%; adjusted odds ratio [OR] 1.93, 95% confidence interval [CI] 1.07 to 3.48, p = 0.02). Of those surviving to discharge (n = 821), on multivariable logistic regression analysis, delirium was independently associated with increased risk of 30-day (adjusted OR 4.24, 95% CI 2.77 to 6.47, p <0.001) and 90-day (adjusted OR 3.72, 95% CI 2.51 to 5.54, p <0.001) rehospitalizations for ADHF and higher nursing home placement (adjusted OR 2.70, 95% CI 1.59 to 5.30, p <0.001) after adjusting for age, gender, cardiac risk factors, dementia, activities of daily living, instrumental activities of daily living, coronary artery disease, atrial fibrillation, left ventricular ejection fraction, angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, β blockers, Charlson co-morbidity index, and other potential confounders. Furthermore, delirium was strongly associated with 90-day all-cause mortality in patients discharged from the hospital (adjusted hazard ratio 2.10, CI 1.53 to 2.88, p <0.0001). In conclusion, acute delirium serves as an important prognostic determinant of in-hospital and posthospital discharge outcomes including increased ADHF readmission risk in older hospitalized patients with ADHF. Thus, delirium plays an important role in the risk stratification and prognosis of patients with ADHF.

Exercise-induced ST-segment elevation in ECG lead aVR is a useful indicator of significant left main or ostial LAD coronary artery stenosis.

OBJECTIVES The authors tested the hypothesis that exercise treadmill testing (ETT)-induced ST-segment elevation (STE) in electrocardiographic lead aVR is an important indicator of significant left main coronary artery (LMCA) or ostial left anterior descending coronary artery (LAD) stenosis. BACKGROUND Although STE in lead aVR is an indicator of LMCA or very proximal LAD occlusion in acute coronary syndromes, its predictive power in the setting of ETT is uncertain. METHODS Rest and stress electrocardiograms, clinical and stress test parameters, and single photon-emission computed tomographic myocardial perfusion imaging (MPI) data, when available, were obtained in 454 subjects (378 with MPI) who underwent cardiac catheterization and standard Bruce ETT ≤ 6 months before catheterization. Patients were selected for LMCA or ostial LAD disease (≥ 50% stenosis) with or without other coronary artery disease (CAD), CAD (≥ 70% stenosis) without significant LMCA or ostial LAD, or no significant CAD. Univariate followed by multivariate logistic regression analyses of clinical, electrocardiographic, stress test, and single photon-emission computed tomographic MPI variables were used to identify significant correlates of LMCA or ostial LAD stenosis. Bayesian analysis of the data also was performed. RESULTS LMCA (n = 38) or ostial LAD (n = 42) stenosis occurred in 75 patients (5 patients had both). The remainder had CAD without LMCA or ostial LAD stenosis (n = 276) or no CAD (n = 103). In multivariate analysis, the strongest predictor was stress-induced STE in lead aVR (p < 0.0001, area under the curve 0.82). Both left ventricular ejection fraction (after stress) and percent reversible LAD ischemia on single photon-emission computed tomographic MPI also contributed significantly in multivariate analysis (p < 0.005 and p < 0.05, respectively, areas under the curve 0.60 and 0.64, respectively). Although additional electrocardiographic, stress test, and MPI variables were significant univariate predictors, none was statistically significant in multivariate analysis. At 1-mm STE in lead aVR, sensitivity for LMCA or ostial LAD stenosis was 75%, specificity was 81%, overall predictive accuracy was 80%, and post-test probability increased nearly 3 times from 17% to 45%. CONCLUSIONS Stress (ETT)-induced STE in lead aVR is an important indicator of significant LMCA or ostial LAD stenosis and should not be ignored.

Single Resting hsTnT Level Predicts Abnormal Myocardial Stress Test in Acute Chest Pain Patients With Normal Initial Standard Troponin

OBJECTIVES The goal of this study was to determine the ability of a single, resting high-sensitivity troponin T (hsTnT) measurement to predict abnormal myocardial perfusion imaging (MPI) in patients presenting with acute chest pain to the emergency department (ED). BACKGROUND HsTnT assays precisely detect very low levels of troponin T, which may be a surrogate for the presence and extent of myocardial ischemia. METHODS We included all patients from the ROMICAT I (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial, an observational cohort study, who underwent both single-photon emission computed tomography (SPECT)-MPI stress testing and 64-slice computed tomography angiography (CTA) and in whom hsTnT measurements were available. We assessed the discriminatory value of hsTnT for abnormal SPECT-MPI and the association of reversible myocardial ischemia by SPECT-MPI and the extent of coronary atherosclerosis by CTA to hsTnT levels. RESULTS Of the 138 patients (mean age 54 ± 11 years, 46% male), 19 (13.7%) had abnormal SPECT-MPI. Median hsTnT levels were significantly different between patients with normal and abnormal SPECT-MPI (9.41 pg/ml [interquartile range (IQR): 5.73 to 19.20 pg/ml] vs. 4.89 pg/ml [IQR: 2.34 to 7.68 pg/ml], p = 0.001). Sensitivity of 80% and 90% to detect abnormal SPECT-MPI was reached at hsTnT levels as low as 5.73 and 4.26 pg/ml, respectively. Corresponding specificity was 62% and 46%, and negative predictive value was 96% and 96%, respectively. HsTnT levels had good discriminatory ability for prediction of abnormal SPECT-MPI (area under the curve: 0.739, 95% confidence interval: 0.609 to 0.868). Both reversible myocardial ischemia and the extent of coronary atherosclerosis (combined model r(2) = 0.19 with partial of r(2) = 0.12 and r(2) = 0.05, respectively) independently and incrementally predicted the measured hsTnT levels. CONCLUSIONS In patients with acute chest pain, myocardial perfusion abnormalities and coronary artery disease are predicted by resting hsTnT levels. Prospective evaluations are warranted to confirm whether resting hsTnT could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and improve the effectiveness of patient management.

Defining left ventricular noncompaction using cardiac computed tomography.

Purpose: Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by a distinctive 2-layered appearance of the myocardium because of increased trabeculation and deep intertrabecular recesses. Echocardiography serves as the initial noninvasive diagnostic test. Currently, magnetic resonance imaging (MRI) is increasingly being used to diagnose LVNC because of its improved temporal and spatial resolution. So far, no criteria have been proposed to define pathologic LVNC with the use of computed tomography (CT). Materials and Methods: We analyzed CT images using an American Heart Association 17-segment model in 8 patients previously diagnosed with LVNC by clinical diagnosis, echocardiography, and/or MRI, as well as in 11 patients with nonischemic dilated cardiomyopathy, 11 patients with hypertrophic cardiomyopathy, 10 patients with severe aortic stenosis, 9 patients with severe aortic regurgitation, 10 patients with left ventricular hypertrophy due to essential hypertension, and, additionally, in a control group of 20 patients who had normal CT scans without a history of cardiovascular disease. The distribution of LVNC was assessed by qualitative analysis of 17 myocardial segments for the presence or absence of any degree of noncompaction. Each segment was analyzed in each of the 3 end-diastolic long-axis views for the presence or absence of noncompaction, and the most prominent trabeculation was chosen for measurement. The left ventricular apex was excluded. Thickness of noncompacted and compacted myocardium was measured perpendicular to the compacted myocardium. The ratio of noncompacted to compacted (NC:C) myocardium was calculated for each segment. Receiver operating characteristics were used to generate cutoff values with sensitivity and specificity to distinguish the LVNC group from other groups. Results: An end-diastolic NC:C ratio >2.3 distinguished pathologic LVNC with 88% sensitivity and 97% specificity; positive and negative predictive values were 78% and 99%, respectively. Conclusions: CT using the standard MRI NC:C ratio cutoff >2.3 accurately characterizes pathologic LVNC.

Early Resting Myocardial Computed Tomography Perfusion for the Detection of Acute Coronary Syndrome in Patients With Coronary Artery Disease

Background—Acute rest single-photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) has high predictive value for acute coronary syndrome (ACS) in emergency department patients. Prior studies have shown excellent agreement between rest/stress computed tomography perfusion (CTP) and SPECT-MPI, but the value of resting CTP (rCTP) in acute chest pain triage remains unclear. We sought to determine the diagnostic accuracy of early rCTP, incremental value beyond obstructive coronary artery disease (CAD; ≥50% stenosis), and compared early rCTP to late stress SPECT-MPI in patients with CAD presenting with suspicion of ACS to the emergency department. Methods and Results—In this prespecified subanalysis of 183 patients (58.1±10.2 years; 33% women), we included patients with any CAD by coronary computed tomography angiography (CCTA) from Rule Out Myocardial Infarction Using Computer-Assisted Tomography I. rCTP was assessed semiquantitatively, blinded to CAD interpretation. Overall, 31 had ACS and 48 had abnormal rCTP. Sensitivity and specificity of rCTP for ACS were 48% (95% confidence interval [CI], 30%–67%) and 78% (95% CI, 71%–85%), respectively. rCTP predicted ACS (adjusted odds ratio, 3.40 [95% CI, 1.37–8.42]; P=0.008) independently of obstructive CAD, and sensitivity for ACS increased from 77% (95% CI, 59%–90%) for obstructive CAD to 90% (95% CI, 74%–98%) with addition of rCTP (P=0.05). In a subgroup undergoing late rest/stress SPECT-MPI (n=81), CCTA/rCTP had noninferior discriminatory value to CCTA/SPECT-MPI (area under the curve, 0.88 versus 0.90; P=0.64) using a noninferiority margin of 10%. Conclusions—Early rCTP provides incremental value beyond obstructive CAD to detect ACS. CCTA/rCTP is noninferior to CCTA/SPECT-MPI to discriminate ACS and presents an attractive alternative to triage patients presenting with acute chest pain. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00990262.

Long term outcomes in octogenarians undergoing percutaneous coronary intervention: Comparison of bare metal versus drug eluting stent

BACKGROUND Octogenarians have been under-represented in percutaneous coronary intervention (PCI) trials, thus making difficult to choose the best type of stent in this patient population. We compared the outcomes of drug eluting (DES) and bare metal stent (BMS) at one year after implantation in this special population. METHODS A total of 320 consecutive patients over 80 years undergoing PCI with BMS (n=218) or DES (n=102) were retrospectively studied. One year major adverse cardiac events (MACEs) defined as cardiac death, non-fatal myocardial infarction and target vessel revascularization (TVR) were compared between the two groups. Cox regression analysis was used for data analysis. RESULTS The one year incidence of MACE was higher in the BMS group (18.8% vs 9.8%, adjusted hazard ratio [HR] 2.33; 95% confidence interval [C.I.]: 1.12 to 4.86 p=0.02). Diabetes mellitus was an independent predictor for increased MACE (adjusted HR: 1.99; C.I. 1.06 to 3.77, p=0.03). One year incidence of TVR was higher in the BMS group (10.0% vs 3.9% adjusted HR: 2.94; C.I. 1.01 to 8.59 p=0.045). There was no difference in cardiac death between the two groups. CONCLUSION During one year follow-up, octogenarians treated with BMS had an increased risk of MACE compared with those treated with DES. DES should be preferred in indications recognized from current PCI guidelines.

Clinical experiences of delayed contrast enhancement with cardiac computed tomography: case series

BackgroundMyocardial delayed enhancement (MDE) by gadolinium-enhanced cardiac MRI is well established for myocardial scar assessment in ischemic and non-ischemic heart disease. The role of MDE by cardiac CT (CT-MDE) is not yet defined.FindingsWe reviewed all clinical cases of CT-MDE at a tertiary referral center to present the cases as a case series. All clinical cardiac CT exams which utilized CT-MDE imaging between January 1, 2005 and October 1, 2010 were collected as a series and their findings were also compared with available myocardial imaging to assess for myocardial abnormalities, including echocardiography (wall motion, morphology), cardiac MRI (delayed enhancement, morphology), SPECT MPI (perfusion defects). 5,860 clinical cardiac CT exams were performed during the study period. CT-MDE was obtained in 18 patients and was reported to be present in 9 patients. The indications for CT-MDE included ischemic and non-ischemic heart diseases. In segments positive for CT-MDE, there was excellent agreement of CT with other modalities: echocardiography (n=8) demonstrated abnormal morphology and wall motion (k=1.0 and k=0.82 respectively); prior MRI (n=2) demonstrated abnormal delayed enhancement (MR-MDE) (k=1.0); SPECT MPI (n=1) demonstrated fixed perfusion defects (k=1.0). In the subset of patients without CT-MDE, no abnormal segments were identified by echocardiography (n=8), MRI (n=1) and nuclear MPI (n=0).ConclusionsCT-MDE was performed in rare clinical situations. The indications included both ischemic and non-ischemic heart disease and there was an excellent agreement between CT-MDE and abnormal myocardium by echocardiography, cardiac MRI, and nuclear MPI.