Prognostic Value of NT-Pro Brain Natriuretic Peptide During Exercise Recovery in Ischemic Heart Failure of Reduced, Midrange, and Preserved Ejection Fraction.

BACKGROUND: Ischemic heart disease is a leading cause of heart failure (HF), which continues to carry a high mortality despite considerable improvements in diagnosis and treatment. N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) measured at rest is a recognized diagnostic and prognostic marker of HF of reduced ejection fraction (HFrEF); however, its value in patients with HF of midranged/preserved ejection fraction (HFmrEF/HFpEF) is not well established. We examined the prognostic value of NT-pro-BNP during recovery from exercise in patients with ischemic HF (IHF) of any ejection fraction. METHODS: Patients (n = 213) with HF (123 HFrEF, 90 HFmrEF/HFpEF) underwent cardiopulmonary exercise testing. Doppler echocardiography was used to estimate resting pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE). NT-pro-BNP was determined at rest, peak exercise, and after 1 min of exercise recovery. RESULTS: Patients with HFrEF had higher plasma levels of NT-pro-BNP at rest, peak exercise, and recovery than those with HFmrEF/HFpEF (984 ± 865 vs 780 ± 805; 1012 ± 956 vs 845 ± 895; 990 ± 1013 vs 808 ± 884 pg/mL; P < .01, respectively), whereas ΔNT-pro-BNP peak/rest and ΔNT-pro-BNP recovery/peak were similar (60 ± 100 vs 50 ± 96; -25 ± 38 vs -20 ± 41 pg/mL, P > .05). During the tracking period (22.4 ± 20.3 mo), 34 patients died, 2 underwent cardiac transplantation, and 3 had left ventricular assist device implantation. In a multivariate regression model, only NT-pro-BNP during exercise recovery and TAPSE/PASP were retained in the regression for the prediction of adverse events (χ2 = 11.4, P <.001). CONCLUSIONS: NT-pro-BNP value during exercise recovery may be a robust predictor of adverse events in patients with IHF across a wide range of ejection fraction.

N-Terminal-pro-Brain natriuretic peptide dynamics during effort phenotypes ischemic heart failure and determines prognosis regardless of ejection fraction.

Ischemic heart disease leading to heart failure (HF) portends a high overall morbidity and mortality. A higher N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) at rest reflects HF severity and impaired cardiac output, most often secondary to reduced ejection fraction (EF). As an insufficient increase in cardiac output during exertion is common in all HF phenotypes, we examined the value of NT-pro-BNP during exercise testing as a risk stratification index for ischemic HF secondary to either reduced (HFrEF) or mid-ranged/preserved EF (HFmrEF/HFpEF). 213 patients (123 HFrEF; 90 HFmrEF/HFpEF) underwent cardiopulmonary exercise testing (CPET). NT-pro-BNP was determined at rest and peak exercise. The distribution of HFrEF and HFmrEF/HFpEF etiology in subjects with and without oxygen consumption trajectory flattening during CPET was similar (p > 0.05). Patients with HFrEF had higher plasma levels of NT-pro-BNP at rest and peak exercise than those with HFmrEF/HFpEF (984 vs. 780; 1012 vs. 845 pg/mL, p < 0.01, respectively), whereas ΔNT-pro-BNPpeak/rest was similar (60 vs. 50 pg/mL, p > 0.05). During the tracking period (22.4 ± 20.3 months) 34 patients died, and there were 2 cardiac transplantations and 3 LVAD implantations. In a multivariate regression model only the NT-pro-BNPpeak and ΔNT-pro-BNPpeak/rest were retained in the regression for the prediction of adverse events (Chi-square:8.97, p = 0.003). ROC analysis demonstrated that NT-pro-BNPpeak ≥1506 pg/mL and ΔNT-pro-BNPpeak/rest ≥108 pg/mL were optimal for identifying patients with a risk (Sn = 76.9, 74.4 %; Sp = 84.7, 80.9 %, respectively). NT-pro-BNP changes during effort and absolute peak values reached provide novel insights emerging as new and strong predictors of adverse events in HF of any EF.

Stress hormones at rest and following exercise testing predict coronary artery disease severity and outcome.

OBJECTIVES: Despite considerable knowledge regarding the importance of stress in coronary artery disease (CAD) pathogenesis, its underestimation persists in routine clinical practice, in part attributable to lack of a standardized, objective assessment. The current study examined the ability of stress hormones to predict CAD severity and prognosis at basal conditions as well as during and following an exertional stimulus. MATERIALS AND METHODS: Forty Caucasian subjects with significant coronary artery lesions (≥50%) were included. Within 2 months of coronary angiography, cardiopulmonary exercise testing (CPET) on a recumbent ergometer was performed in conjunction with stress echocardiography (SE). At rest, peak and after 3 min of recovery following CPET, plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and NT-pro-brain natriuretic peptide (NT-pro-BNP) were measured by immunoassay sandwich technique, radioimmunoassay, and radioimmunometric technique, respectively. Subjects were subsequently followed a mean of 32 ± 10 months. RESULTS AND DISCUSSION: Mean ejection fraction was 56.7 ± 9.6%. Subjects with 1-2 stenotic coronary arteries (SCA) demonstrated a significantly lower plasma cortisol levels during CPET compared to those with 3-SCA (p < .05), whereas ACTH and NT-pro-BNP were not significantly different (p > .05). Among CPET, SE, and hormonal parameters, cortisol at rest and during CPET recovery demonstrated the best predictive value in distinguishing between 1-, 2-, and 3-SCA [area under ROC curve 0.75 and 0.77 (SE = 0.11, 0.10; p = .043, .04) for rest and recovery, respectively]. ΔCortisol peak/rest predicted cumulative cardiac events (area under ROC curve 0.75, SE = 0.10, p = .049). CONCLUSIONS: Cortisol at rest and following an exercise test holds predictive value for CAD severity and prognosis, further demonstrating a link between stress and unwanted cardiac events.

Oxygen consumption and carbon-dioxide recovery kinetics in the prediction of coronary artery disease severity and outcome.

BACKGROUND: Revascularization appears to be beneficial only in patients with high levels of ischemia. This study examined the utility of gas analysis during the recovery phase of cardiopulmonary exercise testing (CPET) in predicting coronary artery disease (CAD) severity and prognosis. METHODS: 40 Caucasian patients (21.2% females), mean age 63.5±7.6 with significant coronary artery lesions (≥50%) were studied. Within two months of coronary angiography, CPET on a treadmill (TM) and recumbent ergometer (RE) were performed on two visits 2-4days apart; subjects were subsequently followed 32±10months. Myocardial wall motion was recorded by echocardiography at rest and peak exercise. Ischemia was quantified by the wall motion score index (WMSI). RESULTS: Mean ejection fraction was 56.7±9.6%. Patients with 1-2 stenotic coronary arteries (SCA) showed a poorer CPET response during the recovery phase than patients with 3-SCA. ROC analysis revealed the change of carbon-dioxide output (∆VCO2) recovery/peak (area under ROC curve 0.77, p=0.02, Sn=87.5%, Sp=70.4%) and oxygen uptake (∆VO2) recovery/peak during TM CPET (area under ROC curve 0.76, p=0.03, Sn 75.0%, Sp 77.8%) were significant in distinguishing between 1-2-SCA and 3-SCA. The same variables predicted ΔWMSI peak/rest on univariate analysis (p<0.05). Multivariate Cox analysis revealed a high predictive value of ∆VO2 recovery/peak obtained during TM CPET for composite endpoint of cumulative cardiac events (HR=1.27, CI=1.07-1.51, p=0.008). CONCLUSIONS: The current study suggests CPET parameters in recovery hold predictive value for CAD severity and prognosis. TM testing seems to be a better approach in the assessment of CAD severity and prognosis.