Timothy J. Vittorio

End-tidal CO2 pressure and cardiac performance during exercise in heart failure.

INTRODUCTION In patients with heart failure (HF), end-tidal CO2 pressure (PetCO2) is related to ventricular function at rest and has been shown to predict prognosis. However, little is known about the association between ventricular performance and PetCO2 responses to exercise. METHODS Forty-eight patients with HF and 13 normal subjects underwent cardiopulmonary exercise testing (CPX), while cardiac output and other hemodynamic measurements at rest and during exercise were obtained using a novel, noninvasive, bioreactance device based on assessment of relative phase shifts of electric currents injected across the thorax, heart rate, and ventricular ejection time. CPX responses and indices of cardiac performance were compared between normal subjects and HF patients achieving above and below a PetCO2 of 36 mm Hg at the ventilatory threshold (PetCO2@VT). RESULTS HF patients with an abnormal PetCO2@VT (<36 mm Hg) had a lower exercise capacity, a lower .VO2@VT, a higher .V_E/.VCO2 slope, and lower oxygen uptake efficiency slope (OUES) values compared with normal subjects and patients achieving a normal PetCO2@VT. Patients with reduced PetCO2@VT had lower peak cardiac output responses to exercise (20.0 +/- 10, 17.8 +/- 6, and 13.7 +/- 7 L x min for normal subjects and HF patients with normal and abnormal PetCO2 responses to exercise, respectively, P = 0.04). PetCO2@VT was inversely related to the .V_E/.VCO2 slope (r = -0.78, P < 0.001) and directly related to the OUES (r = 0.55, P < 0.001). CONCLUSION Reduced PetCO2 reflects impairments in the functional, ventilatory, and cardiac performance response to exercise in patients with HF. PetCO2 can supplement other clinical and CPX indices in the functional and prognostic evaluation of patients with HF.

A Multicenter Study of Noninvasive Cardiac Output by Bioreactance During Symptom-limited Exercise

BACKGROUND Hemodynamic responses to exercise were assessed in patients with varying degrees of chronic heart failure (CHF) to determine the feasibility of using bioreactance during exercise testing in multicenter studies of CHF. METHODS AND RESULTS A total of 210 symptomatic CHF patients and 22 subjects without heart failure were subjected to symptom-limited exercise testing on a bicycle (105) or treadmill (127) while measuring gas exchange for VO(2), cardiac output (CO) noninvasively by a bioreactance technique, heart rate, and blood pressure. Peak CO (pCO) and VO(2) (pVO(2)) during exercise were lower in patients with higher New York Heart Association (NYHA) class, in females and in older patients. Multiple linear regression analysis showed that pCO (L/min)=19.6+4.M -2.1.NYHA+1.9.G -0.09.Age, where M=1 for treadmill and 0 for bicycle and G=1 for males and 0 for females. Similarly, pVO(2) (mL/kg/min)=24+2.1.M -2.9.NYHA+1.26.G -0.08.Age. VO(2) and CO were also highly correlated to each other: pCO (mL/kg/min)=0.059+0.007.pVO(2)+0.036.M -0.025.G. Similar correlations were determined for other parameters of exercise, including left ventricular power, and the ratio of peak/resting VO(2) (cardiovascular reserve), the ratio of peak/resting CO (cardiac reserve), and total peripheral vascular resistance. CONCLUSION Bioreactance-based noninvasive measurements of CO at rest and during exertion identified abnormalities of cardiovascular function consistent with those identified by pVO(2) and in prior studies using invasive CO measurements. This technique might therefore be useful for indexing disease severity, prognostication, and for tracking responses to treatment in clinical practice and in clinical trials.

Atrial natriuretic peptide stability

OBJECTIVE Atrial natriuretic peptide (ANP) is a key regulator in the homeostasis of water excretion and has emerged as an important prognostic marker for symptomatic chronic heart failure (CHF). The stability of ANP represents a crucial factor in assessing its use as a cardiac biomarker. Accordingly, we assessed the stability of ANP in blood samples collected from healthy controls and CHF subjects for a 12 month period. METHODS Blood samples from 10 healthy controls and 12 symptomatic CHF subjects with left ventricular systolic dysfunction were drawn. Determination of plasma ANP was performed by a standardized radioimmunoassay protocol. RESULTS The ANP levels of healthy subjects were 68.5+/-11.6 pg/mL at baseline and 69.9+/-17.2 pg/mL at 12 months (p=0.71). The ANP concentrations of CHF subjects were 199.25+/-44.8 pg/mL at baseline and 197.83+/-47.4 pg/mL at 12 months (p=0.70) respectively. CONCLUSION ANP is a stable molecule with no evidence of degradation when stored at -80 degrees C.

The Effect of Nesiritide on Renal Function and Other Clinical Parameters in Patients With Decompensated Heart Failure and Preserved Ejection Fraction

The role of nesiritide in patients with decompensated heart failure with preserved ejection fraction (dHFpEF) has not been previously studied. In this investigation, the authors retrospectively analyzed the effect of nesiritide on renal function and clinical outcomes in patients admitted with dHFpEF. Of the 658 patients included, 328 were treated with nesiritide while 330 patients were treated with standard diuretic therapy. In both the nesiritide and no nesiritide groups, there was a significant change in mean glomerular filtration rate (GFR) and creatinine at 72 hours as well as at day of discharge (P<.001). This trend did not progress at 1 month in the nesiritide group, although it did in the no nesiritide group. At 1 month after therapy, however, there was a significant difference between the two groups in the mean change of GFR and creatinine (P<.001). There was no significant difference in >25% decrease of GFR anytime through day 30 (25% vs 29.69%, P=.236) between the two groups. On multivariate analysis, nesiritide was an important predictor of renal function at 1 month (P<.05). Thus, nesiritide can be administered safely without negatively impacting long-term renal function in patients admitted with dHFpEF.

Comparison of high- versus low-tissue affinity ACE-inhibitor treatment on circulating aldosterone levels in patients with chronic heart failure.

Introduction. Previous animal studies of chronic heart failure (CHF) suggest that angiotensin-converting enzyme (ACE) inhibitors of differing tissue avidity provide varying levels of renin-angiotensin system (RAS) suppression. Human studies have not consistently confirmed these animal findings. We hypothesised that production of circulating aldosterone (ALDO) would be suppressed to a greater extent in subjects treated with an ACE-inhibitor of higher tissue avidity. We randomised subjects with stable CHF to receive the low-tissue affinity ACE-inhibitor enalapril (ENAL) or the high-tissue affinity ACE-inhibitor trandolapril (TRAN), and assessed circulating ALDO levels at baseline and after eight weeks of treatment. Methods. Thirty clinically stable subjects with CHF and left ventricular ejection fraction (LVEF ) < 40% who were in a steady-state fluid balance were enrolled into a prospective, randomised double-blind trial. After a one month run-in period for standardisation to initial ACE-inhibition with ENAL, baseline circulating ALDO levels were measured and patients were randomised to receive ENAL 40 mg versus O TRAN 4 mg (or the maximally tolerated doses) for eight weeks. Final determination of ALDO levels were made at the end of the 8-week study period. Results. Baseline clinical characteristics including age, diabetes, LVEF, serum sodium, potassium and creatinine concentrations, and background medications were similar in both groups. We found no statistically significant difference in circulating ALDO levels between the ENAL and TRAN groups at the end of the 8-week study period. [ENAL (12.6 vs. 13.3 ng/dL);TRAN (12.5 vs. 14.5 ng/dL);p=NS]. Conclusion. We found no statistically significant difference in circulating ALDO levels between high- and low-tissue affinity ACE-inhibitor therapy. Further studies assessing ALDO production at the tissue level is warranted.