Integrating Right Ventricular Pressure Waveform Analysis With Two-Point Volume Measurement for Quantification of Systolic and Diastolic Function: Experimental Validation and Clinical Application.

OBJECTIVE: To define in an experimental model the variance, accuracy, precision, and concordance of single-beat measures of right ventricular (RV) contractility and diastolic capacitance relative to conventional reference standards, and apply the methods to a clinical data set. DESIGN: A retrospective, observational analysis of recorded pressure waveforms and RV volume measurements. SETTING: At a university laboratory. PARTICIPANTS: Archived data from previous studies of anesthetized swine and awake patients undergoing clinically-indicated right-heart catheterization. INTERVENTIONS: Recording of RV pressure with simultaneous measurement of RV volume by conductance (swine) or 3-dimensional (3D) echocardiography (humans) during changes in contractility and/or loading conditions. MEASUREMENTS AND MAIN RESULTS: Using experimental data, single-beat measures of RV contractility quantified as end-systolic elastance, and diastolic capacitance quantified as the predicted volume at an end-diastolic pressure of 15 mmHg (V15), were compared to multi-beat, preload- variant, reference standards using correlation, Bland-Altman analysis, and 4-quadrant concordance testing. This analysis indicated that the methods were not directly interchangeable with reference standards, but were sufficiently robust to suggest potential clinical utility. Clinical application supported this potential by demonstrating enhanced assessment of the response to inhaled nitric oxide in patients undergoing diagnostic right-heart catheterization. CONCLUSIONS: Study results supported the possibility of integrating automated RV pressure analysis with RV volume measured by 3D echocardiography to create a comprehensive assessment of RV systolic and diastolic function at the bedside.

Noninvasive determinants of pulmonary hypertension in interstitial lung disease.

Pulmonary hypertension (PH) in interstitial lung disease (ILD) is associated with increased mortality and impaired exertional capacity. Right heart catheterization is the diagnostic standard for PH but is invasive and not readily available. Noninvasive physiologic evaluation may predict PH in ILD. Forty-four patients with PH and ILD (PH-ILD) were compared with 22 with ILD alone (non-PH ILD). Six-min walk distance (6MWD, 223 ± 131 vs. 331 ± 125 m, p = 0.02) and diffusing capacity for carbon monoxide (DLCO, 33 ± 14% vs. 55 ± 21%, p < 0.001) were lower in patients with PH-ILD. PH-ILD patients exhibited a lower gas-exchange derived pulmonary vascular capacitance (GXCAP, 251 ± 132 vs. 465 ± 282 mL × mmHg, p < 0.0001) and extrapolated maximum oxygen uptake (VO2max) (56 ± 32% vs. 84 ± 37%, p = 0.003). Multivariate analysis was performed to determine predictors of VO2 max. GXCAP was the only variable that predicted extrapolated VO2 max among PH-ILD and non-PH ILD patients. Receiver operating characteristic curve analysis assessed the ability of individual noninvasive variables to distinguish between PH-ILD and non-PH ILD patients. GXCAP (area under the curve [AUC] 0.85 ± 0.04, p < 0.0001) and delta ETCO2 (AUC 0.84 ± 0.04, p < 0.0001) were the strongest predictors of PH-ILD. A CART analysis selected GXCAP, estimated right ventricular systolic pressure (eRVSP) by echocardiogram, and FVC/DLCO ratio as predictive variables for PH-ILD. With this analysis, the AUC improved to 0.94 (sensitivity of 0.86 and sensitivity of 0.93). Patients with a GXCAP ≤ 416 mL × mmHg had an 82% probability of PH-ILD. Patients with GXCAP ≤ 416 mL × mmHg and high FVC/DLCO ratio >1.7 had an 80% probability of PH-ILD. Patients with GXCAP ≤ 416 mL × mmHg and an elevated eRVSP by echocardiogram >43 mmHg had 100% probability of PH-ILD. The incorporation of GXCAP with either eRVSP or FVC/DLCO ratio distinguishes between PH-ILD and non-PH-ILD with high probability and may therefore assist in determining the need to proceed with a diagnostic right heart catheterization and potential initiation of pulmonary arterial hypertension-directed therapy in PH-ILD patients.

Diagnostic utility of sub-maximum cardiopulmonary exercise testing in the ambulatory setting for heart failure with preserved ejection fraction.

Pulmonary hypertension is commonly associated with heart failure with preserved ejection fraction. In heart failure with preserved ejection fraction, the elevated left-sided filling pressures result in isolated post-capillary pulmonary hypertension or combined pre- and post-capillary pulmonary hypertension. Although right heart catheterization is the gold standard for diagnosis, it is an invasive test with associated risks. The ability of sub-maximum cardiopulmonary exercise test as an adjunct diagnostic tool in pulmonary hypertension-associated heart failure with preserved ejection fraction is not known. Forty-six patients with heart failure with preserved ejection fraction and pulmonary hypertension (27 patients with combined pre- and post-capillary pulmonary hypertension and 19 patients with isolated post-capillary pulmonary hypertension) underwent sub-maximum cardiopulmonary exercise test followed by right heart catheterization. The study also included 18 age- and gender-matched control subjects. Several sub-maximum gas exchange parameters were examined to determine the ability of sub-maximum cardiopulmonary exercise test to distinguish between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Conventional echocardiogram measures did not distinguish between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Compared to isolated post-capillary pulmonary hypertension, combined pre- and post-capillary pulmonary hypertension had greater ventilatory equivalent for carbon dioxide (VE/VCO2) slope, reduced delta end-tidal CO2 change during exercise, reduced oxygen uptake efficiency slope, and reduced gas exchange determined pulmonary vascular capacitance. The latter was significantly associated with right heart catheterization determined pulmonary artery compliance (r = 0.5; p = 0.0004). On univariate analysis, sub-maximum VE/VCO2, delta end-tidal carbon dioxide, and gas exchange determined pulmonary vascular capacitance emerged as independent predictors of the extrapolated maximum oxygen uptake (%predicted) (ß-coefficient values of -7.32, 95% CI: -13.3 - (-1.32), p = 0.01; 8.01, 95% CI: 1.96-14.05, p = 0.01; 8.78, 95% CI: 2.26-15.29, p = 0.01, respectively). Sub-maximum gas exchange parameters obtained during cardiopulmonary exercise test in an ambulatory setting allows for discrimination between isolated post-capillary pulmonary hypertension and combined pre- and post-capillary pulmonary hypertension. Additionally, sub-maximum cardiopulmonary exercise test derived VE/VCO2, delta end-tidal carbon dioxide, and gas exchange determined pulmonary vascular capacitance influences aerobic capacity in heart failure with preserved ejection fraction.