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      Exercise gas exchange in continuous-flow left ventricular assist device recipients

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          Abstract

          Exercise ventilation/perfusion matching in continuous-flow left ventricular assist device recipients (LVAD) has not been studied systematically. Twenty-five LVAD and two groups of 15 reduced ejection fraction chronic heart failure (HFrEF) patients with peak VO 2 matched to that of LVAD (HFrEF-matched) and ≥14 ml/kg/min (HFrEF≥14), respectively, underwent cardiopulmonary exercise testing with arterial blood gas analysis, echocardiogram and venous blood sampling for renal function evaluation. Arterial-end-tidal PCO 2 difference (P(a-ET)CO 2) and physiological dead space-tidal volume ratio (VD/VT) were used as descriptors of alveolar and total wasted ventilation, respectively. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (TAPSE/PASP) and blood urea nitrogen/creatinine ratio were calculated in all patients and used as surrogates of right ventriculo-arterial coupling and circulating effective volume, respectively. LVAD and HFrEF-matched showed no rest-to-peak change of P(a-ET)CO 2 (4.5±2.4 vs. 4.3±2.2 mm Hg and 4.1±1.4 vs. 3.8±2.5 mm Hg, respectively, both p >0.40), whereas a decrease was observed in HFrEF≥14 (6.5±3.6 vs. 2.8±2.0 mm Hg, p <0.0001). Rest-to-peak changes of P(a-ET)CO 2 correlated to those of VD/VT (r = 0.70, p <0.0001). Multiple regression indicated TAPSE/PASP and blood urea nitrogen/creatinine ratio as independent predictors of peak P(a-ET)CO 2. LVAD exercise gas exchange is characterized by alveolar wasted ventilation, i.e. hypoperfusion of ventilated alveoli, similar to that of advanced HFrEF patients and related to surrogates of right ventriculo-arterial coupling and circulating effective volume.

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          Most cited references36

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          Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis.

          Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP
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            Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure.

            This study was undertaken to determine which exercise and radionuclide ventriculographic variables predict prognosis in advanced heart failure. Although cardiopulmonary exercise testing is frequently used to predict prognosis in patients with advanced heart failure, little is known about the prognostic significance of ventriculographic variables. The results of maximal symptom-limited cardiopulmonary exercise testing and first-pass radionuclide ventriculography in patients with advanced heart failure referred for evaluation for cardiac transplantation were analyzed. Sixty-seven patients with advanced heart failure (mean [+/- SD]; age 51 +/- 10 years, New York Heart Association functional classes III (58%) and IV (18%); mean left ventricular ejection fraction 0.22 +/- 0.07) underwent simultaneous upright bicycle ergometric cardiopulmonary exercise testing and first-pass rest/exercise radionuclide ventriculography. Mean peak oxygen consumption (VO2) was 11.8 +/- 4.2 ml/kg per min, and mean peak age- and gender-adjusted percent predicted oxygen consumption (%VO2) was 38 +/- 11.9%. Univariate predictors of overall survival included right ventricular ejection fraction > or = 0.35 at rest and > or = 0.35 at exercise and %VO2 > or = 45% (all p or = 0.35 at exercise (p or = 45% (p = 0.01) were selected as independent predictors of overall survival. Univariate predictors of event-free survival included right ventricular ejection fraction > or = 0.35 at rest (p = 0.01) and > or = 0.35 at exercise (p or = 45% (p = 0.05). Right ventricular ejection fraction > or = 0.35 at exercise (p = 0.01) was the only independent predictor of event-free survival in a multivariate proportional hazards model. Cardiac index at rest, VO2, left ventricular ejection fraction at rest, and exercise-related increase or decrease > 0.05 in left or right ventricular ejection fraction were not predictive of overall or event-free survival in any univariate or multivariate analysis. 1) Right ventricular ejection fraction > or = 0.35 at rest and exercise is a more potent predictor of survival in advanced heart failure than VO2 or %VO2; 2) %VO2 rather than VO2 predicts survival in advanced heart failure; 3) neither %VO2 nor VO2 predicts survival to the combined end point of death or admission for inotropic or mechanical support in patients with advanced heart failure.
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              Lung function and exercise gas exchange in chronic heart failure.

              The ventilatory response to exercise in patients with chronic heart failure (HF) is greater than normal for a given metabolic rate. The objective of the present study was to determine the mechanism(s) for the high ventilatory output in patients with chronic HF. Centers in Germany, Italy, Japan, and the United States participated in this study. Each center contributed studies on patients and normal subjects of similar age and sex. One hundred thirty patients with chronic HF and 52 healthy subjects participated. Spirometric and breath-by-breath gas exchange measurements were made during rest and increasing cycle exercise. Arterial blood was sampled for measurement of pH, PaCO2, PaO2, and lactate during exercise in 85 patients. Resting forced expiratory volume in 1 second (FEV1) and vital capacity (VC) were proportionately reduced at all levels of impairment. Patients with more severe HF had greater tachypnea and a smaller tidal volume (VT) at a given exercise expired volume per unit time (VE). This was associated with an expiratory flow pattern characteristic of lung restriction. VE and VCO2 as a function of VO2 were increased during exercise in HF patients. The increases were greater the lower the peak VO2 per kilogram of body weight. The ratio of VD (physiological dead space) to VT and the difference between arterial and end tidal PCO2 at peak VO2 also increased inversely with peak VO2/kg. In contrast, the difference between alveolar and arterial PO2 and PaCO2 were both normal, on average, at peak VO2 regardless of the level of impairment. The more severe the exercise limitation, the higher the lactate and the lower the HCO3- at a given VO2, although pH was tightly regulated. The increase in VE in chronic HF patients is caused by an increase in VD/VT due to high ventilation/perfusion mismatching, an increase in VCO2 relative to VO2 resulting from HCO3- buffering of lactic acid, and a decrease in PaCO2 due to tight regulation of arterial pH. With regard to the excessive VE in HF patients, the increases in VD/VT and VCO2 relative to VO2 are more important as the patient becomes more exercise limited. Regional hypoperfusion but not hypoventilation typifies lung gas exchange in HF. This and other mechanisms might account for the restrictive changes leading to exercise tachypnea in HF patients.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draft
                Role: ConceptualizationRole: Supervision
                Role: ConceptualizationRole: Supervision
                Role: Data curationRole: Formal analysisRole: Supervision
                Role: Data curationRole: Investigation
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: Investigation
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 June 2018
                2018
                : 13
                : 6
                : e0187112
                Affiliations
                [1 ] Exercise Pathophysiology Laboratory, Cardiac Rehabilitation Division, Scientific Institute of Veruno IRCCS, Istituti Clinici Scientifici Maugeri Spa SB, Veruno (NO), Italy
                [2 ] Centro Cardiologico Monzino IRCCS and Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy
                [3 ] Bioengineering Service, Scientific Institute of Veruno IRCCS, Istituti Clinici Scientifici Maugeri Spa SB, Veruno (NO), Italy
                [4 ] Echocardiography Laboratory, Cardiac Rehabilitation Division, Scientific Institute of Veruno IRCCS, Istituti Clinici Scientifici Maugeri Spa SB, Veruno (NO), Italy
                Universita degli Studi di Napoli Federico II, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-1595-6227
                Article
                PONE-D-17-22519
                10.1371/journal.pone.0187112
                5983474
                29856742
                e87be67d-896e-434b-b757-1a51212bcb97
                © 2018 Mezzani et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 June 2017
                : 13 October 2017
                Page count
                Figures: 2, Tables: 6, Pages: 15
                Funding
                The authors received no specific funding for this work.
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