Xing-Guo Sun

Oscillatory breathing and exercise gas exchange abnormalities prognosticate early mortality and morbidity in heart failure.

OBJECTIVES The goal of this study was to identify better predictors of early death in patients with chronic left ventricular heart failure (CHF). Potential predictors, derived from cardiopulmonary exercise testing, were compared with other commonly used cardiovascular measurements. BACKGROUND The prediction of early death in patients with CHF remains challenging. METHODS Five hundred eight patients with CHF due to systolic dysfunction underwent resting cardiovascular measurements, 6-min walking tests, and cardiopulmonary exercise testing. The peak oxygen uptake (.VO(2)), peak oxygen pulse, anaerobic threshold, ratio of ventilation to carbon dioxide output (.VE/.VCO(2)), slope of .VE versus .VCO(2), and presence or absence of a distinctive oscillatory breathing pattern (OB) were ascertained. Outcomes were 6-month mortality and morbidity, the latter a sum of cardiac hospitalizations and deaths. RESULTS The single best predictor of mortality was an elevated lowest .VE/.VCO(2) (> or =155% predicted). Adding OB on the basis of stepwise regression (optimal 2-predictor model), the odds ratio for mortality increased from 9.4 to 38.9 (p < 0.001). The slope of .VE versus .VCO(2) slope, peak .VO(2), peak oxygen pulse, and anaerobic threshold combined with OB were also strong predictors. OB also increased the odds ratio 2- to 3-fold for each of these (p < 0.01). Kaplan-Meier survival curves and area under the receiver-operating characteristic curve confirmed that lowest .VE/.VCO(2) and OB were superior. For morbidity, elevated lowest .VE/.VCO(2) or lower peak .VO(2) with OB were the best predictors. No nonexercise measurements discriminated mortality and morbidity. CONCLUSIONS Cardiopulmonary exercise testing parameters are powerful prognosticators of early mortality and morbidity in patients with CHF, especially the optimal 2-predictor model of a combination of elevated lowest .VE/.VCO(2) and OB.

Usefulness of right-to-left shunting and poor exercise gas exchange for predicting prognosis in patients with pulmonary arterial hypertension.

We hypothesized that the longitudinal changes in peak oxygen uptake, ventilatory efficiency, and exercise-induced right-to-left shunting in patients with pulmonary arterial hypertension (PAH) would predict outcomes better than baseline measurements alone. Patients with PAH die prematurely. Identifying prognostic markers is critical for treating patients with PAH; however, longitudinal prognostic information of PAH is limited. We enrolled 103 patients with PAH into a long-term, prospective outcome study using serial cardiopulmonary exercise testing to measure the peak oxygen uptake, ventilatory efficiency (ratio of ventilation to carbon dioxide output at the anaerobic threshold), right-to-left shunting, and other factors in patients treated with optimal therapy. The patients were followed up for a mean of 4.7 years. During the study period, 20 patients died, and 3 underwent lung transplantation. The baseline peak oxygen uptake and ventilatory efficiency was 0.79 L/min and 49 (normal <34), respectively, reflecting severe disease. Poorer ventilatory efficiency and greater New York Heart Association classification were associated with poor outcome at baseline and at follow-up. On multivariate analysis, the persistence or development of an exercise-induced right-to-left shunt strongly predicted death or transplantation (p <0.0001), independent of the hemodynamics and all other exercise measures, including peak oxygen uptake and ventilatory efficiency. The absence of a shunt at baseline was associated with a 20% rate of nonsurvival, which decreased to 7% at follow-up. A poorer ventilatory efficiency appeared to be associated with a poor outcome in patients without a shunt. In conclusion, a persistent exercise-induced right-to-left shunt and poor ventilatory efficiency were highly predictive of poor outcomes in patients with pulmonary arterial hypertension.

Effect of Sildenafil on Ventilatory Efficiency and Exercise Tolerance in Pulmonary Hypertension

The pulmonary vasculopathy in pulmonary arterial hypertension (PAH) results in increased resistance to pulmonary blood flow, limiting the cardiac output required for the increased O2 demands of exercise.

Oxygen Uptake Efficiency Plateau Best Predicts Early Death in Heart Failure

BACKGROUND The responses of oxygen uptake efficiency (ie, oxygen uptake/ventilation = VO(2)/VE) and its highest plateau (OUEP) during incremental cardiopulmonary exercise testing (CPET) in patients with chronic left heart failure (HF) have not been previously reported. We planned to test the hypothesis that OUEP during CPET is the best single predictor of early death in HF. METHODS We evaluated OUEP, slope of VO(2) to log(VE) (oxygen uptake efficiency slope), oscillatory breathing, and all usual resting and CPET measurements in 508 patients with low-ejection-fraction (< 35%) HF. Each had further evaluations at other sites, including cardiac catheterization. Outcomes were 6-month all-reason mortality and morbidity (death or > 24 h cardiac hospitalization). Statistical analyses included area under curve of receiver operating characteristics, ORs, univariate and multivariate Cox regression, and Kaplan-Meier plots. RESULTS OUEP, which requires only moderate exercise, was often reduced in patients with HF. A low % predicted OUEP was the single best predictor of mortality (P < .0001), with an OR of 13.0 (P < .001). When combined with oscillatory breathing, the OR increased to 56.3, superior to all other resting or exercise parameters or combinations of parameters. Other statistical analyses and morbidity analysis confirmed those findings. CONCLUSIONS OUEP is often reduced in patients with HF. Low % predicted OUEP (< 65% predicted) is the single best predictor of early death, better than any other CPET or other cardiovascular measurement. Paired with oscillatory breathing, it is even more powerful.

Arterial H+ regulation during exercise in humans

Resting arterial H+ concentration ([H+]a) is in the nanomolar range (40±2 nm/L) while its production is in the millimolar range/min, with little variation from subject to subject. To determine the precision with which [H(+)]a is regulated during exercise, [H+]a, PaCO2 and ventilation (V˙(E)) were measured during progressively increasing work rate exercise in 16 normal subjects. (V˙(E)) increased with [H+]a, the latter attributable to PaCO2 increase below the lactic acidosis threshold (LAT) (ΔV˙(E)/Δ[H+]a ≈ 15   L   min(-1)   nanomol(-1)). [H+]a and PaCO2 increased, simultaneously, as work rate was increased below LAT. PaCO2 reversed direction of change between LAT and ventilatory compensation point (VCP). Above LAT, [H+]a increase relative to (V˙(E)) increase was greater than below LAT. PaCO2 decreased above the LAT, while [H+]a continued to increase. Thus the exercise acidosis was converted from respiratory, below, to a metabolic, above the LAT. We conclude that [H+]a is increased and regulated over the full range of exercise, but with less sensitivity above the LAT.

A Simple New Visualization of Exercise Data Discloses Pathophysiology and Severity of Heart Failure

Background The complexity of cardiopulmonary exercise testing data and their displays tends to make assessment of patients, including those with heart failure, time consuming. Methods and Results We postulated that a new single display that uses concurrent values of oxygen uptake / ventilation versus carbon dioxide output / ventilation ratios (–versus–), plotted on equal X–Y axes, would better quantify normality and heart failure severity and would clarify pathophysiology. Consecutive –versus– values from rest to recovery were displayed on X–Y axes for patients with Class II and IV heart failure and for healthy subjects without heart failure. The displays revealed distinctive patterns for each group, reflecting sequential changes in cardiac output, arterial and mixed venous O2 and CO2 content differences, and ventilation (). On the basis of exercise tests of 417 healthy subjects, reference formulas for highest and , which normally occur during moderate exercise, are presented. Absolute and percent predicted values of highest and were recorded for 10 individuals from each group: Those of healthy subjects were significantly higher than those of patients with Class II heart failure, and those of patients with Class II heart failure were higher than those of patients with Class IV heart failure. These values differentiated heart failure severity better than peak , anaerobic threshold, peak oxygen pulse, and slopes. Resting –versus– values were strikingly low for patients with Class IV heart failure, and with exercise, increased minimally or even decreased. With regard to the pathophysiology of heart failure, high values during milder exercise, previously attributed to ventilatory inefficiency, seem to be caused primarily by reduced cardiac output rather than increased . Conclusion –versus– measurements and displays, extractable from future or existing exercise data, separate the 3 groups (healthy subjects, patients with Class II heart failure, and patients with Class IV heart failure) well and confirm the dominant role of low cardiac output rather than excessive in heart failure pathophysiology. (J Am Heart Assoc. 2012;1:e001883 doi: 10.1161/JAHA.112.001883.)