Fabricio Martins Valois

Heart rate recovery in pulmonary arterial hypertension: relationship with exercise capacity and prognosis.

BACKGROUND Delayed postexercise heart rate recovery (HRR) has been associated with disability and poor prognosis in chronic cardiopulmonary diseases. The usefulness of HRR to predict exercise impairment and mortality in patients with pulmonary arterial hypertension (PAH), however, remains largely unexplored. METHODS Seventy-two patients with PAH of varied etiology (New York Heart Association classes I-IV) and 21 age- and gender-matched controls underwent a maximal incremental cardiopulmonary exercise test (CPET), with heart rate being recorded up to the fifth minute of recovery. RESULTS Heart rate recovery was consistently lower in the patients compared with the controls (P < .05). The best cutoff for HRR in 1 minute (HRR(1 min)) to discriminate the patients from the controls was 18 beats. Compared with patients with HRR(1 min) ≤ 18 (n = 40), those with HRR(1 min) >18 (n = 32) had better New York Heart Association scores, resting hemodynamics and 6-minute walking distance. In fact, HRR(1 min) >18 was associated with a range of maximal and submaximal CPET variables indicative of less severe exercise impairment (P < .05). The single independent predictor of HRR(1 min) ≤ 18 was the 6-minute walking distance (odds ratio [95% CI] 0.99 [0.98-1.00], P < .05). On a multiple regression analysis that considered only CPET-independent variables, HRR(1 min) ≤ 18 was the single predictor of mortality (hazard ratio [95% CI] 1.19 [1.03-1.37], P < .05). CONCLUSIONS Preserved HRR(1 min) (>18 beats) is associated with less impaired responses to incremental exercise in patients with PAH. Conversely, a delayed HRR(1 min) response has negative prognostic implications, a finding likely to be clinically useful when more sophisticated (and costlier) analyses provided by a full CPET are not available.

Optimizing the evaluation of excess exercise ventilation for prognosis assessment in pulmonary arterial hypertension.

Background Increased ventilatory ( V · E) response to carbon dioxide output ( V · CO2) is a key finding of incremental cardiopulmonary exercise testing in both heart failure and pulmonary arterial hypertension (PAH). As with heart failure, measures of excessive exercise ventilation considering high-to-peak exercise V · E– V · CO2 might have higher prognostic relevance than those restrained to sub-maximal exercise in PAH. Design Cross-sectional and observational study on a tertiary center. Methods Eighty-four patients (36 idiopathic and 48 with associated conditions) were followed up for up to five years. Excessive exercise ventilation was calculated as a slope (Δ V · E/Δ V · CO2 to the respiratory compensation point (RCP) and to exercise cessation (PEAK)) and as a ratio ( V · E/ V · CO2 at the anaerobic threshold (AT) and at PEAK). Results Thirteen patients died and three had atrial septostomy. Multivariable regression analyses revealed that Δ V · E/Δ V · CO2(PEAK) <55 and V · E/ V · CO2(PEAK) <57 were better related to prognosis than Δ V · E/Δ V · CO2(RCP) and V · E/ V · CO2(AT) (p < 0.01). Δ oxygen uptake ( V · O2)/Δ work rate >5.5 ml/min per W was the only other independent prognostic index. According to a Kaplan–Meier survival analysis, 96.9% (90.8% to 100%) of patients showing Δ V · E/Δ V · CO2(PEAK) <55 and Δ V · O2/Δ work rate >5.5 ml/min per W were free from a PAH-related event. In contrast, 74.7% (70.1% to 78.2%) with both parameters outside these ranges had a negative outcome. Conclusion Measurements of excessive exercise ventilation which consider all data points maximize the usefulness of incremental cardiopulmonary exercise testing in the prognosis evaluation of PAH.

Contrasting Cardiopulmonary Responses to Incremental Exercise in Patients with Schistosomiasis-Associated and Idiopathic Pulmonary Arterial Hypertension with Similar Resting Hemodynamic Impairment

It has been reported that schistosomiasis-associated PAH (Sch-PAH) has a more benign clinical course compared with idiopathic PAH (IPAH). We therefore hypothesized that Sch-PAH subjects would present with less impaired cardiopulmonary and metabolic responses to exercise than IPAH patients, even with similar resting pulmonary hemodynamic abnormalities. The aim of this study was to contrast physiologic responses to incremental exercise on cycle ergometer between subjects with Sch-PAH and IPAH. We performed incremental cardiopulmonary exercise tests (CPET) in subjects newly diagnosed with IPAH (n = 9) and Sch-PAH (n = 8), within 1 month of the hemodynamic study and before the initiation of specific therapy for PAH. There were no significant between-group differences in cardiac index, pulmonary vascular resistance or mean pulmonary artery pressure. However, mean peak oxygen uptake (VO2) was greater in Sch-PAH than IPAH patients (75.5±21.4 vs 54.1±16.1% predicted, p = 0.016), as well as the ratio of increase in VO2 to work rate (8.2±1.0 vs 6.8±1.8 mL/min/W, p = 0.03). Additionally, the slope of the ventilatory response as a function of CO2 output was lower in Sch-PAH (40.3±3.9 vs 55.6±19.8; p = 0.04), and the heart rate response for a given change in VO2 was also diminished in Sch-PAH compared to IPAH (80.1±20.6 vs 123.0±39.2 beats/L/min; p = 0.02). In conclusion, Sch-PAH patients had less impaired physiological responses to exercise than IPAH subjects with similar resting hemodynamic dysfunction. Our data suggest a more preserved cardiopulmonary response to exercise in Sch-PAH which might be related to its better clinical course compared to IPAH.

Clinical usefulness of end-tidal CO2 profiles during incremental exercise in patients with chronic thromboembolic pulmonary hypertension

INTRODUCTION Great ventilation to carbon dioxide output (ΔV˙E/ΔV˙CO2) and reduced end-tidal partial pressures for CO2 (PetCO2) during incremental exercise are hallmarks of chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (IPAH). However, CTEPH is more likely to involve proximal arteries, which may lead to poorer right ventricle-pulmonary vascular coupling and worse gas exchange abnormalities. Therefore, abnormal PetCO2 profiles during exercise may be more prominent in patients with CTEPH and could be helpful to indicate disease severity. METHODS Seventy patients with CTEPH and 34 with IPAH underwent right heart catheterization and cardiopulmonary exercise testing. According to PetCO2 pattern during exercise, patients were classified as having an increase or stabilization in PetCO2 up to the gas exchange threshold (GET), an abrupt decrease in the rest-exercise transition or a progressive and slow decrease throughout exercise. A subgroup of patients with CTEPH underwent a constant work rate exercise test to obtain arterial blood samples during steady-state exercise. RESULTS Multivariate logistic regression analyses showed that progressive decreases in PetCO2 and SpO2 were better discriminative parameters than ΔV˙E/ΔV˙CO2 to distinguish CTEPH from IPAH. This pattern of PetCO2 was associated with worse functional impairment and greater reduction in PaCO2 during exercise. CONCLUSION Compared to patients with IPAH, patients with CTEPH present more impaired gas exchange during exercise, and PetCO2 abnormalities may be used to identify more clinically and hemodynamically severe cases.

Intrapulmonary vascular dilatations are common in portopulmonary hypertension and may be associated with decreased survival.

We read with interest the recently published article by Fussner et al. in Liver Transplantation. The authors showed that intrapulmonary vascular dilatations (IPVDs), detected by agitated saline contrast-enhanced transthoracic echocardiography (cTTE), were common in patients with portopulmonary hypertension (POPH)—59% of patients. Moreover, this finding was associated with decreased survival, and the authors suggest the possibility of a pathophysiological overlap between POPH and hepatopulmonary syndrome in patients with end-stage liver disease. Interestingly, this feature was previously described in patients with schistosomiasis. Early reports of the disease identified a unique pattern of pulmonary involvement in patients with schistosomiasis: pulmonary hypertension with central cyanosis in the absence of intracardiac shunt. In 1 study, IPVD was found in 20% of patients with schistosomiasis cor pulmonale. According to necroscopic studies, cyanosis was associated with arteriovenous fistulae, possibly due to bypass of Schistosoma eggs in pulmonary circulation. Furthermore, other investigators confirm this finding and hypothesized that it could be related to repeated worm infestation, common in endemic areas. The pathophysiology of schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is not completely understood, but it probably shares some similarities with POPH, in a model without liver cirrhosis. Sch-PAH is potentially the most common cause of pulmonary hypertension worldwide and is associated with higher survival rates compared to IPAH. Our group recently published an article contrasting physiological responses to incremental exercise in cardiopulmonary exercise tests (CPETs) between naive patients with Sch-PAH (n 5 8) and with idiopathic pulmonary arterial hypertension (IPAH) (n 5 9) with similar resting hemodynamics. Interestingly, Sch-PAH showed less impaired physiological responses to incremental exercise than IPAH patients, suggesting a more preserved cardiopulmonary response to exercise in Sch-PAH, which could be related to its better clinical course compared to IPAH. However, at that time, the mechanisms involved were not identified. Even though none of the patients with Sch-PAH had cyanosis or hypoxemia (only 3 had SpO2 90% at the end of the incremental CPET), cTTE was performed after the publication, and IPVD was detected in 6/8 (75%) Sch-PAH patients (data not published). It is noteworthy that despite the high prevalence of IVPD in this study, only 2 patients died to date (1 of them was without IPVD), which contrasts with the poor prognosis of the presence of IPVD in patients with cirrhosis described by Fussner et al. The clinical relevance of the presence of IPVD in patients with Sch-PAH is not clear, but it is possible to hypothesize that IPVD could attenuate right ventricular stress during exercise. Further studies are needed in order to obtain a better understanding of the natural history of IPVD associated with schistosomiasis as well as to assess the impact of this finding on the exercise capacity and survival of affected patients. Fussner et al. suggested that patients with POPH should be evaluated for IPVD with cTTE, until the relevance of IPVD in this population is clarified. At this time, we believe that it is reasonable to also recommend cTTE in patients with Sch-PAH, which could lead to a better understanding of pulmonary vascular diseases associated with liver dysfunction. Address reprint requests to Fabricio M. Valois, M.D., Ph.D., Division of Respiratory Diseases, Department of Medicine, Universidade Federal de Sao Paulo, Sao Paulo, Brazil. E-mail: fabriciomv@globo.com