Palau P; Seller J; Domínguez E; Gómez I; Ramón JM; Sastre C; de la Espriella R; Santas E; Miñana G; Chorro FJ; González-Juanatey JR; Núñez J;

Clinical Cardiology [Clin Cardiol] 2020 Feb 19. Date of Electronic Publication: 2020 Feb 19.

Background: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has emerged as a crucial pathophysiological mechanism. Beta-blockers, drugs with negative chronotropic effects, are commonly used in HFpEF, although current evidence does not support its routine use in these patients.
Hypothesis: We postulate beta-blockers may have deleterious effects in HFpEF and ChI. This work aims to evaluate the short-term effect of beta-blockers withdrawal on functional capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF and ChI.
Methods: This is a prospective, crossover, randomized (1:1) and multicenter study. After randomization, the clinical and cardiac rhythm will be continuously registered for 30 days. PeakVO2 is assessed by cardiopulmonary exercise testing (CPET) at 15 and 30 days in both groups. Secondary endpoints include quality of life, cognitive, and safety assessment. Patients with stable HFpEF, functional class New York Heart Association (NYHA) II-III, chronic treatment with beta-blockers, and ChI will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 20% loss rate, and delta change of mean peakVO2: +1.2 mL/kg/min (SD ± 2.0)] of 52 patients is necessary to test our hypothesis.
Results: Patients started enrolling in October 2018. As January 14th, 2020, 28 patients have been enrolled. It is projected to enroll the last patient at the end of July 2020.
Conclusions: Optimizing therapy that improves functional capacity remains an unmeet priority in HFpEF. Deprescribing beta-blockers in patients with HFpEF and ChI seems a plausible intervention to improve functional capacity. This trial is an attempt towards precision medicine in this complex syndrome.
Trial Registration: ClinicalTrials.gov: NCT03871803.

Itani L; El Masri D; Kreidieh D; Tannir H; El Ghoch M;

Internal And Emergency Medicine [Intern Emerg Med] 2020 Feb 20. Date of Electronic Publication: 2020 Feb 20.

No abstract available

Schwaab B; Kafsack F; Markmann E; Schütt M;

Cardiovascular Endocrinology & Metabolism [Cardiovasc Endocrinol Metab] 2020 Feb 21; Vol. 9 (1), pp. 3-8. Date of Electronic Publication: 20200221 (Print Publication: 2020).

In patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM), physical activity is strongly advised as nonpharmacological therapy. In general, a moderate aerobic exercise intensity is recommended. It was also proposed, however, that greater intensities tend to yield even greater benefits in HbA1c. Hence, the most appropriate exercise intensity seems not to be established yet. We compared the effect of moderate (aerobic) and vigorous (anaerobic) activity on postprandial plasma glucose.
Methods: In 10 consecutive patients (63 ± 12 years, BMI 28.3 ± 2.6 kg/m2, fasting plasma glucose 6.1 ± 1.2 mmol/l), 2-hour plasma glucose was ≥11.1 mmol/l in the oral glucose tolerance test at rest (OGTT-0). Cardiopulmonary exercise test (CPX) was performed until a respiratory exchange ratio (RER) ≥1.20, beeing anaerobic (CPX-1), followed by OGTT-1. A steady-state CPX of 30-minute duration was performed targeting an RER between 0.90 and 0.95, being aerobic (CPX-2), followed by OGTT-2.
Results: In CPX-1, maximum exercise intensity (maxIntensity) averaged at 99 ± 30 Watt and peak oxygen consumption (VO2peak) reached 15.9 ± 2.8 ml/min/kg. In CPX-2, aerobic intensity averaged at 29 ± 9 Watt, representing 31% of maxIntensity and 61% of VO2peak. After aerobic exercise, 2-hour plasma glucose was significantly reduced to an average of 9.4 ± 2.3 mmol/l (P < 0.05). Anaerobic exercise did not reduce 2-hour plasma glucose as compared to OGTT-0 (12.6 ± 2.2 vs 12.6 ± 3.9 mmol/l).
Conclusion: Aerobic exercise intensity was very low in our patients with CHD and T2DM. Postprandial plasma glucose was reduced only by aerobic exercise. Larger studies on the optimal exercise intensity are needed in this patient cohort.

Zivelonghi C; Konigstein M; Azzano A; Agostoni P; Topilski Y; Banai S; Verheye S

Eurointervention: Journal Of Europcr In Collaboration With The Working Group On Interventional Cardiology Of The European Society Of Cardiology [EuroIntervention] 2020 Feb 25. Date of Electronic Publication: 2020 Feb 25.

Aims: Refractory angina is still a major public health problem. The Coronary Sinus Reducer (CSR) has recently been introduced as an alternative treatment to reduce symptoms in these patients. Aim of this study is to investigate objective improvements in effort tolerance and oxygen kinetics as assessed by cardiopulmonary exercise testing (CPET) in patients suffering from refractory angina undergoing CSR implantation.
Methods and Results: In this multicentre prospective study, patients with chronic refractory angina undergoing CSR implantation were scheduled for CPET before the index procedure and at 6-month follow-up. Main endpoints of this analysis were improvements in VO 2 max and in VO 2 at anaerobic threshold (AT). Clinical events and improvements in symptoms were also recorded. A total of 37 patients formed the study population. CSR implantation procedure was successful and without complications in all. At follow-up CPET significant improvement in VO 2 max (+0.97 ml/kg/min [+11.3%], 12.2±3.6 ml/kg/min at baseline vs 13.2±3.7 ml/kg/min, p=0.026), and workload (+12.9[+34%]; 68±28 W vs 81±49W, p=0.05) were observed, with non-significant differences in VO 2 at AT (9.84±3.4 ml/kg/min vs 10.74±3.05 ml/kg/min, p=0.06). Canadian Cardiovascular Society (CCS) grade improved from a mean of 3.2±0.5 to 1.6±0.8 (p<0.01), and significant benefits in all Seattle Angina Questionnaire variables were shown.
Conclusions: In patients with obstructive coronary artery disease suffering from refractory angina, the implantation of CSR was associated with objective improvement in exercise capacity and oxygen kinetics at CPET, suggesting a possible reduction of myocardial ischemia.

Badagliacca R; Rischard F; Papa S; Kubba S; Vanderpool R;Yuan JX; Garcia JGN; Airhart S; Poscia R; Pezzuto B; DManzi G; Miotti C; Luongo F; Scoccia G; Torre Rn Msn R;Fedele F; Vizza CD;

The Journal Of Heart And Lung Transplantation: The Official Publication Of The International Society For Heart Transplantation [J Heart Lung Transplant] 2020 Jan 21. Date of Electronic Publication: 2020 Jan 21.

Background: Despite advances in drug development, life expectancy in idiopathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient outcome is still unfavorable. The aim of this study was to apply cluster analysis to improve phenotyping of patients with IPAH and analyze long-term clinical outcome of derived clusters.
Methods: Patients with IPAH from 2 referral centers (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurrence.
Results: The cluster analysis identified 4 IPAH phenotypes. Cluster 1 was characterized by young patients, mild pulmonary hypertension (PH), mild right ventricular (RV) dilation and high oxygen (O2) pulse; Cluster 2 by severe PH and RV dilation and high O2 pulse; and Cluster 3 by male patients, severe PH and RV dilation, and low O2 pulse. Cluster 4 patients were older and overweight, with mild PH and RV dilation and low O2 pulse. After a mean follow-up of 995 ± 623 days, 123 (48.8%) patients had clinical worsening. Cluster 1 patients presented the best prognosis, whereas Cluster 3 had the highest rates of clinical worsening. Compared with Cluster 1, risk of clinical worsening ranged from 4.12 (confidence interval [CI] 1.43-11.92; p = 0.009) for Cluster 4 to 7.38 (CI 2.80-19.40) for Cluster 2 and 13.8 (CI 5.60-34.0; p = 0.0001) for Cluster 3.
Conclusions: Cluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within patients with IPAH and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making. CONDENSED ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of this study was to apply cluster analysis to improve phenotyping of IPAH. Patients with IPAH (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size, and oxygen pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multidimensional IPAH phenotyping for improved patient care and trial quality.

Takayanagi Y; Koike A; Kubota H; Wu L; Nishi I; Sato A; Aonuma K; Kawakami Y; Ieda M;

Drug Discoveries & Therapeutics [Drug Discov Ther] 2020 Feb 17. Date of Electronic Publication: 2020 Feb 17.

The pulse wave transit time (PWTT) is easily measured as the time from the R wave of an electrocardiogram to the arrival of the pulse wave measured by an oxygen saturation monitor at the earlobe. We investigated whether the change of PWTT during exercise testing reflects cardiopulmonary function. Eighty-nine cardiac patients who underwent cardiopulmonary exercise testing (CPX) were enrolled. We analyzed the change of PWTT during exercise and the relationship between the shortening of the PWTT and CPX parameters. PWTT was significantly shortened from rest to peak exercise (204.6 ± 33.6 vs. 145.6 ± 26.4 msec, p < 0.001) in all of the subjects. The patients with heart failure had significantly higher PWTT at peak exercise than the patients without heart failure (152.7 ± 27.1 vs. 140.4 ± 24.8 msec, p = 0.031). The shortening of PWTT from rest to peak exercise showed significant positive correlations with the peak O 2 uptake (VO 2 ) (r = 0.56, p < 0.001), anaerobic threshold (r = 0.40, p = 0.016), and % increase of systolic blood pressure during exercise (r = 0.75, p < 0.001), and a negative correlation with the slope of the increase in ventilation versus the increase in CO 2 output (VE-VCO 2 slope) (r = – 0.42, p = 0.010) in the patients with heart failure. PWTT was shortened during exercise as the exercise intensity increased. In the patients with heart failure, the shortening of PWTT from rest to peak exercise was smaller in those with lower exercise capacity and those with higher VE-VCO 2 slope, an established index known to reflect the severity of heart failure.

Stubbs DJ; Grimes LA; Ercole A;

Plos One [PLoS One] 2020 Feb 03; Vol. 15 (2), pp. e0226480. Date of Electronic Publication: 20200203 (Print Publication: 2020).

Introduction: Cardiopulmonary exercise testing (CPET) is widely used within the United Kingdom for preoperative risk stratification. Despite this, CPET’s performance in predicting adverse events has not been systematically evaluated within the framework of classifier performance.
Methods: After prospective registration on PROSPERO (CRD42018095508) we systematically identified studies where CPET was used to aid in the prognostication of mortality, cardiorespiratory complications, and unplanned intensive care unit (ICU) admission in individuals undergoing non-cardiopulmonary surgery. For all included studies we extracted or calculated measures of predictive performance whilst identifying and critiquing predictive models encompassing CPET derived variables.
Results: We identified 36 studies for qualitative review, from 27 of which measures of classifier performance could be calculated. We found studies to be highly heterogeneous in methodology and quality with high potential for bias and confounding. We found seven studies that presented risk prediction models for outcomes of interest. Of these, only four studies outlined a clear process of model development; assessment of discrimination and calibration were performed in only two and only one study undertook internal validation. No scores were externally validated. Systematically identified and calculated measures of test performance for CPET demonstrated mixed performance. Data was most complete for anaerobic threshold (AT) based predictions: calculated sensitivities ranged from 20-100% when used for predicting risk of mortality with high negative predictive values (96-100%). In contrast, positive predictive value (PPV) was poor (2.9-42.1%). PPV appeared to be generally higher for cardiorespiratory complications, with similar sensitivities. Similar patterns were seen for the association of Peak VO2 (sensitivity 85.7-100%, PPV 2.7-5.9%) and VE/VCO2 (Sensitivity 27.8%-100%, PPV 3.4-7.1%) with mortality.
Conclusions: In general CPET’s ‘rule-out’ capability appears better than its ability to ‘rule-in’ complications. Poor PPV may reflect the frequency of complications in studied populations. Our calculated estimates of classifier performance suggest the need for a balanced interpretation of the pros and cons of CPET guided pre-operative risk stratification.

Origuchi H; Momomura SI;Nohara R; Daida H; Masuda T; Kohzuki M; Makita S; Ueshima K; Nagayama M; Omiya K; Adachi H; Goto Y;

Circulation Journal: Official Journal Of The Japanese Circulation Society [Circ J] 2020 Feb 08. Date of Electronic Publication: 2020 Feb 08.

Background: There is little evidence regarding the effect of outpatient cardiac rehabilitation (CR) on exercise capacity or the long-term prognosis in patients after coronary artery bypass graft surgery (CABG). This study aimed to determine whether participation in outpatient CR improves exercise capacity and long-term prognosis in post-CABG Japanese patients in a multicenter cohort.
Methods and Results: We enrolled 346 post-CABG patients who underwent cardiopulmonary exercise testing during early (2-3 weeks) and late (3-6 months) time points after surgery. They formed the Active (n=240) and Non-Active (n=106) CR participation groups and were followed for 3.5 years. Primary endpoint was a major adverse cardiac event (MACE): all-cause death or rehospitalization for acute myocardial infarction/unstable angina/worsening heart failure. Peak oxygen uptake at 3-5 months from baseline was significantly more increased in Active than in Non-Active patients (+26±24% vs. +19±20%, respectively; P<0.05), and the MACE rate was significantly lower in Active than Non-Active patients (3.4% vs. 10.5%, respectively; P=0.02). Multivariate Cox proportional hazard analysis showed that participation in outpatient CR was a significant prognostic determinant of MACE (P=0.03).
Conclusions: This unique study showed that a multicenter cohort of patients who underwent CABG and actively participated in outpatient CR exhibited greater improvement in exercise capacity and better survival without cardiovascular events than their counterparts who did not participate.

Vonbank K; Marzluf B; Knötig M; Funk GC;

Respiration; International Review Of Thoracic Diseases [Respiration] 2020 Jan 31, pp. 1-6. Date of Electronic Publication: 2020 Jan 31.

Background: In moderate-to-severe chronic obstructive pulmonary disease (COPD) patients the 6-min walk test (6MWT) is often exhaustive and correlates with the incremental cycle cardiopulmonary exercise test (CPET).
Objectives: The aim of this study was to assess the agreement between oxygen uptake (VO2) measured during the 6MWT by portable equipment and incremental cycle exercise in COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-IV.
Methods: A total of 30 patients with COPD GOLD I-IV (14 patients GOLD stage I and II and 16 patients GOLD stage III and IV) underwent a 6MWT and an incremental CPET. Breath-by-breath analysis for VO2, carbon dioxide output (VCO2), and minute ventilation (VE) were measured during each test. Blood gas analysis and lactate measurements were performed before, during, and after the test.
Results: VO2 in COPD patients GOLD stage I and II was 16.2 ± 4.2 mL/kg/min measured by 6MWT and 20.5 ± 7.0 mL/kg/min measured by CPET as compared to GOLD stage III and IV (11.2 ± 3.7 mL/kg/min measured by 6MWT and 15.5 ± 4.3 mL/kg/min measured by CPET). No significant correlation in VO2 measurements could be found between both tests in COPD GOLD I and II (r = 0.17), whereas the VO2 significantly correlated in patients with COPD stage III and IV (r = 0.7).
Conclusions: A significant relationship between VO2 measured by 6MWT and CPET could only be found in patients with more severe COPD but not in milder stages. 6MWT and CPET provide different VO2 measurements in COPD patients. The two methods cannot be used interchangeably.

Di Maria MV; Patel SS; Fernie JC; Rausch CM;

Pediatric Cardiology [Pediatr Cardiol] 2020 Jan 31. Date of Electronic Publication: 2020 Jan 31.

Exercise performance declines as patients who have undergone Fontan operation enter adolescence. However, the effect of altitude on functional capacity after Fontan remains inadequately studied. Our aim was to describe exercise performance in a cohort of patients with Fontan physiology living at increased altitude and compare to a normal control group and relate these data to invasively derived hemodynamics. We hypothesized that peak oxygen consumption ([Formula: see text]) would be decreased, in association with elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVRi). Patients were evaluated in a multidisciplinary clinic for patients with Fontan physiology. Evaluation included cardiopulmonary exercise test and cardiac catheterization at predetermined intervals. Descriptive statistics were calculated. Associations of catheterization and exercise testing measures with [Formula: see text] were estimated with Spearman correlation coefficients. One hundred patients with age- and gender-matched controls were included in the analysis. The mean age was 13.3 ± 3.9 years, with mean weight of 47.1 ± 18.4 kg. The mean [Formula: see text] was 29.0 ± 7.8 ml/kg/min, significantly lower than the control group, 40.2 ± 8.4 ml/kg/min (p < 0.0001). There was no statistically significant linear correlation between [Formula: see text] and mPAP or PVRi. We characterized exercise performance in a large cohort with Fontan physiology living at increased altitude and showed a decrease in [Formula: see text] compared to controls. Our data do not support the hypothesis that moderately increased altitude has a detrimental effect on exercise performance, nor is there a substantial link between poor cavopulmonary hemodynamics and exercise in this setting.