Bartolini S; Baldasseroni S; Fattirolli F; Silverii MV; Piccioli L; Perfetto F; Di Mario C; Martone R; Taborchi G;
Morini S; Cappelli F;

Internal and emergency medicine [Intern Emerg Med] 2020 Sep 12. Date of Electronic Publication: 2020 Sep 12.

CardioPulmonary Exercise Test (CPET) is the gold standard to evaluate functional capacity in patients at high risk of heart failure (HF). Few studies with a limited number of subjects and conflicting results, analyzed the role of CPET in patients with systemic amyloidosis. Aims of our study were the assessment of the response to exercise in patients with Transthyretin amyloid (ATTR) cardiomyopathy (CA), and the correlation of clinical, biohumoral and echocardiographic parameters with CPET parameters, such as VO ₂ peak and VE/VCO ₂ slope. From February 2018 to March 2019, 72 cardiac ATTR patients were prospectively enrolled and underwent a complete clinical, biohumoral, echocardiographic and CPET assessment. All patients completed the exercise stress test protocol, without any adverse event. At CPET, they achieved a mean VO ₂ peak of 14 mL/Kg/min and a mean VE/VCO ₂ slope of 31. The blood pressure response to exercise was inadequate in 26 (36%) patients (flat in 25 and hypotensive in 1), while 49/72 patients (69%) showed an inadequate heart rate recovery. In multivariate analysis, s’ tricuspidalic was the only independent predictor of VO ₂ peak, while in the two test models performed to avoid collinearity, both TAPSE and s’ tricuspidalic were the strongest independent predictors of VE/VCO ₂ slope. Our data demonstrate the role of right ventricular function as an independent predictor of exercise capacity and ventilatory efficiency in ATTR. In CPET evaluation, a significant proportion of patients presented an abnormal arterial pressure response and heart rate variation to exercise.

Kinoshita M; Inoue K; Higashi H; Akazawa Y; Sasaki Y; Fujii A; Uetani T; Inaba S; Aono J; Nagai T; Nishimura K; Ikeda S; Yamaguchi O

ESC heart failure [ESC Heart Fail], ISSN: 2055-5822, 2020 Sep 13; Publisher: John Wiley & Sons Ltd on behalf of the European Society of Cardiology; PMID: 32924319

Aims: Traditional criteria for heart transplantation by cardiopulmonary exercise testing (CPX) include peak oxygen uptake (VO ₂ ) < 14 mL/kg/min. Reaching a sufficient exercise load is challenging for patients with refractory heart failure (HF) because of their exercise intolerance. Recently, a substantial impact of right ventricular (RV) dysfunction was highlighted on urgent heart transplantation and mortality. This study aims to investigate the impact of RV contractile reserve, assessed by low-load exercise stress echocardiography (ESE), on exercise intolerance defined as peak VO ₂  < 14 mL/kg/min, in patients with HF.
Methods and Results: We prospectively examined 67 consecutive patients hospitalized for HF who underwent ESE and CPX under a stabilized HF condition. Although low-load ESE was defined as 25 W load exercise, an increment in RV systolic (s’) velocity was regarded as the preservation of RV contractile reserve. All patients completed low-load ESE. During low-load ESE, the variation in RV s’ velocity significantly correlated with peak VO ₂ (r = 0.787, P < 0.001). The change in RV s’ velocity during low-load ESE accurately identified patients with peak VO ₂  < 14 mL/kg/min (area under the curve, 0.95; sensitivity, 92%; specificity, 85%). The intraclass correlation coefficient for intra-observer and inter-observer agreement for the change in RV s’ velocity was 0.96 (95% confidence interval, 0.88-0.99, P < 0.001) and 0.86 (95% confidence interval, 0.64-0.95, P < 0.001), respectively. The RV-to-pulmonary circulation (PC) coupling, which was assessed by the slope of the relationship between RV s’ velocity and pulmonary artery systolic pressure at rest and low-load exercise, was worse in the low-peak VO ₂ group (<14 mL/kg/min) than the preserved-peak VO ₂ group (≥14 mL/kg/min).
Conclusions: The change in RV s’ velocity during low-load ESE could estimate the exercise capacity in HF patients. The assessments of RV contractile reserve and RV-to-PC coupling could be clinically beneficial to distinguish high-risk HF patients.

Argudo N; Rodó-Pin A; Martínez-Llorens J; Marco E; Visa L; Messaggi-Sartor M; Balañá-Corberó A; Ramón JM; Rodríguez-Chiaradía DA; Grande L; Pera M;

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus [Dis Esophagus] 2020 Sep 17. Date of Electronic Publication: 2020 Sep 17.

Patients requiring surgery for locally advanced esophagogastric cancer often require neoadjuvant therapy (NAT), which may have a detrimental impact on cardiorespiratory reserve. The aims of this study were to investigate the feasibility and tolerability of a 5-week preoperative high-intensity interval training program after NAT, and to assess the potential effects of the training protocol on exercise capacity, muscle function, and health-related quality of life (HRQL). We prospectively studied consecutive patients with resectable locally advanced esophageal and gastric cancer in whom NAT was planned (chemo- or chemoradiotherapy). Feasibility was assessed with the TELOS (Technological, Economics, Legal, Operational, and Scheduling) components, and data on exercise tolerability (attendance and occurrence of adverse or unexpected events). Exercise capacity was assessed with peak oxygen uptake (VO2peak) in a cardiopulmonary exercise test at baseline, post-NAT, and following completion of a high-intensity interval exercise training (25 sessions). Changes in muscle strength and HRQL were also assessed. Of 33 recruited subjects (mean age 65 years), 17 received chemoradiotherapy and 16 chemotherapy. All the TELOS components were addressed before starting the intervention; from a total of 17 questions considered as relevant for a successful implementation, seven required specific actions to prevent potential concerns. Patients attended a mean of 19.4 (6.4) exercise sessions. The predefined level of attendance (≥15 sessions of scheduled sessions) was achieved in 27 out of 33 (81.8%) patients. Workload progression was adequate in 24 patients (72.7%). No major adverse events occurred. VO2peak decreased significantly between baseline and post-NAT (19.3 vs. 15.5 mL/Kg/min, P < 0.05). Exercise led to a significant improvement of VO2peak (15.5 vs. 19.6 mL/kg/min, P < 0.05). Exercise training was associated with clinically relevant improvements in some domains of HRQL, with the social and role function increasing by 10.5 and 11.6 points, respectively, and appetite loss and fatigue declining by 16 and 10.5, respectively. We conclude that a structured exercise training intervention is feasible and safe following NAT in patients with esophagogastric cancer, and it has positive effects to restore exercise capacity to baseline levels within 5 weeks with some improvements in HRQL.

Christopoulos G, Bois J, Allison TG, Rodriguez-Porcel M, Chareonthaitawee P;

J Nucl Cardiol. 2019 Feb;26(1):92-106. doi: 10.1007/s12350-017-0910-3. Epub 2017 May 15.

OBJECTIVE: The diagnostic yield of combined cardiopulmonary exercise testing (CPET) and myocardial perfusion imaging (MPI) in patients referred for stress testing has received limited study.
METHODS: We evaluated consecutive patients who underwent combined CPET-MPI at a single tertiary referral center between 2011 and 2015. An abnormal CPET was defined as any of the following: reduced oxygen consumption, cardiac output impairment, or pulmonary impairment. Normal MPI was defined as the absence of resting or stress perfusion defect. The primary study outcome was change in clinical decision-making after CPET-MPI including management of pulmonary disease, management of deconditioning, heart failure management, and referral for cardiac catheterization. Outcomes of patients with normal and abnormal MPI were presented based on the specific CPET abnormality.
RESULTS: 415 patients were included in the study. Of the 269 patients that had normal MPI, 206 (77%) had abnormal CPET. Patients with abnormal CPET and normal MPI, compared with patients that had normal CPET and normal MPI, were more frequently diagnosed with pulmonary disease (11.7% vs 3.2%, P = .04) and deconditioning (33.5% vs 17.4%, P = .01). Of the 146 patients that had abnormal MPI, 128 (88%) had abnormal CPET. Patients with abnormal CPET and abnormal MPI, compared with patients that had normal CPET and abnormal MPI, did not statistically differ with regard to the study outcome.
CONCLUSION: An abnormal CPET, if the MPI was normal, prompted further evaluation and led to management of pulmonary disease and deconditioning.

Rosato E;Leodori G;Gigante A;Di Paolo M;Paone G;Palange P;

Clinical and experimental rheumatology [Clin Exp Rheumatol] 2020 May-Jun; Vol. 38 Suppl 125 (3), pp. 85-91. Date of Electronic Publication: 2020 Aug 26.

Objectives: Major vascular complication, such as digital ulcers (DUs), pulmonary arterial hypertension (PAH) and scleroderma renal crisis (SRC) are hallmarks of systemic sclerosis (SSc). Interstitial lung disease (ILD) is the major cause of mortality in SSc. The aim of study is to identify cardiopulmonary exercise testing (CPET) variables that predict MVC and mortality for ILD in SSc patients.
Methods: In this cohort study, 45 SSc patients underwent clinical evaluation, echocardiography, pulmonary function tests (PFTs), high resolution computerised tomography (HRCT) and CPET. PFTs and echocardiography were performed annually for a 5-year follow-up.
Results: 16 (35.6%) SSc patients had MVC: 14 new DUs (31.1%), 1 PAH (2.2%) and 1 SRC (2.2%). At univariate regression analysis, mRss [HR 1.099 (1.008-1.199), p<0.05], NVC patterns (active and late) [HR 0.032 (0.004-0.250), p<0.001], V’E/V’CO2 slope [HR 1.123 (1.052-1.198), p<0.001] were predictive of new onset of MVC. In multivariate analysis, NVC patterns (active and late) (HR 0.044 (0.004-0.486), p<0.05), V’E/V’CO2 (HR 1.094 (1.020-1.198), p<0.05) were predictive of new onset of MVC. The 5-year mortality for ILD is 8.9%. In univariate analysis, DLco [(HR 0.927(CI 0.874- 0.983), p<0.05], V’E/V’CO2 slope and lung parenchymal with radiological patterns of ILD [(1.2.02 (CI 1.018-1.419), p<0.05], represent risk factors for 5-year mortality for ILD [HR 1.142 (1.030-1.267), p<0.05]. In multivariate analysis, only V’E/V’CO2 slope [1.268 (CI 1.003-1.602), p<0.05] represents a risk factor for 5-year mortality for ILD.
Conclusions: V’ E/V’ CO2 slope is a prognostic marker of MVC and five-year mortality for ILD.

Fermoyle CC;Stewart GM;Borlaug BA;Johnson BD;

Journal of cardiac failure [J Card Fail] 2020 Aug 01. Date of Electronic Publication: 2020 Aug 01.

Elevated left ventricular filling pressure (measured as mean pulmonary capillary wedge pressure) at rest or with exercise is diagnostic of heart failure with preserved ejection fraction. However, the capacity of the right ventricle to compensate for a high mean pulmonary capillary wedge pressure and thus maintain an appropriate transpulmonary gradient (TPG) and perfusion of the pulmonary capillaries is likely an important contributor to gas exchange efficiency and exercise capacity. Therefore, this study aimed to determine whether a higher TPG at peak exercise is associated with superior exercise capacity and gas exchange. Gas exchange data from dyspneic patients referred for exercise right heart catheterization were retrospectively analyzed and patients were split into two groups based on TPG. Patients with a higher TPG at peak exercise had a higher peak VO ₂ (1025 ± 227 vs 823 ± 276, P = .038), end-tidal partial pressure of carbon dioxide (42.2 ± 7.9 vs 38.0 ± 4.7, P = .044), and gas exchange estimates of pulmonary vascular capacitance (408 ± 90 vs 268 ± 108, P = .001). A higher TPG at peak exercise correlated with a higher peak oxygen uptake, O ₂ pulse, and stroke volume (R = 0.42, 0.44 and 0.42, respectively, all P < 0.05). These findings indicate that a greater TPG with exercise might be important for improving exercise capacity in heart failure with preserved ejection fraction.

Sabbahi A;Arena R;Kaminsky LA;Myers J;Fernhall B; Sundeep C;Phillips SA;

Journal of human hypertension [J Hum Hypertens] 2020 Aug 31. Date of Electronic Publication: 2020 Aug 31.

It has been established that blacks have higher overall incidence and prevalence of hypertension compared to their white counterparts. However, the maximum blood pressure (BP) response of blacks to exercise has not been characterized. A total of 5996 apparently healthy men from the Fitness Registry and Importance of Exercise: A National Database (FRIEND) who underwent maximum cardiopulmonary exercise tests on a cycle ergometer were included in this analysis. Of these participants, 1245 (21%) self-identified as black while the remaining 4751 (79%) identified as white. All subjects had a respiratory exchange ratio (RER) of ≥1.0 and had no reports of cardiovascular or pulmonary disease. Systolic BP (BP) response to exercise was indexed according to increase in workload (SBP/MET-slope). Both racial groups were subdivided into age groups by decade. Black men had higher peak SBP and higher SBP/MET-slopes compared to white men across all age groups (p < 0.001). Resting SBP was not different between blacks and whites except within the 18-29-year age group. The differences in peak SBP and SBP/MET-slope between age and race groups indicate that black men have an exaggerated BP response to exercise irrespective of resting BP values. Further investigation is warranted to determine the underlying mechanisms responsible and clinical implications for this exaggerated BP response to exercise.

Taylor JL;Holland DJ;Keating SE;Leveritt MD;Gomersall SR;Rowlands AV;Bailey TG;Coombes JS;

JAMA cardiology [JAMA Cardiol] 2020 Sep 02. Date of Electronic Publication: 2020 Sep 02.

Importance: High-intensity interval training (HIIT) is recognized as a potent stimulus for improving cardiorespiratory fitness (volume of oxygen consumption [VO2] peak) in patients with coronary artery disease (CAD). However, the feasibility, safety, and long-term effects of HIIT in this population are unclear.
Objective: To compare HIIT with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and efficacy of improving VO2 peak in patients with CAD.
Design, Setting, and Participants: In this single-center randomized clinical trial, participants underwent 4 weeks of supervised training in a private hospital cardiac rehabilitation program, with subsequent home-based training and follow-up over 12 months. A total of 96 participants with angiographically proven CAD aged 18 to 80 years were enrolled, and 93 participants were medically cleared for participation following a cardiopulmonary exercise test. Data were collected from May 2016 to December 2018, and data were analyzed from December 2018 to August 2019.
Interventions: A 4 × 4-minute HIIT program or a 40-minute MICT program (usual care). Patients completed 3 sessions per week (2 supervised and 1 home-based session) for 4 weeks and 3 home-based sessions per week thereafter for 48 weeks.
Main Outcomes and Measures: The primary outcome was change in VO2 peak during the cardiopulmonary exercise test from baseline to 4 weeks. Further testing occurred at 3, 6, and 12 months. Secondary outcomes were feasibility, safety, adherence, cardiovascular risk factors, and quality of life.
Results: Of 93 randomized participants, 78 (84%) were male, the mean (SD) age was 65 (8) years, and 46 were randomized to HIIT and 47 to MICT. A total of 86 participants completed testing at 4 weeks for the primary outcome, including 43 in the HIIT group and 43 in the MICT group; 69 completed testing at 12 months for VO2 peak, including 32 in the HIIT group and 37 in the MICT group. After 4 weeks, HIIT improved VO2 peak by 10% compared with 4% in the MICT group (mean [SD] oxygen uptake: HIIT, 2.9 [3.4] mL/kg/min; MICT, 1.2 [3.4] mL/kg/min; P = .02). After 12 months, there were similar improvements from baseline between groups, with a 10% improvement in the HIIT group and a 7% improvement in the MICT group (mean [SD] oxygen uptake: HIIT, 2.9 [4.5] mL/kg/min; MICT, 1.8 [4.3] mL/kg/min; P = .30). Both groups had high feasibility scores and low rates of withdrawal due to serious adverse events (3 participants in the HIIT group and 1 participant in the MICT group). One event occurred following exercise (hypotension) in the HIIT group. Over 12 months, both home-based HIIT and MICT had low rates of adherence (HIIT, 18 of 34 [53%]; MICT, 15 of 37 [41%]; P = .35) compared with the supervised stage (HIIT, 39 of 44 [91%]; MICT, 39 of 43 [91%]; P > .99).
Conclusions and Relevance: In this randomized clinical trial, a 4-week HIIT program improved VO2 peak compared with MICT in patients with CAD attending cardiac rehabilitation. However, improvements in VO2 peak at 12 months were similar for both groups. HIIT was feasible and safe, with similar adherence to MICT over 12-month follow-up. These findings support inclusion of HIIT in cardiac rehabilitation programs as an adjunct or alternative modality to moderate-intensity exercise.

Niu S, Wang F, Yang S, Jin Z, Han X, Zou S, Guo D), Guo C;

J Int Med Res. 2020 Aug;48(8)

OBJECTIVES: We aimed to determine the predictive value of cardiopulmonary exercise testing (CPX) in the prognosis of patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). METHODS: We conducted a retrospective study including patients who underwent CPX within 1 year of PCI between September 2012 and October 2017. Patients were followed-up until the occurrence of a major adverse cardiac event (MACE) or administrative censoring (September 2019). A Cox regression model was used to identify significant predictors of a MACE. Model performance was evaluated in terms of discrimination (C-statistic) and calibration (calibration-in-the-large).
RESULTS: In total, 184 patients were included and followed-up for a median 51 months (interquartile range: 36-67 months) and 32 events occurred. Multivariable analysis revealed that body mass index and Gensini score were significant predictors of a MACE. Four CPX-related variables were found to be predictive of a MACE: premature CPX termination, peak oxygen uptake, heart rate reserve, and ventilatory equivalent for carbon dioxide slope. The final prediction model had a C-statistic of 0.92 and calibration-in-the-large 0.58%.
CONCLUSION: CPX-related parameters may have high predictive value for poor outcomes in patients with ACS who undergo PCI, indicating a need for appropriate treatment and timely management.

Savi D; Schiavetto S; Simmonds NJ; Righelli D; Palange P.

Journal of Cystic Fibrosis. 18(3):420-424, 2019 05.

The combination of the corrector lumacaftor with the potentiator ivacaftor
has been approved for treatment of cystic fibrosis (CF) patients
homozygous for the Phe508del CFTR mutation. There are no reports detailing
the effect of lumacaftor-ivacaftor on physical activity (PA) and exercise
tolerance. We performed incremental cardiopulmonary exercise testing
(CPET) and we assessed PA pre- and post 2years initiation of
lumacaftor-ivacaftor in three CF adults. PA of mild intensity improved by
+13% in patient 1, + 84% in patients 2 and+89% in patient 3. Oxygen uptake
increased both at anaerobic threshold and at peak exercise (patient 1+33%,
patient 2+42% and patient 3+20%). Daily physical activities and exercise
tolerance improved after two years of lumacaftor-ivacaftor therapy.