Category Archives: Publications

The impact of combined cardiopulmonary exercise testing and SPECT myocardial perfusion imaging on downstream evaluation and management.

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.

Reduced ventilatory efficiency during exercise predicts major vascular complications and mortality for interstitial lung disease in systemic sclerosis.

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.

Pulmonary Vascular Pressures and Gas Exchange Response to Exercise in Heart Failure With Preserved Ejection Fraction.

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.

Characterization of the blood pressure response during cycle ergometer cardiopulmonary exercise testing in black and white men : Data from the Fitness Registry and Importance of Exercise: A National Database (FRIEND).

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.

Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation: The FITR Heart Study Randomized Clinical Trial.

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.

Predictive value of cardiopulmonary fitness parameters in the prognosis of patients with acute coronary syndrome after percutaneous coronary intervention.

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.

Effects of Lumacaftor/Ivacaftor on physical activity and exercise tolerance in three adults with cystic fibrosis.

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.

Pulmonary Hypertension in Advanced Heart Failure: Assessment and Management of the Failing RV and LV. [Review]

Rao SD; Menachem JN; Birati EY; Mazurek JA.

Current Heart Failure Reports. 16(5):119-129, 2019 10.

PURPOSE OF REVIEW: In patients with heart failure with reduced ejection
fraction, the presence of pulmonary hypertension (PH-LHD) has a
significant impact on their prognosis. The purpose of this review is to
explain the methods of diagnosing PH-LHD and then discuss the available
therapeutic options.
RECENT FINDINGS: We begin by examining the methods of assessment of
PH-LHD-echocardiography, cardiopulmonary exercise testing, and right heart
catheterization-with a particular focus on the importance of accurate
measurement to ensure the proper determination of PH-LHD. We then focus
primarily on management of PH-LHD, with an examination of trials of
therapeutic options, use of mechanical circulatory support, and
transplantation. This review highlights the complexities in diagnosis and
management of PH-LHD. We outline a number of useful ways to maximize the
yield of diagnostic testing, as well as give suggestions on the use of
medical therapies, the role of both temporary mechanical support and left
ventricular assist device, and finally the ways to best bridge these
patients to transplantation.

Ventilatory Efficacy After Transcatheter Aortic Valve Replacement Predicts Mortality and Heart Failure Events in Elderly Patients.

Murata M; Adachi H; Nakade T; Miyaishi Y; Kan H; Okonogi S; Kuribara J;
Yamashita E; Kawaguchi R; Ezure M.

Circulation Journal. 83(10):2034-2043, 2019 09 25.
VI 1

BACKGROUND: We aimed to clarify the predictors of death or heart failure
(HF) in elderly patients who undergo transcatheter aortic valve
replacement (TAVR). Methods and Results: We prospectively enrolled 83
patients (age, 83+/-5 years) who underwent transthoracic echocardiography
(TTE) and cardiopulmonary exercise testing (CPET) with impedance
cardiography post-TAVR. We investigated the association of TTE and CPET
parameters with death and the combined outcome of death and HF
hospitalization. Over a follow-up of 19+/-9 months, peak oxygen uptake
(VO2) was not associated with death or the combined outcome. The minimum
ratio of minute ventilation (VE) to carbon dioxide production (VCO2) and
the VE vs. VCO2slope were higher in patients with the combined outcome.
After adjusting for age, sex, Society of Thoracic Surgeons score and peak
VO2, ventilatory efficacy parameters remained independent predictors of
the combined outcome (minimum VE/VO2: hazard ratio, 1.108; 95% confidence
interval, 1.010-1.215; P=0.031; VE vs. VCO2slope: hazard ratio, 1.035; 95%
confidence interval, 1.001-1.071; P=0.044), and had a greater area under
the receiver-operating characteristic curve. The VE vs. VCO2slope >=34.6
was associated with higher rates of the combined outcome, as well as lower
cardiac output at peak work rate during CPET.
CONCLUSIONS: In elderly patients, lower ventilatory efficacy post-TAVR is
a predictor of death and HF hospitalization, reflecting lower cardiac
output at peak exercise.

Muscle Cramping in the Marathon: Dehydration and Electrolyte Depletion vs. Muscle Damage.

Martínez-Navarro I; Montoya-Vieco A;Collado E;Hernando B; Panizo N; Hernando C;

Journal of strength and conditioning research [J Strength Cond Res] 2020 Aug 12. Date of Electronic Publication: 2020 Aug 12.

Our aim was to compare dehydration variables, serum electrolytes, and muscle damage serum markers between runners who suffered exercise-associated muscle cramps (EAMC) and runners who did not suffer EAMC in a road marathon. We were also interested in analyzing race pacing and training background. Nighty-eight marathoners took part in the study. Subjects were subjected to a cardiopulmonary exercise test. Before and after the race, blood and urine samples were collected and body mass (BM) was measured. Immediately after the race EAMC were diagnosed. Eighty-eight runners finished the marathon, and 20 of them developed EAMC (24%) during or immediately after the race. Body mass change, post-race urine specific gravity, and serum sodium and potassium concentrations were not different between crampers and noncrampers. Conversely, runners who suffered EAMC exhibited significantly greater post-race creatine kinase (464.17 ± 220.47 vs. 383.04 ± 253.41 UI/L, p = 0.034) and lactate dehydrogenase (LDH) (362.27 ± 72.10 vs. 307.87 ± 52.42 UI/L, p = 0.002). Twenty-four hours post-race also values of both biomarkers were higher among crampers (CK: 2,438.59 ± 2,625.24 vs. 1,166.66 ± 910.71 UI/L, p = 0.014; LDH: 277.05 ± 89.74 vs. 227.07 ± 37.15 UI/L, p = 0.021). The difference in the percentage of runners who included strength conditioning in their race training approached statistical significance (EAMC: 25%, non-EAMC: 47.6%; p = 0.074). Eventually, relative speed between crampers and noncrampers only differed from the 25th km onward (p < 0.05). Therefore, runners who suffered EAMC did not exhibit a greater degree of dehydration and electrolyte depletion after the marathon but displayed significantly higher concentrations of muscle damage biomarkers.