Category Archives: Publications

Age-related change in peak oxygen uptake and change of cardiovascular risk factors. The HUNT study.

Letnes JM; Dalen H; Aspenes ST; Salvesen Ø; Wisløff U; Nes BM;

Progress in cardiovascular diseases [Prog Cardiovasc Dis] 2020 Sep 21. Date of Electronic Publication: 2020 Sep 21.

Background: Large longitudinal studies on change in directly measured peak oxygen uptake (VO 2peak ) is lacking, and its significance for change of cardiovascular risk factors is uncertain. We aimed to assess ten-year change in VO 2peak and the influence of leisure-time physical activity (LTPA), and the association between change in VO 2peak and change in cardiovascular risk factors.
Methods and Results: A healthy general population sample had their VO 2peak directly measured in two (n = 1471) surveys of the Nord-Trøndelag Health Study (HUNT3; 2006-2008 and HUNT4; 2017-19). Average ten-year decline in VO 2peak was non-linear and progressed from 3% in the third to about 20% in the eight decade in life and was more pronounced in men. The fit linear mixed models including an additional 2933 observations from subjects participating only in HUNT3 showed similar age-related decline. Self-reported adherence to LTPA recommendations was associated with better maintenance of VO 2peak , with intensity seemingly more important than minutes of LTPA with higher age. Adjusted linear regression analyses showed that one mL/kg/min better maintenance of VO 2peak was associated with favorable changes of individual cardiovascular risk factors (all p ≤ 0.002). Using logistic regression one mL/kg/min better maintenance of VO 2peak was associated with lower adjusted odds ratio of hypertension (0.95 95% CI 0.92 to 0.98), dyslipidemia (0.92 95% CI 0.89 to 0.94), and metabolic syndrome (0.86 95% CI 0.83 to 0.90) at follow-up.
Conclusions: Although VO 2peak declines progressively with age, performing LTPA and especially high-intensity LTPA is associated with less decline. Maintaining VO 2peak is associated with an improved cardiovascular risk profile.

Functional Capacity Past Age 40 in Patients With Congenital Ventricular Septal Defects.

Maagaard M; Eckerström F; Boutrup N; Hjortdal VE;

Journal of the American Heart Association [J Am Heart Assoc] 2020 Sep 23, pp. e015956. Date of Electronic Publication: 2020 Sep 23.

Background Ventricular septal defects (VSD), when treated correctly in childhood, are considered to have great prognoses, and the majority of patients are discharged from follow-up when entering their teens. Young adults were previously found to have poorer functional capacity than healthy peers, but the question remains whether functional capacity degenerates further with age.
Methods and Results A group of 30 patients with surgically closed VSDs (51±8 years) with 30 matched, healthy control participants (52±9 years) and a group of 30 patients with small unrepaired VSDs (55±12 years) and 30 matched control participants (55±10 years) underwent cardiopulmonary exercise testing using an incremental workload protocol and noninvasive gas measurement. Peak oxygen uptake was lower in participants with closed VSDs than matched controls (24±7 versus 34±9 mL/min per kg, P <0.01) and with unrepaired VSDs than matched controls (26±5 versus 32±8 mL/min per kg, P <0.01). Patients demonstrated lower oxygen uptake from exercise levels at 20% of maximal workload compared with respective control groups ( P <0.01). Peak ventilation was lower in patients with surgically closed VSDs than control participants (1.0±0.3 versus 1.4±0.4 L/min per kg, P <0.01) but similar in patients with unrepaired VSDs and control participants ( P =0.14). Exercise capacity was 29% lower in older patients with surgically closed VSDs than healthy peers, whereas younger patients with surgically closed VSDs previously demonstrated 18% lower capacity compared with peers. Older patients with unrepaired VSDs reached 21% lower exercise capacity, whereas younger patients with unrepaired VSDs previously demonstrated 17% lower oxygen uptake than healthy peers.
Conclusions Patients with VSDs demonstrate poorer exercise capacity than healthy peers. The difference between patients and control participants increased with advancing age-and increased most in patients with operated VSDs-compared with previous findings in younger patients. Results warrant continuous follow-up for these simple defects.

Establishment of exercise intensity for patients with chronic heart failure equivalent to anaerobic threshold based on 6-minute walking test.

Luo Q; Li C; Zhuang B; Li G; Luo L; Ni Y; Huang Z; Wang L; Song H; Yan W; Shen Y;

Annals of palliative medicine [Ann Palliat Med] 2020 Aug 27. Date of Electronic Publication: 2020 Aug 27.Publication Model:

Background: The study aimed to investigate the relationship between the aerobic exercise intensity determined by 6-minute walking distance (6MWD) and its counterpart based on anaerobic threshold (AT) in chronic heart failure (CHF) individuals for exploring suitable means for CHF exercise rehabilitation.
Methods: We retrospectively analyzed data in patient with CHF, who performed cardiopulmonary exercise test (CPET) and 6-minute walking test (6MWT) uniformly. Anthropometric characteristics, left ventricular ejection fraction (LVEF), and multiple parameters of 6MWT and AT were collected.
Results: The results of the analysis revealed that the 6MWD was correlated with the AT positively [CHF group: r=0.433, heart failure with reduced ejection fraction (HFrEF) group: r=0.395, heart failure with intermediate ejection fraction (HFmEF) group: r=0.477, heart failure with preserved ejection fraction (HFpEF) group: r=0.445; all P<0.05]. The regression analysis showed that the linear equation model developed can predict exercise intensity based on AT (EIAT) by exercise intensity based on 6MWD (EI6MWD), the aerobic exercise intensity based on AT and 6MWD respectively, of CHF patients.
Conclusions: There is a correlation between EI6MWD and EIAT. 74.6-87.4% of EI6MWD in patients with CHF is equivalent to EIAT. It is feasible to establish the aerobic exercise intensity of patients with CHF equivalent to AT based on 6MWD.

Poor right ventricular function is associated with impaired exercise capacity and ventilatory efficiency in transthyretin cardiac amyloid patients.

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.

Impact of right ventricular contractile reserve during low-load exercise on exercise intolerance in heart failure.

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.

Feasibility, tolerability, and effects of exercise-based prehabilitation after neoadjuvant therapy in esophagogastric cancer patients undergoing surgery: an interventional pilot study.

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.

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.