Nakade T; Adachi H; Murata M; Naito S;

Circulation Journal: Official Journal Of The Japanese Circulation Society [Circ J] 2019 Nov 28. Date of Electronic Publication: 2019 Nov 28.

Background: Cardiopulmonary exercise testing (CPX) is used in the prognostic evaluation of patients with heart failure with reduced ejection fraction (HFrEF). In these patients, the ventilation feedback system is dysfunctional, and overactive peripheral chemoreceptors may be responsible for the early appearance of the respiratory compensation point (RCP) after the anaerobic threshold (AT). The mechanism of RCP appearance remains unknown and very few studies have reported the relationship between RCP and heart failure. We hypothesized that the duration between the RCP and AT (RCP-AT time) can predict the severity of cardiac disorders and prognosis in patients with HFrEF.Methods and Results:We enrolled 143 patients with HFrEF who underwent symptom-limited maximal CPX between 2012 and 2016. During a median follow-up of 1.4 years, cardiovascular death occurred in 45 participants (31%). The patients who died had a significantly shorter RCP-AT time and lower hemoglobin (Hb) levels than those who survived (P<0.001 and P=0.01, respectively). Cox regression analyses revealed RCP-AT time and Hb level to be independent predictors of cardiovascular death in patients with HFrEF (P<0.001 and P=0.018, respectively).
Conclusions: RCP-AT time can better predict prognosis in patients with HFrEF than the magnitude of increase in oxygen consumption within the isocapnic buffering domain (∆V̇O2AT-RCP). It may be useful as a new prognostic indicator in these patients.

Vainshelboim B; Arena R; Kaminsky LA; Myers J;

Chest [Chest] 2019 Nov 30. Date of Electronic Publication: 2019 Nov 30

Background: Established reference standards for the ventilatory threshold (VT) are lacking. The aim of this study was to develop reference standards for the VT derived from cardiopulmonary exercise testing (CPX) using treadmill and cycle ergometry.
Methods: Seven laboratories experienced in CPX administration with established quality control procedures contributed to the “Fitness Registry and the Importance of Exercise: A National Database” (FRIEND) from April 2014 through February 2019. VT data from 27 states in the US and Ontario Province of Canada, comprising 9,350 tests [treadmill (n=1,195), cycle ergometer (n=8,155)] in men (n=7,540) and women (n=1,810) aged 20-79 years who were free from smoking and known cardiovascular, pulmonary, metabolic and/or neoplastic disease were used to develop the reference standards. Comparisons of VT values were made between exercise testing modes, sex, and age groups.
Results: VT values on the treadmill were higher compared to cycle ergometry; men had higher VTs compared to women on both test modalities and the highest VT values achieved were in the 20-29 year age group compared to all other age groups (all p<.001). The rates of decline in VT from age groups 20-29 to 70-79 years were 23% and 35% in men and 47% and 30% in women for treadmill and cycle ergometry tests, respectively.
Conclusions: In addition to previous reference standards from FRIEND for cardiorespiratory fitness, the VT reference standards reported herein provide valuebale information on functional metric. These data have important implications for CPX interpretation and aerobic exercise prescription in the clinical and fitness settings.

Sanz-de la Garza M; Vaquer-Seguí A; Durán K; Blanco I; Burgos F; Alsina X;Bijnens B; Sitges M;

European Journal Of Preventive Cardiology [Eur J Prev Cardiol] 2019 Dec 04, pp. 2047487319891779. Date of Electronic Publication: 2019 Dec 04.

Background: The mechanisms underlying the high interindividual variability demonstrated for right-ventricular (RV) adaptation to exercise have not yet been identified, but different pulmonary vascular adaptations among individuals could be involved. Pulmonary transit of agitated saline (PTAS) during exercise has been demonstrated to be a good estimator of vascular reserve.
Aim: The aim of this study was to evaluate the presence of PTAS among endurance athletes (EAs) of both sexes and its influence on RV adaptation to exercise.
Methods: A total of 100 highly trained EAs performed a maximal cardiopulmonary exercise test. Bi-ventricular functional and structural characteristics as well as PTAS were evaluated at baseline and at peak exercise. Athletes were distributed between two groups based on the amount of PTAS during exercise as high (HTPAS; >12 bubbles) and low (LPTAS; ≤12 bubbles).
Results: Overall, 11 EAs exhibited an intra-cardiac shunt at rest and 1 met the criteria for chronic pulmonary disease and were excluded from the study. Among the remaining 88 EAs (51% women), 47 (53%) athletes were classified as HPTAS and 41 (47%) as LPTAS. HPTAS capability was associated with significantly larger RV contractile reserve, larger pulmonary vascular reserve and an enhanced maximal exercise capacity. On multivariate analysis, females were the only independent correlate of the HPTAS capability.
Conclusion: In highly trained endurance athletes, a HPTAS capability during exercise corresponded to an increase in pulmonary vascular and RV contractile reserves as well as an enhanced maximal exercise capacity. The long-term clinical or performance implications of the absence or presence of pulmonary shunting, and the subsequent RV afterload increase while performing exercise, remains to be determined.

Schlüter K; Schneider J; Sprave T; Wiskemann J; Rosenberger F;

Medicine And Science In Sports And Exercise [Med Sci Sports Exerc] 2019 Dec; Vol. 51 (12), pp. 2443-2450.

Purpose: High-intensity interval training (HIIT) is a time-efficient and promising tool for enhancing physical fitness. However, there is lack of research concerning safety and feasibility of HIIT in cancer survivors. Therefore, two different HIIT protocols were investigated in terms of safety, feasibility, and acute exercise responses.
Methods: Forty cancer survivors (20 breast and 20 prostate cancer survivors, 62.9 ± 9.2 yr, BMI 27.4 ± 3.9 kg·m, 6 to 52 wk after the end of primary therapy) completed a maximal cardiopulmonary exercise test and two HIIT protocols on a cycle ergometer: 10 × 1 min at peak power output (10 × 1) and 4 × 4 min at 85%-95% peak HR (4 × 4). Safety (adverse events), acute physiological responses (HR, blood lactate concentration) and acute psychological responses (RPE, enjoyment) were recorded.
Results: No major but three minor adverse events occurred. Ninety-five percent of participants were able to complete each HIIT protocol. Estimated energy expenditure (159 ± 15 vs 223 ± 45 kcal, P < 0.001), HR (128 ± 20 vs 139 ± 18 bpm; P < 0.001), blood lactate concentration (5.4 ± 1.0 vs 5.9 ± 1.9 mmol·L; P = 0.035), and RPE legs/breathing (13.8 ± 2.0/13.1 ± 2.0 vs 14.6 ± 2.1/14.3 ± 2.0; P = 0.038/0.003) were significantly higher in the 4 × 4. Enjoyment did not differ between protocols (P = 0.301).
Conclusions: The two HIIT protocols as single sessions appear safe and in the vast majority of breast and prostate cancer survivors after the end of primary therapy also feasible and enjoyable. The 4 × 4 elicited higher energy expenditure and higher cardio-circulatory and metabolic strain and might therefore be preferred if a high training stimulus is intended.Entry Date(s):

The American Journal Of Cardiology [Am J Cardiol] 2019 Oct 10. Date of Electronic Publication: 2019 Oct 10.

van Wezenbeek J; Canada JM; Ravindra K; Carbone S; Kadariya D; Trankle CR; Wohlford G; Buckley L; Del Buono MG; Viscusi M; Tchoukina I; Shah KB; VCU Arena R; Van Tassell B; Abbate A;

The American Journal Of Cardiology [Am J Cardiol] 2019 Oct 10. Date of Electronic Publication: 2019 Oct 10.

Impaired cardiorespiratory fitness (CRF) in heart failure (HF) is influenced by a complex array of cardiac and extracardiac factors. The study aimed to identify clinical determinants of CRF measured as peak oxygen consumption (peak VO2) in HF patients, and to determine a peak VO2 prediction model using regression equations. Retrospective analysis of 200 HF patients who completed treadmill cardiopulmonary exercise testing and underwent Doppler echocardiography and/or biomarker analysis on the same day was performed. After univariate linear regression analysis, a multivariate peak VO2 prediction model was developed using significant variables in a stepwise linear regression analysis. In subjects with repeated testing, Pearson’s correlation was used to assess correlations between measured and predicted change in peak VO2 (Δpeak VO2) over time. Mean age was 57 years, with 55% being male. Stepwise linear regression was used to generate a weighted model for peak VO2: 30.895 + (-0.112•age[years]) + (0.296•hemoglobin [g/dl]) + (-0.101•E/e'[unit change]) + (-0.202• body mass index [kg/m2]) + (-0.593• N-terminal pro-brain natriuretic peptide [logN pg/ml])) + (-1.349•CRP [log mg/L]). Predicted peak VO2 correlated strongly with measured peak VO2 in HF with reduced ejection fraction and HF with preserved ejection fraction patients (r = +0.63, p <0.001; r = +0.64, p <0.001, respectively). Predicted Δpeak VO2 correlated with measured Δpeak VO2 (r = +0.23, p <0.001).
In conclusion, in patients with HF across a wide range of left ventricular ejection fraction, age, systemic inflammation, oxygen carrying capacity, obesity, and elevated filling pressures are the strongest predictors of impaired CRF. The proposed CRF model allows prediction of peak VO2 in HF patients and may be used to estimate peak VO2 changes over time.

Vukomanovic V; Suzic-Lazic J; Celic V; Cuspidi C; Skokic D; Esposito A; Grassi G; Tadic M;

Acta Diabetologica [Acta Diabetol] 2019 Nov 08. Date of Electronic Publication: 2019 Nov 08.

Aims: This study investigated the association between cardiorespiratory fitness and right ventricular (RV) strain in uncomplicated diabetic patients.
Methods: This cross-sectional study involved 70 controls and 61 uncomplicated patients with type 2 diabetes, who underwent laboratory analysis, comprehensive echocardiographic study and cardiopulmonary exercise testing.
Results: RV endocardial and mid-myocardial longitudinal strains were significantly reduced in diabetic subjects (- 27.5 ± 4.2% vs. - 25.3 ± 4.3%, p = 0.004 for endocardial strain; - 25.6 ± 3.5% vs. - 24.1 ± 3.2%, p = 0.012 for mid-myocardial strain). The same was revealed for endocardial and mid-myocardial of RV free wall. There was no difference in RV epicardial strain. VO2 was significantly lower in the diabetic group (27.8 ± 4.5 ml/kg/min vs. 21.5 ± 4.2 ml/kg/min, p < 0.001), whereas ventilation/carbon dioxide slope was significantly higher in diabetic subjects (25.4 ± 2.9 vs. 28.6 ± 3.3). Heart rate recovery was significantly lower in diabetic patients. HbA1c and global RV endocardial longitudinal strain were independently associated with peak VO2 and oxygen pulse in the whole study population.
Conclusion: Diabetes impacts RV mechanics, but endocardial and mid-myocardial layers are more affected than epicardial layer. RV endocardial strain and HbA1c were independently associated with cardiorespiratory fitness in the whole study population. Our findings show that impairment in RV strain and cardiorespiratory fitness may be useful indicators in early type 2 diabetes, prior to the development of further complications.

Barry OM; Gauvreau K; Reichman JR; Bourette L; Curran T; O’Neill J; Pymm JL; Alexander ME;

JACC. Clinical Electrophysiology [JACC Clin Electrophysiol] 2018 Oct; Vol. 4 (10), pp. 1319-1327. Date of Electronic Publication: 2018 Jul 25.

Objectives: This study quantified the incidence of arrhythmias during pediatric exercise stress tests (ESTs) and evaluated criteria to identify patients at risk of clinically important arrhythmias.
Background: The incidence of clinically important arrhythmias during pediatric ESTs and criteria for identifying high-risk patients are poorly characterized.
Methods: A retrospective review of ESTs performed from 2013 to 2015 was studied. Arrhythmias were categorized into 4 classes based on need for test termination and intervention. Risk factors evaluated included having an implantable cardioverter-defibrillator (ICD), cardiomyopathy, severe ventricular dysfunction, complex arrhythmia history, coronary disease with concern for ischemia, pulmonary hypertension, select poorly palliated congenital heart disease (CHD), and concerning symptoms. Negative predictive values (NPVs) were calculated.
Results: During the study period, 5307 ESTs were performed. Median age of the subjects was 16 years (interquartile range: 13 to 24 years); 20% had complex CHD. At least 1 high-risk criterion was present in 507 tests (10%); having an ICD (37%) and cardiomyopathy (36%) were the most common criteria. Some arrhythmias were seen in 46% of tests, but only 33 events (0.6%) required test termination. Three events (0.06%) required cardiopulmonary resuscitation, all with high-risk criteria. Absence of a high-risk criterion had a 99.7% (95% confidence interval [CI]: 99.5% to 99.8%) NPV for an arrhythmia that required test termination and a 99.96% (95% CI: 99.85% to 99.99%) NPV for an arrhythmia that required intervention beyond test termination.
Conclusions: Although self-terminating arrhythmias are common, dangerous arrhythmias are rare during ESTs in a high-volume pediatric cardiology program. Pre-defined high-risk criteria identified all patients with the most serious events. The absence of any criteria predicted a low risk for arrhythmias that required test termination. These data permitted informed choices regarding supervision of ESTs.

Kawashima K; Hirashiki A; Nomoto K; Kokubo M; Shimizu A; Sakurai T; Kondo I; Arai H; Toba K; Murohara T;

International Heart Journal [Int Heart J] 2019 Nov 15. Date of Electronic Publication: 2019 Nov 15.

The Kihon Checklist (KCL) is a reliable tool for determining frailty status in the elderly. However, there is no information in the literature about the relationship between frailty status and exercise capacity. Here, we examined the associations between cardiopulmonary exercise testing parameters and frailty status in elderly patients with stable heart failure (HF).Ninety-two elderly patients with stable HF were evaluated using cardiopulmonary exercise testing and the KCL. A KCL score of 0-3 was classified as robust, 4-7 as pre-frail, and ≥ 8 as frail. Mean age, peak VO2, and KCL score were 81.7 years, 13.2 mL/kg/minute, and 10.7, respectively. KCL score was significantly correlated with peak VO2 (r = -0.527, P < 0.001) and peak work rate (r = -0.632, P < 0.001). In patients with frailty (n = 63), the peak work rate (WR) was significantly lower than it was in patients without frailty (n = 29; 39.9 versus 69.5 W, respectively; P < 0.001). Multivariate analysis revealed that peak WR and peak systolic blood pressure were significant, independent predictors of frailty (β = -0.108 and -0.045, respectively). In a diagnostic performance plot analysis, a cutoff value for peak WR of 51.9 W was the best predictor of frailty.Frailty status was significantly associated with peak WR and peak systolic blood pressure in elderly patients with stable HF. Therefore, cardiopulmonary exercise testing may be useful for assessing frailty status in this patient population.

Uribe-Heredia G; Arroyo-Espliguero R; Viana-Llamas MC; Piccone-Saponara LG; Álvaro-Fernández H;
García-Magallón B; Torán-Martínez C; Silva-Obregón A; Izquierdo-Alonso JL

Journal Of Cardiopulmonary Rehabilitation And Prevention [J Cardiopulm Rehabil Prev] 2019 Nov 08. Date of Electronic Publication: 2019 Nov 08.

Purpose: Diabetes mellitus (DM) is associated with long-term cardiovascular complications, including ischemic heart disease (IHD). Nonetheless, DM may directly impair myocardial and lung structure and function. The aim of this study was to assess the impact of type 2 DM (T2DM) and glycemic control on cardiopulmonary exercise capacity in patients with IHD.
Methods: The study involved a cross-sectional analysis of 91 consecutive patients (57 ± 10 yr, 90% men) who underwent a cardiopulmonary exercise test at the beginning of an exercise-based standard phase-II cardiac rehabilitation program, 2 to 3 mo after an acute coronary syndrome. Association of T2DM with cardiopulmonary exercise test parameters was assessed using multiple linear regression analysis controlling for prespecified potential confounders.
Results: There were 26 (29%) diabetic subjects among IHD patients included in the study. After adjustment, T2DM was an independent predictor of a reduced peak oxygen uptake (VO2peak) (P = .005), a reduced pulse O2 trajectory (P = .001), a steeper minute ventilation to carbon dioxide output (VE/VCO2) slope (P = .046), and an increased dead space-to-tidal volume ratio (VD/VT) at peak exercise (P = .049). Glycated hemoglobin (HbA1c) levels were significantly associated with a reduced forced expiratory volume in the first second of expiration (FEV1) (P = .013), VE (P = .001), and VT (P = .007). VO2peak (P trend < .001), VO2 at anaerobic threshold (P trend < .001), and pulse O2 trajectory (P trend < .001) decreased among HbA1c tertiles.
Conclusions: Patients with IHD and a previous diagnosis of T2DM had a reduced aerobic capacity and a ventilation-perfusion mismatch compared with nondiabetic patients. Poor glycemic control in men further deteriorates aerobic capacity probably due to ventilatory inefficiency

Lindheimer JB; Cook DB; Klein-Adams JC; Qian W; Hill HZ; Lange G; Ndirangu DS; Wylie GR; Falvo MJ;

Plos One [PLoS One] 2019 Nov 12; Vol. 14 (11), pp. e0224833. Date of Electronic Publication: 20191112 (Print Publication: 2019).

Introduction: The components of minute ventilation, respiratory frequency and tidal volume, appear differentially regulated and thereby afford unique insight into the ventilatory response to exercise. However, respiratory frequency and tidal volume are infrequently reported, and have not previously been considered among military veterans with Gulf War Illness. Our purpose was to evaluate respiratory frequency and tidal volume in response to a maximal cardiopulmonary exercise test in individuals with and without Gulf War Illness.
Materials and Methods: 20 cases with Gulf War Illness and 14 controls participated in this study and performed maximal cardiopulmonary exercise test on a cycle ergometer. Ventilatory variables (minute ventilation, respiratory frequency and tidal volume) were obtained and normalized to peak exercise capacity. Using mixed-design analysis of variance models, with group and time as factors, we analyzed exercise ventilatory patterns for the entire sample and for 11 subjects from each group matched for race, age, sex, and height.
Results: Despite similar minute ventilation (p = 0.57, η2p = 0.01), tidal volume was greater (p = 0.02, η2p = 0.16) and respiratory frequency was lower (p = 0.004, η2p = 0.24) in Veterans with Gulf War Illness than controls. The findings for respiratory frequency remained significant in the matched subgroup (p = 0.004, η2p = 0.35).
Conclusion: In our sample, veterans with Gulf War Illness adopt a unique exercise ventilatory pattern characterized by reduced respiratory frequency, despite similar ventilation relative to controls. Although the mechanism(s) by which this pattern is achieved remains unresolved, our findings suggest that the components of ventilation should be considered when evaluating clinical conditions with unexplained exertional symptoms.