Scally C; Rudd A; Mezincescu A; Wilson H; Srivanasan J; Horgan G;
Broadhurst P; Newby DE; Henning A; Dawson DK.

Circulation. 137(10):1039-1048, 2018 03 06.

BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized acute
heart failure syndrome precipitated by intense emotional stress. Although
there is an apparent rapid and spontaneous recovery of left ventricular
ejection fraction, the long-term clinical and functional consequences of
takotsubo cardiomyopathy are ill-defined.

METHODS: In an observational case-control study, we recruited 37 patients
with prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and
comorbidity-matched control subjects. Patients completed the Minnesota
Living with Heart Failure Questionnaire. All participants underwent
detailed clinical phenotypic characterization, including serum biomarker
analysis, cardiopulmonary exercise testing, echocardiography, and cardiac
magnetic resonance including cardiac 31P-spectroscopy.

RESULTS: Participants were predominantly middle-age (64+/-11 years) women
(97%). Although takotsubo cardiomyopathy occurred 20 (range 13-39) months
before the study, the majority (88%) of patients had persisting symptoms
compatible with heart failure (median of 13 [range 0-76] in the Minnesota
Living with Heart Failure Questionnaire) and cardiac limitation on
exercise testing (reduced peak oxygen consumption, 24+/-1.3 versus
31+/-1.3 mL/kg/min, P<0.001; increased VE/Vco2 slope, 31+/-1 versus
26+/-1, P=0.002). Despite normal left ventricular ejection fraction and
serum biomarkers, patients with prior takotsubo cardiomyopathy had
impaired cardiac deformation indices (reduced apical circumferential
strain, -16+/-1.0 versus -23+/-1.5%, P<0.001; global longitudinal strain,
-17+/-1 versus -20+/-1%, P=0.006), increased native T1 mapping values
(1264+/-10 versus 1184+/-10 ms, P<0.001), and impaired cardiac energetic
status (phosphocreatine/gamma-adenosine triphosphate ratio, 1.3+/-0.1
versus 1.9+/-0.1, P<0.001).

CONCLUSIONS: In contrast to previous perceptions, takotsubo
cardiomyopathy has long-lasting clinical consequences, including
demonstrable symptomatic and functional impairment associated with
persistent subclinical cardiac dysfunction. Taken together our findings
demonstrate that after takotsubo cardiomyopathy, patients develop a
persistent, long-term heart failure phenotype.

Rocco IS, Viceconte M, Pauletti HO, Matos-Garcia BC,Marcondi NO, Bublitz C, Bolzan DW, Moreira RSL, Reis MS, Hossne NA Jr, Gomes WJ, Arena R, Guizilini S.

Disabil Rehabil. 2019 Mar;41(5):534-540. doi: 10.1080/09638288.2017.1401673. Epub
2017 Dec 26.

PURPOSE: We aimed to investigate the ability of oxygen uptake kinetics to predict
short-term outcomes after off-pump coronary artery bypass grafting.
METHODS: Fifty-two patients aged 60.9 ± 7.8 years waiting for off-pump coronary
artery bypass surgery were evaluated. The 6-min walk test distance was performed
pre-operatively, while simultaneously using a portable cardiopulmonary testing
device. The transition of oxygen uptake kinetics from rest to exercise was
recorded to calculate oxygen uptake kinetics fitting a monoexponential regression
model. Oxygen uptake at steady state, constant time, and mean response time
corrected by work rate were analysed. Short-term clinical outcomes were evaluated
during the early post-operative of off-pump coronary artery bypass surgery.
RESULTS: Multivariate analysis showed body mass index, surgery time, and mean
response time corrected by work rate as independent predictors for short-term
outcomes. The optimal mean response time corrected by work rate cut-off to
estimate short-term clinical outcomes was 1.51 × 10-3 min2/ml. Patients with
slower mean response time corrected by work rate demonstrated higher rates of
hypertension, diabetes, EuroSCOREII, left ventricular dysfunction, and impaired
6-min walk test parameters. The per cent-predicted distance threshold of 66% in
the pre-operative was associated with delayed oxygen uptake kinetics.
CONCLUSIONS: Pre-operative oxygen uptake kinetics during 6-min walk test predicts
short-term clinical outcomes after off-pump coronary artery bypass surgery. From
a clinically applicable perspective, a threshold of 66% of pre-operative
predicted 6-min walk test distance indicated slower kinetics, which leads to
longer intensive care unit and post-surgery hospital length of stay. Implications
for rehabilitation Coronary artery bypass grafting is a treatment aimed to
improve expectancy of life and prevent disability due to the disease progression;
The use of pre-operative submaximal functional capacity test enabled the
identification of patients with high risk of complications, where patients with
delayed oxygen uptake kinetics exhibited worse short-term outcomes; Our findings
suggest the importance of the rehabilitation in the pre-operative in order to
“pre-habilitate” the patients to the surgical procedure; Faster oxygen uptake
on-kinetics could be achieved by improving the oxidative capacity of muscles and
cardiovascular conditioning through rehabilitation, adding better results
following cardiac surgery.

Radtke T, Crook S, Kaltsakas G, et al

Eur Respir Rev. 2019 Dec 18;28(154). pii: 180101. doi:
10.1183/16000617.0101-2018. Print 2019 Dec 31.

The objective of this document was to standardise published cardiopulmonary
exercise testing (CPET) protocols for improved interpretation in clinical
settings and multicentre research projects. This document: 1) summarises the
protocols and procedures used in published studies focusing on incremental CPET
in chronic lung conditions; 2) presents standard incremental protocols for CPET
on a stationary cycle ergometer and a treadmill; and 3) provides patients’
perspectives on CPET obtained through an online survey supported by the European
Lung Foundation. We systematically reviewed published studies obtained from
EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception
to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects
were included. The literature supports a test protocol with a resting phase
lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental
phase with work rate increased linearly at least every minute, followed by a
recovery phase of at least 2-3 min. Patients responding to the survey (n=295)
perceived CPET as highly beneficial for their diagnostic assessment and informed
the Task Force consensus. Future research should focus on the individualised
estimation of optimal work rate increments across different lung diseases, and
the collection of robust normative data.

Blanco I; Valeiro B; Torres-Castro R; Barberán-García A; Torralba Y; Moisés J; Sebastián L;Osorio J; Rios J; Gimeno-Santos E; Roca J;Barberà JA;

Archivos De Bronconeumologia [Arch Bronconeumol] 2019 Nov 23. Date of Electronic Publication: 2019 Nov 23.

Introduction: The impact of pulmonary hypertension (PH) on exercise tolerance in chronic obstructive pulmonary disease (COPD) has not been fully elucidated. It is necessary to characterize pulmonary hemodynamics in patients with moderate to severe COPD in order to improve their management. The aim of the study was to determine whether in COPD the presence of PH is associated with reduced exercise tolerance in a cohort of stable COPD patients.
Methods: Cross-sectional analysis of 174 COPD patients clinically stable: 109 without PH and 65 with PH (COPD-PH). We assessed socio-demographic data, lung function, quality of life, dyspnea, cardiopulmonary exercise testing (CPET), constant workload endurance time (CWET), and six-minute walk test (6MWT). We elaborated a logistic regression model to explore the impact of PH on exercise capacity in COPD patients.
Results: COPD-PH patients showed lower exercise capacity both at maximal (CPET) (43(20) versus 68(27) Watts and 50(19)% versus 71(18)% predicted peak oxygen consumption (VO2peak), COPD-PH and COPD, respectively), and at submaximal tests (6MWT) (382(94) versus 486(95) m). In addition, the COPD-PH group had lower endurance time than the non-PH COPD group (265(113) s and 295(164) s, respectively).
Conclusions: The presence of PH is an independent factor that impairs exercise capacity in COPD.

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.