Sato T; Yamauchi H; Suzuki S; Yoshihisa A; Yamaki T; Sugimoto K; Kunii H;
Nakazato K; Suzuki H; Saitoh S; Takeishi Y.

International Heart Journal. 54(5):311-7, 2013.

Impaired renal function is a strong predictor of mortality in chronic
heart failure (CHF). However, the impact of chronic kidney disease (CKD)
on prognostic factors has not been rigorously examined in CHF. The purpose
of this study was to compare prognostic factors between CHF patients with
and without CKD. Consecutive 505 patients with CHF, who performed
cardiopulmonary exercise testing before discharge, were enrolled. Patients
were divided into two groups: CKD group (eGFR < 60 mL/minute/1.73 m2, n =
213) and non-CKD group (eGFR >= 60 mL/minute/1.73 m2, n = 292). The
patients were followed up to register cardiac events including cardiac
death and re-hospitalization due to worsening heart failure. There were
115 events during the follow-up period (746 +/- 238 days), and the cardiac
event rate was higher in the CKD group than in the non-CKD group (34%
versus 14%, P < 0.001). Multivariate Cox hazard analysis demonstrated that
body mass index (P < 0.001), log BNP (P < 0.001), peak VO2 (P < 0.05), and
left atrial dimension (P < 0.05) were independent parameters to predict
cardiac events after discharge in the non-CKD group. In contrast, peak VO2
(P < 0.01), log BNP (P < 0.01), and the concentrations of hemoglobin (P <
0.05) and uric acid (P < 0.05) were independent prognostic factors in the
CKD group. Prognostic factors were different between CHF patients with and
without CKD, and this should be considered when managing CHF patients with
CKD.

Pardaens S; Calders P; Derom E; De Sutter J.

Acta Cardiologica. 68(5):495-504, 2013 Oct.

Exercise intolerance is a hallmark feature of chronic heart failure and is
associated with poor prognosis. This review provides an update on
cardiopulmonary exercise variables, proven to be prognostically important
in heart failure. Besides the widely accepted peak oxygen consumption
(peak VO2) and VEN/VCO2 slope, other exercise variables – exercise
oscillatory ventilation (EOV) and partial pressure of end-tidal CO2,
(PETCO2) – should gain attention in the interpretation of cardiopulmonary
exercise testing. In addition to prognosis, the pathophysiological origin
is also discussed. Different mechanisms underlie these exercise variables
with an important contribution of haemodynamic, pulmonary and peripheral
abnormalities. Given the different pathophysiological origin, a
multivariate assessment with the inclusion of all the aforementioned
parameters should be encouraged, not only for diagnostic and prognostic
purposes but also for evaluating the effect of interventions.

Ritzel A; Otto F; Bell M; Sabin G; Wieneke H.

Acta Cardiologica. 70(1):43-50, 2015 Feb.

BACKGROUND: Heart failure with normal left ventricular ejection fraction
(HFNEF) accounts for about one third of all heart failure patients with
considerable mortality. The metabolic syndrome (MS) is a risk factor for
diastolic dysfunction and HFNEF. We hypothesized that modifying metabolic
burden by exercise training and weight loss might improve left ventricular
diastolic function, heart failure symptoms and rehospitalization rate.

METHODS AND RESULTS: Forty patients with HFNEF, MS and prediabetes were
enrolled in this prospective study. Echocardiography and cardiopulmonary
exercise testing (CPET) were done at baseline and after 3 months lifestyle
modification (LSM). NT-pro BNP and adiponectin were determined at baseline
as both peptidehormones play a crucial role in MS and heart failure. After
discharge a 3-month LSM program with the aim of weight reduction by diet
and exercise was started. After the intervention period a weight reduction
of >= 2% was defined as successful LSM (group A = 23 patients), while a
weight reduction < 2% was classified as unsuccessful LSM (group B = 17
patients). At baseline NT-pro BNP (424 +/- 381 versus 121 +/- 99 pg/ml, P
< 0.01) and adiponectin (10.1 +/- 6.2 versus 4.6-2.0 micro&#32;g/ml, P <
0.01) were higher in group A than in group B. After 3 months of LSM, CPET
showed a significant improve- ment of VO2 peak (P < 0.01), EqCO2 (P <
0.001), O2-pulse (P = 0.02) and VE / VCO2 slope (P = 0.01) in group A.
After one year of follow-up a modest but significant reduction of left
atrial size and mitral flow to mitral annulus velocity ratio E/E’ was seen
in group A. LSM resulted in significant improvement of NYHA status (P =
0.03) and higher freedom of rehospitalization (P = 0.04) in group A.

CONCLUSION: Successful lifestyle modification in obese, prediabetic
patients with HFNEF improves diastolic left ventricular function and
cardiopulmonary exercise capacity. As these measures result in improved
NYHA status and less hospitalization, LSM might be a promising approach to
prevent chronic diastolic heart failure.

Shantsila E; Haynes R; Calvert M; Fisher J; Kirchhof P; Gill PS; Lip GY.

BMJ Open. 6(10):e012241, 2016 10 05.

INTRODUCTION: Patients with atrial fibrillation frequently suffer from
heart failure with preserved ejection fraction. At present there is no
proven therapy to improve physical capacity and quality of life in
participants with permanent atrial fibrillation with preserved left
ventricular contractility.

OBJECTIVE: The single-centre IMproved exercise tolerance In heart failure
With PReserved Ejection fraction by Spironolactone On myocardial fibrosiS
In Atrial Fibrillation (IMPRESS-AF) trial aims to establish whether
treatment with spironolactone as compared with placebo improves exercise
tolerance (cardiopulmonary exercise testing), quality of life and
diastolic function in patients with permanent atrial fibrillation.

METHODS AND ANALYSIS: A total of 250 patients have been randomised in
this double-blinded trial for 2-year treatment with 25 mg daily dose of
spironolactone or matched placebo. Included participants are 50 years old
or older, have permanent atrial fibrillation and ejection fraction >55%.
Exclusion criteria include contraindications to spironolactone, poorly
controlled hypertension and presence of severe comorbidities with life
expectancy <2 years. The primary outcome is improvement in exercise
tolerance at 2 years and key secondary outcomes include quality of life
(assessed using the EuroQol EQ-5D-5L (EQ-5D) and Minnesota Living with
Heart Failure (MLWHF) questionnaires), diastolic function and all-cause
hospitalisation.

ETHICS AND DISSEMINATION: The study has been approved by the National
Research and Ethics Committee West Midlands-Coventry and Warwickshire (REC
reference number 14/WM/1211). The results of the trial will be published
in an international peer-reviewed journal.

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.