Category Archives: Publications

Performance of cardiopulmonary exercise testing for the prediction of post-operative complications in non cardiopulmonary surgery: A systematic review.

Stubbs DJ; Grimes LA; Ercole A;

Plos One [PLoS One] 2020 Feb 03; Vol. 15 (2), pp. e0226480. Date of Electronic Publication: 20200203 (Print Publication: 2020).

Introduction: Cardiopulmonary exercise testing (CPET) is widely used within the United Kingdom for preoperative risk stratification. Despite this, CPET’s performance in predicting adverse events has not been systematically evaluated within the framework of classifier performance.
Methods: After prospective registration on PROSPERO (CRD42018095508) we systematically identified studies where CPET was used to aid in the prognostication of mortality, cardiorespiratory complications, and unplanned intensive care unit (ICU) admission in individuals undergoing non-cardiopulmonary surgery. For all included studies we extracted or calculated measures of predictive performance whilst identifying and critiquing predictive models encompassing CPET derived variables.
Results: We identified 36 studies for qualitative review, from 27 of which measures of classifier performance could be calculated. We found studies to be highly heterogeneous in methodology and quality with high potential for bias and confounding. We found seven studies that presented risk prediction models for outcomes of interest. Of these, only four studies outlined a clear process of model development; assessment of discrimination and calibration were performed in only two and only one study undertook internal validation. No scores were externally validated. Systematically identified and calculated measures of test performance for CPET demonstrated mixed performance. Data was most complete for anaerobic threshold (AT) based predictions: calculated sensitivities ranged from 20-100% when used for predicting risk of mortality with high negative predictive values (96-100%). In contrast, positive predictive value (PPV) was poor (2.9-42.1%). PPV appeared to be generally higher for cardiorespiratory complications, with similar sensitivities. Similar patterns were seen for the association of Peak VO2 (sensitivity 85.7-100%, PPV 2.7-5.9%) and VE/VCO2 (Sensitivity 27.8%-100%, PPV 3.4-7.1%) with mortality.
Conclusions: In general CPET’s ‘rule-out’ capability appears better than its ability to ‘rule-in’ complications. Poor PPV may reflect the frequency of complications in studied populations. Our calculated estimates of classifier performance suggest the need for a balanced interpretation of the pros and cons of CPET guided pre-operative risk stratification.

Active Participation in Outpatient Cardiac Rehabilitation Is Associated With Better Prognosis After Coronary Artery Bypass Graft Surgery - J-REHAB CABG Study.

Origuchi H; Momomura SI;Nohara R; Daida H; Masuda T; Kohzuki M; Makita S; Ueshima K; Nagayama M; Omiya K; Adachi H; Goto Y;

Circulation Journal: Official Journal Of The Japanese Circulation Society [Circ J] 2020 Feb 08. Date of Electronic Publication: 2020 Feb 08.

Background: There is little evidence regarding the effect of outpatient cardiac rehabilitation (CR) on exercise capacity or the long-term prognosis in patients after coronary artery bypass graft surgery (CABG). This study aimed to determine whether participation in outpatient CR improves exercise capacity and long-term prognosis in post-CABG Japanese patients in a multicenter cohort.
Methods and Results: We enrolled 346 post-CABG patients who underwent cardiopulmonary exercise testing during early (2-3 weeks) and late (3-6 months) time points after surgery. They formed the Active (n=240) and Non-Active (n=106) CR participation groups and were followed for 3.5 years. Primary endpoint was a major adverse cardiac event (MACE): all-cause death or rehospitalization for acute myocardial infarction/unstable angina/worsening heart failure. Peak oxygen uptake at 3-5 months from baseline was significantly more increased in Active than in Non-Active patients (+26±24% vs. +19±20%, respectively; P<0.05), and the MACE rate was significantly lower in Active than Non-Active patients (3.4% vs. 10.5%, respectively; P=0.02). Multivariate Cox proportional hazard analysis showed that participation in outpatient CR was a significant prognostic determinant of MACE (P=0.03).
Conclusions: This unique study showed that a multicenter cohort of patients who underwent CABG and actively participated in outpatient CR exhibited greater improvement in exercise capacity and better survival without cardiovascular events than their counterparts who did not participate.

Agreement between Cardiopulmonary Exercise Test and Modified 6-Min Walk Test in Determining Oxygen Uptake in COPD Patients with Different Severity Stages.

Vonbank K; Marzluf B; Knötig M; Funk GC;

Respiration; International Review Of Thoracic Diseases [Respiration] 2020 Jan 31, pp. 1-6. Date of Electronic Publication: 2020 Jan 31.

Background: In moderate-to-severe chronic obstructive pulmonary disease (COPD) patients the 6-min walk test (6MWT) is often exhaustive and correlates with the incremental cycle cardiopulmonary exercise test (CPET).
Objectives: The aim of this study was to assess the agreement between oxygen uptake (VO2) measured during the 6MWT by portable equipment and incremental cycle exercise in COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-IV.
Methods: A total of 30 patients with COPD GOLD I-IV (14 patients GOLD stage I and II and 16 patients GOLD stage III and IV) underwent a 6MWT and an incremental CPET. Breath-by-breath analysis for VO2, carbon dioxide output (VCO2), and minute ventilation (VE) were measured during each test. Blood gas analysis and lactate measurements were performed before, during, and after the test.
Results: VO2 in COPD patients GOLD stage I and II was 16.2 ± 4.2 mL/kg/min measured by 6MWT and 20.5 ± 7.0 mL/kg/min measured by CPET as compared to GOLD stage III and IV (11.2 ± 3.7 mL/kg/min measured by 6MWT and 15.5 ± 4.3 mL/kg/min measured by CPET). No significant correlation in VO2 measurements could be found between both tests in COPD GOLD I and II (r = 0.17), whereas the VO2 significantly correlated in patients with COPD stage III and IV (r = 0.7).
Conclusions: A significant relationship between VO2 measured by 6MWT and CPET could only be found in patients with more severe COPD but not in milder stages. 6MWT and CPET provide different VO2 measurements in COPD patients. The two methods cannot be used interchangeably.

Exercise Performance at Increased Altitude After Fontan Operation: Comparison to Normal Controls and Correlation with Cavopulmonary Hemodynamics.

Di Maria MV; Patel SS; Fernie JC; Rausch CM;

Pediatric Cardiology [Pediatr Cardiol] 2020 Jan 31. Date of Electronic Publication: 2020 Jan 31.

Exercise performance declines as patients who have undergone Fontan operation enter adolescence. However, the effect of altitude on functional capacity after Fontan remains inadequately studied. Our aim was to describe exercise performance in a cohort of patients with Fontan physiology living at increased altitude and compare to a normal control group and relate these data to invasively derived hemodynamics. We hypothesized that peak oxygen consumption ([Formula: see text]) would be decreased, in association with elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVRi). Patients were evaluated in a multidisciplinary clinic for patients with Fontan physiology. Evaluation included cardiopulmonary exercise test and cardiac catheterization at predetermined intervals. Descriptive statistics were calculated. Associations of catheterization and exercise testing measures with [Formula: see text] were estimated with Spearman correlation coefficients. One hundred patients with age- and gender-matched controls were included in the analysis. The mean age was 13.3 ± 3.9 years, with mean weight of 47.1 ± 18.4 kg. The mean [Formula: see text] was 29.0 ± 7.8 ml/kg/min, significantly lower than the control group, 40.2 ± 8.4 ml/kg/min (p < 0.0001). There was no statistically significant linear correlation between [Formula: see text] and mPAP or PVRi. We characterized exercise performance in a large cohort with Fontan physiology living at increased altitude and showed a decrease in [Formula: see text] compared to controls. Our data do not support the hypothesis that moderately increased altitude has a detrimental effect on exercise performance, nor is there a substantial link between poor cavopulmonary hemodynamics and exercise in this setting.

Cardiovascular Functional Reserve Before and After Kidney Transplant.

Lim K, Ting SMS, Hamborg T, McGregor G, Oxborough D, Tomkins C, Xu D, Thadhani R, Lewis G, Bland R, Banerjee P, Fletcher S, Krishnan NS, Higgins R, Zehnder D, Hiemstra TF.

JAMA Cardiol. 2020 Feb 5. doi: 10.1001/jamacardio.2019.5738. [Epub ahead of

Importance: Restitution of kidney function by transplant confers a survival
benefit in patients with end-stage renal disease. Investigations of mechanisms
involved in improved cardiovascular survival have relied heavily on static
measures from echocardiography or cardiac magnetic resonance imaging and have
provided conflicting results to date.
Objectives: To evaluate cardiovascular functional reserve in patients with
end-stage renal disease before and after kidney transplant and to assess
functional and morphologic alterations of structural-functional dynamics in this
Design, Setting, and Participants: This prospective, nonrandomized,
single-center, 3-arm, controlled cohort study, the Cardiopulmonary Exercise
Testing in Renal Failure and After Kidney Transplantation (CAPER) study, included
patients with stage 5 chronic kidney disease (CKD) who underwent kidney
transplant (KTR group), patients with stage 5 CKD who were wait-listed and had
not undergone transplant (NTWC group), and patients with hypertension only (HTC
group) seen at a single center from April 1, 2010, to January 1, 2013. Patients
were followed up longitudinally for up to 1 year after kidney transplant.
Clinical data collection was completed February 2014. Data analysis was performed
from June 1, 2014, to March 5, 2015. Further analysis on baseline and prospective
data was performed from June 1, 2017, to July 31, 2019.
Main Outcomes and Measures: Cardiovascular functional reserve was objectively
quantified using state-of-the-art cardiopulmonary exercise testing in parallel
with transthoracic echocardiography.
Results: Of the 253 study participants (mean [SD] age, 48.5 [12.7] years; 141
[55.7%] male), 81 were in the KTR group, 85 in the NTWC group, and 87 in the HTC
group. At baseline, mean (SD) maximum oxygen consumption (V̇O2max) was
significantly lower in the CKD groups (KTR, 20.7 [5.8] mL · min-1 · kg-1; NTWC,
18.9 [4.7] mL · min-1 · kg-1) compared with the HTC group (24.9 [7.1] mL · min-1
· kg-1) (P < .001). Mean (SD) cardiac left ventricular mass index was higher in
patients with CKD (KTR group, 104.9 [36.1] g/m2; NTWC group, 113.8 [37.7] g/m2)
compared with the HTC group (87.8 [16.9] g/m2), (P < .001). Mean (SD) left
ventricular ejection fraction was significantly lower in the patients with CKD
(KTR group, 60.1% [8.6%]; NTWC group, 61.4% [8.9%]) compared with the HTC group
(66.1% [5.9%]) (P < .001). Kidney transplant was associated with a significant
improvement in V̇O2max in the KTR group at 12 months (22.5 [6.3] mL · min-1 ·
kg-1; P < .001), but the value did not reach the V̇O2max in the HTC group (26.0
[7.1] mL · min-1 · kg-1) at 12 months. V̇O2max decreased in the NTWC group at 12
months compared with baseline (17.7 [4.1] mL · min-1 · kg-1, P < .001). Compared
with the KTR group (63.2% [6.8%], P = .02) or the NTWC group (59.3% [7.6%],
P = .003) at baseline, transplant was significantly associated with improved left
ventricular ejection fraction at 12 months but not with left ventricular mass
Conclusions and Relevance: The findings suggest that kidney transplant is
associated with improved cardiovascular functional reserve after 1 year. In
addition, cardiopulmonary exercise testing was sensitive enough to detect a
decline in cardiovascular functional reserve in wait-listed patients with CKD.
Improved V̇O2max may in part be independent from structural alterations of the
heart and depend more on ultrastructural changes after reversal of uremia.


The Role of Cardiac Rehabilitation in Reducing Major Adverse Cardiac Events in Heart Transplant Patients.

Uithoven KE; Smith JR; Medina-Inojosa JR; Squires RW; Olson TP;

Journal Of Cardiac Failure [J Card Fail] 2020 Jan 22. Date of Electronic Publication: 2020 Jan 22.

Background: Methods for reducing major adverse cardiac events (MACE) in heart transplant (HTx) patients are critical for long-term quality outcomes.
Methods and Results: Patients with cardiopulmonary exercise testing (CPET) prior to HTx and at least one session of cardiac rehabilitation (CR) after HTx were included. Exercise sessions were evaluated as ≥23 or <23 sessions based on recursive partitioning. 140 HTx patients (women: N=41 (29%), age: 52±12 years, BMI: 27±5 kg/m2) were included. Mean follow-up was 4.1±2.7 years and 44 patients (31%) had a MACE: Stroke (n=1), Percutaneous intervention (n=5), HF (n=6), Myocardial infarction (n=1), rejection (n=16), or death (n=15). CR was a significant predictor of MACE with ≥23 sessions associated with a ∼60% reduction in MACE risk (HR: 0.42, 95% CI: 0.19-0.94, p=0.035). This remained after adjusting for age, sex, and history of diabetes (DM) (HR: 0.41, 95% CI: 0.18-0.94, p=0.035) and BMI and pre-HTx VO2peak (HR: 0.40, 95% CI: 0.18-0.92, p=0.031).
Conclusion: After adjustment for covariates of age, sex, DM, BMI, and pre-HTx VO2peak, CR attendance of ≥23 exercise sessions was predictive of lower MACE risk following HTx. In post-HTx patients, CR was associated with MACE prevention and should be viewed as a critical tool in post-HTx treatment strategy.

High-intensity interval training is effective and superior to moderate continuous training in patients with heart failure with preserved ejection fraction: A randomized clinical trial.

Donelli da Silveira A; Beust de Lima J; Dos Santos Macedo D; Zanini M; Nery R; Antero Laukkanen J; Stein R;

European Journal Of Preventive Cardiology [Eur J Prev Cardiol] 2020 Jan 21, pp. 2047487319901206. Date of Electronic Publication: 2020 Jan 21.

Background: Heart failure with preserved ejection fraction (HFpEF) is a prevalent syndrome, with exercise intolerance being one of its hallmarks, contributing to worse quality of life and mortality. High-intensity interval training is an emerging training option, but its efficacy in HFpEF patients is still unknown.
Design: Single-blinded randomized clinical trial.
Methods: Single-blinded randomized clinical trial with exercise training 3 days per week for 12 weeks. HFpEF patients were randomly assigned to high-intensity interval training or moderate continuous training. At baseline and after 12 week follow-up, patients underwent clinical assessment, echocardiography and cardiopulmonary exercise testing (CPET).
Results: Mean age was 60 ± 9 years and 63% were women. Both groups (N = 19) showed improved peak oxygen consumption (VO2), but high-intensity interval training patients (n = 10) had a significantly higher increase, of 22%, compared with 11% in the moderate continuous training (n = 9) individuals (3.5 (3.1 to 4.0) vs. 1.9 (1.2 to 2.5) mL·kg-1·min-1, p < 0.001). Ventilatory efficiency and other CPET measures, as well as quality of life score, increased equally in the two groups. Left ventricular diastolic function also improved with training, reflected by a significant reduction in E/e’ ratio by echocardiography (-2.6 (-4.3 to -1.0) vs. -2.2 (-3.6 to -0.9) for high-intensity interval training and moderate continuous training, respectively; p < 0.01). There were no exercise-related adverse events.
Conclusions: This randomized clinical trial provided evidence that high-intensity interval training is a potential exercise modality for HFpEF patients, being more effective than moderate continuous training in improving peak VO2. However, the two strategies were equally effective in improving ventilatory efficiency and other CPET parameters, quality of life score and diastolic function after 3 months of training.

Cardiorespiratory Fitness Normalized to Fat-Free Mass and Mortality Risk.

Imboden MT; Kaminsky LA; Peterman JE; Hutzler HL; Whaley MH; Fleenor BS; Harber MP;

Medicine And Science In Sports And Exercise [Med Sci Sports Exerc] 2020 Jan 24. Date of Electronic Publication: 2020 Jan 24.

Purpose: Cardiorespiratory fitness (CRF) is known to be directly related to fat-free mass (FFM), therefore it has been suggested that normalizing CRF to FFM (VO2peakFFM) may be the most accurate expression of CRF as related to exercise performance and cardiorespiratory function. However, the influence of VO2peakFFM (ml·kgFFMmin) on predicting mortality has been largely unexplored. This study aimed to primarily assess the relationship between VO2peakFFM and all-cause and disease-specific mortality risk in apparently healthy adults. Further, this study sought to compare the predictive ability of VO2peakFFM to VO2peak normalized to total body weight (VO2peakTBW) for mortality outcomes.
Methods: Participants included 2,905 adults (1,555 men, 1,350 women) who completed a cardiopulmonary exercise test (CPX) between 1970-2016 to determine CRF. Body composition was assessed using the skinfold method to estimate FFM. CRF was expressed as VO2peakTBW and VO2peakFFM. Participants were followed for 19.0 ± 11.7 years after their CPX for mortality outcomes. Cox-proportional hazard models were performed to determine the relationship of VO2peakFFM with mortality outcomes. Parameter estimates were assessed to compare the predictive ability of CRF expressed as VO2peakTBW and VO2peakFFM.
Results: Overall, VO2peakFFM was inversely related to all-cause, CVD, and cancer mortality, with a 16.2, 8.4, and 8.0% lower risk per 1 ml·kgFFM·min improvement, respectively (p<0.01). Further, assessment of the parameter estimates showed VO2peakFFM to be a significantly stronger predictor of all-cause mortality than VO2peakTBW (parameter estimates: -0.49 vs. -0.16).
Conclusion: Body composition is an important factor when considering the relationship between CRF and mortality risk. Clinicians should consider normalizing CRF to FFM when feasible, as it will strengthen the predictive power of the measure.

Haemodynamic and metabolic phenotyping of hypertensive patients with and without heart failure by combining cardiopulmonary and echocardiographic stress test.

Pugliese NR; Mazzola M; Fabiani I; Gargani L; De Biase N; Pedrinelli R; Natali A; Dini FL;

European Journal Of Heart Failure [Eur J Heart Fail] 2020 Jan 16. Date of Electronic Publication: 2020 Jan 16.

Aim: We combined cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) to identify early haemodynamic and metabolic alterations in patients with hypertension (HT) with and without heart failure with preserved ejection fraction (HFpEF).
Methods and Results: Fifty stable HFpEF-HT outpatients (mean age 68 ± 14 years) on optimal medical therapy, 63 well-controlled HT subjects (mean age 63 ± 11 years) and 32 age and sex-matched healthy controls (mean age 59 ± 15 years) underwent a symptom-limited graded ramp bicycle CPET-ESE. The acquisition protocol included left ventricular cardiac output, global longitudinal strain, E/e’, peak oxygen consumption (VO2 ), non-invasive arterial-venous oxygen content difference (AVO2 diff) and lung ultrasound B-lines. There was a decline in peak VO2 from controls (24.4 ± 3 mL/min/kg) to HFpEF-HT (15.2 ± 2 mL/min/kg), passing through HT (18.7 ± 2 mL/min/kg; P < 0.0001). HFpEF-HT displayed a lower peak cardiac output (9.8 ± 0.9 L/min) compared to HT (12.6 ± 1.0 L/min; P = 0.02) and controls (13.3 ± 1.0 L/min; P = 0.01). Peak AVO2 diff was reduced in HFpEF-HT and HT (13.3 ± 2 and 13.5 ± 2 mL/dL vs. controls: 16.9 ± 2 mL/dL; P < 0.0001). A different left ventricular contractility was observed among groups, expressed as low-load global longitudinal strain (-16.8 ± 5% in HFpEF-HT, -18.2 ± 3% in HT, and 20.9 ± 3% in controls; P < 0.0001), and distribution of E/e’ and B-lines [HFpEF-HT: 13.7 ± 3 and 16, interquartile range (IQR) 10-22; HT: 9.5 ± 2 and 8, IQR 4-10; controls: 6.2 ± 2 and 0, IQR 0-2; P < 0.0001].
Conclusions: Reduced peak VO2 values in HT with and without HFpEF may be the result of decreased AVO2 diff. CPET-ESE can also identify mild signs of left ventricular systo-diastolic dysfunction and pulmonary congestion, promoting advances in personalized therapy.

Resting respiratory lung volumes are “healthier” than exercise respiratory volumes in different types of palliated or corrected congenital heart disease.

Fabi M; Balducci A; Cazzato S; Aceti A; Gallucci M; Di Palmo E; Gargiulo G; Donti A; Lanari M;

Pediatric Pulmonology [Pediatr Pulmonol] 2020 Jan 17. Date of Electronic Publication: 2020 Jan 17.

Aims: Cardiac surgery has improved life expectancy of patients with congenital heart diseases (CHDs). Exercise capacity is an important determinant of survival in patients with CHDs. There is a lack of studies focusing on the role of resting respiratory performance in reducing exercise tolerance in these patients.
Objectives: To determine the prevalence and severity of respiratory functional impairment in different types of corrected/palliated CHDs, and its impact on an exercise test.
Materials and Methods: Retrospective single-center study involving 168 corrected/palliated patients with CHD and 52 controls. Patients CHD were divided into subgroups according to the presence of native pulmonary blood flow or total cavopulmonary connection (TCPC). All subjects performed complete pulmonary function tests and gas diffusion; patients with CHD also performed cardiopulmonary exercise test (CPX).
Results: Mean values of lung volumes were within the normal range in all CHD groups. Comparing to controls, patients with the reduced pulmonary flow and with TCPC had the highest reduction in lung volumes. CPX was reduced in all groups, most severely in TCPC, and it was correlated to decreased dynamic volumes in all CHD groups except in TCPC. Younger age at intervention and number of surgical operations negatively affected lung volumes.
Conclusions: Respiratory function is within the normal range in our patients with different CHDs at rest but altered in all CHDs during exercise when cardiorespiratory balance is likely to be inadequate. Comparing the different groups, patients with reduced pulmonary flow and TCPC are the most impaired.