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
print]

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
population.
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
index.
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.

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.

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.

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.

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.

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.

Francesco Carli, Guillaume Bousquet-Dion, Rashami Awasthi, Noha Elsherbini, Sender Liberman , Marylise Boutros, Barry Stein , Patrick Charlebois, Gabriela Ghitulescu, Nancy Morin, Thomas Jagoe , Celena Scheede-Bergdahl, Enrico Maria Minnella , Julio F Fiore Jr

JAMA Surg 2020 Jan 22  [On line ahead of print]

Importance: Research supports use of prehabilitation to optimize physical status before and after colorectal cancer resection, but its effect on postoperative complications remains unclear. Frail patients are a target for prehabilitation interventions owing to increased risk for poor postoperative outcomes.
Objective: To assess the extent to which a prehabilitation program affects 30-day postoperative complications in frail patients undergoing colorectal cancer resection compared with postoperative rehabilitation.
Design, setting, and participants: This single-blind, parallel-arm, superiority randomized clinical trial recruited patients undergoing colorectal cancer resection from September 7, 2015, through June 19, 2019. Patients were followed up for 4 weeks before surgery and 4 weeks after surgery at 2 university-affiliated tertiary hospitals. A total of 418 patients 65 years or older were assessed for eligibility. Of these, 298 patients were excluded (not frail [n = 290], unable to exercise [n = 3], and planned neoadjuvant treatment [n = 5]), and 120 frail patients (Fried Frailty Index,≥2) were randomized. Ten patients were excluded after randomization because they refused surgery (n = 3), died before surgery (n = 3), had no cancer (n = 1), had surgery without bowel resection (n = 1), or were switched to palliative care (n = 2). Hence, 110 patients were included in the intention-to-treat analysis (55 in the prehabilitation [Prehab] and 55 in the rehabilitation [Rehab] groups). Data were analyzed from July 25 through August 21, 2019.
Interventions: Multimodal program involving exercise, nutritional, and psychological interventions initiated before (Prehab group) or after (Rehab group) surgery. All patients were treated within a standardized enhanced recovery pathway.
Main outcomes and measures: The primary outcome included the Comprehensive Complications Index measured at 30 days after surgery. Secondary outcomes were 30-day overall and severe complications, primary and total length of hospital stay, 30-day emergency department visits and hospital readmissions, recovery of walking capacity, and patient-reported outcome measures.
Results: Of 110 patients randomized, mean (SD) age was 78 (7) years; 52 (47.3%) were men and 58 (52.7%) were women; 31 (28.2%) had rectal cancer; and 87 (79.1%) underwent minimally invasive surgery. There was no between-group difference in the primary outcome measure, 30-day Comprehensive Complications Index (adjusted mean difference, -3.2; 95% CI, -11.8 to 5.3; P = .45). Secondary outcome measures were also not different between groups.
Conclusions and relevance: In frail patients undergoing colorectal cancer resection (predominantly minimally invasive) within an enhanced recovery pathway, a multimodal prehabilitation program did not affect postoperative outcomes. Alternative strategies should be considered to optimize treatment of frail patients preoperatively.

Balmain BN; Weinstein K; Bernhardt V; Marines-Price R; Tomlinson AR; Babb TG;

Respiratory Physiology & Neurobiology [Respir Physiol Neurobiol] 2019 Dec 30; Vol. 274, pp. 103365. Date of Electronic Publication: 2019 Dec 30.

We investigated the contributions of obesity on multidimensional aspects of dyspnea on exertion (DOE) in patients referred for clinical cardiopulmonary exercise testing (CPET). Ratings of perceived breathlessness (RPB, Borg scale 0-10) were collected in obese (BMI ≥ 30; n = 47) and nonobese (BMI ≤ 25; n = 27) patients during two (one lower: ∼30 W; and one higher: ∼50 W) 4-6 min constant load cycling bouts. Multidimensional dyspnea profiles (MDP) were collected in the final 26 obese and 14 nonobese patients of the sample. RPB was greater (p = 0.05) in obese (3.3 ± 2.2 vs 2.4 ± 1.4) at lower work rates, but similar at higher work rates (4.9 ± 2.2 vs 4.4 ± 1.8). MDP sensory score including unpleasantness was 4.3 ± 2.2 in obese vs 2.5 ± 1.9 in nonobese (p < 0.001). The affective score was 1.9 ± 2.2 vs 0.7 ± 0.7, respectively (p < 0.01). Breathing sensations including ‘air hunger’, ‘effort’, and ‘breathing at lot’ were greater (p < 0.05) in obese, making these patients more frustrated/angry (p < 0.05). Obesity should be considered as a potential independent influencing factor that provokes DOE and unpleasantness when assessing breathlessness during CPET.

Ozemek C; Arena R; Fernhall B

Exercise And Sport Sciences Reviews [Exerc Sport Sci Rev] 2020 Jan; Vol. 48 (1), pp. 2-3.

NO abstract available

Sabbahi A; Severin R; Ozemek C; Phillips SA; Arena R;

Expert Review Of Respiratory Medicine [Expert Rev Respir Med] 2020 Jan 03, pp. 1-11. Date of Electronic Publication: 2020 Jan 03.

Introduction: Pulmonary hypertension (PH) is a broad pathophysiological disorder primarily characterized by increased pulmonary vascular resistance due to multiple possible etiologies. Patients typically present with multiple complaints that worsen as disease severity increases. Although initially discouraged due to safety concerns, exercise interventions for patients with PH have gained wide interest and multiple investigations have established the effective role of exercise training in improving the clinical profile, exercise tolerance, and overall quality of life.Areas covered: In this review, we discuss the pathophysiology of PH during rest and exercise, the role of cardiopulmonary exercise testing (CPX) in the diagnosis and prognosis of PAH, the role of exercise interventions in this patient population, and the expected physiological adaptations to exercise training.Expert opinion: Exercise testing, in particular CPX, provides a wealth of clinically valuable information in the PH population. Moreover, the available evidence strongly supports the safety and efficacy of exercise training as a clinical tool in improving exercise tolerance and quality of life. Although clinical trials investigating the role of exercise in this PH population are relatively few compared to other chronic conditions, current available evidence supports the clinical implementation of exercise training as a safe and effective treatment modality.