Category Archives: Publications

Impact of closed loop stimulation on prognostic cardiopulmonary variables in patients with chronic heart failure and severe chronotropic incompetence: a pilot, randomized, crossover study.

Proff J; Merkely B; Papp R; Lenz C; Nordbeck P; Butter C; Meyerhoefer J;
Doering M; MacCarter DJ; Ingel K; Thouet T; Landmesser U; Roser MJ

Europace. 23(11):1777-1786, 2021 11 08.

AIMS: Clinical effects of rate-adaptive pacing in heart failure patients
with chronotropic incompetence (CI) undergoing cardiac resynchronization
therapy (CRT) remain unclear. Closed loop stimulation (CLS) is a new
rate-adaptive sensor in CRT devices. We evaluated the effectiveness of CLS
in CRT patients with severe CI, focusing primarily on key prognostic
variables assessed by cardiopulmonary exercise (CPX) testing.

METHODS AND RESULTS: In the randomized, crossover, multicentre BIO

CREATE study, 20 CRT patients with severe CI and NYHA Class II/III
(60%/40%) were randomized 1:1 to the sequence DDD-40 mode to DDD-CLS mode,
or the sequence DDD-CLS mode to DDD-40 mode (1 month in each mode).
Patients underwent symptom-limited treadmill-based CPX test in each mode.
An improvement (decrease) of the ventilatory efficiency (VE) slope of >=5%
during CLS was regarded as positive response to CLS. Seventeen patients
with full data sets had a mean intra-individual VE slope change of -1.8
+/- 3.0 (-4.1%) with CLS (P = 0.23). Eight patients (47%) were CLS
responders, with a -6.1 +/- 2.7 (-16.4%) slope change (P = 0.029).
Compared to non-responders, CLS responders had a higher left ventricular
(LV) ejection fraction (46 +/- 3 vs. 36 +/- 9%; P = 0.0070), smaller
end-diastolic LV volume (121 +/- 34 vs. 181 +/- 41 mL; P = 0.0085),
smaller end-systolic LV volume (65 +/- 23 vs. 114 +/- 39 mL; P = 0.0076),
and were predominantly in NYHA Class II (P = 0.0498).

CONCLUSION: The data of the present pilot study are compatible with the
notion that CLS activation may improve VE slope in CRT patients with
severe CI and less advanced heart failure. Further research is needed to
determine the long-term clinical outcomes of CLS.

Sub-maximal aerobic exercise training reduces haematocrit and ameliorates symptoms in Andean highlanders with chronic mountain sickness.

Macarlupu JL; Vizcardo-Galindo G; Figueroa-Mujica R; Voituron N;
Richalet JP; Villafuerte FC

Experimental Physiology. 106(11):2198-2209, 2021 11.

ABSTRACT: Excessive erythrocytosis is the hallmark sign of chronic
mountain sickness (CMS), a debilitating syndrome associated with
neurological symptoms and increased cardiovascular risk. We have shown
that unlike sedentary residents at the same altitude, trained individuals
maintain haematocrit within sea-level range, and thus we hypothesise that
aerobic exercise training (ET) might reduce excessive haematocrit and
ameliorate CMS signs and symptoms. Eight highlander men (38 +/- 12 years)
with CMS (haematocrit: 70.6 +/- 1.9%, CMS score: 8.8 +/- 1.4) from Cerro
de Pasco, Peru (4340 m) participated in the study. Baseline assessment
included haematocrit, CMS score, pulse oximetry, maximal cardiopulmonary
exercise testing and in-office plus 24 h ambulatory blood pressure (BP)
monitoring. Blood samples were collected to assess cardiometabolic,
erythropoietic, and haemolysis markers. ET consisted of pedalling exercise
in a cycloergometer at 60% of V O 2 peak for 1 h/day, 4 days/week for 8
weeks, and participants were assessed at weeks 4 and 8. Haematocrit and
CMS score decreased significantly by week 8 (to 65.6 +/- 6.6%, and 3.5 +/-
0.8, respectively, P < 0.05), while V O 2 peak and maximum workload
increased with ET (33.8 +/- 2.4 vs. 37.2 +/- 2.0 ml/min/kg, P < 0.05; and
172.5 +/- 9.4 vs. 210.0 +/- 27.8 W, P < 0.01; respectively). Except for an
increase in high-density lipoprotein cholesterol, other blood markers and
BP showed no differences. Our results suggest that reduction of
haematocrit and CMS symptoms results mainly from haemodilution due to
plasma volume expansion rather than to haemolysis. In conclusion, we show
that ET can effectively reduce haematocrit, ameliorate symptoms and
improve aerobic capacity in CMS patients, suggesting that regular aerobic
exercise might be used as a low-cost non-invasive and non-pharmacological
management strategy.

Impaired Ventilatory Efficiency, Dyspnea and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study.

Phillips DB; Elbehairy AF; James MD; Vincent SG; Milne KM; de-Torres JP; Neder JA;Kirby M; Jensen D; Stickland MK; Guenette JA; Smith BM; Aaron SD; Tan WC; Bourbeau J; O’Donnell DE;

American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2022 Mar 25.
Date of Electronic Publication: 2022 Mar 25.

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [V̇E/V̇CO2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD).
Objectives: To determine: 1) the association between high V̇E/V̇CO2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort.
Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing and chest computed tomography (CT). Impaired exercise ventilatory efficiency was defined by a nadir V̇E/V̇CO2 above the upper limit of normal (V̇E/V̇CO2>ULN), using population-based normative values.
Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with GOLD 1 COPD, and 200 with GOLD 2-4 COPD. Participants with V̇E/V̇CO2>ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale≥2, odds ratio=1.77[1.31-2.39]) and abnormally low peak oxygen uptake (V̇O2peak<LLN, odds ratio=4.58[3.06-6.86]). The carbon monoxide transfer coefficient (KCO) had a stronger correlation with nadir V̇E/V̇CO2 (r=-0.38, p<0.001) than other relevant lung function and CT metrics. The prevalence of V̇E/V̇CO2>ULN was 24% in COPD (similar in GOLD 1 and 2-4), which was greater than in never-smokers (13%) and ever-smokers (12%).
Conclusions: V̇E/V̇CO2>ULN was associated with greater dyspnea and low VO2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.

Impact of accelerated washout of Technetium-99m-sestamibi on exercise tolerance in patients with acute coronary syndrome: single-center experience.

Kato T; Noda T; Tanaka S; Yagasaki H; Iwama M;Tanihata S; Arai M; Minatoguchi S; Okura H

Heart and vessels [Heart Vessels] 2022 Mar 27.
Date of Electronic Publication: 2022 Mar 27.

Technetium-99m-sestamibi ( 99m Tc-sestamibi) single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with acute coronary syndrome (ACS) could be used to assess area-at-risks, as well as myocardial infarct or saved sizes. In patients with ACS, accelerated washout of 99m Tc-sestamibi during early and delayed imaging in the acute phase may suggest mitochondrial dysfunction in the injured but salvaged myocardium. However, the link between 99m Tc-sestamibi accelerated washout and exercise tolerance is unknown. The purpose of this study was to investigate a possible association between 99m Tc-sestamibi accelerated washout and exercise tolerance in acute ACS patients as they progressed into the chronic phase. One hundred and sixty-five patients with ACS who underwent 99m Tc-sestamibi SPECT MPI during the acute phase were recruited. On this basis, we calculated the total perfusion deficits (TPDs) for early (1 h after tracer injection) and delayed (4 h after tracer injection) images using automated quantification software. We then subtracted the early TPDs from the delayed TPDs to calculate the ΔTPD. We conducted a cardiopulmonary exercise test in acute and chronic phases. We divided two groups according to the median ΔTPD (the ΔTPD ≥ 4 group and the ΔTPD < 4 group) and compared anaerobic threshold (AT; ml/kg/min) between the groups. For anaerobic threshold (AT) improvement in data analysis, we employed multivariate logistic regression analysis. A total of 101 ST-segment elevation myocardial infarctions, 36 non-ST-elevation myocardial infarctions, and 28 unstable angina pectoris events were reported as ACS. From acute phase (10.8 ± 4.2 ml/kg/min) to chronic phase (11.9 ± 2.3 ml/kg/min), the AT in the ΔTPD ≥ 4 group was significantly increased (p < 0.0001). This trend was also seen in the ΔTPD < 4 group from acute (11.4 ± 1.8 ml/kg/min) to chronic phase (12.1 ± 2.2 ml/kg/min, p = 0.015). AT was lower in the ΔTPD ≥ 4 group in the acute phase (p = 0.027), but there was no difference in AT between the two groups in the chronic phase (p = 0.60). ΔTPD and the absence of diabetes were both independent predictors of AT improvement in multivariate logistic regression analysis. Receiver-operating characteristic curve analysis determined that ΔTPD = 6 was the best cut-off value, with 60.0% sensitivity and 71.4% specificity, respectively. The accelerated washout of 99m Tc-sestamibi in patients with ACS during the acute phase could help to predict improvement in exercise tolerance in the chronic phase.

Characterising recovery following abdominal aortic aneurysm repair using cardiopulmonary exercise testing and patient reported outcome measures.

Dodds N; Angell J; Lewis SL; Pyke M; White P; Darweish-Medniuk A; Mitchell DC; Tolchard S;

Disability and rehabilitation [Disabil Rehabil] 2022 Mar 29, pp. 1-7.
Date of Electronic Publication: 2022 Mar 29.

Purpose: Surgery is associated with a post-operative stress response, changes in cardiopulmonary reserve, and metabolic demand. Here recovery after abdominal aortic aneurysm repair is investigated using cardiopulmonary exercise testing and patient-reported questionnaires.
Materials and Methods: Patients undergoing open ( n  = 21) or endovascular ( n  = 21) repair undertook cardiopulmonary exercise tests, activity, and health score questionnaires pre-operatively and, 8 and 16 weeks, post-operatively. Oxygen uptake and ventilatory parameters were measured, and routine blood tests were undertaken.
Results: Recovery was characterised by falls in anaerobic threshold, peak oxygen uptake, and oxygen pulse at 8 weeks which appeared to be associated with operative severity; the fall in peak oxygen uptake was greater following open vs. endovascular repair (3.5 vs. 1.6 ml . kg -1. min -1 ) and anaerobic threshold showed a similar tendency (3.1 vs. 1.7 ml . kg -1. min -1 ). In the smaller number of patients re-tested these changes resolved by 16 weeks. Reported health and activity did not change.
Conclusions: Aortic repair is associated with falls in the anaerobic threshold, peak oxygen uptake, and oxygen pulse of a magnitude that reflects operative severity and appears to resolve by 16 weeks. Thus, post-operatively patients may be at higher risk of further metabolic insult e.g. infection. This further characterises physiological recovery from aortic surgery and may assist in defining post-operative shielding time.IMPLICATIONS FOR REHABILITATIONAbdominal aortic aneurysm repair is a life-saving operation, the outcome from which is influenced by pre-operative cardiopulmonary reserve; individuals with poor reserve being at greater risk of peri-operative complications and death. However, for this operation, the physiological impact of surgery has not been studied.In a relatively small sample, this study suggests that AAA repair is associated with a significant decline in cardiopulmonary reserve when measured 8 weeks post-operatively and appears to recover by 16 weeks. Moreover, the impact may be greater in endovascular vs. open repair.

Validity of anaerobic threshold measured in resistance exercise.

Masuda T; Takeuchi S; Kubo Y; Nishida Y;

Journal of physical therapy science [J Phys Ther Sci] 2022 Mar; Vol. 34 (3), pp. 199-203.
Date of Electronic Publication: 2022 Mar 14.

[Purpose] Intensity for resistance exercise is estimated based on the maximum muscle strength. Exercise prescription without evaluating the biological response has a challenge. This study aimed to confirm whether anaerobic threshold measured using cardiopulmonary exercise test in resistance exercise is appropriate or not. [Participants and Methods] Resistance exercise adopted for the study was right-leg knee extension. The participants were 10 healthy young males. We investigated whether the oxygen uptake kinetics achieved a steady state within 3 min during the constant-load test with knee extension at 80% anaerobic threshold using cardiopulmonary exercise test with knee extension. If oxygen uptake kinetics achieved a steady state within 3 min, the exercise intensity measured using cardiopulmonary exercise test was considered appropriate. [Results] Anaerobic threshold was measured using the conventional approach in all participants. The steady state of oxygen uptake kinetics could be achieved within 3 min. In the constant-load test with knee extension at 80% anaerobic threshold, the oxygen uptake kinetics achieved a steady state within 3 min. [Conclusion] Based on the findings, the anaerobic threshold obtained using cardiopulmonary exercise test with resistance exercise was judged as appropriate. The results of this study contribute to the accurate setting of exercise load for resistance exercise and condition setting for the evaluation of skeletal muscle function.

Which preoperative assessment modalities best identify patients who are suitable for enhanced recovery after liver transplantation? – A systematic review of the literature and expert panel recommendations.

Crespo G; Hessheimer AJ; Armstrong MJ; Berzigotti A; Monbaliu D; Spiro M; Rapti DA; Lai JC;

Clinical transplantation [Clin Transplant] 2022 Mar 16, pp. e14644.
Date of Electronic Publication: 2022 Mar 16.

Background: To implement Enhanced Recovery After Surgery (ERAS) protocols for liver transplant (LT) candidates, it is essential to identify tools that can help risk stratify patients by their risk of early adverse post-LT outcomes.
Objective: We aimed to identify pre-LT tools that assess functional capacity, frailty, and muscle mass that can best risk stratify patients by their risk of adverse post-LT outcomes.
Methods: We first conducted a systematic review following PRISMA guidelines, expert panel review and recommendations using the GRADE approach (PROSPERO ID CRD42021237434). After confirming there are no studies evaluating assessment modalities for ERAS protocols for LT recipients specifically, the approach of the review focused on pre-LT modalities that identify LT recipients at higher risk of worse early post-LT outcomes (≤90 days), considering that this is particularly pertinent when evaluating candidates for ERAS.
Results: Twenty-two studies were included in the review, encompassing three different types of pre-LT modalities: evaluation of physical function (including frailty and general physical scores like the Karnofsky Performance Status (KPS), assessment of cardiopulmonary capacity, and estimation of muscle mass and composition. The majority of studies evaluated frailty assessment and muscle mass. Most studies, except for liver frailty index (LFI), were retrospective and single-center. All assessment modalities could identify, in different grade, LT recipients with higher risk of early post-LT mortality, length of stay or postoperative complications.
Conclusions: We identified 4 pre-LT assessment tools that could be used to identify patients who are suitable for ERAS protocols: 1) KPS (quality of evidence moderate, grade of recommendation strong), 2) LFI (quality of evidence moderate, grade of recommendation strong), 3) abdominal muscle mass by CT (quality of evidence moderate, grade of recommendation strong), and 4) cardiopulmonary exercise testing (CPET) (quality of evidence moderate, grade of recommendation weak). We recommend that selection of the appropriate tool depends on the specific clinical setting and available resources to administer the tool, and that use of a tool be incorporated into the routine pre-operative assessment when considering implementation of ERAS protocols for LT.

Impact of continuous vs. interval training on oxygen extraction and cardiac function during exercise in type 2 diabetes mellitus.

Van Ryckeghem L; Keytsman C; De Brandt J; Verboven K; Verbaanderd E; Marinus N; Franssen WMA;
Frederix I;Bakelants E;Petit T; Jogani S; Stroobants S; Dendale P; Verwerft J; Hansen D;

European journal of applied physiology [Eur J Appl Physiol] 2022 Apr; Vol. 122 (4), pp. 875-887.
Date of Electronic Publication: 2022 Jan 17.

Purpose: Exercise training improves exercise capacity in type 2 diabetes mellitus (T2DM). It remains to be elucidated whether such improvements result from cardiac or peripheral muscular adaptations, and whether these are intensity dependent.
Methods: 27 patients with T2DM [without known cardiovascular disease (CVD)] were randomized to high-intensity interval training (HIIT, n = 15) or moderate-intensity endurance training (MIT, n = 12) for 24 weeks (3 sessions/week). Exercise echocardiography was applied to investigate cardiac output (CO) and oxygen (O 2 ) extraction during exercise, while exercise capacity [([Formula: see text] (mL/kg/min)] was examined via cardiopulmonary exercise testing at baseline and after 12 and 24 weeks of exercise training, respectively. Changes in glycaemic control (HbA1c and glucose tolerance), lipid profile and body composition were also evaluated.
Results: 19 patients completed 24 weeks of HIIT (n = 10, 66 ± 11 years) or MIT (n = 9, 61 ± 5 years). HIIT and MIT similarly improved glucose tolerance (p Time  = 0.001, p Interaction  > 0.05), [Formula: see text] (mL/kg/min) (p Time  = 0.001, p Interaction  > 0.05), and exercise performance (W peak ) (p Time  < 0.001, p Interaction  > 0.05). O 2 extraction increased to a greater extent after 24 weeks of MIT (56.5%, p 1  = 0.009, p Time  = 0.001, p Interaction  = 0.007). CO and left ventricular longitudinal strain (LS) during exercise remained unchanged (p Time  > 0.05). A reduction in HbA1c was correlated with absolute changes in LS after 12 weeks of MIT (r = - 0.792, p = 0.019, LS at rest) or HIIT (r = - 0.782, p = 0.038, LS at peak exercise).
Conclusion: In patients with well-controlled T2DM, MIT and HIIT improved exercise capacity, mainly resulting from increments in O 2 extraction capacity, rather than changes in cardiac output. In particular, MIT seemed highly effective to generate these peripheral adaptations.

Subclinical Cardiac Dysfunction is Associated with Reduced Cardiorespiratory Fitness and Cardiometabolic Risk Factors in Firefighters

Denise L. Smith; Elliot L. Graham; Julie A. Douglas;  Kepra Jack; Michael J. Conner;
Ross Arena; Sundeep Chaudhry;

The American Journal of Medicine (2022) 000:1−9

BACKGROUND: Past studies have documented the ability of cardiopulmonary exercise testing to detect cardiac
dysfunction in symptomatic patients with coronary artery disease. Firefighters are at high risk for
work-related cardiac events. This observational study investigated the association of subclinical cardiac
dysfunction detected by cardiopulmonary exercise testing with modifiable cardiometabolic risk factors in
asymptomatic firefighters.
METHODS: As part of mandatory firefighter medical evaluations, study subjects were assessed at 2 occupational
health clinics serving 21 different fire departments. Mixed effects logistic regression analyses were
used to estimate odds ratios (ORs) and account for clustering by fire department.
RESULTS: Of the 967 male firefighters (ages 20-60 years; 84% non-Hispanic white; 14% on cardiovascular
medications), nearly two-thirds (63%) had cardiac dysfunction despite having normal predicted cardiorespiratory
fitness (median peak VO2 = 102%). In unadjusted analyses, cardiac dysfunction was significantly
associated with advanced age, obesity, diastolic hypertension, high triglycerides, low high-density lipoprotein
(HDL) cholesterol, and reduced cardiorespiratory fitness (all P values < .05). After adjusting for age
and ethnicity, the odds of having cardiac dysfunction were approximately one-third higher among firefighters
with obesity and diastolic hypertension (OR = 1.39, 95% confidence interval [CI] = 1.03-1.87 and
OR = 1.36, 95% CI = 1.03-1.80) and more than 5 times higher among firefighters with reduced cardiorespiratory
fitness (OR = 5.41, 95% CI = 3.29-8.90).
CONCLUSION: Subclinical cardiac dysfunction detected by cardiopulmonary exercise testing is a common
finding in career firefighters and is associated with substantially reduced cardiorespiratory fitness and cardiometabolic risk factors. These individuals should be targeted for aggressive risk factor modification to
increase cardiorespiratory fitness as part of an outpatient prevention strategy to improve health and safety.