Category Archives: Publications

Poor Cardiorespiratory Fitness Is a Risk Factor for Sepsis in Patients Awaiting Liver Transplantation.

Wallen MP; Woodward AJ; Hall A; Skinner TL; Coombes JS; Macdonald GA;

Transplantation [Transplantation] 2019 Mar; Vol. 103 (3), pp. 529-535.

Background: Patients with advanced liver disease are at increased risk of infection and other complications. A significant proportion of patients also have poor fitness and low muscle mass. The primary aim of this study was to investigate if cardiorespiratory fitness and body composition are risk factors for sepsis and other complications of advanced liver disease.
Methods: Patients being listed for liver transplantation underwent cardiopulmonary exercise testing to determine ventilatory threshold (VT). Computed tomography was used to measure skeletal muscle and subcutaneous and visceral adipose tissue indexes. All unplanned hospital admissions, deaths or delistings before transplantation were recorded.
Results: Eighty-two patients (aged 55.1 [50.6-59.4] years, median (interquartile range); male 87%] achieved a median VT of 11.7 (9.7-13.4) mL·kg·min. Their median model of end-stage liver disease, incorporating serum sodium score was 18 (14-22); and 37 had hepatocellular carcinoma. There were 50 admissions in 31 patients; with 16 admissions for sepsis in 13 patients. Patients with sepsis had a significantly lower VT (sepsis, 9.5 [7.8-11.9]; no sepsis, 11.8 [10.5-13.8] mL·kg·min; P = 0.003]. No body composition variables correlated with sepsis, nor were there any significant associations between VT and unplanned admissions for other indications. Multivariate logistic regression demonstrated that VT was independently associated with a diagnosis of sepsis (P = 0.03). Poisson regression revealed that VT was a significant predictor for the number of septic episodes (P = 0.02); independent of age, model of end-stage liver disease, incorporating serum sodium score, hepatocellular carcinoma diagnosis, presence of ascites, and β-blocker use.
Conclusions: Poor cardiorespiratory fitness is an independent risk factor for the development of sepsis in advanced liver disease.

The efficacy of ‘static’ training interventions for improving indices of cardiorespiratory fitness in premenopausal females.

Herrod PJJ; Blackwell JEM; Moss BF; Gates A; Atherton PJ; Lund JN; Williams JP; Phillips BE;

European Journal Of Applied Physiology [Eur J Appl Physiol] 2019 Mar; Vol. 119 (3), pp. 645-652. Date of Electronic Publication: 2018 Dec 27.

Purpose: Cardiovascular disease (CVD) is the leading cause of death worldwide. Many risk factors for CVD can be modified pharmacologically; however, uptake of medications is low, especially in asymptomatic people. Exercise is also effective at reducing CVD risk, but adoption is poor with time-commitment and cost cited as key reasons for this. Repeated remote ischaemic preconditioning (RIPC) and isometric handgrip (IHG) training are both inexpensive, time-efficient interventions which have shown some promise in reducing blood pressure (BP) and improving markers of cardiovascular health and fitness. However, few studies have investigated the effectiveness of these interventions in premenopausal women.
Method: Thirty healthy females were recruited to twelve supervised sessions of either RIPC or IHG over 4 weeks, or acted as non-intervention controls (CON). BP measurements, flow-mediated dilatation (FMD) and cardiopulmonary exercise tests (CPET) were performed at baseline and after the intervention period.
Results: IHG and RIPC were both well-tolerated with 100% adherence to all sessions. A statistically significant reduction in both systolic (- 7.2 mmHg) and diastolic (- 6 mmHg) BP was demonstrated following IHG, with no change following RIPC. No statistically significant improvements were observed in FMD or CPET parameters in any group.
Conclusions: IHG is an inexpensive and well-tolerated intervention which may improve BP; a key risk factor for CVD. Conversely, our single arm RIPC protocol, despite being similarly well-tolerated, did not elicit improvements in any cardiorespiratory parameters in our chosen population.

Cardiopulmonary Exercise Testing-A Valuable Tool, Not Gatekeeper When Referring Patients With ACHD for Transplant Evaluation.

Menachem JN; Reza N; Mazurek JA; Burstein D; Birati EY; Kim YY; Molina M;Partington SL; Tanna M; Tobin L; Wald J; Goldberg LR;

World Journal For Pediatric & Congenital Heart Surgery [World J Pediatr Congenit Heart Surg] 2019 Mar 04, pp. 2150135118825263. Date of Electronic Publication: 2019 Mar 04.

Introduction:: Treatment of patients with adult congenital heart disease (ACHD) with advanced therapies including heart transplant (HT) is often delayed due to paucity of objective prognostic markers for the severity of heart failure (HF). While the utility of Cardiopulmonary Exercise Testing (CPET) in non-ACHD patients has been well-defined as it relates to prognosis, CPET for this purpose in ACHD is still under investigation.
Methods:: We performed a retrospective cohort study of 20 consecutive patients with ACHD who underwent HT between March 2010 and February 2016. Only 12 of 20 patients underwent CPET prior to transplantation. Demographics, standard measures of CPET interpretation, and 30-day and 1-year post transplantation outcomes were collected.
Results:: Patient Characteristics. Twenty patients with ACHD were transplanted at a median of 40 years of age (range: 23-57 years). Of the 12 patients who underwent CPET, 4 had undergone Fontan procedures, 4 had tetralogy of Fallot, 3 had d-transposition of the great arteries, and 1 had Ebstein anomaly. Thirty-day and one-year survival was 100%. All tests included in the analysis had a peak respiratory quotient _1.0. The median peak oxygen consumption per unit time (_VO2) for all diagnoses was 18.2 mL/kg/min (46% predicted), ranging from 12.2 to 22.6.
Conclusion:: There is a paucity of data to support best practices for patients with ACHD requiring transplantation. While it cannot be proven based on available data, it could be inferred that outcomes would have been worse or perhaps life sustaining options unavailable if providers delayed referral because of the lack of attainment of CPET-specific thresholds.

Non-invasive Hemodynamic CMR Parameters Predicting Maximal Exercise Capacity in 54 Patients with Ebstein’s Anomaly.

Meierhofer C; Kühn A; Müller J; Shehu N; Hager A; Martinoff S; Stern H; Ewert P; Vogt M;

Pediatric Cardiology [Pediatr Cardiol] 2019 Feb 06. Date of Electronic Publication: 2019 Feb 06.

Background: Exercise capacity is a well-defined marker of outcome in congenital heart disease. We analyzed seventeen cardiovascular magnetic resonance (CMR) derived parameters and their correlation to exercise capacity in patients with Ebstein’s anomaly (EA).
Methods: Fifty-four surgery free patients, age 5 to 69 years (median 30 years) prospectively underwent CMR examination and cardiopulmonary exercise testing (CPET). The following volume/flow parameters were compared with peak oxygen uptake as the percentage of normal (peakVO2%) using univariate and multivariate analysis: right and left ventricular ejection fraction (RVEF and LVEF), the indexed end-diastolic and end-systolic volumes (RVEDVi, RVESVi, LVEDVi, and LVESVi), the indexed stroke volumes (RVSVi and LVSVi), the total normalized right and left heart volumes; the total right to left heart volume ratio (R/L-ratio). The indexed antegrade flow (ante), indexed net flow (net) as well as cardiac index (CI) in the aorta (Ao) and pulmonary artery (PA) were used.
Results: RVEF (R2 0.2788), indexed flow PA net (R2 0.2330), and PA ante (R2 0.1912) showed the best correlation with peakVO2% (all p < 0.001) in the univariate model. Further significant correlation could also be demonstrated with CI-PA, LVEF, LVSVi, Aorta net, RVESVi, and Aorta ante. Multivariate analysis for RVEF and indexed net flow PA revealed a R2 of 0.4350.
Conclusion: Functional CMR parameters as RVEF and LVEF and flow data of cardiac forward flow correlate to peakVO2%. Evaluation of the indexed net flow in the pulmonary artery and the overall function of the right ventricle best predicts the maximal exercise capacity in patients with EA.

Isocapnic buffering period: From physiology to clinics.

Carriere C; Corrà U; Piepoli M; Bonomi A; Salvioni E; Binno S; Magini A; Sciomer S; Pezzuto B;
Gentile P; Schina M; Sinagra G; Agostoni P

European Journal Of Preventive Cardiology [Eur J Prev Cardiol] 2019 Feb 12, pp. 2047487319829950. Date of Electronic Publication: 2019 Feb 12.

Background: During cardiopulmonary exercise test, the isocapnic buffering period ranges between anaerobic threshold (AT) and respiratory compensation point (RCP). We investigated whether oxygen uptake (VO2) increase during the isocapnic buffering period (ΔVO2AT-RCP) is related to heart failure severity and prognosis.
Methods: We retrospectively analysed reduced ejection fraction heart failure patients who attained RCP at cardiopulmonary exercise test. The study endpoint was the composite of cardiovascular mortality and urgent heart transplantation/left ventricular assist device implantation. Hazard ratio was assessed to identify the increase of risk associated with ΔVO2AT-RCP (below and above the median of ΔVO2AT-RCP).
Results: AT and RCP were both identified in 782 (39.2%) out of 1995 reduced ejection fraction heart failure cases. Left ventricular ejection fraction and peak VO2 were 33 ± 9% and 16.5 ± 4.5 mL/kg per min (61 ± 16% of predicted value), suggesting moderate heart failure. At five years, endpoint did not vary between patients below and above the median ΔVO2AT-RCP (3.85 mL/min per kg (25-75th interquartile range = 2.69-5.46)). ΔVO2AT-RCP correlated with several parameters associated to heart failure prognosis, such as peak VO2, VE/VCO2 slope, brain natriuretic peptide and left ventricular ejection fraction. The ΔVO2AT-RCP value was associated with prognosis at univariate but not at multivariable analysis, where only VE/VCO2 slope endured.
Conclusion: ΔVO2AT-RCP correlates with several parameters linked to heart failure severity. Isocapnic buffering period stratifies heart failure patients, but not more than other prognostic indices.

Exercise training program in patients with NYHA III class systolic heart failure – Parallel comparison to the effects of resynchronization therapy.

Smolis-Bąk E; Chwyczko T; Kowalik I; Borowiec A; Maciąg A; Szwed H; Dąbrowski R

Advances In Medical Sciences [Adv Med Sci], ISSN: 1898-4002, 2019 Feb 26; Vol. 64 (2), pp. 241-245

Purpose: The aim of this study was to assess exercise capacity and echocardiographic parameters in patients with heart failure with reduced ejection fraction (HFrEF) in NYHA III functional class, after cardiac resynchronization therapy (CRT) or implantable cardioverter-defibrillator (ICD) implantation followed by 6 months of supervised rehabilitation in ICD patients.
Materials and Methods: The study included patients with HFrEF and impaired left ventricle systolic function (LVEF ≤ 35%), divided into two groups: CRT group – patients after CRT-D implantation > six weeks, and ICD-rehab group – patients after ICD implantation > six weeks, followed by 6 months of supervised aerobic interval training and the conditioning exercises. At baseline and after 6 months in all the patients cardiopulmonary exercise tests (CPX) and standard echocardiographic examinations were performed.
Results: The study included 61 patients (49-77 years) with HFrEF. At baseline, the values of CPX parameters were similar in both groups. After completing training almost all CPX parameters in the ICD-rehab group significantly improved, except for anaerobic threshold (AT). In the CRT group significant improvements were found in 2 parameters: peak oxygen uptake (VO2) and exercise tolerance (metabolic equivalents, METs). Significant reductions in left and right ventricle diameters and an increase in LVEF were observed in both groups after 6 months.
Conclusions: Significant improvement in exercise tolerance capacity and increase of LVEF were observed in similar extent both in heart failure patients with CRT and with ICD undergoing the rehabilitation program. Regular, controlled exercise trainings provided additional, safe and easy to conduct therapeutic option for heart failure patients with no indications for CRT.

Cardiopulmonary responses to maximal aerobic exercise in patients with cystic fibrosis.

Williams CA; Wedgwood KCA; Mohammadi H; Prouse K; Tomlinson OW; Tsaneva-Atanasova K

Plos One [PLoS One], ISSN: 1932-6203, 2019 Feb 13; Vol. 14 (2), pp. e0211219; Publisher: Public Library of Science; PMID: 30759119;

Cystic fibrosis (CF) is a debilitating chronic condition, which requires complex and expensive disease management. Exercise has now been recognised as a critical factor in improving health and quality of life in patients with CF. Hence, cardiopulmonary exercise testing (CPET) is used to determine aerobic fitness of young patients as part of the clinical management of CF. However, at present there is a lack of conclusive evidence for one limiting system of aerobic fitness for CF patients at individual patient level. Here, we perform detailed data analysis that allows us to identify important systems-level factors that affect aerobic fitness. We use patients’ data and principal component analysis to confirm the dependence of CPET performance on variables associated with ventilation and metabolic rates of oxygen consumption. We find that the time at which participants cross the gas exchange threshold (GET) is well correlated with their overall performance. Furthermore, we propose a predictive modelling framework that captures the relationship between ventilatory dynamics, lung capacity and function and performance in CPET within a group of children and adolescents with CF. Specifically, we show that using Gaussian processes (GP) we can predict GET at the individual patient level with reasonable accuracy given the small sample size of the available group of patients. We conclude by presenting an example and future perspectives for improving and extending the proposed framework. The modelling and analysis have the potential to pave the way to designing personalised exercise programmes that are tailored to specific individual needs relative to patient’s treatment therapies.

Cardiopulmonary Exercise Testing-A Valuable Tool, Not Gatekeeper When Referring Patients With ACHD for Transplant Evaluation.

Menachem JN; Reza N; Mazurek JA; Burstein D; Birati EY; Fox A; Kim YY; Molina M; Partington SL; Tanna M; Tobin L; Wald J; Goldberg LR

World Journal For Pediatric & Congenital Heart Surgery [World J Pediatr Congenit Heart Surg], ISSN: 2150-136X, 2019 Mar 04

Introduction:: Treatment of patients with adult congenital heart disease (ACHD) with advanced therapies including heart transplant (HT) is often delayed due to paucity of objective prognostic markers for the severity of heart failure (HF). While the utility of Cardiopulmonary Exercise Testing (CPET) in non-ACHD patients has been well-defined as it relates to prognosis, CPET for this purpose in ACHD is still under investigation.
Methods:: We performed a retrospective cohort study of 20 consecutive patients with ACHD who underwent HT between March 2010 and February 2016. Only 12 of 20 patients underwent CPET prior to transplantation. Demographics, standard measures of CPET interpretation, and 30-day and 1-year post transplantation outcomes were collected.
Results:: Patient Characteristics. Twenty patients with ACHD were transplanted at a median of 40 years of age (range: 23-57 years). Of the 12 patients who underwent CPET, 4 had undergone Fontan procedures, 4 had tetralogy of Fallot, 3 had d-transposition of the great arteries, and 1 had Ebstein anomaly. Thirty-day and one-year survival was 100%. All tests included in the analysis had a peak respiratory quotient _1.0. The median peak oxygen consumption per unit time (_VO2) for all diagnoses was 18.2 mL/kg/min (46% predicted), ranging from 12.2 to 22.6.
Conclusion:: There is a paucity of data to support best practices for patients with ACHD requiring transplantation. While it cannot be proven based on available data, it could be inferred that outcomes would have been worse or perhaps life sustaining options unavailable if providers delayed referral because of the lack of attainment of CPET-specific thresholds.

Cardiac vagal dysfunction and myocardial injury after non-cardiac surgery: a planned secondary analysis of the measurement of Exercise Tolerance before surgery study.

Abbott TEF; Pearse RM; Cuthbertson BH; Wijeysundera DN; Ackland GL; METS study investigators

British Journal Of Anaesthesia [Br J Anaesth], ISSN: 1471-6771, 2019 Feb; Vol. 122 (2), pp. 188-197

Background: The aetiology of perioperative myocardial injury is poorly understood and not clearly linked to pre-existing cardiovascular disease. We hypothesised that loss of cardioprotective vagal tone [defined by impaired heart rate recovery ≤12 beats min-1 (HRR ≤12) 1 min after cessation of preoperative cardiopulmonary exercise testing] was associated with perioperative myocardial injury.
Methods: We conducted a pre-defined, secondary analysis of a multi-centre prospective cohort study of preoperative cardiopulmonary exercise testing. Participants were aged ≥40 yr undergoing non-cardiac surgery. The exposure was impaired HRR (HRR≤12). The primary outcome was postoperative myocardial injury, defined by serum troponin concentration within 72 h after surgery. The analysis accounted for established markers of cardiac risk [Revised Cardiac Risk Index (RCRI), N-terminal pro-brain natriuretic peptide (NT pro-BNP)].
Results: A total of 1326 participants were included [mean age (standard deviation), 64 (10) yr], of whom 816 (61.5%) were male. HRR≤12 occurred in 548 patients (41.3%). Myocardial injury was more frequent amongst patients with HRR≤12 [85/548 (15.5%) vs HRR>12: 83/778 (10.7%); odds ratio (OR), 1.50 (1.08-2.08); P=0.016, adjusted for RCRI). HRR declined progressively in patients with increasing numbers of RCRI factors. Patients with ≥3 RCRI factors were more likely to have HRR≤12 [26/36 (72.2%) vs 0 factors: 167/419 (39.9%); OR, 3.92 (1.84-8.34); P<0.001]. NT pro-BNP greater than a standard prognostic threshold (>300 pg ml-1) was more frequent in patients with HRR≤12 [96/529 (18.1%) vs HRR>12 59/745 (7.9%); OR, 2.58 (1.82-3.64); P<0.001].
Conclusions: Impaired HRR is associated with an increased risk of perioperative cardiac injury. These data suggest a mechanistic role for cardiac vagal dysfunction in promoting perioperative myocardial injury.