Paolillo S; Veglia F; Salvioni E; MECKI Score Research Group

European Journal Of Heart Failure [Eur J Heart Fail] 2019 Feb; Vol. 21 (2), pp. 208-217. Date of Electronic Publication: 2019 Jan 11.

Aims: Exercise-derived parameters, specifically peak exercise oxygen uptake (peak VO2 ) and minute ventilation/carbon dioxide relationship slope (VE/VCO2 slope), have a pivotal prognostic value in heart failure (HF). It is unknown how the prognostic threshold of peak VO2 and VE/VCO2 slope has changed over the last 20 years in parallel with HF prognosis improvement.
Methods and Results: Data from 6083 HF patients (81% male, age 61 ± 13 years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993-2000 (n = 440), group 2 2001-2005 (n = 1288), group 3 2006-2010 (n = 2368), and group 4 2011-2015 (n = 1987). We compared the 10-year survival of groups and analysed how the overall risk (cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation) changed over time according to peak VO2 and VE/VCO2 slope and to major clinical and therapeutic variables. At 10 years, a progressively higher survival from group 1 to group 3 was observed, with no further improvement afterwards. A 20% risk for peak VO2 15 mL/min/kg (95% confidence interval 16-13), 9 (11-8), 4 (4-2) and 5 (7-4) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO2 slope value for a 20% risk was 32 (37-29), 47 (51-43), 59 (64-55), and 57 (63-52), respectively.
Conclusions: Heart failure prognosis improved over time up to 2010 in a HF population followed by experienced centres. The peak VO2 and VE/VCO2 slope cut-offs identifying a definite risk progressively decreased and increased over time, respectively. The prognostic threshold of peak VO2 and VE/VCO2 slope must be updated whenever HF prognosis improves.
(© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Lanier GM; Fallon JT; Naidu SS;

Cardiology Clinics [Cardiol Clin] 2019 Feb; Vol. 37 (1), pp. 73-82. Date of Electronic Publication: 2018 Oct 29.

Hypertrophic cardiomyopathy affects 0.5% of the population. Advanced testing is considered, including cardiac catheterization, endomyocardial biopsy, and cardiopulmonary exercise testing. Right and left heart catheterization provides essential hemodynamic data, identifies patients who might benefit from septal reduction therapy, and assesses for comorbidities. Pathologic analysis reveals ventricular hypertrophy, myocardial disarray, and endocardial and interstitial fibrosis. Routine endomyocardial biopsy is not recommended unless other conditions that cause hypertrophy need to be ruled out. Cardiopulmonary exercise testing provides useful physiologic data, allows monitoring of the response to medication and surgical interventions, estimates prognosis, and guides referral for orthotopic heart transplantation.

Hock J; Häcker AL; Reiner B; Oberhoffer R; Hager A; Ewert P; Müller J;

Archives Of Disease In Childhood [Arch Dis Child] 2019 Feb; Vol. 104 (2), pp. 129-133. Date of Electronic Publication: 2018 Jul 03.

Objective: Functional outcome measures are of growing importance in the aftercare of patients with congenital heart disease. This study addresses the functional status with regard to exercise capacity, health-related physical fitness (HRPF) and arterial stiffness in a recent cohort of children, adolescents and young adults with tetralogy of Fallot (ToF) after repair.
Design: Single-centre, uncontrolled and prospective cohort study.
Setting: Outpatient department of the German Heart Centre Munich; July 2014-January 2018.
Patients: One hundred and six patients with ToF after repair (13.5±3.7 years, 40 females) were included. Data were compared with a recent cohort of healthy controls (HCs) (n=1700, 12.8±2.6 years, 833 females).
Main Outcome Measures: Patients underwent a symptom-limited cardiopulmonary exercise test, performed an HRPF test (FitnessGram) and had an assessment of their arterial stiffness (Mobil-O-Graph).
Results: Compared with HC, patients with ToF showed lower predicted [Formula: see text]O2 peak (ToF: 80.4% ± 16.8% vs HC: 102.6% ± 18.1%, p<0.001), impaired ventilatory efficiency (ToF: 29.6 ± 3.6 vs HC: 27.4 ± 2.9, p<0.001), chronotropic incompetence (ToF: 167 ± 17 bpm vs HC: 190 ± 17 bpm, p<0.001) and reduced HRPF (ToF z-score: -0.65 ± 0.87 vs HC z-score: 0.03 ± 0.65, p<0.001). Surrogates of arterial stiffness, central and peripheral systolic blood pressure, did not differ between the two groups.
Conclusions: Contemporary children, adolescents and young adults with ToF still have functional limitations. How impaired HRPF and limited exercise capacity interact and how they can be modified needs to be evaluated in further intervention studies.

Pugliese NR; Fabiani I; Santini C; Rovai I; Pedrinelli R; Natali A; Dini FL;

European Heart Journal Cardiovascular Imaging [Eur Heart J Cardiovasc Imaging] 2019 Feb 11. Date of Electronic Publication: 2019 Feb 11.

Aims: To characterize heart failure (HF) with mid-range ejection fraction (HFmrEF), combining cardiopulmonary exercise test, and exercise stress echocardiography.
Methods and results: We studied 169 consecutive subjects (age 62.3 ± 11 years; 74% male): 30 healthy controls, 45 patients with HF and preserved EF (HFpEF), 40 HFmrEF, and 54 with HF and reduced EF (HFrEF). Left ventricular (LV) stroke volume (SV), EF, elastance, global longitudinal strain, E/E’, oxygen consumption (VO2), and arterial-venous oxygen content difference (AVO2diff) were measured in all exercise stages. HFmrEF revealed baseline features intermediate between HFrEF and HFpEF, except for B-type natriuretic peptide levels, which was similar to HFpEF and significantly lower than HFrEF. Peak VO2 was not significantly different between HF groups. HFrEF exhibited a significantly lower peak SV as compared to either HFpEF or HFmrEF (74.3 ± 21.8 mL vs. 88.0 ± 17.4 mL and 96.5 ± 25.1 mL; P < 0.01), whereas peak heart rate was not significantly different between HF groups. A significantly reduced AVO2diff at peak exercise was apparent in HFpEF and HFmrEF (15.2 ± 3.3 mL/dL and 13.3 ± 4.2 mL/dL) vs. HFrEF (17.±6.6 mL/dL; P < 0.01), whereas no significant difference was reported between HFpEF and HFmrEF. Multivariate analysis in the overall population and all groups revealed peak parameters as independent predictors of peak VO2 (R2 = 0.90, P < 0.0001); AVO2diff showed the largest standardized regression coefficient.
Conclusion: In HFpEF and HFmrEF, effort intolerance is predominantly due to peripheral factors (AVO2diff), whereas in HFrEF peak VO2 is restricted by low increases in SV. Individual therapy according to which component of VO2 is more impaired is advisable.

Foulkes S; Howden EJ; Bigaran A; Janssens K; Antill Y; Loi S; Claus P; Haykowsky MJ; Daly RM; Fraser SF;
La Gerche A;

Medicine And Science In Sports And Exercise [Med Sci Sports Exerc] 2019 Mar 01. Date of Electronic Publication: 2019 Mar 01.

Purpose: Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (VO2peak). We sought to determine whether changes in VO2peak and cardiac function persisted at 12-months post-AC completion, and whether changes in cardiac function explain the heightened long-term heart failure risk.
Methods: Women with breast cancer scheduled for AC (n=28) who participated in a non-randomized trial of exercise training (ET; n=14) or usual care (UC; n=14) during AC completed a follow-up evaluation 12-months post-AC completion (16-months from baseline). At baseline, 4-months, and 16-months, participants underwent a resting echocardiogram (left ventricular ejection fraction, LVEF; global longitudinal strain, GLS), a blood sample (troponin; b-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate (HR) and cardiac output (Qc) at rest, and during intense exercise.
Results: Seventeen women (UC: n=8; ET: n=9) completed evaluation at baseline, 4-months and 16-months. At 4-months, AC was associated with 18% and 6% reductions in VO2peak in the UC and ET groups respectively, that persisted at 16-months (UC: -16%; ET: -7%), and was not attenuated by ET (interaction, P=0.10). Exercise Qc was lower at 16-months compared to baseline and 4-months (P<0.001), which was due to a blunted augmentation of SV during exercise (P=0.032; a 14% reduction in peak SV), with no changes in HR response. There was a small reduction in resting LVEF (baseline to 4-months) and GLS (between 4-months and 16-months), and an increase in troponin (baseline to 4-months), but only exercise Qc was associated with VO2peak (R=0.47, P<0.01).
Conclusion: Marked reductions in VO2peak persisted 12-months following anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function.

Badagliacca R; Papa S; Poscia R; Valli G; Pezzuto B; Manzi G; Torre R; Gianfrilli D; Sciomer S; Palange P; Naeije R;Fedele F; Vizza CD;

he Journal Of Heart And Lung Transplantation: The Official Publication Of The International Society For Heart Transplantation [J Heart Lung Transplant] 2019 Mar; Vol. 38 (3), pp. 306-314. Date of Electronic Publication: 2018 Dec 06.

Background: The added value of cardiopulmonary exercise testing (CPET) in the follow-up of patients with stable pulmonary arterial hypertension (PAH) remains undefined.
Methods: Idiopathic, heritable, and drug-induced PAH patients free from clinical worsening (CW) after 1 year of treatment were enrolled in derivation (n = 80) and validation (n = 80) cohorts at an interval of 6 years and followed for 3 years. Prognostic models were constructed and validated in low-risk patients in World Health Organization (WHO) Functional Class I or II with cardiac index (CI) ≥2.5 liters/min/m2 and right atrial pressure (RAP) <8 mm Hg. Discrimination and calibration were assessed.
Results: Forty-one derivation cohort patients had CW (51.2%) during 722 ± 349 days. Changes (∆) in WHO classification and CI and absolute value of RAP were independent predictors of CW. With addition of CPET variables, peak oxygen uptake (VO2 peak) and ∆CI independently improved the power of the prognostic model. Receiver operating characteristic (ROC)-derived cut-off values for ∆CI and VO2 peak were 0.40 liter/min/m2 and 15.7 ml/kg/min (≥60% predicted value), respectively. Twenty-nine validation cohort patients had CW (36.2%) during 710 ± 282 days. Different combinations of cut-off values of VO2 peak and ∆CI defined 4 groups. The event-free survival rates at 1, 2, and 3 years were 100%, 100%, and 100%, respectively, for the high ∆CI with high VO2 peak combination; 100%, 88%, and 71% for low ∆CI/high VO2 peak; 80%, 54%, and 40% for high ∆CI/low VO2 peak; and 72%, 54%, and 33% for low ∆CI/low VO2 peak.
Conclusions: The combinations of baseline VO2 peak and change in CI during follow-up is important in prognostication of low-risk patients with idiopathic, heritable, and drug-induced PAH.

Suryanegara J; Cassidy S; Ninkovic V; Popovic D; Grbovic M; Okwose N; Trenell MI; MacGowan GG; Jakovljevic DG;

Acta Diabetologica [Acta Diabetol] 2019 Mar; Vol. 56 (3), pp. 321-329. Date of Electronic Publication: 2018 Nov 01.

Aim: The present study assessed the effect of high intensity interval training on cardiac function during prolonged submaximal exercise in patients with type 2 diabetes.
Methods: Twenty-six patients with type 2 diabetes were randomized to a 12 week of high intensity interval training (3 sessions/week) or standard care control group. All patients underwent prolonged (i.e. 60 min) submaximal cardiopulmonary exercise testing (at 50% of previously assess maximal functional capacity) with non-invasive gas-exchange and haemodynamic measurements including cardiac output and stroke volume before and after the intervention.
Results: At baseline (prior to intervention) there was no significant difference between the intervention and control group in peak exercise oxygen consumption (20.3 ± 6.1 vs. 21.7 ± 5.5 ml/kg/min, p = 0.21), and peak exercise heart rate (156.3 ± 15.0 vs. 153.8 ± 12.5 beats/min, p = 0.28). During follow-up assessment both groups utilized similar amount of oxygen during prolonged submaximal exercise (15.0 ± 2.4 vs. 15.2 ± 2.2 ml/min/kg, p = 0.71). However, cardiac function i.e. cardiac output during submaximal exercise decreased significantly by 21% in exercise group (16.2 ± 2.7-12.8 ± 3.6 L/min, p = 0.03), but not in the control group (15.7 ± 4.9-16.3 ± 4.1 L/min, p = 0.12). Reduction in exercise cardiac output observed in the exercise group was due to a significant decrease in stroke volume by 13% (p = 0.03) and heart rate by 9% (p = 0.04).
Conclusion: Following high intensity interval training patients with type 2 diabetes demonstrate reduced cardiac output during prolonged submaximal cardiopulmonary exercise testing. Ability of patients to maintain prolonged increased metabolic demand but with reduced cardiac output suggests cardiac protective role of high intensity interval training in type 2 diabetes.

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.

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.

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.