Lai S, Mastroluca D, Matino S, Panebianco V, Vitarelli A,
Capotosto L, Turinese I, Marinelli P, Rossetti M, Galani A,
Baiocchi P, D’Angelo AR, Palange P.

Kidney Blood Press Res. 2017;42(6):1290-1302. doi: 10.1159/000486011. Epub 2017
Dec 15.

BACKGROUND/AIMS: Cardiovascular disease is the most frequent cause of morbidity
and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients,
often before the onset of renal failure, and the pathogenetic mechanism is not
yet well elucidated. The aim of the study was to identify early and noninvasive
markers of cardiovascular risk in young ADPKD patients, in the early stages of
disease.
METHODS: A total of 26 patients with ADPKD and 24 control group, matched for age
and sex, were enrolled, and we have assessed inflammatory indexes, mineral
metabolism, metabolic state and markers of atherosclerosis and endothelial
dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI),
flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass
index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake
(V’O2max), and O2 uptake at lactic acid threshold (V’O2@LT).
RESULTS: The ADPKD patients compared to control group, showed a significant
higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model
Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT
(cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001,
p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and
25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of
exercise tolerance, as V’O2max, V’O2max/Kg and V’O2max (% predicted) (p<0.001,
p<0.001, p=0.018; respectively), and metabolic response indexes (V’O2@LT, V’O2
@LT%, V’O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover,
inflammatory indexes were significantly higher in ADPKD patients, and we found a
positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507,
p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585,
p=0.002).
CONCLUSION: In our study, ADPKD patients, in the early stages of disease, showed
a greater insulin resistance, endothelial dysfunction, inflammation and mineral
metabolism disorders, respect to control group. Moreover, these patients
presented reduced tolerance to stress, and decreased anaerobic threshold to CPET.
Our results indicate a major and early cardiovascular risk in ADPKD patients.
Therefore early and noninvasive markers of cardiovascular risk and CPET should be
carried out, in ADPKD patients, in the early stages of disease, despite the cost
implication.

Campodonico J; Piepoli M; Clemenza F; Bonomi A; Paolillo S; Salvioni E; Corrà U; Binno S; Veglia F; Lagioia R; Sinagra G; Cattadori G; Scardovi AB; Metra M; Senni M; Scrutinio D; Raimondo R; Emdin M; Magrì D; Parati G; Re F;Cicoira M; Minà C; Limongelli G; Correale M; Frigerio M; Bussotti M; Perna E; Battaia E; Guazzi M; Badagliacca R; DiLenarda A; Maggioni A; Passino C; Sciomer S; Pacileo G; Mapelli M; Vignati C; Lombardi C; Filardi PP; Agostoni P;

International Journal Of Cardiology [Int J Cardiol] 2018 Aug 06. Date of Electronic Publication: 2018 Aug 06.

Background: The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned.
Methods and Results: We analyzed data from HF patients (958 patients (801 males, 84%, age 67 ± 11 years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving β-blockers (n = 777, 81%) vs. those not treated with β-blockers (n = 181, 19%). We also analyzed the role β1-selectivity and the role of daily β-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577-2304) days in the entire population, 1203 (614-2420) and 1325 (569-2300) days in patients not receiving and receiving β-blockers. 224 (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000 events/year) events were recorded, respectively. At 10-year patients treated with β-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as regards β1selective drugs (53%) vs. β1-β2 blockers (47%). Survival improved in parallel with β-blocker dose increase (HR 0.296, 0.496, 0.490 for the high, medium, and low dose vs. no β-blockers, p < 0.0001).
Conclusion: HF patients with AF taking a β-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards β1 selectivity) but this does not mean that β-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with β-blocker use.

Marcadet DM; Pavy B; Bosser G; Claudot F; Corone S; Douard H; Iliou MC; Amedro P; Le Tourneau T; Cueff C; Avedian T; Solal AC; Carré F;

Archives Of Cardiovascular Diseases [Arch Cardiovasc Dis] 2018 Aug 06. Date of Electronic Publication: 2018 Aug 06.

The exercise test is performed routinely in cardiology; its main indication is the diagnosis of myocardial ischemia, evaluated along with the subject’s pretest probability and cardiovascular risk level. Other criteria, such as analysis of repolarization, must be taken into consideration during the interpretation of an exercise test, to improve its predictive value. An exercise test is also indicated for many other cardiac diseases (e.g. rhythm and conduction disorders, severe asymptomatic aortic stenosis, hypertrophic cardiomyopathy, peripheral artery disease, hypertension). Moreover, an exercise test may be indicated for specific populations (women, the elderly, patients with diabetes mellitus, patients in a preoperative context, asymptomatic patients and patients with congenital heart defects). Some cardiac diseases (such as chronic heart failure or arterial pulmonary hypertension) require a cardiopulmonary exercise test. Finally, an exercise test or a cardiopulmonary exercise test is indicated to prescribe a cardiac rehabilitation programme, adapted to the patient.

Marcadet DM; Pavy B; Bosser G; Claudot F; Corone S; Douard H; Iliou MC; Vergès-Patois B; Amedro P; Le Tourneau T; Cueff C; Avedian T; Solal AC; Carré F;

Archives Of Cardiovascular Diseases [Arch Cardiovasc Dis] 2018 Aug 06. Date of Electronic Publication: 2018 Aug 06.

The exercise test is still a key examination in cardiology, used for the diagnosis of myocardial ischemia, as well as for the clinical evaluation of other heart diseases. The cardiopulmonary exercise test can further define functional capacity and prognosis for any given cardiac pathology. These new guidelines focus on methods, interpretation and indications for an exercise test or cardiopulmonary exercise test, as summarized below. The safety rules associated with the exercise test must be strictly observed. Interpretation of exercise tests and cardiopulmonary exercise tests must be multivariable. Functional capacity is a strong predictor of all-cause mortality and cardiovascular events. Chest pain, ST-segment changes and an abnormal ST/heart rate index constitute the first findings in favor of myocardial ischemia, mostly related to significant coronary artery disease. Chronotropic incompetence, abnormal heart rate recovery, QRS changes (such as enlargement or axial deviations) and the use of scores (based on the presence of various risk factors) must also be considered in exercise test interpretation for a coronary artery disease diagnosis. Arrhythmias or conduction disorders arising during the exercise test must be considered in the assessment of prognosis, in addition to a decrease or low increase in blood pressure during the exercise phase. When performing a cardiopulmonary exercise test, peak oxygen uptake and the volume of expired gas/carbon dioxide output slope are the two main variables used to evaluate prognosis.  [PART 2 FOLLOWS]

Kaminsky LA; Harber MP; Imboden MT; Arena R; Myers J;

Medicine And Science In Sports And Exercise [Med Sci Sports Exerc] 2018 Aug 07. Date of Electronic Publication: 2018 Aug 07.

Purpose: Cardiopulmonary exercise testing (CPX) provides valuable clinical information, including peak ventilation (VEpeak), which has been shown to have diagnostic and prognostic value in the assessment of patients with underlying pulmonary disease. This report provides reference standards for VEpeak derived from CPX on treadmills in apparently healthy individuals.
Methods: Nine laboratories in the United States experienced in CPX administration with established quality control procedures contributed to the Fitness Registry and the Importance of Exercise National Database from 2014 to 2017. Data from 5232 maximal exercise tests from men and women without cardiovascular or pulmonary disease were used to create percentiles of VEpeak for both men and women by decade between 20-79 years. Additionally, prediction equations were developed for VEpeak using descriptive information.
Results: VEpeak was found to be significantly different between men and women and across age groups (p<0.05). The rate of decline in VEpeak was 8.0%/decade for both men and women. A stepwise regression model of 70% of the sample revealed sex, age, and height were significant predictors of VEpeak. The equation was cross-validated with data from the remaining 30% of the sample with a final equation developed from the full sample (r=0.73). Additionally, a linear regression model revealed forced expiratory volume in one second significantly predicted VEpeak (r=0.73).
Conclusions: Reference standards were developed for VEpeak for the United States population. Cardiopulmonary exercise testing laboratories will be able to provide interpretation of VEpeak from these age and sex specific percentile reference values or alternatively can use these non-exercise prediction equations incorporating sex, age, and height or with a single predictor of forced expiratory volume in one second.

Neder JA; Rocha A; Arbex F; Berton DC; Faria M; Sperandio PA; Nery LE; O’Donnell DE;

Expert Review Of Cardiovascular Therapy [Expert Rev Cardiovasc Ther] 2018 Aug 13. Date of Electronic Publication: 2018 Aug 13.

Introduction: Heart failure with reduced ejection fraction (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist, particularly in the elderly. Given their rising prevalence and the contemporary trend to longer life expectancy, overlapping HF-COPD will become a major cause of morbidity and mortality in the next decade. Areas covered: Drawing on current clinical and physiological constructs, the consequences of negative cardiopulmonary interactions on the interpretation of pulmonary function and cardiopulmonary exercise tests in HF-COPD are discussed. Although those interactions may create challenges for the diagnosis and assessment of disease stability, they provide a valuable conceptual framework to rationalize HF-COPD treatment. The impact of COPD or HF on the pharmacological treatment of HF or COPD, respectively, is then comprehensively discussed. Authors finalize by outlining how the non-pharmacological treatment (i.e. rehabilitation and exercise reconditioning) can be tailored to the specific needs of patients with HF-COPD. Expert commentary: Randomized clinical trials testing the efficacy and safety of new medications for HF or COPD should include a sizeable fraction of patients with these coexistent pathologies. Multidisciplinary clinics involving cardiologists and respirologists trained in both diseases (with access to unified cardiorespiratory rehabilitation programs) are paramount to decrease the humanitarian and social burden of HF-COPD.

Hunt KJ; Anandakumaran P; Loretz JA; Saengsuwan J;

Clinical Physiology And Functional Imaging [Clin Physiol Funct Imaging] 2018 Jan; Vol. 38 (1), pp. 108-117.

Purpose: Self-paced maximal testing methods may be able to exploit central mediation of function-limiting fatigue and therefore have potential to generate more valid estimates of peak oxygen uptake. The aim of this study was to investigate the feasibility of a new method for self-paced peak performance testing on treadmills and to compare peak and submaximal performance outcomes with those obtained using a non-self-paced (‘computer-paced’) method employing predetermined speed and slope profiles.
Methods: The proposed self-paced method is based upon automatic subject positioning using feedback control together with an exercise intensity which is driven by a predetermined, individualized work-rate ramp.
Results: Peak oxygen uptake was not significantly different for the computer-paced (CP) versus self-paced (SP) protocols: 4·38 ± 0·48 versus 4·34 ± 0·46 ml min-1 , P = 0·42. Likewise, there were no significant differences in the other peak and submaximal cardiopulmonary parameters, viz. peak heart rate, peak respiratory exchange ratio and the first and second ventilatory thresholds. Ramp duration for CP was longer than for SP: 494·5 ± 71·1 versus 371·3 ± 86·0 s, P = 0·00072. Concomitantly, the peak rate of work done against gravity was higher for CP: 264·8 ± 40·8 versus 203·8 ± 53·4 W, P = 0·0021.
Conclusions: The self-paced approach was found to be feasible for estimation of the principal performance outcomes: the method was technically implementable, it was acceptable to the subjects and it showed good responsiveness. Further investigation of the self-paced method, with adjustment of the target ramp-phase duration or modification of the work-rate calculation equations, is warranted.

Kokubo T; Tajima A; Miyazawa A; Maruyama Y;

Physical Therapy Research [Phys Ther Res] 2018 Apr 20; Vol. 21 (1), pp. 9-15. Date of Electronic Publication: 20180420 (Print Publication: 2018).

Purpose: The aim of this study was to evaluate the oxygen uptake in patients with cardiovascular disease during the low-impact dance program and to compare the findings with the values at peak oxygen uptake (VO2) and aerobic threshold (AT).
Methods: The study included 19 patients with cardiovascular disease [age, 68.3±8.7 years; left-ventricular ejection fraction, 60.3%±8.7%; peak VO2, 6.6±1.1 metabolic equivalents (METs)] who were receiving optimal medical treatment. Their heart rate and VO2 were monitored during cardiopulmonary exercise testing (CPET) and during the low impact dance. The dance involved low-impact dynamic sequences. The patients completed two patterns of low-impact dance, and metabolic gas exchange measurements were obtained using a portable ergospirometry carried in a backpack during the dance sessions.
Results: The mean values of VO2 (4.0±0.2 METs and 3.9±0.3 METs) and those of heart rate (105.2±2.9 bpm and 96.8±2.6 bpm) during the dance program were not significantly differ from the AT value (4.5±0.2 METs) obtained in CPET. The median (and interquartile range) RPE reported after the dance exercise trials was 11 (9-13). No signs of overexertion were observed in any of the patients during either dance exercise trial.
Conclusions: The results suggest that it is reasonable to consider the low-impact dance program as an aerobic exercise program in cardiac rehabilitation. Our findings have important implications for exercise training programs in the cardiac rehabilitation setting and for future studies.

Udholm S; Aldweib N; Hjortdal VE; Veldtman GR;

Open Heart [Open Heart] 2018 Jul 03; Vol. 5 (1), pp. e000812. Date of Electronic Publication: 20180703 (Print Publication: 2018)

Objective: Exercise impairment is common in Fontan patients. Our aim is to systematically review previous literature to determine the prognostic value of exercise capacity in older adolescent and adult Fontan patients with respect to late outcome. Additionally, we reviewed the determinants of exercise capacity in Fontan patients and changes in exercise capacity over time.
Methods: PubMed, CINAHL, Embase, The Cochrane Library and Scopus were searched systematically for studies reporting exercise capacity and late outcome such as mortality, cardiac transplantation and hospitalisation. Studies were eligible for inclusion if more than 30 patients were included and mean age was ≥16 years.
Results: Four thousand and seven hundred and twenty-two studies were identified by the systematic search. Seven studies fulfilled the inclusion and exclusion criteria. The total number of patients was 1664 adult Fontan patients. There were 149 deaths and 35 heart transplantations. All eligible studies were retrospective cohort studies. The correlation between exercise capacity and late outcome was identified, and HRs were reported.
Conclusion: In Fontan patients, the best predictors of death and transplantation were a decline in peak VO2, heart rate variables and exercise oscillatory ventilation. Peak VO2 was not strongly predictive of mortality or hospitalisation in Fontan patients. Several variables were strong and independent predictors of hospitalisation and morbidity.

De Lorenzo A; Da Silva CL; Castro Souza FC; De Souza Leao Lima R

Physiological Research [Physiol Res] 2018 Jul 25. Date of Electronic Publication: 2018 Jul 25.

This study investigated the value of oxygen (O(2)) pulse curves obtained during cardiopulmonary exercise testing (CPET) for the diagnosis of coronary artery disease (CAD). Forty patients with known coronary anatomy (35.0 % normal, 27.0 % single-vessel and 38.0 % multivessel CAD) underwent CPET with radiotracer injection at peak exercise, followed by myocardial scintigraphy. O(2) pulse curves were classified as: A-normal, B-probably normal (normal slope with low peak value); C-probably abnormal (flat, with low peak value); or D- definitely abnormal (descending slope). Sensitivity, specificity, positive and negative predictive values of the O(2) pulse curve pattern (A or B vs. C or D) for the diagnosis of CAD were, respectively, 38.5 %, 81.3 %, 76.9 %, and 44.8 %. The concordance rate between the abnormal O2 pulse curve pattern and ischemia in myocardial scintigraphy was 38.1 %. Age and the extent of scintigraphic perfusion defect, but not the abnormal O(2) pulse curve patterns (B or C or both combined) were independently associated with CAD. In conclusion, the O(2) pulse curve pattern has low diagnostic performance for the diagnosis of obstructive CAD, and the abnormal curve pattern was not associated with myocardial ischemia defined by scintigraphy.