Darlington O. Okonko,  Agnieszka Grzeslo,  Tomasz Witkowski,
Amit K. J. Mandal,  Robert M. Slater,  Michael Roughton,
Gabor Foldes, Thomas Thum,  Jacek Majda,
Waldemar Banasiak,  Constantinos G. Missouris,
Philip A. Poole-Wilson, Stefan D. Anker, Piotr Ponikowski,

Journal of the American College of Cardiology Vol. 51: No. 2, 2008

Objectives. We tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure (CHF) and iron deficiency.
Background. Anemia is common in heart failure. Iron metabolism is disturbed, and administration of iron might improve both symptoms and exercise tolerance.
Methods. We randomized 35 patients with CHF (age 64
13 years, peak oxygen consumption [pVO2] 14.0
2.7 ml/kg/min) to 16 weeks of intravenous iron (200 mg weekly until ferritin 500 ng/ml, 200 mg monthly thereafter) or
no treatment in a 2:1 ratio. Ferritin was required to be 100 ng/ml or ferritin 100 to 300 ng/ml with transferrin
saturation 20%. Patients were stratified according to hemoglobin levels (12.5 g/dl [anemic group] vs. 12.5
to 14.5 g/dl [nonanemic group]). The observer-blinded primary end point was the change in absolute pVO2.
Results. The difference (95% confidence interval [CI]) in the mean changes from baseline to end of study between the iron and control groups was 273 (151 to 396) ng/ml for ferritin (p  0.0001), 0.1 (0.8 to 0.9) g/dl for hemoglobin
(p  0.9), 96 (12 to 205) ml/min for absolute pVO2 (p  0.08), 2.2 (0.5 to 4.0) ml/kg/min for pVO2/kg
(p  0.01), 60 (6 to 126) s for treadmill exercise duration (p  0.08), 0.6 (0.9 to 0.2) for New York
Heart Association (NYHA) functional class (p  0.007), and 1.7 (0.7 to 2.6) for patient global assessment
(p  0.002). In anemic patients (n  18), the difference (95% CI) was 204 (31 to 378) ml/min for absolute
pVO2 (p  0.02), and 3.9 (1.1 to 6.8) ml/kg/min for pVO2/kg (p  0.01). In nonanemic patients, NYHA functional
class improved (p  0.06). Adverse events were similar.
Conclusions Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients.

Huang SC; Casaburi R; Liao MF; Liu KC; Chen YJ; Fu TC; Su HR;

Scientific Reports [Sci Rep] 2019 Feb 18; Vol. 9 (1), pp. 2180. Date of Electronic Publication: 2019 Feb 18.

We hypothesized that blood lactate concentration([Lac]blood) is a function of cardiopulmonary variables, exercise intensity and some anthropometric elements during aerobic exercise. This investigation aimed to establish a mathematical model to estimate [Lac]blood noninvasively during constant work rate (CWR) exercise of various intensities. 31 healthy participants were recruited and each underwent 4 cardiopulmonary exercise tests: one incremental and three CWR tests (low: 35% of peak work rate for 15 min, moderate: 60% 10 min and high: 90% 4 min). At the end of each CWR test, venous blood was sampled to determine [Lac]blood. 31 trios of CWR tests were employed to construct the mathematical model, which utilized exponential regression combined with Taylor expansion. Good fitting was achieved when the conditions of low and moderate intensity were put in one model; high-intensity in another. Standard deviation of fitting error in the former condition is 0.52; in the latter is 1.82 mmol/liter. Weighting analysis demonstrated that, besides heart rate, respiratory variables are required in the estimation of [Lac]blood in the model of low/moderate intensity. In conclusion, by measuring noninvasive cardio-respiratory parameters, [Lac]blood during CWR exercise can be determined with good accuracy. This should have application in endurance training and future exercise industry.

Arena R; Ozemek C

Expert Review Of Cardiovascular Therapy [Expert Rev Cardiovasc Ther] 2019 Feb 21. Date of Electronic Publication: 2019 Feb 21.

Boukovala M; Müller J; Ewert P; Hager A;

The American Journal Of Cardiology [Am J Cardiol] 2019 Jan 08. Date of Electronic Publication: 2019 Jan 08.

With rising survival rates of patients with congenital heart disease (CHD), functional health variables have become the key aspect in treatment evaluation. The effectiveness of various treatment options on the health-related quality of life (HRQoL) and the objectively measured exercise capacity as peak oxygen uptake (VO2 peak) remains rather unclear and hence, its investigation is the primary aim of this study. Data from 1014 patients (≥14-years-old, various CHD) were retrospectively reviewed. The patients had completed at least twice the SF-36 questionnaire on HRQoL prior to a cardiopulmonary exercise test. Each patient was assigned to 1 of 4 treatment groups (i.e., surgery, catheter intervention, drug therapy, and surveillance) according to the received treatment between the baseline and the follow-up examination. After 4.0 ± 2.2 years of follow-up, patients with surgery and catheter intervention showed an increase in the physical summary score of HRQoL as compared to the other treatment groups (p <0.001). This effect remained also significant in a multivariable model accounting for anthropometric and baseline data. No significant differences in the mental summary score of HRQoL and the VO2 peak were evident between the different treatment groups in the multivariable model. No significant correlation was found between the changes in HRQoL and VO2 peak over time. In conclusion, despite insignificant changes in aerobic capacity, adolescents and adults with CHD report better physical HRQoL following surgery and catheter intervention compared to the other treatment options. HRQoL and exercise capacity need to be considered concurrently in the evaluation of adolescents and adults with CHD.

Van Brussel M; Bongers BC; Hulzebos EHJ; Burghard M; Takken T;

Pediatric Exercise Science [Pediatr Exerc Sci] 2019 Jan 28, pp. 1-10. Date of Electronic Publication: 2019 Jan 28.

The use of cardiopulmonary exercise testing in pediatrics provides critical insights into potential physiological causes of unexplained exercise-related complaints or symptoms, as well as specific pathophysiological patterns based on physiological responses or abnormalities. Clinical interpretation of the results of a cardiopulmonary exercise test in pediatrics requires specific knowledge with regard to pathophysiological responses and interpretative strategies that can be adapted to address concerns specific to the child’s medical condition or disability. In this review, the authors outline the 7-step interpretative approach that they apply in their outpatient clinic for diagnostic, prognostic, and evaluative purposes. This approach allows the pediatric clinician to interpret cardiopulmonary exercise testing results in a systematic order to support their physiological reasoning and clinical decision making.

Abbott TEF; Pearse RM; Cuthbertson BH; Wijeysundera DN; Ackland GL;

British Journal Of Anaesthesia [Br J Anaesth] 2019 Feb; Vol. 122 (2), pp. 188-197. Date of Electronic Publication: 2018 Dec 17.

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.

Li MH; Bolshinsky V; Ismail H; Burbury K; Ho KM; Riedel B; Amin B; Heriot A;

Canadian Journal Of Anaesthesia = Journal Canadien D’anesthesie [Can J Anaesth] 2019 Jan 28. Date of Electronic Publication: 2019 Jan 28.

Purpose: Preoperative fitness training has been listed as a top ten research priority in anesthesia. We aimed to capture the current practice patterns and perspectives of anesthetists and colorectal surgeons in Australia and New Zealand regarding preoperative risk stratification and prehabilitation to provide a basis for implementation research.
Methods: During 2016, we separately surveyed fellows of the Australian and New Zealand College of Anaesthetists (ANZCA) and members of the Colorectal Society of Surgeons in Australia and New Zealand (CSSANZ). Our outcome measures investigated the responders’ demographics, practice patterns, and perspectives. Practice patterns examined preoperative assessment and prehabilitation utilizing exercise, hematinic, and nutrition optimization.
Results: We received 155 responses from anesthetists and 71 responses from colorectal surgeons. We found that both specialty groups recognized that functional capacity was linked to postoperative outcome; however, fewer agreed that robust evidence exists for prehabilitation. Prehabilitation in routine practice remains low, with significant potential for expansion. The majority of anesthetists do not believe their patients are adequately risk stratified before surgery, and most of their colorectal colleagues are amenable to delaying surgery for at least an additional two weeks. Two-thirds of anesthetists did not use cardiopulmonary exercise testing as they lacked access. Hematinic and nutritional assessment and optimization is less frequently performed by anesthetists compared with their colorectal colleagues.
Conclusions: An unrecognized potential window for prehabilitation exists in the two to four weeks following cancer diagnosis. Early referral, larger multi-centre studies focusing on long-term outcomes, and further implementation research are required.

Huang W, Oliveira RKF, Lei H, Systrom DM, Waxman AB

J Card Fail. 2018 Mar;24(3):169-176. doi: 10.1016/j.cardfail.2017.11.003. Epub
2017 Nov 24.

BACKGROUND: In heart failure with preserved ejection fraction (HFpEF), the
prognostic value of pulmonary vascular dysfunction (PV-dysfunction), identified
by elevated pulmonary vascular resistance (PVR) at peak exercise, is not
completely understood. We evaluated the long-term prognostic implications of
PV-dysfunction in HFpEF during exercise in consecutive patients undergoing
invasive cardiopulmonary exercise testing for unexplained dyspnea.
METHODS: Patients with HFpEF were classified into 2 main groups: resting HFpEF
(n = 104, 62% female, age 61 years) with a pulmonary arterial wedge pressure
(PAWP) >15 mmHg at rest; and exercise HFpEF (eHFpEF; n = 81) with a PAWP <15 mmHg
at rest, but >20 mmHg during exercise. The eHFpEF group was further subdivided
into eHFpEF + PV-dysfunction (peak PVR ≥80 dynes/s/cm-5; n = 55, 60% female, age
64) group and eHFpEF – PV-dysfunction (peak PVR <80 dynes/s/cm-5; n = 26, 42%
female, age 54 years) group. Outcomes were analyzed for the first 9 years of
follow-up and included any cause mortality and heart failure (HF)-related
hospitalizations. The mean follow-up time was 6.7 ± 2.6 years (0.5-9.0).
RESULTS: Mortality rate did not differ among the groups. However, survival free
of HF-related hospitalization was lower for the eHFpEF + PV-dysfunction group
compared with eHFpEF – PV-dysfunction (P = .01). These findings were similar
between eHFpEF + PV-dysfunction and the resting HFpEF group (P = .774). By Cox
analysis, peak PVR ≥80 dynes/s/cm-5 was a predictor of HF-related hospitalization
for eHFpEF (hazard ratio 5.73, 95% confidence interval 1.05-31.22, P = .01). In
conclusion, the present study provides insight into the impact of PV-dysfunction
on outcomes of patients with exercise-induced HFpEF. An elevated peak PVR is
associated with a high risk of HF-related hospitalization.