Rovai S; Zaffalon D; Cittar M; Felli LF; Salvioni E; Galotta A; Mattavelli I; Carriere C; Mapelli M; Merlo M; Vignati C; Sinagra G; Agostoni P;

ESC heart failure [ESC Heart Fail] 2022 May 17.
Date of Electronic Publication: 2022 May 17.

Aims: In heart failure (HF), anaerobic threshold (AT) may be indeterminable but its value held a relevant prognostic role. AT is evaluated joining three methods: V-slope, ventilatory equivalent, and end-tidal methods. The possible non-concordance between the V-slope (met AT) and the other two methods (vent AT) has been highlighted in healthy individuals and named double threshold (DT).
Methods and Results: We reanalysed 1075 cardiopulmonary exercise tests of HF patients recruited in the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score database. We identified DT in 43% of cases. Met AT precedes vent AT being met-ventΔVO ₂ 221 (interquartile range: 129-319) mL/min. Peak VO ₂ , 1307 ± 485 vs. 1343 ± 446 mL/min (63 ± 17 vs. 63 ± 17 percentage of predicted), was similar between DT+ and DT- patients. Differently, DT+ showed a lower ventilatory vs. carbon dioxide production (VE/VCO ₂ ) slope (29.6 ± 6.1 vs. 31.0 ± 6.3), a lower peak exercise end-tidal oxygen tension (PetO ₂ ) 115.3 (111.5-118.9) vs. 116.4 (112.4-120.2) mmHg, and a higher carbon dioxide tension (PetCO ₂ ) 34.2 (30.9-37.1) vs. 32.4 (28.7-35.5) mmHg. Vent AT showed a significant higher VO ₂ , 957 ± 318 vs. 719 ± 252 mL/min, VCO ₂ , 939 ± 319 vs. 627 ± 226 mL/min, ventilation, 31.0 ± 8.3 vs. 22.5 ± 6.3 L/min, respiratory exchange ratio, 0.98 ± 0.08 vs. 0.87 ± 0.07, PetO ₂ , 108 (104-112) vs. 105 (101-109) mmHg, PetCO ₂ , 37 (34-40) vs. 36 (33-39) mmHg, and VE/VO ₂ ratio, 33.5 ± 6.7 vs. 32.6 ± 6.9, but lower VE/VCO ₂ ratio, 33 (30-37) vs. 36 (32-41), compared with met AT. At 2 year survival by Kaplan-Meier analysis, even adjusted for confounders, DT resulted not associated with survival.
Conclusions: Double threshold is frequently observed in HF patients. DT+ is associated to a decreased ventilatory response during exercise.

Abela M; Bonello J; Sammut MA;

European heart journal. Case reports [Eur Heart J Case Rep] 2022 May 02; Vol. 6 (5), pp. ytac190.
Date of Electronic Publication: 2022 May 02 (Print Publication: 2022).

Background: Athletes presenting with 1st-degree atrioventricular block (AVB) on 12-lead electrocardiogram (ECG) may present a diagnostic conundrum, especially when significantly prolonged and associated with higher degrees of block. A pragmatic stepwise approach to the evaluation of these patients is, therefore, crucial.
Case Summary: A 19-year-old waterpolo player was referred for assessment of a 1st-degree heart block and one isolated episode of syncope. All other cardiac investigations were within normal limits except for a 24-h ambulatory ECG which showed Mobitz 1 AVB and episodes of 2:1 block occurring in the context of Wenchebach. An electrophysiological study (EPS) was performed which effectively excluded infranodal conductive tissue disease, confirming physiological intranodal block.
Discussion: The increase in vagal tone is one of the physiological adaptations to an increased demand in cardiac output in athletes, which explains the presence of 1st-degree AVB in up to 7.5% of athletes. The presence of 2:1 AVB on 24 h ECG raises doubts whether the 1st-degree AVB on resting ECG is pathological or physiological, especially considering this particular patient had suffered an episode of syncope. When this diagnostic uncertainty persists despite non-invasive investigations, including cardiopulmonary exercise testing, invasive EPS may be required to assess the refractoriness of the AV node and at what level within the cardiac conductive system block occurs. The electrophysiological study can effectively rule out infranodal disease by confirming physiological intranodal block using incremental atrial pacing.

Villaseca-Rojas Y; Varela-Melo J; Torres-Castro R; Vasconcello-Castillo L; Mazzucco G; Vilaró J; Blanco I;

Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2022 May 04; Vol. 9, pp. 874700.
Date of Electronic Publication: 2022 May 04 (Print Publication: 2022).

Background: Congenital heart disease (CHD) entails structural defects in the morphogenesis of the heart or its main vessels. Analyzing exercise capacity of children and adolescents with CHD is important to improve their functional condition and quality of life, since it can allow timely intervention on poor prognostic factors associated with higher risk of morbidity and mortality.
Objective: To describe exercise capacity in children and adolescents with CHD compared with healthy controls.
Methods: A systematic review was carried out. Randomized clinical trials and observational studies were included assessing exercise capacity through direct and indirect methods in children and adolescents between 5 and 17 years-old. A sensitive analysis was performed including studies with CHD repaired participants. Additionally, it was sub-analyzed by age range (< and ≥ 12 years old). Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of the evidence.
Results: 5619 articles were found and 21 were considered for the review. Eighteen articles used the direct exercise capacity measurement method by cardiopulmonary exercise test (CPET). The CHD group showed significant differences in peak oxygen consumption (VO ₂ peak) with a value of -7.9 ml/Kg/min (95% CI: -9.9, -5.9, p = 0.00001), maximum workload (Wmax) -41.5 (95% CI: -57.9, -25.1 watts, p = 0.00001), ventilatory equivalent (VE/VCO ₂) slope 2.6 (95% CI: 0.3, 4.8), oxygen pulse (O ₂ pulse)-2.4 ml/beat (95% CI: -3.7, -1.1, p = 0.0003), and maximum heart rate (HRmax) -15 bpm (95% CI: -18, -12 bpm, p = 0.00001), compared with healthy controls. Adolescents (≥ 12 yrs) with CHD had a greater reduction in VO ₂ peak (-10.0 ml/Kg/min (95% CI: -12.0, -5.3), p < 0.00001), Wmax (-45.5 watts (95% CI: -54.4, -36.7), p < 0.00001) and HRmax (-21 bpm (95% CI: -28, -14), p <0.00001).
Conclusion: Suffering CHD in childhood and adolescence is associated with lower exercise capacity as shown by worse VO ₂ peak, Wmax, VE/VCO ₂ slope, O ₂ pulse, and HRmax compared with matched healthy controls. The reduction in exercise capacity was greater in adolescents.

Ladlow P; O’Sullivan O; Bennett AN; Barker-Davies R; Houston A; Chamley R; May S; Mills D; Dewson D;
Rogers-Smith K; Ward C; TayloJ;Mulae J; Naylor J; Nicol ED; Holdsworth DA;

Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2022 May 19.
Date of Electronic Publication: 2022 May 19.

Background: A failure to fully recover following coronavirus disease 2019 (COVID-19) may have a profound impact on high functioning populations ranging from front-line emergency services to professional or amateur/recreational athletes.
Aim: To describe the medium-term cardiopulmonary exercise profiles of individuals with ‘persistent symptoms’ and individuals who feel ‘recovered’ after hospitalization or mild-moderate community infection following COVID-19 to an age, sex and job-role matched control group.
Methods: 113 participants underwent cardiopulmonary functional tests at a mean 159±7 days (~5 months) following acute illness; 27 hospitalized with persistent symptoms (hospitalized-symptomatic), 8 hospitalized and now recovered (hospitalized-recovered); 34 community managed with persistent symptoms (community-symptomatic); 18 community managed and now recovered (community-recovered), and 26 controls.
Results: Hospitalized groups had the least favorable body composition (body mass, body mass index and waist circumference) compared to controls. Hospitalized-symptomatic and community-symptomatic individuals had a lower oxygen uptake (V̇O ₂ ) at peak exercise (hospitalized-symptomatic, 29.9±5.0ml/kg/min; community-symptomatic, 34.4±7.2ml/kg/min; vs. control 43.9±3.1ml/kg/min, both p<0.001). Hospitalized-symptomatic individuals had a steeper V̇E/V̇CO ₂ slope (lower ventilatory efficiency) (30.5±5.3 vs. 25.5±2.6, p=0.003) vs. controls. Hospitalized-recovered had a significantly lower oxygen uptake at peak (32.6±6.6ml/kg/min vs. 43.9 ±13.1ml/kg/min, p=0.015) compared to controls. No significant differences were reported between community-recovered individuals and controls in any cardiopulmonary parameter.
Conclusion: Medium term findings suggest community-recovered individuals did not differ in cardiopulmonary fitness from physically active healthy controls. This suggests their readiness to return to higher levels of physical activity. However, the hospitalized-recovered group and both groups with persistent symptoms had enduring functional limitations, warranting further monitoring, rehabilitation and recovery.

Ricci F; Bufano G; Galusko V; Sekar B; Benedetto U; Awad WI; Di Mauro M;
Gallina S; Ionescu A; Badano L; Khanji MY

European Heart Journal Quality of Care & Clinical Outcomes. 8(3):238-248,
2022 May 05.

Tricuspid regurgitation (TR) is a highly prevalent condition and an
independent risk factor for adverse outcomes. Multiple clinical guidelines
exist for the diagnosis and management of TR, but the recommendations may
sometimes vary. We systematically reviewed high-quality guidelines with a
specific focus on areas of agreement, disagreement, and gaps in evidence.
We searched MEDLINE and EMBASE (1 January 2011 to 30 August 2021), the
Guidelines International Network International, Guideline Library,
National Guideline Clearinghouse, National Library for Health Guidelines
Finder, Canadian Medical Association Clinical Practice Guidelines
Infobase, Google Scholar, and websites of relevant organizations for
contemporary guidelines that were rigorously developed (as assessed by the
Appraisal of Guidelines for Research and Evaluation II tool). Three
guidelines were finally retained. There was consensus on a TR grading
system, recognition of isolated functional TR associated with atrial
fibrillation, and indications for valve surgery in symptomatic vs.
asymptomatic patients, primary vs. secondary TR, and isolated TR forms.
Discrepancies exist in the role of biomarkers, complementary multimodality
imaging, exercise echocardiography, and cardiopulmonary exercise testing
for risk stratification and clinical decision-making of progressive TR and
asymptomatic severe TR, management of atrial functional TR, and choice of
transcatheter tricuspid valve intervention (TTVI). Risk-based thresholds
for quantitative TR grading, robust risk score models for TR surgery,
surveillance intervals, population-based screening programmes, TTVI
indications, and consensus on endpoint definitions are lacking.

Pugliese NR; DE Biase N; Balletti A; Filidei F; Pieroni A; D’Angelo G;
Armenia S; Mazzola M; Gargani L; Del Punta L; Asomov M; Cerri E; Franzoni F;
Nesti L; Mengozzi A; Paneni F; Masi S

Minerva Cardiology and Angiology. 70(3):370-384, 2022 Jun.

Heart failure (HF) is a complex clinical syndrome characterized by
different etiologies and a broad spectrum of cardiac structural and
functional abnormalities. Current guidelines suggest a classification
based on left ventricular ejection fraction (LVEF), distinguishing HF with
reduced (HFrEF) from preserved (HFpEF) LVEF. HF should also be thought of
as a continuous range of conditions, from asymptomatic stages to
clinically manifest syndrome. The transition from one stage to the next is
associated with a worse prognosis. While the rate of HF-related
hospitalization is similar in HFrEF and HFpEF once clinical manifestations
occur, accurate knowledge of the steps and risk factors leading to HF
progression is still lacking, especially in HFpEF. Precise hemodynamic and
metabolic characterization of patients with or at risk of HF may help
identify different disease trajectories and risk factors, with the
potential to identify specific treatment targets that might offset the
slippery slope towards overt clinical manifestations. Exercise can unravel
early metabolic and hemodynamic alterations that might be silent at rest,
potentially leading to improved risk stratification and more effective
treatment strategies. Cardiopulmonary exercise testing (CPET) offers
valuable aid to investigate functional alterations in subjects with or at
risk of HF, while echocardiography can assess cardiac structure and
function objectively, both at rest and during exercise (exercise stress
echocardiography [ESE]). The purpose of this narrative review was to
summarize the potential advantages of using an integrated CPET-ESE
evaluation in the characterization of both subjects at risk of developing
HF and patients with stable HF.

Apostolo A; Vignati C; Della Rocca M; De Martino F; Berna G; Campodonico
J; Contini M; Muratori M; Palermo P; Mapelli M; Alimento M; Pezzuto B;
Agostoni P

Journal of Cardiac Failure. 28(3):509-514, 2022 03.

BACKGROUND: In advanced heart failure (HF), levosimendan increases peak
oxygen uptake (VO2). We investigated whether peak VO2 increase is linked
to cardiovascular, respiratory, or muscular performance changes.

METHODS AND RESULTS: Twenty patients hospitalized for advanced HF
underwent, before and shortly after levosimendan infusion, 2 different
cardiopulmonary exercise tests: (a) a personalized ramp protocol with
repeated arterial blood gas analysis and standard spirometry including
alveolar-capillary gas diffusion measurements at rest and at peak
exercise, and (b) a step incremental workload cardiopulmonary exercise
testing with continuous near-infrared spectroscopy analysis and cardiac
output assessment by bioelectrical impedance analysis.Levosimendan
significantly decreased natriuretic peptides, improved peak VO2 (11.3
[interquartile range 10.1-12.8] to 12.6 [10.2-14.4] mL/kg/min, P < .01)
and decreased minute ventilation to carbon dioxide production relationship
slope (47.7 +/- 10.7 to 43.4 +/- 8.1, P < .01). In parallel, spirometry
showed only a minor increase in forced expiratory volume, whereas the peak
exercise dead space ventilation was unchanged. However, during exercise, a
smaller edema formation was observed after levosimendan infusion, as
inferable from the changes in diffusion components, that is, the membrane
diffusion and capillary volume. The end-tidal pressure of CO2 during the
isocapnic buffering period increased after levosimendan (from 28 +/- 3 mm
Hg to 31 +/- 2 mm Hg, P < .01). During exercise, cardiac output increased
in parallel with VO2. After levosimendan, the total and oxygenated tissue
hemoglobin, but not deoxygenated hemoglobin, increased in all exercise
phases.

CONCLUSIONS: In advanced HF, levosimendan increases peak VO2, decreases
the formation of exercise-induced lung edema, increases ventilation
efficiency owing to a decrease of reflex hyperventilation, and increases
cardiac output and muscular oxygen delivery and extraction.

Argillander TE; Heil TC; Melis RJF; van Duijvendijk P; Klaase JM;
van Munster BC

BACKGROUND: Abdominal cancer surgery is associated with considerable
morbidity in older patients. Assessment of preoperative physical status is
therefore essential. The aim of this review was to describe and compare
the objective physical tests that are currently used in abdominal cancer
surgery in the older patient population with regard to postoperative
outcomes.

METHODS: Medline, Embase, CINAHL and Web of Science were searched until
31 December 2020. Non-interventional cohort studies were eligible if they
included patients >=65 years undergoing abdominal cancer surgery, reported
results on objective preoperative physical assessment such as
Cardiopulmonary Exercise Testing (CPET), field walk tests or muscle
strength, and on postoperative outcomes.

RESULTS: 23 publications were included (10 CPET, 13 non-CPET including
Timed Up & Go, grip strength, 6-minute walking test (6MWT) and incremental
shuttle walk test (ISWT)). Meta-analysis was precluded due to
heterogeneity between study cohorts, different cut-off points, and
inconsistent reporting of outcomes. In CPET studies, ventilatory anaerobic
threshold and minute ventilation/carbon dioxide production gradient were
associated with adverse outcomes. ISWT and 6MWT predicted outcomes in two
studies. Tests addressing muscle strength and function were of limited
value. No study compared different physical tests.

DISCUSSION: CPET has the ability to predict adverse postoperative
outcomes, but it is time-consuming and requires expert assessment. ISWT or
6MWT might be a feasible alternative to estimate aerobic capacity. Muscle
strength and function tests currently have limited value in risk
prediction. Future research should compare the predictive value of
different physical instruments with regard to postoperative outcomes in
older surgical patients.

Zhou N; Scoubeau C; Forton K; Loi P; Closset J; Deboeck G; Moraine JJ;
Klass M; Faoro V

Obesity Facts. 15(2):248-256, 2022.

INTRODUCTION: Patients undergoing weight loss surgery do not improve their
aerobic capacity or peak oxygen uptake (VO2peak) after bariatric surgery
and some still complain about asthenia and/or breathlessness. We
investigated the hypothesis that a post-surgery muscular limitation could
impact the ventilatory response to exercise by evaluating the post-surgery
changes in muscle mass, strength, and muscular aerobic capacity, measured
by the first ventilatory threshold (VT).

METHODS: Thirteen patients with obesity were referred to our university
exercise laboratory before and 6 months after bariatric surgery and were
matched by sex, age, and height to healthy subjects with normal weight.
All subjects underwent a clinical examination, blood sampling, and body
composition assessment by dual-energy X-ray absorptiometry, respiratory
and limb muscle strength assessments, and cardiopulmonary exercise testing
on a cyclo-ergometer.

RESULTS: Bariatric surgery resulted in a loss of 34% fat mass, 43%
visceral adipose tissue, and 12% lean mass (LM) (p < 0.001). Absolute
handgrip, quadriceps, or respiratory muscle strength remained unaffected,
while quadriceps/handgrip strength relative to LM increased (p < 0.05).
Absolute VO2peak or VO2peak/LM did not improve and the first VT was
decreased after surgery (1.4 +/- 0.3 vs. 1.1 +/- 0.4 L min-1, p < 0.05)
and correlated to the exercising LM (LM legs) (R = 0.84, p < 0.001).

CONCLUSIONS: Although bariatric surgery has numerous beneficial effects,
absolute VO2peak does not improve and the weight loss-induced LM reduction
is associated to an altered muscular aerobic capacity, as reflected by an
early VT triggering early exercise hyperventilation.

Brown JT; Saigal A; Karia N; Patel RK; Razvi Y; Constantinou N; Steeden
JA; Mandal S; Kotecha T; Fontana M; Goldring J; Muthurangu V; Knight DS

Journal of the American Heart Association. 11(9):e024207, 2022 May 03.

Background Ongoing exercise intolerance of unclear cause following
COVID-19 infection is well recognized but poorly understood. We
investigated exercise capacity in patients previously hospitalized with
COVID-19 with and without self-reported exercise intolerance using
magnetic resonance-augmented cardiopulmonary exercise testing.
Methods and Results Sixty subjects were enrolled in this single-center prospective
observational case-control study, split into 3 equally sized groups: 2
groups of age-, sex-, and comorbidity-matched previously hospitalized
patients following COVID-19 without clearly identifiable postviral
complications and with either self-reported reduced (COVIDreduced) or
fully recovered (COVIDnormal) exercise capacity; a group of age- and
sex-matched healthy controls. The COVID reduced group had the lowest peak
workload (79W [Interquartile range (IQR), 65-100] versus controls 104W
[IQR, 86-148]; P=0.01) and shortest exercise duration (13.3+/-2.8 minutes
versus controls 16.6+/-3.5 minutes; P=0.008), with no differences in these
parameters between COVIDnormal patients and controls. The COVIDreduced
group had: (1) the lowest peak indexed oxygen uptake (14.9 mL/minper kg
[IQR, 13.1-16.2]) versus controls (22.3 mL/min per kg [IQR, 16.9-27.6];
P=0.003) and COVIDnormal patients (19.1 mL/min per kg [IQR, 15.4-23.7];
P=0.04); (2) the lowest peak indexed cardiac output (4.7+/-1.2 L/min per
m2) versus controls (6.0+/-1.2 L/min per m2; P=0.004) and COVIDnormal
patients (5.7+/-1.5 L/min per m2; P=0.02), associated with lower indexed
stroke volume (SVi:COVIDreduced 39+/-10 mL/min per m2 versus COVIDnormal
43+/-7 mL/min per m2 versus controls 48+/-10 mL/min per m2; P=0.02). There
were no differences in peak tissue oxygen extraction or biventricular
ejection fractions between groups. There were no associations between
COVID-19 illness severity and peak magnetic resonance-augmented
cardiopulmonary exercise testing metrics. Peak indexed oxygen uptake,
indexed cardiac output, and indexed stroke volume all correlated with
duration from discharge to magnetic resonance-augmented cardiopulmonary
exercise testing (P<0.05).
Conclusions Magnetic resonance-augmented
cardiopulmonary exercise testing suggests failure to augment stroke volume
as a potential mechanism of exercise intolerance in previously
hospitalized patients with COVID-19. This is unrelated to disease severity
and, reassuringly, improves with time from acute illness.