Ladefoged BT; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Pedersen ALD;Dybro AM; Clemmensen TS; DGillmore J; Poulsen SH

ESC heart failure [ESC Heart Fail] 2024 Dec 03.
Date of Electronic Publication: 2024 Dec 03.

Aims: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is a cardiomyopathy causing myocardial hypoperfusion and impaired cardiac mitochondrial function. Trimetazidine is an antianginal agent used in patients with stable angina pectoris, which improves cardiac contractility and mitochondrial function. The aim of the study was to investigate the effect of trimetazidine on invasive haemodynamics and cardiac mitochondrial function in ATTRwt.
Methods: In a randomized, double-blind, placebo-controlled, crossover trial, 22 patients with ATTRwt received 4 weeks of trimetazidine and placebo in randomized order. After each treatment period followed examinations with endomyocardial biopsies taken for high-resolution respirometry and right heart catheterization at rest and during a cardiopulmonary exercise test. The primary endpoint was mean pulmonary artery wedge pressure (mPAWP) during peak exercise. The secondary endpoint was cardiac mitochondrial oxidative phosphorylation capacity. Exploratory endpoints were echocardiographic parameters, cardiac biomarker levels and quality of life.
Results: Trimetazidine did not significantly reduce mPAWP during peak exercise (31 ± 12 vs. 31 ± 13 mmHg, P = 0.61) or improve the cardiac mitochondrial oxidative phosphorylation capacity (73.4 ± 7.7 vs. 75.3 ± 7.7 pmol O ₂ /(mg*s), P = 0.81) compared with placebo, nor did treatment with trimetazidine improve ejection fraction (P = 0.93), global longitudinal strain (P = 0.23), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P = 0.92) or the patients’ quality of life (P = 0.98).
Conclusions: In ATTRwt, treatment with trimetazidine did not improve mPAWP or cardiac mitochondrial oxidative phosphorylation capacity compared with placebo.

Reichenberger F; Department of Pneumology, Augustinum Hospital Munich, Munich, Germany.
Popp F; Hoffmann M;  Fischinger C; von Wulffen W; DKneidinger N; Welcker M;

BMC pulmonary medicine [BMC Pulm Med] 2024 Nov 23; Vol. 24 (1), pp. 581.
Date of Electronic Publication: 2024 Nov 23.

Background: Seropositive rheumatoid arthritis (RA) is associated with significant cardiovascular and pulmonary morbidity. However, screening for early detection of pulmonary involvement especially interstitial lung disease (ILD) is not established in RA.
Methods: We propose a non-invasive radiation-free approach to screen for interstitial lung involvement (ILI) by means of pulmonary function tests (PFT) and pleuro-pulmonary transthoracic ultrasound (LUS) with additional cardiopulmonary exercise tests (CPET) with ECG, and echocardiography. We included patients with confirmed diagnosis of seropositive RA according to ACR criteria, but without symptoms for or known cardiopulmonary disease. ILD was suspected when significant LUS abnormalities and additional PFT changes were present.
Results: We included 67 consecutive patients (78% female, mean age 61 ± 12 years, 48% active or previous smokers), who fulfilled the inclusion criteria and gave written informed consent. We found 48% of patients with suspected changes in PFT with a diffusion capacity (DLCOc-SB) ≤ 80%, among them 7% with forced vital capacity (FVC) ≤ 80%. In 40% of patients, we found noticeable changes in LUS, 24% with an ILD compatible pattern. In 16% of cases, LUS abnormalities and additional PFT changes were present, and ILI was suspected. Additional findings included obstructive lung disease (n = 11), subpleural consolidation (n = 6) including one confirmed lung cancer, minimal pleural effusion (n = 6), and ischemic cardiac disease (n = 2). None of the patients showed signs of pulmonary vascular involvement.
Conclusions: ILI was suspected in 16% of cases using a new radiation-free screening protocol in asymptomatic RA patients.

Tuan SH;  National Cheng Kung University, Tainan 701,Taiwan
Huang IC; Huang WC; Chen GB; Sun SF; Lin KL;

Life (Basel). 2024 Nov 6;14(11):1429. doi: 10.3390/life14111429.

(1) Background: Heart failure (HF) leads to functional disability and major cardiovascular events (MACEs). Cardiopulmonary exercise testing (CPET) is the gold standard for assessing aerobic capacity and prognostic stratification. This study aimed to evaluate the predischarge CPET variables in patients with acute decompensated HF and identify the submaximal CPET variables with prognostic value.
(2) Methods: A retrospective cohort study was conducted at a tertiary center in Taiwan. Patients surviving their first episode of decompensated HF and undergoing predischarge CPET (February 2017 to January 2023) were analyzed. Follow-up was conducted until a MACE or administrative censoring (up to 5 years). Cox regression identified the significant predictors of MACE.
(3) Results: The study included 553, 485, and 267 patients at the 3-month, 1-year, and 5-year follow-ups, respectively. MACE rates were 15.0%, 34.2%, and 50.9%. The VE/VCO2 slope was a significant predictor of MACE at all intervals. A VE/VCO2 slope >38.95 increased the risk of MACE by 2.49-fold at 3 months and 1.81-fold at 1 year (both p < 0.001). A slope > 37.35 increased the 5-year MACE risk by 1.75-fold (p = 0.002).
(4) Conclusions: The VE/VCO2 slope is a significant submaximal CPET predictor of MACE in patients post-acute decompensated HF for both short- and long-term outcomes.

Eysenck W; London Bridge Hospital UK
Sulke N; Patel N; Furniss S; Veasey R; Freemantle N; Bodagh N;

The British journal of cardiology [Br J Cardiol] 2024 Apr 16; Vol. 31 (2), pp. 014.
Date of Electronic Publication: 2024 Apr 16 (Print Publication: 2024).

Our objective was to compare the efficacy of atrial fibrillation (AF) ablation versus permanent pacemaker (PPM) with atrioventricular node ablation (AVNA) versus direct current cardioversion (DCCV) for persistent AF in patients ≥65 years old. Seventy-seven patients (aged 66-86, mean 75.4 years) with persistent AF were randomised (1:1:1) to AF ablation + amiodarone (± DCCV), PPM with AVNA (+DCCV) or DCCV + amiodarone. The primary end point was persistent AF recurrence, measured with an implanted cardiac monitor or PPM.
Cardiopulmonary exercise testing (CPET) was performed at baseline and six months. Symptom questionnaires were completed monthly. Follow-up was 12 months. The primary end point occurred in fewer patients following AF ablation + amiodarone than DCCV + amiodarone (seven patients, 28% vs. 15 patients, 60%; hazard ratio [HR] 0.559, 95% confidence interval [CI] 0.293 to 1.065, p=0.073) with no differences between DCCV + amiodarone and PPM with AVNA (HR 0.990, 95%CI 0.539 to 1.818, p=0.973). AF ablation + amiodarone resulted in a lower AF burden at 12 months compared with DCCV + amiodarone (17.0 ± 37.9% vs. 61.7 ± 48.6%, p<0.0001). Modified European Heart Rhythm Association (EHRA) symptom class improved in all patients (baseline 2.4 ± 0.495 vs. 12-month follow-up 1.84 ± 0.081, p=0.00001). Six-month CPET demonstrated a higher VO ₂ peak in sinus rhythm (SR) compared with baseline in AF (12.1 ± 4.2 ml/kg/min at baseline to 15.3 ± 4.2 ml/kg/min at six months, p=0.013). In conclusion, in older patients with persistent AF, ablation + amiodarone resulted in a lower AF burden at 12 months than DCCV + amiodarone. There was a non-significant trend toward reduced recurrence of device detected persistent AF episodes. All therapies improved symptoms despite DCCV restoring SR in <50% of patients at 12 months. CPET demonstrated improved VO ₂ peak with SR restoration.

Faigenbaum AD; Department of Kinesiology and Health Sciences, The College of New Jersey, Ewing, NJ, USA.
Kang J; Ingui J; Fish A; Dimatteo J;Leazier I; Bush JA; DeRatamess NA;

International journal of exercise science [Int J Exerc Sci] 2024 Nov 01; Vol. 17 (4), pp. 1530-1539.
Date of Electronic Publication: 2024 Nov 01 (Print Publication: 2024).

The aim of this study was to compare the warm-up effects of a treadmill walking warm-up (TW) with a dynamic warm-up (DW) on the responses to cardiopulmonary exercise testing (CPET) in youth. A sample of 16 active youth (age 13.6 ± 1.8 yr) were tested for peak oxygen uptake (VO ₂ peak) using the Fitkids treadmill test protocol on 2 nonconsecutive days following different 6-min warm-up procedures. The TW consisted of walking on a treadmill at 2.2 mph and 0% grade whereas the DW consisted of 12 bodyweight exercises with a 2 kg medicine ball. Maximal heart rate (HR) was significantly higher following DW vs TW (200.8 ± 6.16 vs. 197.9 ± 7.3 bpm, respectively; p < 0.05), whereas no significant differences were found between DW and TW for VO ₂ peak (50.5 ± 9.9 vs 50.6 ± 11.1 ml/kg/min), maximal minute ventilation (V _E ; 93.0 ±21.4 vs. 92.7 ±21.2 L/min), maximal respiratory exchange ratio (1.19 ± 0.08 vs 1.22 ± 0.08), and total exercise test time (668.1 ± 103.5 vs 686.3 ± 97.0 s), respectively. During the Fitkids treadmill test protocol HR and V _E were significantly higher following DW vs TW at stage 1, stage 2, stage 3 and stage 4, and oxygen uptake was significantly higher following DW vs TW during stage 1 (all p < 0.05). Findings indicate a DW elicits a higher maximal HR and higher submaximal HR, V _E , and oxygen uptake values than TW during CPET in youth, although no differences in VO ₂ peak were observed.

Hughes DL; Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL.
Lizaola-Mayo B; Wheatley-Guy CM; Vargas HE; Bloomer PM; Wolf C; Carey EJ; Forman DE; Duarte-Rojo A;

Transplantation direct [Transplant Direct] 2024 Nov 15; Vol. 10 (12), pp. e1725.
Date of Electronic Publication: 2024 Nov 15 (Print Publication: 2024).

Background: Cardiovascular disease and physical decline are prevalent and associated with morbidity/mortality in liver transplant (LT) patients. Cardiopulmonary exercise testing (CPX) provides comprehensive cardiopulmonary and exercise response assessments. We investigated cardiorespiratory fitness (CRF) and cardiac stress generated during CPX in LT candidates.
Methods: LT candidates at 2 centers underwent CPX. Standard-of-care cardiac stress testing (dobutamine stress echocardiography, DSE) results were recorded. Physical function was assessed with liver frailty index and 6-min walk test. CPX/DSE double products were calculated to quantify cardiac stress. To better study the association of CPX-derived metrics with physical function, the cohort was divided into 2 groups based on 6-min walk test median (372 m).
Results: Fifty-four participants (62 ± 8 y; 65% men, Model for End-Stage Liver Disease-Na 14 [10-18]) underwent CPX. Peak oxygen consumption was 14.1 mL/kg/min for an anerobic threshold of 10.2 mL/kg/min, with further CRF decline in the lower 6MWT cohort despite lack of liver frailty index-frailty in 90%. DSE was nondiagnostic in 18% versus 4% of CPX ( P  = 0.058). All CPX were negative for ischemia. A double product of ≥25 000 was observed in 32% of CPX and 11% of DSE ( P  = 0.020). Respiratory function testing was normal. No patient presented major cardiovascular events at 30 d post-LT.
Conclusions: CPX provided efficient and effective combined cardiopulmonary risk and frailty assessments of LT candidates in a 1-stop test. The CRF was found to be very low despite preserved physical function or lack of frailty.

Tashiro M; Department of Cardiovascular Medicine, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
Goda A; Yanagisawa Y; Nakamaru R; Funabashi S; Takeuchi S;Soejima K; Kohno T;

Clinical research in cardiology : official journal of the German Cardiac Society [Clin Res Cardiol] 2024 Nov 18.
Date of Electronic Publication: 2024 Nov 18.

Backgrounds: Heart rate (HR) and stroke volume (SV)-the components of cardiac output-have a complementary relationship. Poor HR increase during exercise is associated with poor exercise tolerance in heart failure (HF) with preserved ejection fraction (HFpEF), but its prognostic impact remains unclear. Furthermore, whether the compensation for poor HR increase with SV during exercise is associated with prognosis remains unknown.
Methods: We evaluated 129 consecutive hospitalized HF patients with sinus rhythm and left ventricular ejection fractions > 40% who underwent cardiopulmonary exercise testing before discharge from the index hospitalization.
Results: Patients (age: 66 [55-74] years; 73% male) were divided into four groups by median HR reserve (HRR; peak-rest HR: 34 bpm) and O ₂ pulse, a surrogate for SV, reserve (peak-rest O ₂ pulse: 4.8 mL/beat). During a mean follow-up of 562 [294-961] days, cardiovascular events (cardiovascular death and/or HF rehospitalizations) occurred in 24 patients. Kaplan-Meier analysis identified significant differences in outcomes among the four groups (χ ²  = 27.3, p < 0.001). Using the preserved HRR/preserved O ₂ pulse reserve group (n = 33) as a reference, the impaired HRR/impaired O ₂ pulse reserve group (n = 37) was associated with poor outcomes (adjusted hazard ratio: 5.66, 95% CI 1.15-27.74, p = 0.033), whereas the impaired HRR/preserved O ₂ pulse reserve group (n = 31) was not (adjusted hazard ratio: 0.38, 95% CI 0.03 to 4.76, p = 0.455).
Conclusion: The overlap of lower increases in HR and O ₂ pulse, a surrogate for SV, during exercise was associated with an extremely poor prognosis in HFpEF.

Dmytriiev K; Division of Pulmonary Medicine,  Edmonton, Alberta T6G 2G3, Canada.
Stickland MK; Weatherald J;

Heart failure clinics [Heart Fail Clin] 2025 Jan; Vol. 21 (1), pp. 51-61. Date of Electronic Publication: 2024 Oct 15.

Heart failure clinics [Heart Fail Clin] 2025 Jan; Vol. 21 (1), pp. 51-61.
Date of Electronic Publication: 2024 Oct 15.

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that has a high impact on patients’ quality of life, morbidity and mortality. PAH is characterized by extensive pulmonary vascular remodeling that results in an increase in pulmonary vascular resistance and right ventricular afterload, and can lead to right heart failure. Patients with PAH exhibit inefficient ventilation, high dead space ventilation, dynamic hyperinflation, and ventricular-arterial uncoupling, which can contribute to high dyspnea and low exercise tolerance. Cardiopulmonary exercise testing can help to diagnose PAH, define prognosis and treatment response in PAH, as well as discriminate between different pulmonary vascular diseases.
Competing Interests: Disclosure K. Dmytriiev has nothing to disclose; M.K. Stickland has nothing to disclose, J. Weatherald has received grants or contracts to his institution from Astra Zeneca, Bayer, Janssen, Sanofi, and Merck; consulting fees from Janssen and Merck; honoraria from Janssen and Merck; advisory board payments from Janssen and Merck, payment for expert testimony from Sprigings Intellectual Property Law; travel support from Janssen; participation on Data Safety and Monitoring Board for the Université de Laval; and has unpaid leadership role at the Pulmonary Hypertension Association of Canada.

Landsteiner I; Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Ikoma T; Lewis GD;

Heart failure clinics [Heart Fail Clin] 2025 Jan; Vol. 21 (1), pp. 35-49.
Date of Electronic Publication: 2024 Oct 18.

Cardiopulmonary exercise testing (CPET) permits the assessment of gas exchange, electrocardiogram, and hemodynamic patterns throughout exercise, providing a window into multi-organ physiologic reserve during exercise. CPET provides risk stratification and informs management of advanced heart failure (HF). Increasingly, CPET is combined with echocardiography, or invasive right heart catheterization, which enables high-resolution assessment of cardiac and extracardiac limitations to exercise. CPET also represents a cornerstone in the evaluation process for advanced HF interventions. This review underscores the importance and utility of CPET in managing patients with advanced HF.