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Purpose of Review: Cardiac amyloidosis (CA) constitutes an important etiology of heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF). Since patients with CA show early exhaustion, we aimed to investigate whether non-exertional variables of cardiopulmonary exercise testing (CPET) provide additional information in comparison to traditional peak oxygen consumption (VO 2peak )., Recent Findings: We retrospectively investigated CPET variables of patients with HFpEF and HFmrEF with (n = 21) and without (n = 21, HF) CA at comparable age and ejection fraction. Exertional and non-exertional CPET variables as well as laboratory and echocardiographic markers were analyzed. The primary outcome was the difference in CPET variables between groups. The secondary outcome was rehospitalization in patients with CA during a follow-up of 24 months. Correlations between CPET, NTproBNP, and echocardiographic variables were calculated to detect patterns of discrimination between the groups. HF patients with CA were inferior to controls in most exertional and non-exertional CPET variables. Patients with CA were hospitalized more often (p = 0.002), and rehospitalization was associated with VE/VCO 2 (p = 0.019), peak oxygen pulse (p = 0.042), the oxygen equivalent at the first ventilatory threshold (p = 0.003), circulatory (p = 0.024), and ventilatory power (p < .001), but not VO 2peak (p = 0.127). Higher performance was correlated with lower E/e' and NTproBNP as well as higher resting heart rate and stroke volume in CA. Patients with CA displayed worse non-exertional CPET performance compared to non-CA HF patients, which was associated with rehospitalization. Differences between correlations of resting echocardiography and CPET variables between groups emphasize different properties of exercise physiology despite comparable ejection fraction., (© 2024. The Author(s).)

Aims: Pulmonary capillary wedge pressure (PAWP) ≥25 mmHg during bicycle ergometry is recommended to uncover occult heart failure with preserved ejection fraction. We hypothesized that PAWP increase would differ in available diastolic stress tests and that the margin of PAWP ≥25 mmHg would only be reliably achieved through ergometry., Methods and Results: We conducted a prospective, single-arm study in patients with an intermediate risk for heart failure with preserved ejection fraction according to the ESC HFA-PEFF score. A total of 19 patients underwent four stress test modalities in randomized order: leg raise, fluid challenge, handgrip, and bicycle ergometry. The primary outcome was the difference (Δ) between resting and exercise PAWP in each modality. Secondary outcomes were differences (Δ) in mean pulmonary artery pressure (mPAP), cardiac output (CO), as well as the ratios between mPAP and PAWP to CO. Compared to resting values, passive leg raise (Δ7.7 ± 8.0 mmHg, p = 0.030), fluid challenge (Δ9.2 ± 6.4 mmHg, p = 0.003), dynamic handgrip (Δ9.6 ± 7.5 mmHg, p = 0.002), and bicycle ergometry (Δ22.3 ± 5.0 mmHg, p < 0.001) uncovered increased PAWP during exercise. Amongst these, bicycle ergometry also demonstrated the highest ΔmPAP (27.2 ± 7.1 mmHg, p < 0.001), ΔCO (3.3 ± 2.6 L/min, p < 0.001), ΔmPAP/CO ratio (2.3 ± 2.0 mmHg/L/min, p < 0.001), and ΔPAWP/CO ratio (2.2 ± 1.4 mmHg/L/min, p < 0.001) compared to other modalities. PAWP ≥25 mmHg was only reliably achieved in bicycle ergometry (31.1 ± 3.9 mmHg). In all other modalities only 10.5% of patients achieved PAWP ≥25 mmHg (handgrip 18.4 ± 6.6 mmHg, fluid 18.1 ± 5.6 mmHg, leg raise 16.5 ± 7.0 mmHg)., Conclusions: We demonstrate that bicycle ergometry exhibits a distinct haemodynamic response with higher increase of PAWP compared to other modalities. This finding needs to be considered for valid detection of exercise PAWP ≥25 mmHg when non-bicycle tests remain inconclusive., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Phosphodiesterase-5 inhibitors (PDE5I) are frequently implemented after left ventricular assist device (LVAD) implantation to improve haemodynamics in patients with early postoperative right ventricular (RV) failure. It is unknown if long-term PED5I therapy beyond the early post-operative period provides any clinical benefit in stable outpatients, who have recovered from post-operative RV failure under univentricular device support. This study aimed to investigate the impact of PDE5I discontinuation on RV function and cardiopulmonary exercise capacity in patients on durable LVAD support., Methods and Results: We enrolled 31 clinically stable LVAD recipients on long-term oral PDE5I therapy. The mean age was 53 years, and 90% were male. Patients discontinued PDE5I and underwent cardiopulmonary exercise testing, echocardiography, LVAD interrogation, and biomarker analysis at baseline and 4 weeks after PDE5I withdrawal. At 4 weeks, no significant changes were observed in echocardiographic indices of RV morphology and function but an increase in peak tricuspid regurgitation velocity (2.1 vs. 2.4 m/s, P = 0.01). Peak oxygen consumption (11.4 vs. 11.8 mL/min/kg, P = 0.52), minute ventilation/carbon dioxide production slope (33 vs. 35, P = 0.56), N-terminal pro-brain natriuretic peptide (1455 vs. 1399 pg/mL, P = 0.55), flow and power readings of the device, and quality of life (Kansas City Cardiomyopathy Questionnaire score 78.3% vs. 77.5%, P = 0.62) exhibited no significant changes. We observed an increase in 6-min walking distance (346 vs. 364 m, P = 0.03). Two patients were hospitalized for non-cardiac reasons (subtherapeutic INR, driveline infection). No patient was hospitalized for cardiac decompensation., Conclusions: In LVAD patients with a history of early post-operative RV failure, discontinuation of long-term PDE5I therapy was not associated with deterioration of RV function, exercise capacity, and quality of life. PDE5I should be critically evaluated until more evidence regarding the net clinical benefit of this pharmacologic intervention becomes available., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: High-intensity interval training (HIIT) of 4 minutes at 80%-90% of peak oxygen consumption (VO 2peak ) has been shown to be feasible in patients with left ventricular assist devices (LVADs). The effect of shorter bouts of HIIT, which reduce the anaerobic burden, has not been investigated compared to moderate continuous training (MCT)., Methods and Results: We conducted a prospective, monocentric study (NCT05121077) randomizing patients with LVADs into 20 minutes of MCT (n = 10) or short bouts (≤ 90 seconds) of HIIT (n = 10) following cardiopulmonary exercise testing at 50%-60% and 80%-90% of VO 2peak . Each of the 18 supervised sessions (3×/week, t 0- t 1 ) included 10 minutes of strengthening training. The primary outcome was the increase of VO 2peak in the 2 groups between t 0 and t 1 . Secondary outcomes were changes in the 12-item Kansas City Cardiomyopathy Questionnaire, the 6-minute walk distance and the percentage of VO 2peak at the first ventilatory threshold. VO 2peak significantly increased with HIIT (13.0 ± 4.6mL/kg/min vs 14.6 ± 4.3mL/kg/min; P = 0.037), but not with MCT (11.8 ± 3.3mL/kg/min vs 13.1 ± 3.3mL/kg/min; P = 0.322), without between-group differences (P = 0.853). Secondary outcomes improved from t 0- t 1 in MCT and HIIT, without differences between the groups., Conclusions: Short bouts of HIIT are feasible, and they improved VO 2peak and functional parameters in patients in this pilot prospective study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Heart failure with preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) ejection fraction (EF) remains a controversial categorization. Whether these three categories reflect a distinct pattern of exercise limitation in cardiopulmonary exercise testing (CPET) needs to be investigated. We aimed to analyze whether CPET variables differ between all heart failure categories (HF)., Methods: We analyzed CPET variables of stable HFpEF (n = 123), HFmrEF (n = 31), and HFrEF (n = 153; 74 patients with and 79 patients without left ventricular assist device, LVAD) patients. The association between HF and peak oxygen consumption (VO 2peak ) was used as a primary outcome, while the association between HF, oxygen uptake efficiency slope (OUES), and increase of O 2 pulse (ΔO 2 pulse) were analyzed as secondary outcomes., Results: VO 2peak displayed a consistent decline across all HF categories (19.8 ml ± 6.2/kg/min vs. 17.5 ± 7.9 ml/kg/min vs. 13.7 ± 4.0 ml/kg/min, p < 0.001). OUES only showed differences between HFpEF and HFrEF (1.8 ± 0.6 vs. 1.4 ± 0.5, p < 0.001) as well as HFmrEF and HFrEF (1.9 ± 0.9 vs. 1.4 ± 0.5, p = 0.004). ΔO 2 pulse differed between HFpEF and HFrEF (7.7 ± 3.5 ml/beat/kg*100 vs. 5.5 ± 3.0 ml/beat/kg*100, p < 0.001) as well as HFpEF and HFmrEF (7.7 ± 3.5 ml/beat/kg*100 vs. 6.3 ± 4.1 ml/beat/kg*100, p = 0.049). Outcome variables did not differ between HFrEF with and without LVAD support (VO 2peak : p = 0.364, OUES: p = 0.129, ΔO 2 pulse: p = 0.564)., Conclusions: HF did not display a distinct CPET profile. Thus, EF-based categorization does not entirely reflect exercise limitations. CPET variables could contribute to better characterize HF phenotypes., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Beta-blocker (BB) therapy is a main pillar in treating patients with heart failure and reduced ejection fraction and has shown a prognostic benefit. However, evidence for application of BB in heart failure with preserved ejection fraction (HFpEF), especially in the absence of coronary artery disease, atrial fibrillation or arterial hypertension, is scarce. HFpEF is characterized by elevations in left atrial pressure and reduced compliance of the left ventricle leading to a hampered increase of cardiac output (CO) during exercise, which results in exertional dyspnea. This may be due to either a limited increase in stroke volume or reduced chronotropy during physical activity. We critically discuss the pathophysiological background of HFpEF, current data on BB in heart failure therapy, as well as the potential benefits and harms of BB therapy in HFpEF. Furthermore, we argue that non-cardio selective BB with peripheral activity to reduce afterload may be more suitable in this population than cardio-selective BB. Although preliminary data on BB in HFpEF are available, multicenter prospective trials to assess a reduction of cardiovascular morbidity are warranted. Future trials need to focus on phenotyping HFpEF patients and assess who may benefit most from tailored BB therapy., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Beta blockers (BB) reduce chronotropic response and exercise capacity in heart failure with preserved ejection fraction (HFpEF). To analyze the influence of BB on exercise performance and O 2 pulse increase as a surrogate for stroke volume in HFpEF., Methods: We retrospectively analyzed the influence of BB intake (yes: n = 48/no: n = 51) on peak oxygen uptake (VO 2peak), oxygen uptake efficiency slope (OUES), and increase of O 2 pulse in HFpEF patients undergoing cardiopulmonary exercise testing (CPET). Associations of outcome variables and risk category of the algorithm of the Heart Failure Association of the European Society of Cardiology (HFA-PEFF score) were calculated., Results: Patients on BB showed lower VO 2peak (p = .003) and OUES (p = .002), with a dominant effect in the high-risk (p = .020; 0.002), but not in the low risk-group (p = .434; p = .499). In the intermediate group BB showed a trend towards lower VO 2peak (p = .078) and lower values for OUES (p = .020). Patients on BB also demonstrated a lower increase of O 2 pulse during exercise (p = .002), without differences between HFA-PEFF risk groups (low: p = .322, intermediate: p = .269, high: p = .313)., Conclusions: BB reduce exercise capacity and O 2 pulse increase in HFpEF patients. Direct quantification of O 2 pulse increase may help to improve the discrimination of HFpEF patients., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Exercise oscillatory ventilation (EOV), indicating pathological fluctuations on pulmonary arterial pressure, is associated with mortality in patients with heart failure (HF). Whether left ventricular assist device (LVAD)-induced ventricular unloading can reverse EOV and may prevent short-term rehospitalization has not been investigated., Methods: We performed a retrospective single-center in- and outpatient analysis of patients with (n = 20, LVAD) and without (n = 27, HF) circulatory support and reduced ejection fraction (EF, 22.8 ± 7.9%). The association of cardiopulmonary exercise testing (CPET) variables and 3 months-rehospitalization (3MR) as a primary outcome was analyzed. Furthermore, CPET variables were compared regarding the presence of EOV (+/-)., Results: Lower VO 2peak (11.6 ± 4.9 ml/kg/min vs. 14.4 ± 4.3 ml/kg/min, p = 0.039), lower increase of PETCO 2 (CI = 0.049-1.127; p = 0.068), and higher VE/VCO 2 (43.8 ± 9.5 vs. 38.3 ± 10.6; p = 0.069) were associated with 3MR. Flattening of O 2 pulse (CI = 0.139-2.379; p = 0.487) had no impact on 3MR. EOV was present in 59.5% (n = 28/47) of patients, without a significant difference between LVAD and HF patients (p = 0.959). Patients with HF/EOV+ demonstrated significantly lower VO 2peak compared with HF/EOV- (p = 0.039). LVAD/EOV+ displayed significantly lower EF (p = 0.004) and fewer aortic valve opening than LVAD/EOV- (p = 0.027)., Conclusions: Lower VO 2peak , but not EOV, was associated with 3MR. EOV occurred at a similar rate in LVAD and HF patients, which may illustrate insufficient unloading during exercise in chronic LVAD therapy and may contribute to the limited exercise capacity following LVAD implantation. Simultaneous CPET and right heart catheterization studies are needed to elucidate whether EOV may serve as a non-invasive predictor of insufficient LV unloading necessitating LVAD reprograming., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)