AlEX-DHF: Ablation and Exercise in Diastolic Heart Failure

Overview

The investigators analyze the impact of exercise and ablation in patients with symptomatic short-persistent atrial fibrillation (Afib) and heart failure with preserved ejection fraction (HFpEF). It is hypothesized that the combination of ablation and exercise better improves peak oxygen consumption (VO2peak) through improvement of peripheral (exercise training) and central (ablation) adaptations. Exercise intervention will contain a 12-week combined, video-based, supervised, endurance, resistance and respiratory training.

Detailed description

In a feasibility study the investigators analyze the impact of exercise and ablation in patients with symptomatic short-persistent atrial fibrillation and heart failure with preserved ejection fraction. Patients will be randomized into 2 groups: (1) A control group receiving ablation therapy, and (2) a group receiving ablation therapy and a combination of endurance, strength and respiratory training. The investigators will include 20 patients/group. All patients will receive a smart watch to monitor heart rate and trigger ECG recordings during symptomatic episodes. Smart watch monitoring will be done for 4 weeks. Then all patients will receive baseline examination with laboratory markers, lung function testing, echocardiography, measurement of pulse wave velocity, and screening for sleep apnea. All patients will receive simultaneous cardiopulmonary exercise testing (CPET) and exercise right heart catheterization (exRHC) followed by ablation therapy. Patients will then be randomized into a training and control group. After 2 weeks all patients will receive outpatient CPET to assess changes of VO2peak compared to baseline.

The training group will receive home-based, video-supervised exercise training with a combination of endurance, strength and respiratory training (5x/week). The control group will receive standard recommendations on physical activity. Smart watch monitoring will be continued in all groups until the end of the study. After 12 weeks of training intervention, all groups will undergo echocardiography, lung function testing, measurement of pulse wave velocity and exRHC with simultaneous CPET. All patients will receive 24h Holter monitoring at the end of the study. During exRHC lactate kinetics will be analyzed and improvement of lactate thresholds through exercise training will be determined. The primary outcome is the improvement of VO2peak in the groups. Secondary outcomes are improvements in the ratio of pulmonary capillary wedge pressure/cardiac output (PAWP/CO) and mean pulmonary artery pressure/CO (mPAP/CO). Burden of atrial fibrillation in the groups will also be assessed. All groups will receive optimal drug therapy.

The investigators expect that a combined approach of ablation and exercise training will better improve VO2peak through central (ablation) and peripheral (exercise training) adaptations.

Interventions

• Other Exercise training
  exercise intervention will consist of supervised, home-based, combined training with elements of endurance, resistance and respiratory training

Primary outcome measures

• Delta of peak oxygen consumption [Time frame: 14 weeks]

Secondary outcome measures (7)

• Delta of mean pulmonary artery pressure and cardiac output (mPAP/CO) [Time frame: 14 weeks]
• Delta of pulmonary artery wedge pressure to cardiac output (PAWP/CO) [Time frame: 14 weeks]
• Delta of peak oxygen consumption baseline to post ablation [Time frame: 2 weeks]
• Delta of peak oxygen consumption post ablation to the end of the study [Time frame: 12 weeks]
• Delta of Kansas City Cardiomyopathy Questionnaire score [Time frame: 14 weeks]
• Delta of E/e' [Time frame: 14 weeks]
• Burden of atrial fibrillation in the groups [Time frame: 18 weeks]

Eligibility criteria

Inclusion criteria

• Diagnosed heart failure with preserved ejection fraction
• Symptomatic short-persistent atrial fibrillation (diagnosis within 1 year of study inclusion)

Exclusion criteria

• Paroxysmal, long-persistent or permanent atrial fibrillation
• Clinically unstable coronary artery disease or acute coronary syndrome
• Physical and/or mental inability to perform exercise testing
• Prior ablation therapy
• Precapillary pulmonary hypertension at rest
• Intracardiac shunts
• Left ventricular ejection fraction <50%
• High-degree valve insufficiency or stenosis (greater than grade 1 at rest)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Germany · 1 center

• Department of Medicine, Division of Prevention and Sports Medicine TU Munich — Munich

Publications

• Wernhart S, Goertz A, Hedderich J, Papathanasiou M, Hoffmann J, Rassaf T, Luedike P. Diastolic exercise stress testing in heart failure with preserved ejection fraction: The DEST-HF study. Eur J Heart Fail. 2023 Oct;25(10):1768-1780. doi: 10.1002/ejhf.2995. Epub 2023 Aug 24. PMID 37565370
• Anker SD, Usman MS, Anker MS, Butler J, Bohm M, Abraham WT, Adamo M, Chopra VK, Cicoira M, Cosentino F, Filippatos G, Jankowska EA, Lund LH, Moura B, Mullens W, Pieske B, Ponikowski P, Gonzalez-Juanatey JR, Rakisheva A, Savarese G, Seferovic P, Teerlink JR, Tschope C, Volterrani M, von Haehling S, Zhang J, Zhang Y, Bauersachs J, Landmesser U, Zieroth S, Tsioufis K, Bayes-Genis A, Chioncel O, Andre PMID 37461163
• Houstis NE, Eisman AS, Pappagianopoulos PP, Wooster L, Bailey CS, Wagner PD, Lewis GD. Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Diagnosing and Ranking Its Causes Using Personalized O2 Pathway Analysis. Circulation. 2018 Jan 9;137(2):148-161. doi: 10.1161/CIRCULATIONAHA.117.029058. Epub 2017 Oct 9. PMID 28993402
• Jain CC, Borlaug BA. Hemodynamic assessment in heart failure. Catheter Cardiovasc Interv. 2020 Feb 15;95(3):420-428. doi: 10.1002/ccd.28490. Epub 2019 Sep 10. PMID 31507065
• Mueller S, Winzer EB, Duvinage A, Gevaert AB, Edelmann F, Haller B, Pieske-Kraigher E, Beckers P, Bobenko A, Hommel J, Van de Heyning CM, Esefeld K, von Korn P, Christle JW, Haykowsky MJ, Linke A, Wisloff U, Adams V, Pieske B, van Craenenbroeck EM, Halle M; OptimEx-Clin Study Group. Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advic PMID 33560320
• Rattka M, Pott A, Kuhberger A, Weinmann K, Scharnbeck D, Stephan T, Baumhardt M, Bothner C, Iturbe Orbe M, Rottbauer W, Dahme T. Restoration of sinus rhythm by pulmonary vein isolation improves heart failure with preserved ejection fraction in atrial fibrillation patients. Europace. 2020 Sep 1;22(9):1328-1336. doi: 10.1093/europace/euaa101. PMID 32449907
• Rattka M, Kuhberger A, Pott A, Stephan T, Weinmann K, Baumhardt M, Aktolga D, Teumer Y, Bothner C, Scharnbeck D, Rottbauer W, Dahme T. Catheter ablation for atrial fibrillation in HFpEF patients-A propensity-score-matched analysis. J Cardiovasc Electrophysiol. 2021 Sep;32(9):2357-2367. doi: 10.1111/jce.15200. Epub 2021 Aug 18. PMID 34379370
• Wernhart S, Papathanasiou M, Mahabadi AA, Rassaf T, Luedike P. Betablockers reduce oxygen pulse increase and performance in heart failure patients with preserved ejection fraction. Int J Cardiol. 2023 Jan 1;370:309-318. doi: 10.1016/j.ijcard.2022.10.009. Epub 2022 Oct 8. PMID 36220507

Identifiers

NCT: NCT06650995 · 2024-381-S-SB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗