Trial document





This trial has been registered retrospectively.
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  DRKS00017515

Trial Description

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Title

Clinical characterization of arrhythmia-induced tachymyopathy (AIC)

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Trial Acronym

Tachy-HF-Pilot-Trial

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URL of the Trial

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Brief Summary in Lay Language

Heart failure affects about 1-2% of the population and is associated with increased mortality. Disturbations of heart rhythms often occur as a consequence, but also may be the reason for heart failure. Hardly every fast and persistent rhythm disturbance may lead to heart failure, which is called arrhytmia-induced cardiomyopathy (AIC). The mechanisms are not completely understood. This pilot study shall help to estimate the frequency of heart failure caused by rhythm disturbances, and shed light on the time range in which the heart function recovers after normalization of heart rhythm. For that reason, patients with a newly diagnosed systolic heart failure (viz. reduced pumping capacity) and a present rhythm disturbance leading to a heart rate of >100/min are examined. To qualify for this study (of AIC), other reason for heart failure like acute myocardial infarction or myocarditis must not be present. Patients, hospitalized in the university hospitals Regensburg (recruitment ongoing) and Leipzig (planed as second center) and being treated because of that kind of heart failure, undergo following diagnostic investigations: markers of ‘heart load’ are measured in blood samples, heart function and size are evaluated by echocardiography, a possible myocardial scar is assessed by magnetic resonance imaging, quality of life is captured within a questionnaire and heart rate and rhythm are documented by ECG. After normalization of heart rhythm within the hospital stay, outpatient presentations with ECG, echocardiography, blood collection (for the same markes as above) and quality of life questionnaire are planned after 2, 4 and 6 months after discharge. The Goal is to conclude, if the heart failure was due to the disturbance of heart rhythm or not, which would be called an idiopathic/dilated cardiomyopathy. Additionally, the time to recovery can be estimated by the bimonthly visits, which is evaluated in conjunction with the results from blood samples and quality of life assessment.

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Brief Summary in Scientific Language

Atrial tachyarrhythmias (mainly atrial fibrillation, AF) and heart failure (HF) are growing cardiovascular disease epidemics worldwide. Arrhytmia-induced cardiomyopathy (AIC) is a condition in which tachyarrhythmias or frequent ectopy result in left ventricular systolic dysfunction (LVSD), leading to HF. The hallmark of this condition is partial or complete reversibility once arrhythmia control is achieved. Therefore, the correct diagnosis is essential in order to successfully treat patients. As LVSD displays also rhythm disorders as complications, AIC may be a hidden cause of HF, particularly when “idiopathic cardiomyopathy” with concomitant arrhythmia is diagnosed. The incidence and prevalence of AIC are uncertain.(1-3) In general, ~30% of patients with AF suffer from LVSD. Only a few small and mainly uncontrolled studies are available and they suggest that a high number of 56-88% of these cases finally turn out to have a relevant component of AIC, depending on inclusion criteria.(2, 4, 5) However, the arrhythmia is frequently considered as secondary and not treated effectively when, in fact, immediate rhythm control may be necessary for full recovery of LV function.(1, 3) Full recovery of LV function is reported to occur within weeks to rather several months.(3) Inter-sectional barriers (e.g. inpatient vs. outpatient care) may lead physicians to lose track on the development of LV function after initiation of a causal rhythm control therapy.
Two recent trials have suggested a high incidence of AIC and underline the effectiveness of ablation therapy in HF patients with concomitant AF. Very recently, the CAMERA-MRI trial showed that restoration of sinus rhythm with catheter ablation in patients with AF and LVSD results in significant improvement of LV function.(2) In addition, the CASTLE-AF trial (6) further revealed, that catheter ablation for AF in patients with LVSD is associated with a significant reduction of death from any cause and hospitalization for HF. However, there was no direct relation to AIC. Both trials clearly suggest a need for specific studies investigating the impact of AIC on LV function and clinical outcome. In contrast to AF ablation, anti-arrhythmic strategies have failed to show an impact on mortality in AF-CHF and DIAMOND-CHF.(6, 7)
During first presentation of the patient with LVSD and concomitant arrhythmia, it is unclear whether the patient suffers from idiopathic cardiomyopathy with resulting arrhythmia or from AIC. To date, no sufficient predictors or specific diagnostics have been established in acceptable trials consisting of at least three-digit patient numbers. However, early recognition of AIC seems to be critical, and aggressive treatment aimed at controlling or eliminating the inciting arrhythmia results in symptom resolution and recovery of LV function.(3) There is a clear clinical need for better identification of patients that may respond to (but also will not respond to) rhythm therapy. Therefore, the primary aim of this pilot trial is to elucidate the prevalence of AIC in patients with newly diagnosed idiopathic cardiomyopathy and to estimate the time to recovery of LVSD. For this purpose, patients with a newly diagnosed systolic heart failure and present tachyarrhythmia are eligible. Key exclusion cirteria are a history of previous significant non AIC-LVSD (left ventricular ejection fraction, LVEF<50%), myocardial infarction within the last 3 months and long persistent or permanent AF. To characterize and possibly find predictors for the diagnosis of AIC, following diagnostic investigations are carried out: ECG, patient blood samples are analysed for serum TroponinI and NTproBNP levels, echocardiography and magnetic resonance imaging are performed to assess heart function, size and remodeling. Further, the ‘Minnesota Living with Heart Failure’ questionnaire, which has demonstrated good psychometric properties,(8) will help to quantify the subjective experience of HF (and recovery). Within the initial hospital stay, normalization of rate and rhythm is performed according to the actual guidelines and local expertise with the aim to establish normofrequent sinus rhythm. Follow-up visits are scheduled at 2, 4 and 6 months after the initial hospitalization including ECG, serum TroponinI and NTproBNP, echocardiography and quality of life questionnaire. After the last visit, data of patients with stable, normofrequent sinus rhythm are reviewed and those with an increase of >15% of the initial LVEF or an LVEF≥50% with an improvement of at least 10% are assigned to the AIC group. Patients with stable sinus rhythm and persistent heart failure (LVEF did no increase >15% after 6 months) are diagnosed as idiopathic/dilated cardiomyopathy (DCM) and assign to this group. Collected data then are used to calculate the prevalence of AIC in this collective, to estimate the time to recovery of LVEF and to identify possible predictors for an accelerated identification and diagnoses of AIC-patients.

References:
1. Sossalla S, Vollmann D. Arrhythmieinduzierte Kardiomyopathie - Ursachen, klinische Bedeutung und Behandlung. Dtsch Arztebl Int 2018; 115(19): 335-41.
2. Prabhu S, Taylor AJ, Costello BT, et al. Catheter Ablation Versus Medical Rate control in Atrial Fibrillation and Systolic Dysfunction (CAMERA-MRI). J Am Coll Cardiol 2017; 70:1949-61.
3. Gopinathannair R, Etheridge SP, Marchlinski FE, Spinale FG, Lakkireddy D, Olshansky B. Arrhythmia-Induced Cardiomyopathies: Mechanisms, Recognition, and Management. J Am Coll Cardiol 2015; 66:1714-28.
4. Hsu LF, Jais P, Sanders P, et al. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004; 351:2373-83.
5. Brembilla-Perrot B, Ferreira JP, Manenti V, et al. Predictors and prognostic significance of tachycardiomyopathy: insights from a cohort of 1269 patients undergoing atrial flutter ablation. European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology 2016; 18:394-401.
6. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008; 358:2667-77.
7. Torp-Pedersen C, Moller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999; 341:857-65.
8. Rector TS, Cohn JN. Assessment of patient outcome with the Minnesota Living with Heart Failure questionnaire: reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group. Am Heart J. 1992;124(4):1017–25.

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Organizational Data

  •   DRKS00017515
  •   2019/09/30
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  •   yes
  •   Approved
  •   18-1072-101, Ethikkommission an der Universität Regensburg
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Secondary IDs

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Health Condition or Problem studied

  •   I42.9 -  Cardiomyopathy, unspecified
  •   I50.1 -  Left ventricular failure
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Interventions/Observational Groups

  •   Patients with suspicion of an arrhythmia-induced cardiomyopathy (AIC) undergo the following diagnostic tests within the initial hospital stay: ECG (for rhythm evaluation), blood sample (inter alia troponin I and NTproBNP for quantification of congestion), echocardiography (for evaluation of heart function) and cardiac MRI (check for fibrosis) as done by default for this illness. Additionally, a questionnaire (“Minesota Living with Heart Failure”) is conducted. The anti-arrhythmic therapy within this stay follows guidelines and local expertise with the objective of establishing sinus rhythm. In outpatient visits after two, four and six months after the initial hospital stay diagnostic tests with ECG, blood sample, echocardiography and questionnaire are repeated. Following the last outpatient visit (at six months), patients are finally assigned to arm 1 (AIC), if the left ventricular ejection fraction (LVEF) increased by 15% compared to the initial LVEF, or, if the LVEF is >50% and increased by 10% in this occasion.
  •   Patients, who do not meet these diagnostic criteria of an AIC are assigned to arm 2, which is the control arm, and an dilated cardiomyopathy is diagnosed. We deliberatly choose this study design, as the diagnosis can only be made after a successful rhythm therapy (diagnosis ex juvantibus).
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Non-randomized controlled trial
  •   Blinded
  •   investigator/therapist
  •   Other
  •   Diagnostic
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

The dual primary end point ‘prevalence of arrhythmia-indced cardiomyopathy and time to recovery of systolic heart function” is determined after the outpatient visit at six months. The prevalence of AIC is calculated by the quotient from the number of patients in arm 1 and the total number of patients. For the classification in the specific study arm, LVEF is used, which is measured by echocardiography.

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Secondary Outcome

Diagnostic scoring system to differentiate between AIC and non-AIC: cMRI detected fibrosis (late gadolinium enhancement, LGE) including LGE positive vs. negative LGE, and inverse correlation % LGE, and change LVEF (echocardiography). LV end-diastolic dimension (echocardiography) indexed to body surface are (BSA) (LVEDDI). Left atrial (LA) dimension (echocardiography) indexed to BSA (LAVI). Serum concentrations of N-terminal pro-BNP (NT-pro-BNP) and TroponinI. Symptoms of arrhythmia, NYHA Classification, type of arrhythmia, heart rate (ECG), and age.
Prevalence of AIC: Mitral insufficiency, specific antiarrhythmic therapy applied, hospitalization for heart failure/arrhythmia/cardiovascular, quality of life, AIC recurrence, overall survival, cardiovascular (CV) mortality, sudden cardiac death (SCD), symptoms of arrhythmia, NYHA Classification, type of arrhythmia, and demographic and clinical variables.
These parameters are collected at the initial hospital stay. In the outpatient visits two, four and six months after that, these parameters were measured again except for the cMRI-data.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2018/08/10
  •   50
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Suptraventricular tachycardia (100/min), unexplained left ventricular systolic dysfunction (LVEF <50%), rhythm control strategy, age >18y, informed consent.

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Exclusion Criteria

History of previous significant non AIC-LVSD (EF<50%), myocardial infarction within the last 3 months. Long persistent or permanent AF.

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Addresses

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    • Universitätsklinikum Regensburg
    • Franz-Josef-Strauss-Allee 11
    • 93053  Regensburg
    • Germany
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    • Universitäres Herzzentrum Regensburg, Innere Medizin 2, Abteilung für Kardiologie
    • Mr.  Dr.  Christian  Schach (PI Prof. S. Sossalla) 
    • Franz-Josef-Strauss-Allee 11
    • 93053  Regensburg
    • Germany
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    • Universitäres Herzzentrum Regensburg, Innere Medizin 2, Abteilung für Kardiologie
    • Mr.  Dr.  Christian  Schach 
    • Franz-Josef-Strauss-Allee 11
    • 93053  Regensburg
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinikum Regensburg
    • Franz-Josef-Strauss-Allee 11
    • 93053  Regensburg
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.