Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD

• Spironolactone (Drug): The doses used in the study are the doses used in standard clinical practice. Initial dose is 25 mg/day until study end . The duration of treatment for each patient is 12 months.
• Placebo (Drug): Placebo will be taken once a day at the same time of day. The duration of treatment for each patient is 12 months.

Primary outcomes

• Right ventricle longitudinal strain measured by echocardiography [at year 1]
• Right ventricle infundibulum diameter measured by echocardiography [at year 1]
• number of ventricular extrasystoles > 500 on 24h-Holter ECG [at year 1]

Secondary outcomes

• number of ventricular extrasystoles on 24h-Holter ECG [at year 1]
• number of palpitations [at year 1]
• number of palpitations [at year 3]
• number of ventricular tachycardia [at year 1]
• number of ventricular tachycardia [at year 3]
• number of dyspnea [at year 1]
• number of dyspnea [at year 3]
• number of syncope [at year 1]
• number of syncope [at year 3]
• number of sudden death [at year 1]
• number of sudden death [at year 3]
• number of thoracic pain [at year 1]
• number of thoracic pain [at year 3]
• number of MACE (Major adverse cardiac events) [at year 1]
• number of MACE (Major adverse cardiac events) [at year 3]
• number of hospital admissions [at year 1]
• number of hospital admissions [at year 3]
• left ventricle diameters measured by echocardiography [at year 1]: Morphologic criterion
• left ventricle diameters measured by echocardiography [at year 3]: Morphologic criterion
• left ventricle volumes measured by echocardiography [at year 1]: Morphologic criterion
• left ventricle volumes measured by echocardiography [at year 3]: Morphologic criterion
• left ventricle ejection fraction measured by echocardiography [at year 1]: Morphologic criterion
• left ventricle ejection fraction measured by echocardiography [at year 3]: Morphologic criterion
• Left ventricular global longitudinal strain measured by echocardiography [at year 1]: Morphologic criterion
• aneurism measured by echocardiography [at year 1]: Morphologic criterion
• aneurism measured by echocardiography [at year 3]: Morphologic criterion
• dyskinesia measured by echocardiography [at year 1]: Morphologic criterion
• dyskinesia measured by echocardiography [at year 3]: Morphologic criterion
• evolution of QRS width (50mm/s) on ECG [at year 1]: Morphologic criterion
• number of ventricular extrasystoles on 24h Holter ECG [at year 1]: Rhythmic criterion
• sustained ventricular tachycardia on 24h Holter ECG [at year 1]: Rhythmic criterion
• evolution of PR interval duration on ECG [at year 1]: Rhythmic criterion
• late potentials measured with high amplification ECG [at year 3]: Rhythmic criterion
• number of ventricular extrasystoles by stress test [at year 3]: Rhythmic criterion
• Evolution of functional symptoms by recording adverse events [at year 3]: Functional criteria
• Number of hospital admissions owing to clinical deterioration [at year 3]
• Evolution of telediastolic right ventricle volume measured by echocardiography [at year 3]: according to the genotype of desmosome genes
• arrhythmia burden measured by 24h Holter ECG [at year 3]: according to the genotype of desmosome genes
• Dosage of MMP9 (Matrix metallopeptidase 9) [at year 1]: Quantification of fibrosis
• Dosage of MMP9 (Matrix metallopeptidase 9) [at year 3]: Quantification of fibrosis
• Dosage of TIMP1 (Tissue Inhibitory MetalloProtease 1) [at year 1]: Quantification of fibrosis
• Dosage of TIMP1 (Tissue Inhibitory MetalloProtease 1) [at year 3]: Quantification of fibrosis
• Dosage of TIMP2 (Tissue Inhibitory MetalloProtease 2) [at year 1]: Quantification of fibrosis
• Dosage of TIMP2 (Tissue Inhibitory MetalloProtease 2) [at year 3]: Quantification of fibrosis
• Dosage of IL6 (Interleukin 6) [at year 1]: Quantification of inflammation
• Dosage of IL6 (Interleukin 6) [at year 3]: Quantification of inflammation
• Dosage of IL8 (Interleukin 8) [at year 1]: Quantification of inflammation
• Dosage of IL8 (Interleukin 8) [at year 3]: Quantification of inflammation

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* >18years old
* Diagnosis of ARVD based on Task Force criteria. Two major criteria: 1 morphologic and one rhythmic or 1 major and 2 minor criteria established by the European Society of Cardiology/International Society and Federation of Cardiology.
* Left Ventricular Ejection Fraction >40%
* Written informed consent.

Exclusion Criteria:

* Patients under judicial protection.
* Female patient who is pregnant or lactating, or is of child bearing potential (defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤ 55 years or 12 months if > 55 years) and who did not agree to use highly effective methods of birth control throughout the study.
* No health insurance.
* Right heart failure patient (RV volume>150ml).
* Spironolactone contraindication: anuria, hyperkalemia (K+>5 mmol/l), renal failure (DFGCréat>22 mL/min/1,73 m2), end-stage liver failure, Addison's Disease, hypersensitivity to spironolactone or to any of the excipients (patients with galactose intolerance, lapp lactase deficiency or glucose or galactose malabsorption syndrome), association with eplerenone, association with other hyperkalemic diuretics, association with potassium salts, not recommended in cirrhotic patients (natraemia<125 mmol/l) or in patients likely to present an acidosis.
* Mandatory indication for a combination of ACE inhibitor and sartan or renin inhibitor (each authorized separately).
* Acute phase of systemic disease.
* Uncompensated hypothyroidism.
* Acute hyperthyroidism.
* Normal right ventricular volume.
* Heart transplantation.
* Swallowing disorders.
* Participation in any other interventional clinical investigation that may have an impact on our study.

• Results publication: Alexandrino FB, Faaborg-Andersen CC, daSilva-deAbreu A. Anticoagulation in patients with atrial fibrillation and heart failure: More than meets the eye? Int J Cardiol. 2024 Feb 15;397:131591. doi: 10.1016/j.ijcard.2023.131591. Epub 2023 Nov 17. No abstract available. PMID 37979797

• Philippe Chevalier, MD, PhD, Principal investigator, Hospices Civils de Lyon

NIH grants: 2023