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Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Aims<\/jats:title>\n                <jats:p>The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a\u00a0mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>iPHORECAST has a\u00a0multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50\u202fmg eplerenone once daily or no treatment. The primary endpoint of the study is a\u00a0multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and\/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3\u00a0years.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Baseline results<\/jats:title>\n                <jats:p>A\u00a0total of 84\u00a0presymptomatic PLN p.Arg14del carriers (<jats:italic>n<\/jats:italic>\u202f=\u200942\u00a0per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class\u00a0I and had a\u00a0left ventricular ejection fraction &gt;\u202f45% and &lt;\u202f2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>iPHORECAST is a\u00a0multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12471-021-01584-5","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T10:03:07Z","timestamp":1624010587000},"page":"84-95","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST)"],"prefix":"10.1007","volume":"30","author":[{"given":"W. 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