Restrictive cardiomyopathy (RCM) is a heterogeneous group of diseases characterized by restrictive left ventricular pathophysiology, i.e. a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness. More precisely, the defining feature of RCM is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function. Beyond this shared haemodynamic hallmark, the phenotypic spectrum of RCM is wide. The disorders manifesting as RCM may be classified according to four main disease mechanisms: (i) interstitial fibrosis and intrinsic myocardial dysfunction, (ii) infiltration of extracellular spaces, (iii) accumulation of storage material within cardiomyocytes, or (iv) endomyocardial fibrosis. Many disorders do not show restrictive pathophysiology throughout their natural history, but only at an initial stage (with an evolution towards a hypokinetic and dilated phenotype) or at a terminal stage (often progressing from a hypertrophic phenotype). Furthermore, elements of both hypertrophic and restrictive phenotypes may coexist in some patients, making the classification challenge. Restrictive pathophysiology can be demonstrated by cardiac catheterization or Doppler echocardiography. The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiovascular magnetic resonance, but further investigations may be needed, up to endomyocardial biopsy and genetic evaluation. The spectrum of therapies is also wide and heterogeneous, but disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy.

Cardiologic Centre University of Ferrara Via Savonarola 9 44121 Ferrara Italy

Cardiology Division Fondazione Toscana Gabriele Monasterio via Moruzzi 1 56124 Pisa Italy

Cardiology Division Hadassah Hebrew University Hospital Sderot Churchill 8 Jerusalem Israel

Center for Diagnosis and Treatment of Cardiomyopathies Cardiovascular Department Azienda Sanitaria Universitaria Giuliano Isontina University of Trieste European Reference Network for Rare Low Prevalence and Complex Diseases of the Heart ERN GUARD Heart Via Giacomo Puccini 50 34148 Trieste Italy

General University Hospital and Charles University Opletalova 38 110 00 Staré Město Czech Republic

Health Science Interdisciplinary Center Scuola Superiore Sant'Anna piazza Martiri della Libertà 33 56127 Pisa Italy

Heart Failure Center Clalit Health Services Bnei Brit St 22 Jerusalem Israel

Maria Cecilia Hospital GVM Care and Research Via Corriera 1 48033 Cotignola Ravenna Italy

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