Dilated Cardiomyopathy: A Comprehensive Approach to Diagnosis and Risk Stratification

Dilated cardiomyopathy (DCM) represents one of the most common causes of non-ischemic heart failure, characterised by ventricular dilation alongside systolic dysfunction. Despite advances in therapy, DCM mortality rates remain high, and it is one of the leading causes of heart transplantation. It was recently recognised that many patients present minor structural cardiac abnormalities and express different arrhythmogenic phenotypes before overt heart-failure symptoms. This has raised several diagnostic and management challenges, including the differential diagnosis with other phenotypically similar conditions, the identification of patients at increased risk of malignant arrhythmias, and of those who will have a worse response to medical therapy. Recent developments in complementary diagnostic procedures, namely cardiac magnetic resonance and genetic testing, have shed new light on DCM understanding and management. The present review proposes a comprehensive and systematic approach to evaluating DCM, focusing on an improved diagnostic pathway and a structured stratification of arrhythmic risk that incorporates novel imaging modalities and genetic test results, which are critical for guiding clinical decision-making and improving outcomes.

[1]  L. Mestroni,et al.  Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy , 2022, Journal of the American College of Cardiology.

[2]  P. Lambiase,et al.  2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. , 2022, European heart journal.

[3]  D. Corrado,et al.  Cardiac magnetic resonance imaging of arrhythmogenic cardiomyopathy: evolving diagnostic perspectives , 2022, European Radiology.

[4]  E. Ashley,et al.  European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases , 2022, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[5]  H. Pak,et al.  Prognostic Cardiac Magnetic Resonance Markers of Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy for Predicting Heart Failure Outcomes , 2022, Journal of the American Heart Association.

[6]  Christos G Mihos,et al.  Cardiac geometry, function and mechanics in left ventricular non-compaction cardiomyopathy with preserved ejection fraction , 2022, Journal of Echocardiography.

[7]  G. Abela,et al.  Ventricular non-compaction review , 2021, Heart Failure Reviews.

[8]  M. Dorobanțu,et al.  The prognostic value of right ventricular longitudinal strain and 3D ejection fraction in patients with dilated cardiomyopathy , 2021, The International Journal of Cardiovascular Imaging.

[9]  S. Kazama,et al.  A clinical score for predicting left ventricular reverse remodelling in patients with dilated cardiomyopathy , 2021, ESC heart failure.

[10]  S. Heymans,et al.  Implications of Genetic Testing in Dilated Cardiomyopathy , 2020, Circulation. Genomic and precision medicine.

[11]  A. Mazzanti,et al.  Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria. , 2020, International journal of cardiology.

[12]  James A. White,et al.  Prognostic Value of Late Gadolinium Enhancement for the Prediction of Cardiovascular Outcomes in Dilated Cardiomyopathy , 2020, Circulation. Cardiovascular imaging.

[13]  D. Corrado,et al.  Arrhythmogenic Right Ventricular Cardiomyopathy: Characterization of Left Ventricular Phenotype and Differential Diagnosis With Dilated Cardiomyopathy , 2020, Journal of the American Heart Association.

[14]  G. Efthimiadis,et al.  Emerging concepts in arrhythmogenic dilated cardiomyopathy , 2020, Heart Failure Reviews.

[15]  S. Heymans,et al.  Arrhythmic risk stratification in non-ischaemic dilated cardiomyopathy beyond ejection fraction , 2020, Heart.

[16]  S. Goland,et al.  Peripartum Cardiomyopathy: JACC State-of-the-Art Review. , 2020, Journal of the American College of Cardiology.

[17]  J. Svendsen,et al.  Myocardial fibrosis and the effect of primary prophylactic defibrillator implantation in patients with non-ischemic systolic heart failure-DANISH-MRI. , 2019, American heart journal.

[18]  J. Seidman,et al.  Precision Medicine in the Management of Dilated Cardiomyopathy: JACC State-of-the-Art Review. , 2019, Journal of the American College of Cardiology.

[19]  V. Carriel,et al.  Myocardial fibrosis in arrhythmogenic cardiomyopathy: a genotype-phenotype correlation study. , 2019, European heart journal cardiovascular Imaging.

[20]  M. Link,et al.  2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. , 2019, Heart rhythm.

[21]  M. Link,et al.  Arrhythmogenic right ventricular cardiomyopathy: evaluation of the current diagnostic criteria and differential diagnosis , 2019, European heart journal.

[22]  Y. Pinto,et al.  Multimodality imaging in the diagnosis, risk stratification, and management of patients with dilated cardiomyopathies: an expert consensus document from the European Association of Cardiovascular Imaging. , 2019, European heart journal cardiovascular Imaging.

[23]  L. Mestroni,et al.  Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy. , 2019, Journal of the American College of Cardiology.

[24]  R. Porcher,et al.  Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies. , 2019, Circulation.

[25]  P. Elliott,et al.  Dilated cardiomyopathy and arrhythmogenic left ventricular cardiomyopathy: a comprehensive genotype-imaging phenotype study. , 2019, European heart journal cardiovascular Imaging.

[26]  E. Behr,et al.  Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy , 2019, Circulation.

[27]  L. Steinmetz,et al.  Regional Variation in RBM20 Causes a Highly Penetrant Arrhythmogenic Cardiomyopathy , 2019, Circulation. Heart failure.

[28]  T. Marwick,et al.  Reduction in mortality from implantable cardioverter-defibrillators in non-ischaemic cardiomyopathy patients is dependent on the presence of left ventricular scar , 2018, European heart journal.

[29]  Dudley J Pennell,et al.  Outcome in Dilated Cardiomyopathy Related to the Extent, Location, and Pattern of Late Gadolinium Enhancement , 2019, JACC. Cardiovascular imaging.

[30]  R. Blankstein,et al.  Comparing CMR Mapping Methods and Myocardial Patterns Toward Heart Failure Outcomes in Nonischemic Dilated Cardiomyopathy. , 2019, JACC. Cardiovascular imaging.

[31]  R. Kim,et al.  Feature-Tracking Global Longitudinal Strain Predicts Death in a Multicenter Population of Patients With Ischemic and Nonischemic Dilated Cardiomyopathy Incremental to Ejection Fraction and Late Gadolinium Enhancement. , 2018, JACC. Cardiovascular imaging.

[32]  I. van der Made,et al.  RBM20 Mutations Induce an Arrhythmogenic Dilated Cardiomyopathy Related to Disturbed Calcium Handling , 2018, Circulation.

[33]  J. Cornel,et al.  The Prognostic Value of Late Gadolinium-Enhanced Cardiac Magnetic Resonance Imaging in Nonischemic Dilated Cardiomyopathy: A Review and Meta-Analysis. , 2018, JACC. Cardiovascular imaging.

[34]  Susanna Price,et al.  2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. , 2018, European heart journal.

[35]  G. Barbati,et al.  Usefulness of Addition of Magnetic Resonance Imaging to Echocardiographic Imaging to Predict Left Ventricular Reverse Remodeling in Patients With Nonischemic Cardiomyopathy. , 2018, The American journal of cardiology.

[36]  S. Heymans,et al.  Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology , 2018, Cardiovascular research.

[37]  D. Judge,et al.  Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG) , 2018, Genetics in Medicine.

[38]  R. Płoski,et al.  Rapid and effective response of the R222Q SCN5A to quinidine treatment in a patient with Purkinje-related ventricular arrhythmia and familial dilated cardiomyopathy: a case report , 2018, BMC Medical Genetics.

[39]  D. Pennell,et al.  Sex‐ and age‐based differences in the natural history and outcome of dilated cardiomyopathy , 2018, European journal of heart failure.

[40]  D. O’Regan,et al.  Genetic Etiology for Alcohol-Induced Cardiac Toxicity , 2018, Journal of the American College of Cardiology.

[41]  A. Wilde,et al.  Clinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy. , 2018, JACC. Clinical electrophysiology.

[42]  N. Yamada,et al.  Mortality and Sudden Cardiac Death Risk Stratification Using the Noninvasive Combination of Wide QRS Duration and Late Gadolinium Enhancement in Idiopathic Dilated Cardiomyopathy , 2018, Circulation. Arrhythmia and electrophysiology.

[43]  S. Heymans,et al.  Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias , 2018, European heart journal.

[44]  Kenneth L. Jones,et al.  Filamin C Truncation Mutations Are Associated With Arrhythmogenic Dilated Cardiomyopathy and Changes in the Cell–Cell Adhesion Structures , 2018, JACC. Clinical electrophysiology.

[45]  P. Elliott,et al.  Evolving concepts in dilated cardiomyopathy , 2018, European journal of heart failure.

[46]  H. Aburatani,et al.  Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling , 2018, Scientific Reports.

[47]  M. Emdin,et al.  Late gadolinium enhancement as a predictor of functional recovery, need for defibrillator implantation and prognosis in non-ischemic dilated cardiomyopathy. , 2018, International journal of cardiology.

[48]  P. Schwartz,et al.  Desmoplakin missense and non-missense mutations in arrhythmogenic right ventricular cardiomyopathy: Genotype-phenotype correlation. , 2017, International journal of cardiology.

[49]  J. McMurray,et al.  Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis , 2017, Heart.

[50]  Amit R. Patel,et al.  Role of Cardiac Magnetic Resonance in the Diagnosis and Prognosis of Nonischemic Cardiomyopathy. , 2017, JACC. Cardiovascular imaging.

[51]  D. Judge,et al.  Arrhythmogenic cardiomyopathy: pathology, genetics, and concepts in pathogenesis , 2017, Cardiovascular research.

[52]  D. Pennell,et al.  Association Between Midwall Late Gadolinium Enhancement and Sudden Cardiac Death in Patients With Dilated Cardiomyopathy and Mild and Moderate Left Ventricular Systolic Dysfunction , 2017 .

[53]  Jeroen J. Bax,et al.  Relation of Myocardial Contrast-Enhanced T1 Mapping by Cardiac Magnetic Resonance to Left Ventricular Reverse Remodeling After Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy. , 2017, The American journal of cardiology.

[54]  Y. Pinto,et al.  Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy , 2017, European journal of heart failure.

[55]  James A. White,et al.  Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy: Systematic Review and Meta-Analysis. , 2017, JACC. Heart failure.

[56]  L. Calò,et al.  Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies. , 2016, Journal of the American College of Cardiology.

[57]  W. Stevenson,et al.  Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers. , 2016, Journal of the American College of Cardiology.

[58]  Eugenio Picano,et al.  The clinical use of stress echocardiography in non-ischaemic heart disease: recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. , 2016, European heart journal cardiovascular Imaging.

[59]  Hans Eiskjær,et al.  Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. , 2016, The New England journal of medicine.

[60]  L. Lund,et al.  The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Heart Transplantation Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. , 2016, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[61]  L. Khachatryan,et al.  Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy , 2016, Inflammation Research.

[62]  S. Cook,et al.  The Diagnosis and Evaluation of Dilated Cardiomyopathy. , 2016, Journal of the American College of Cardiology.

[63]  S. Heymans,et al.  Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. , 2016, European heart journal.

[64]  C. Selton-Suty,et al.  Right ventricular dysfunction in patients with idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. , 2016, Archives of cardiovascular diseases.

[65]  Andrea Mazzanti,et al.  2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. , 2016, Revista espanola de cardiologia.

[66]  E. Nagel,et al.  T1-Mapping and Outcome in Nonischemic Cardiomyopathy: All-Cause Mortality and Heart Failure. , 2016, JACC. Cardiovascular imaging.

[67]  T. Biering-Sørensen,et al.  Global Longitudinal Strain Is a Superior Predictor of All-Cause Mortality in Heart Failure With Reduced Ejection Fraction. , 2015, JACC. Cardiovascular imaging.

[68]  L. Mestroni,et al.  Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life‐Threatening Arrhythmias , 2015, Journal of the American Heart Association.

[69]  Reza Razavi,et al.  Myocardial tissue characterization by cardiac magnetic resonance imaging using T1 mapping predicts ventricular arrhythmia in ischemic and non-ischemic cardiomyopathy patients with implantable cardioverter-defibrillators. , 2015, Heart rhythm.

[70]  G. Korosoglou,et al.  T1 mapping in dilated cardiomyopathy with cardiac magnetic resonance: quantification of diffuse myocardial fibrosis and comparison with endomyocardial biopsy. , 2015, European heart journal cardiovascular Imaging.

[71]  A. di Lenarda,et al.  Persistent Recovery of Normal Left Ventricular Function and Dimension in Idiopathic Dilated Cardiomyopathy During Long‐Term Follow‐up: Does Real Healing Exist? , 2015, Journal of the American Heart Association.

[72]  Karen S. Frese,et al.  Atlas of the clinical genetics of human dilated cardiomyopathy. , 2014, European heart journal.

[73]  L. Monserrat,et al.  Desmoplakin truncations and arrhythmogenic left ventricular cardiomyopathy: characterizing a phenotype. , 2014, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[74]  A. Kadish,et al.  Sudden cardiac death risk stratification in patients with nonischemic dilated cardiomyopathy. , 2014, Journal of the American College of Cardiology.

[75]  T. Edvardsen,et al.  Risk prediction of ventricular arrhythmias and myocardial function in Lamin A/C mutation positive subjects. , 2014, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[76]  R. Hauer,et al.  Arrhythmogenic right ventricular dysplasia/cardiomyopathy according to revised 2010 task force criteria with inclusion of non-desmosomal phospholamban mutation carriers. , 2013, The American journal of cardiology.

[77]  D. Hedges,et al.  Dilated cardiomyopathy: the complexity of a diverse genetic architecture , 2013, Nature Reviews Cardiology.

[78]  W. Stevenson,et al.  CMR quantification of myocardial scar provides additive prognostic information in nonischemic cardiomyopathy. , 2013, JACC. Cardiovascular imaging.

[79]  Y. Pinto,et al.  Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases. , 2013, European heart journal.

[80]  Tevfik F Ismail,et al.  Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. , 2013, JAMA.

[81]  R. Hauer,et al.  Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy , 2012, European journal of heart failure.

[82]  Yves Coudière,et al.  Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy. , 2012, Journal of the American College of Cardiology.

[83]  L. Mestroni,et al.  Truncations of titin causing dilated cardiomyopathy. , 2012, The New England journal of medicine.

[84]  Mike Kirby,et al.  ESC Guidelines on the Management of Cardiovascular Diseases During Pregnancy , 2012 .

[85]  Marco Merlo,et al.  Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment. , 2011, Journal of the American College of Cardiology.

[86]  M. Vorgerd,et al.  De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. , 2010, Human molecular genetics.

[87]  E. Donal,et al.  Global longitudinal strain as a major predictor of cardiac events in patients with depressed left ventricular function: a multicenter study. , 2010, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[88]  B. Popescu,et al.  Left ventricular remodelling and torsional dynamics in dilated cardiomyopathy: reversed apical rotation as a marker of disease severity , 2009, European journal of heart failure.

[89]  A. Moss,et al.  Predictive value of ventricular arrhythmia inducibility for subsequent ventricular tachycardia or ventricular fibrillation in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients. , 2006, Journal of the American College of Cardiology.

[90]  T. Marwick,et al.  Reproducibility and accuracy of echocardiographic measurements of left ventricular parameters using real-time three-dimensional echocardiography. , 2004, Journal of the American College of Cardiology.

[91]  Hugh Calkins,et al.  Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. , 2004, The New England journal of medicine.

[92]  W. Grimm,et al.  Noninvasive Arrhythmia Risk Stratification in Idiopathic Dilated Cardiomyopathy: Results of the Marburg Cardiomyopathy Study , 2003, Circulation.