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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


In this position statement the authors propose a framework for the clinical approach to diagnosis in cardiomyopathies based on the recognition of diagnostic ‘red flags’ that can be used to guide rational selection of specialized tests including genetic analysis.
Myocardial Disease

Rationale for a cardiomyopathy-focused clinical approach

In this document, the authors propose a complementary diagnostic strategy built on an understanding of the complex aetiology and clinical presentation of heart muscle disorders.
The details of this scheme differ to a greater or lesser extent between cardiomyopathies, but there are some common principles:

  • Elucidation of a specific cause for a cardiomyopathy can directly influence management of patients and their relatives.

  • Some cardiomyopathies are caused by single gene mutations, whereas others show familial aggregation as a result of a complex genetic background and an interaction with environmental triggers.

  • Diagnostic criteria in familial disorders can differ between probands and their relatives.

  • In the context of a familial disease, the information provided by the relatives can offer diagnostic clues because of the variable expression of the disease.

  • Reanalysis of clinical data is required throughout the diagnostic process as further information emerges.

  • The approach to patients with definite or suspected cardiomyopathy should be multidisciplinary in nature.

Clinical and family history

The first step in achieving a diagnosis is to consider the personal and family history of the affected individual. Age at diagnosis or first presentation is an important pointer to aetiology in all subtypes of cardiomyopathy.
A detailed family history must be taken in order to identify other family members known or suspected to be affected by a myocardial disease or that have features suggestive of a genetic disorder. A ‘negative’ family history, however, does not exclude a genetic aetiology because the disease may be the result of a de novo family. A major objective of pedigree analysis is the determination of the mode of genetic transmission.

Symptoms and physical examination

Cardiomyopathies are a common feature of multi-system diseases. The mechanisms of multi-organ involvement are heterogeneous and include genetic mechanisms, organ infiltration/storage, mitochondrial dysfunction and developmental abnormalities (see Table 2).

Standard electrocardiogram
In this document, a new approach to the interpretation of the electrocardiogram is proposed that integrates classical interpretation with a cardiomyopathy-specific approach that takes into account not only the ECG findings themselves but also the clinical context in which they occur.
The interpretation of the ECG in a patient with definite or suspected cardiomyopathy is guided by some general principles:

  • An abnormal electrocardiogram may be the only phenotypic manifestation of a heart muscle disorder.
  • The electrocardiogram should always be interpreted in the context of the findings on echocardiography and cardiac MRI.
  • A number of electrocardiographic features can, in association with other specific clinical features, suggest the underlying diagnosis.

Routine laboratory findings

Laboratory tests can be helpful in the detection of extra-cardiac conditions. Following table describes tests that should be performed in all patients with a cardiomyopathy and those tests that should only be considered in specific circumstances.

Genetic testing

Inevitably, in the near future there will be growing pressure to perform less targeted screening in patients with cardiomyopathy, but this approach is bound to result in the identification of numerous sequence variants, often novel, with low penetrance and unknown interactions with genetic and environmental modifiers.  This development places even more emphasis on clinical phenotyping and the
definition of sub-phenotypes.


As with the electrocardiogram, echo features are only useful when interpreted in the context of other phenotypic findings.

Cardiac magnetic resonance imaging

The incremental contribution of cardiac magnetic resonance (CMR) imaging to the diagnosis of cardiomyopathies derives from accurate assessment of the morphology and function of the heart without the need for an ‘anatomical window’ and tissue characterization.  The combination of these two features enables CMR to resolve important questions of differential diagnosis and recognize some specific forms of myocardial disease.

Role of endomyocardial biopsy

In the context of cardiomyopathy, endomyocardial biopsy remains a gold standard for the diagnosis of specific disorders including amyloidosis, sarcoidosis, and myocarditis.

Nuclear imaging

In most cardiomyopathies, the contribution of nuclear imaging to diagnosis is limited. Possible exceptions are sarcoidosis and TTR-related amyloidosis.


A key message is that the clinical assessment should not be restricted to cardiological examinations as the cardiomyopathies represent a challenging interface between cardiology and many other medical specialities. Another important aspect is the recognition of ‘red flags’ that guide rational selection of further diagnostic tests including genetic analysis and thereby identify specific subtypes of cardiomyopathy.


The manuscript succeeds in presenting a framework for the practicing clinician regarding the diagnostic evaluation of patients with cardiomyopathy. This approach is useful to all clinicians who care for patients with cardiomyopathy or heart failure. The part on genetic / familial cardiomyopathies is presented in great detail and gives a good overview. Inflammatory causes of cardiomyopathy are not addressed in the present paper, since the Working Group is working on an ESC position paper entirely dedicated to diagnosis and treatment of myocarditis.
It is important that this approach does not necessarily involve the use of novel or particular sophisticated tests, but it does require deliberate analysis of every aspect of the individual and the family as well as an intergrated probabilistic interpretation of cardiac investigation.
The breakthrough points
a) In the contex of familial  disorders the information provided by the relatives can offer diagnostic clues . Families hold an essential dominant and dual role in the evaluation of pts with familial cardiomyopathy being at the same time the subject and the object of the study.
b) Multidisciplinary approach and reanalysis throughout the follow up is required.
c) When the specific cause of cardiomyopathy is identified this influences management.
d) Genetic analysis is significant part of the diagnostic process and essential element for the genetic family screening,


The basic premise, as this Special Article underlines, is that the adoption of a cardiomyopathy specific mindset that combines conventional cardiological assessment with non-cardiac and molecular parameters increases diagnostic accuracy and improves advice and treatment for patients and families.



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Notes to editor

Presented by Aristides Anastasakis
Unit of Inherited Cardiovascular Diseases, 1st Department of Cardiology, Athens University Medical School, Athens, Greece.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.