SIC and SICP: A Position Paper on Rare Cardiomyopathies

Hypertrophy of the cardiac septum, associated with hypertension. Cardiac ultrasound.
The Italian Society of Cardiology and Italian Society of Paediatric Cardiology have published a position paper on diagnosis and management of rare cardiomyopathies.

The Italian Society of Cardiology (SIC) and Italian Society of Paediatric Cardiology (SICP) have published a position paper in the International Journal of Cardiology on the diagnosis and management of rare cardiomyopathies (CMPs).

CMPs present as disorders of the heart muscle in the absence of other culprit diseases. The majority of CMPs are seen in routine clinical practice, occur among less than 1 in 2000 people, and resemble 4 classical morphological subgroups. Each of these subgroups are highly heterogeneous and range in severity from asymptomatic to life-threatening.

Due to the inherent difficulty in diagnosing and treating such heterogeneous conditions, coupled with their rarity, clinicians may be uncertain about how to proceed when encountering these patients. The SIC and SICP members constructed a list of red, yellow, and green flags to aid in decision making and call attention to situations which may require for more vigilance.

Hypertrophic CMPs (HCMs) are characterized by elevated left ventricular wall thickness and approximately 60% of patients harbor a mutation in sarcomeric protein genes. HCMs can onset during infancy to adulthood.

In general, patients suspected to have HCM should undergo a diagnostic workup which includes construction of a pedigree, biochemical evaluation, ECG, and echocardiography in order to evaluate the genetic components and to exclude potential confounding conditions, such as Fabry disease.

Red Flags for the diagnosis and management of HCMs:

  • Infants with severe biventricular involvement must not reach fluid depletion.
  • For patients with mitochondrial disease, drugs or situational stressors which are contraindicated for mitochondrial disease should be avoided.
  • For patients with transthyretin cardiac amyloidosis and heart failure, beta blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are not recommended.
  • Non-dihydropyridine calcium channel blockers are not recommended for patients with transthyretin cardiac amyloidosis.
  • Unless patients present with neurologic involvement, transthyretin silencers should be avoided.
  • Patients with transthyretin cardiac amyloidosis should not undergo liver transplantation.

Dilated CMPs (DCMs) are characterized by left or biventricular systolic dysfunction with chamber dilation. DCM is the most common CMP in adults (1 in 2500) and children (1 in 170,000) and occurs in a 1:3 ratio among men and boys compared with women and girls. Among children, some DCMs appear less severe at baseline but are associated with reduced 5-year survival and freedom from heart transplantation, indicating a more severe prognosis for pediatric populations.

Patients with DCM should be evaluated by a multidisciplinary cardiomyopathy team using a holistic approach, including genetic screening, and testing for inflammatory involvement.

The Red Flag for the diagnosis and management of DCMs:

  • Patients who test positive for viral agents may incur harm from empirical immunosuppressive therapy.

Restrictive CMPs (RCMs) are characterized by impaired ventricular filling in the presence of normal ejection fraction and ventricular wall thickness due to either inherited or induced causes. RCM is rare in children, accounting for up to 5% of CMPs occurring between 6 and 11 years of age among girls. There is overlap between RCM and HCM in which the same molecular defect has been found to cause either RCM or HCM.

Red Flags for the diagnosis and management of RCMs:

  • Beta-blockers are not recommended for genetic RCMs.
  • Digoxin, inotropes, pulmonary vasodilators, and endothelin receptor antagonists are not recommended for RCMs.

Arrhythmogenic CMPs (ACMs) are arrythmias of the right ventricle caused by the progressive replacement of atrophied tissue by fibro-fatty tissue. The prevalence ranges from 1 in 1000 to 5000 and typically presents among men at 20 to 49 years of age.

Historically, diagnosis of ACM relied on the fibro-fatty histology, however, current diagnosis requires anamnestic, clinical, morphological, and electrophysiological parameters.

The Red Flag for the diagnosis and management of ACMs:

  • Administering beta-blockers prophylactically is not recommended for children who are phenotype-negative or for adults carrying a pathogenic or likely pathogenic variant.

Cardiac sarcoidosis (CS) is a rare granulomatous disease with a largely unknown pathogenesis. It is more common among Afro-Caribbean populations (36 per 100,000) than White populations (11 per 100,000) and typically onsets between 25 and 45 years of age. CS can mimic other diseases, such as ACM, HCM, and non-ischemic DCM. Due to its rarity, few studies have been conducted on CS.

The Red Flag for the diagnosis and management of CS:

  • Implantable cardioverter-defibrillators are not recommended among most patients with CS.

The statement authors concluded, “Rare cardiomyopathies and specific etiologies may present in complex clinical syndromes, such as heart failure with reduced or preserved ejection fraction, left ventricular hypertrophy, aortic stenosis or arrhythmic events, ventricular arrhythmias and atrioventricular blocks, both in adult and pediatric patients. A high index of clinical suspicion is required for diagnosis. General cardiologists and pediatric cardiologists should be aware of cardiac and extracardiac red flags, which may provide clues to reach a definitive diagnosis. Nevertheless, a step-by-step clinical evaluation is required to reach etiological diagnosis, not limiting to phenotypic definition, in order to direct disease-specific treatment strategies.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Limongelli G, Adorisio R, Baggio C, et al. Diagnosis and Management of Rare Cardiomyopathies in Adult and Paediatric Patients. A Position Paper of the Italian Society of Cardiology (SIC) and Italian Society of Paediatric Cardiology (SICP). Int J Cardiol. Published online March 29, 2022. doi:10.1016/j.ijcard.2022.03.050