Dilated cardiomyopathy – Non-dilated left cardiomyopathy [135 genes]

Dilated cardiomyopathy is the leading cause of heart failure and heart transplantation. Sometimes it is associated with an increased risk of ventricular arrhythmias and sudden cardiac death.

Dilated cardiomyopathy is defined as systolic dysfunction of the left ventricle (or biventricular) together with dilation that is not explained by abnormal loading conditions (valvulopathies, arterial hypertension, congenital heart disease) or an underlying coronary artery (PMID: 26792875). In addition, there are other conditions related to dilated cardiomyopathy, such as hypokinetic cardiomyopathy (dysfunction without ventricular dilation), myocardial non-compaction (PMID: 34838455) or arrhythmogenic cardiomyopathy with left involvement, which have been included under the term “left cardiomyopathy without dilation” in the new European guidelines. This broad definition and spectrum of diseases make left cardiomyopathy (dilated, hypokinetic, with or without enhancement, and with or without ventricular hypertrabeculation) a group of diseases with similar clinical manifestations but with very diverse causes in which genetics plays a key role, not only in the etiological definition of each case but also in a more exact knowledge of the prognosis that ultimately allows for more individualized management of patients with this disease.

Classically, a prevalence of the disease was described as 1/2,500 individuals, although it is currently accepted that it is a much more common disease, affecting around 1 in 250 (PMID: 23900355).

Genetic study in dilated cardiomyopathy (and left non-dilated cardiomyopathy) allows:

1. A diagnostic confirmation, which is often an important support in the differential diagnosis.
2. The most precise study of a patient’s relatives, so that carriers have access to an early/preclinical diagnosis and non-carriers can be safely discharged from cardiology consultations. It has been shown in this disease that this is a cost-effective strategy.
3. An approach to the prognosis of each patient, depending on the type of genetic variant identified. Our scientific group has been a pioneer in this type of genotype-phenotype correlation analysis.

Once the diagnosis of dilated (or left non-dilated) cardiomyopathy has been established in a patient, the genetic study is indicated, as recommended by current clinical guidelines for the disease (Arbeloet al., 2023), those on the management of patients with heart failure and ventricular arrhythmias (PMID: 35083827, PMID: 36017572), as well as a recent international consensus on genetic study in heart disease (PMID: 35390533).

The performance of the genetic testing in dilated cardiomyopathy (and the spectrum of disease, which includes the new name “non-dilated left cardiomyopathy”) is highly variable. When it comes to familial dilated cardiomyopathy, the performance of identifying a genetic variant that explains it is around 40% (PMID: 32880476, PMID: 35581137). The performance of the study is greater in patients with the onset of the disease at an early age, a family history of the disease, or signs that point to a genetic etiology, such as conduction disorders, low voltages, presence of skeletal myopathy, absence of blockade of left branch.