Dilated Cardiomyopathy (DCM) has a straightforward and apparently “simple” definition:
a heart muscle disease characterized by left ventricular (LV) or biventricular dilation
and systolic dysfunction in the absence of either pressure or volume overload or coronary
artery disease sufficient enough to explain the dysfunction [1]. DCM currently carries
a relatively benign outcome, significantly improved with respect to the past decades.
Contemporary analysis shows the survival/free from heart transplant rate beyond 85%
at 10-year follow-up [2]. Nevertheless, the knowledge regarding pathophysiology, aetiology,
diagnostic workup and prognostic stratification of DCM is rapidly and progressively
evolving, reflecting the clinical management of the disease that remains extremely
challenging in daily practice [3]. Indeed, DCM patients are often relatively young
at the time of diagnosis (between their 30s and 50s) with a low-co-morbidity profile,
and their current diagnostic workup and risk stratification is characterized by several
pitfalls (particularly regarding the arrhythmic risk). Consequently, a not-negligible
proportion of DCM patients still experience an unfavourable prognosis, particularly
in the short-term [2].
One of the reasons behind this complicated scenario is the heterogeneous aetiology
of the disease. DCM is an “umbrella” term describing the final common pathway of different
pathogenic processes and gene–environment interactions. More commonly than once believed,
DCM recognizes a complex genetic background, far from being a monogenic disease, with
multiple unknown epigenetic interactions. On the other side, it might be the result
of possible extrinsic triggers (i.e., tachyarrhythmias, hypertension, alcohol, chemotherapy,
inflammation), which, once removed, promote a reverse remodelling. Therefore, the
term “idiopathic” DCM is progressively vanishing, and investigations on the complex
interaction between environmental factors and genetic background are increasing. Future
research in this perspective is likely to result in better prognostic stratification
and ultimately targeted therapy [4].
Noteworthily, thorough phenotyping (through modern imaging techniques such as speckle
tracking echocardiography or tissue characterization by cardiac magnetic resonance)
and genotyping of DCM patients represent the basis for their optimal clinical management.
Furthermore, compelling evidence shows that DCM is not exclusively a cardiological
disease, requiring a multidisciplinary team (including geneticist, neurologist, radiologist
and other specialists) for accurate management. Therefore, a novel approach to DCM
patients, including comprehensive evaluation, should be promoted to tailor therapeutic
strategies in the era of precision medicine.
Starting from these concepts, the idea of this Special Issue is to explore the DCM
universe providing updated knowledge on pathophysiology, future directions of the
research on DCM and practical guidelines useful for clinical management of DCM patients.
A series of focused reviews, meta-analyses and original articles are reported in this
Special Issue with the precise aim of providing a deep insight into crucial gaps of
knowledge in DCM. In particular, it extensively discusses the pathophysiology, mechanisms
underlying the disease and the interaction between genetic background, molecular pathways
and environmental triggers, as the basis for future targeted therapies [5,6,7]. The
knowledge of precise genetic pathogenesis and molecular mechanisms causing DCM has
stimulated the research towards new treatments targeting gene expression [8,9]. Shifting
from symptomatic treatments to targeted therapy on specific disease mechanisms represents
the new mindset from slowing disease progression to disease reversal. Furthermore,
some articles present in this Special Issue explore the genetic background of DCM,
such as mutations in DES, LMN and TTN, remarking once again the current cultural revolution
in this field of medicine. In the future, we might indeed abandon the current general
definition of DCM, switching towards specific diseases such as Desminopathy, Laminopathy
or Titinopathy and so on, each of them with specific diagnostic workup, prognostic
stratification and therapeutic strategies [10,11,12]. Importantly, the need of a multidisciplinary
network involving different specialists clearly emerges in specific and challenging
diseases, such as Duchenne-related DCM in order to improve the global clinical management
of those challenging patients [13]. Finally, the prognostic stratification of DCM
has been further explored, focusing on (1) the identification of specific subgroups
of DCM without a structural myocardial disease, such as the tachycardia-induced cardiomyopathy
[14]; (2) the application of gender medicine to DCM clinical management [15]; (3)
the usefulness of tissue characterization by cardiac magnetic resonance in the multi-parametric
approach od DCM patients [16] and (4) the role of the left atrium, other than just
the left ventricle, as a therapeutic target of pharmacological and non-pharmacological
treatments in DCM [17]. Finally, a section is dedicated to the characterization of
left ventricular non-compaction that is frequently encountered in clinical practice
in overlap with the DCM phenotype [16,18]. The definition of left ventricular non-compaction
as a specific cardiomyopathy or, more likely, as a specific trait of genetic cardiomyopathy
is debated, and it still represents a gap in knowledge in clinical management, particularly
for the first phases of the disease.
Far from providing the absolute truth, this Special Issue is intended to help physicians
(not only cardiologists) in their everyday clinical practice to deal with patients
affected by DCM in a multifaceted, multidisciplinary and individualized approach.