Non-ischemic cardiomyopathies (NICM) represent a heterogeneous group of pathologies
characterized by absence of obstructive disease of the epicardial coronary vessels and
distinct structural and functional changes of the myocardium. The main identified forms
include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive
cardiomyopathy (RCM), and arrhythmogenic cardiomyopathy proper (ACM). More recently,
further forms of cardiomyopathy have been described, less common and not uniquely
classifiable, including: uncompressed myocardium (LVNC), peripartum cardiomyopathy
(PPCM), structural correlates of arrhythmogenic mitral valve prolapse (AMVP),
Anderson-Fabry disease (AFD), NICM associated with multi- system neuromuscular or
autoimmune diseases, lysosomal diseases, glycogenosis, mitochondrial cytopathies and
canal diseases with structural substrates. Finally, there are "overlap" forms,
characterized by the sharing in the same subject of characteristic aspects of two or more
of the above- mentioned diseases; and of the "undefined" forms, which to date do not
reach the diagnostic criteria for any of the above-mentioned diseases.
To the best of current knowledge, there are two points discovered in scientific research,
namely the description of the arrhythmogenic and "inflammatory" phenotypes in a broad
sense, which are summarized here with the acronym AINICM. In detail:
Arrhythmic manifestations account for the arrhythmogenic component of AINICM, which
is not limited to ACM proper. In fact, most of the above diseases have a
non-arrhythmic clinical presentation and a prevailing tendency to evolve towards a
picture of cardiovascular decompensation. Although sudden arrhythmic death has been
described throughout the spectrum of AINICM, early arrhythmic manifestations of such
diseases have an unknown prevalence, an uncertain association with different disease
genotypes and phenotypes, and still uncertain predictivity of long-term arrhythmic
risk. At the same time, optimal diagnostic and therapeutic pathways in arrhythmias
associated with AINICM are still being studied.
Myocardial inflammation (M-Infl) accounts for the inflammatory component of AINICM,
and has recently been described in association with many AINICM on a genetic basis,
including undefined and arrhythmic forms. The data is of high interest not only in
the diagnostic, but also in prognostic and therapeutic field. In fact, on the one
hand the presence of M-Infl seems to have a physio- pathological role in AINICM; on
the other, as already known in myocarditis, the optimal therapeutic paths of
arrhythmias may differ in patients with and without M-Infl; in particular, also in
the light of the preliminary data available in adult and paediatric AINICM, the
inflammatory forms are expected to respond better to immunosuppressive therapy, the
arrhythmogenic ones to an ablative therapy with frequent need of implantation of
cardiac devices.
Based on the clinical presentation, NICM patients will be divided into arrhythmic
(AINICM) and non-arrhythmic patients as study and control groups , respectively. The
AINICM group will include presentation with ventricular fibrillation (VF), either
sustained or non-sustained ventricular tachycardia (VT; NSVT), frequent premature
ventricular complexes (PVC), supraventricular arrhythmias (SVA) and bradyarrhythmias
(BA). Clinical presentations other than arrhythmic, including chest pain and heart
failure, will define the control group. In parallel, as shown in Figure 1, patients with
any evidence of M-Infl will be compared with those showing no signs of M-Infl.
