The phenotype of mixed CMP
We found mixed CMP more common in the elderly and male patients when
compared to both ICM and NICM. Also, the clinical phenotype in mixed CMP
seem to represent a subset of patients with higher incidences of
comorbidities especially hypertension, chronic kidney diseases, atrial
fibrillation and malignancies when compared to NICM. It is perceivable
that these risk factors would also explain a relatively higher burden of
CAD found in the group with mixed CMP compared to
NICM.13,14 This finding is also consistent with the
studies on idiopathic DCM with coexisting CAD.6-8While the proportion of device therapies and device shocks in mixed CMP
falls in an intermediate category between ICM and NICM, the recorded
minimum VT cycle length is comparable to patients with ICM. In a very
recent study, albeit in a small cohort of 24 patients with mixed CMP
undergoing catheter ablation for ventricular arrhythmias, it was shown
that this subset had a higher incidence of ventricular arrhythmias and
all-cause mortality than both ICM and NICM.9 Our study
reveals all-cause mortality rates of nearly 20% in both the ICM and
mixed CMP cohorts. As the mean age and incidences of coexisting
illnesses especially chronic kidney diseases and malignancies are higher
in the cohort of mixed CMP, it is not surprising that most of the deaths
in this cohort are non-cardiac, unlike the predominantly cardiac deaths
in ICM and NICM. The mixed CMP group revealed higher hazards of
all-cause mortality when compared to NICM (HR: 1.57; 95% CI: 0.91 to
2.68; p=0.1). In a larger study of 2254 heart failure patients with
nonobstructive CAD, when compared to 2656 heart failure patients with no
CAD, there was an increased hazard of cardiovascular death (HR: 1.82;
95% CI: 1.27 to 2.62; p<0.001) and all-cause mortality (HR:
1.18; 95% CI: 1.05 to 1.33; p<0.005).8
Possible pathogenesis in mixed CMP
(Central Illustration- Central Illustration)
While epicardial CAD is only one determinant of myocardial ischemia,
there are multiple contributing factors: 1) Supply-demand mismatch due
to the low coronary perfusion pressures in the setting of severe
myocardial dysfunction, 2) Coronary microvascular dysfunction secondary
to atherosclerosis, 3) Impaired myocardial metabolic control due to the
underlying CMP.15 Coronary perfusion indices like flow
reserves and microvascular resistance have been shown to be associated
with poor prognosis in heart failure independent of ischemic or
nonischemic classification.5,16,17 Electro anatomical
mapping studies have highlighted the mixed pathophysiological substrate
in this subset of mixed CMP.9,18,19 Such mixed
pathological substrates have also been documented in small-scale studies
with LGE-CMRi as well as with perfusion-CMRi.7,20While these can be plausible explanations for the bad prognosis in mixed
CMP, there could be several other contributing factors as well like age
and coexisting illnesses.