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.