Biopsy-based analysis of dilated and non-dilated cardiomyopathy in the Myokard-HI-Trial

Objective: The recent European Society of Cardiology guidelines recommend classifying heart failure patients into 5 different phenotypes. Given the insufficient understanding of the most prevalent phenotypes, such as left ventricular (LV) dilated cardiomyopathy (DCM) and non-dilated cardiomyopathy (NDCM), our objective was to conduct a comparative analysis of these phenotypes using comprehensive histological, hemodynamic, and imaging data.

Methods: From our ongoing Myokard-HI-Trial (n=355), we analyzed 104 patients with DCM and 62 with NDCM, who received cardiac magnetic resonance imaging (MRI) for LV assessment of ejection fraction (LVEF), end-diastolic volume index (LVEDVi), mass index (LVMi), presence of LV late gadolinium enhancement (LGE), and LV T2-weighted sequences as a marker of acute inflammation at the time of LV endomyocardial biopsy (EMB) accompanied by invasive measurement of LV end-diastolic pressure (LVEDP). NDCM and DCM categorization was initially based on the sex-specific LVEDVi from cardiac MRI (females: > 93 ml/m², males: >107 ml/m²).

Results: NDCM and DCM patients did not differ significantly in age and sex, suggesting comparable demographic characteristics (Table 1). However, NDCM patients had a more preserved LVEF, less LV mass increase, and a lower proportion of LV scarring (LGE) on MRI compared to DCM patients (Table 1). Median T2 measures were similar in both groups (47 vs. 48 ms). In contrast, histological findings from LV EMB suggested a larger role of myocardial inflammation in NDCM than in DCM patients, while the prevalence of myocardial fibrosis was similar between both groups (Table 1). In the entire cohort (DCM+NDCM), LGE corresponds to histological fibrosis in 65%, and T2>50ms corresponds to histological inflammation in only 36%. In detail, in the subgroup of NDCM in only 51% and 21% respectively, but in the DCM group with a higher concordance of 73% and 60% compared to histology. 

Discussion and Conclusion: Our study reveals the intricate myocardial remodeling present in both phenotypes, emphasizing the potential of a transition from NDCM to DCM. Additionally, our findings emphasize the importance of integrating multiple diagnostic approaches beyond imaging alone to achieve a comprehensive understanding of myocardial pathology. Further research is essential to uncover the underlying mechanisms driving phenotypic variations and to improve patient care within the context of precision medicine.