Cardiac structure discontinuities revealed by ex-vivo microstructural characterization. A focus on the basal inferoseptal left ventricle region.

BACKGROUND: While the microstructure of the left ventricle (LV) has been largely described, only a few studies investigated the right ventricular insertion point (RVIP). It was accepted that the aggregate cardiomyocytes organization was much more complex due to the intersection of the ventricular cavities but a precise structural characterization in the human heart was lacking even if clinical phenotypes related to right ventricular wall stress or arrhythmia were observed in this region. METHODS: MRI-derived anatomical imaging (150 µm3) and diffusion tensor imaging (600 µm3) were performed in large mammalian whole hearts (human: N = 5, sheep: N = 5). Fractional anisotropy, aggregate cardiomyocytes orientations and tractography were compared within both species. Aggregate cardiomyocytes orientation on one ex-vivo sheep whole heart was then computed using structure tensor imaging (STI) from 21 µm isotropic acquisition acquired with micro computed tomography (MicroCT) imaging. Macroscopic and histological examination were performed. Lastly, experimental cardiomyocytes orientation distribution was then compared to the usual rule-based model using electrophysiological (EP) modeling. Electrical activity was modeled with the monodomain formulation. RESULTS: The RVIP at the level of the inferior ventricular septum presented a unique arrangement of aggregate cardiomyocytes. An abrupt, mid-myocardial change in cardiomyocytes orientation was observed, delimiting a triangle-shaped region, present in both sheep and human hearts. FA's histogram distribution (mean ± std: 0.29 ± 0.06) of the identified region as well as the main dimension (22.2 mm ± 5.6 mm) was found homogeneous across samples and species. Averaged volume is 0.34 cm3 ± 0.15 cm3. Both local activation time (LAT) and morphology of pseudo-ECGs were strongly impacted with delayed LAT and change in peak-to-peak amplitude in the simulated wedge model. CONCLUSION: The study was the first to describe the 3D cardiomyocytes architecture of the basal inferoseptal left ventricle region in human hearts and identify the presence of a well-organized aggregate cardiomyocytes arrangement and cardiac structural discontinuities. The results might offer a better appreciation of clinical phenotypes like RVIP-late gadolinium enhancement or uncommon idiopathic ventricular arrhythmias (VA) originating from this region.

Native T1 time of right ventricular insertion points by cardiac magnetic resonance: relation with invasive haemodynamics and outcome in heart failure with preserved ejection fraction.

AIMS: Increased afterload to the right ventricle (RV) has been shown to induce myocardial fibrosis at the RV insertion points (RVIPs). Such changes can be discrete but potentially detected by cardiac magnetic resonance (CMR) T1-mapping. Whether RVIP fibrosis is associated with prognosis in heart failure with preserved ejection fraction (HFpEF) is unknown. METHODS AND RESULTS: We prospectively investigated 167 consecutive HFpEF patients, a population frequently suffering from post-capillary pulmonary hypertension, who underwent CMR including T1-mapping. About 92.8% also underwent right heart catheterization for haemodynamic assessment.Native T1 times were 995 ± 73 ms at the anterior and 1040 ± 90 ms at the inferior RVIP. By Spearman's rank order testing, RVIP T1 times were significantly correlated with pulmonary artery pressure (mean PAP, r = 0.313 and 0.311 for anterior and inferior RVIP), pulmonary artery wedge pressure (r = 0.301 and 0.251) and right atrial pressure (r = 0.245 and 0.185; P for all <0.05). During a mean follow-up of 43.2 ± 22.6 months, 30 (18.0%) subjects died. By multivariable Cox regression, NTproBNP [Hazard ratio (HR) 2.105, 95% confidence interval (CI) 1.332-3.328; P = 0.001], systolic PAP (HR 1.618, 95% CI 1.175-2.230; P = 0.003), and native T1 time of the anterior RVIP (HR 1.659, 95% CI 1.125-2.445; P = 0.011) were significantly associated with outcome. Also, by Kaplan-Meier analysis, T1 times at the anterior RVIPs had a significant effect on survival (log-rank, P = 0.002). CONCLUSION: Interstitial expansion of the anterior RVIP as detected by CMR T1-mapping reflects haemodynamic alterations, and is independently related with prognosis in HFpEF.