Cardiac Performance, Ventricular-Vascular Interaction and Functional Alterations in Rheumatic Mitral Stenosis A descriptive study employing novel hemodynamic and echocardiographic modalities

Sammanfattning: Background: The assessment of LV systolic and diastolic properties poses significant challenges in the setting of rheumatic mitral stenosis (MS) owing to the inherently load-altered state. While pulmonary hypertension (PH) is a common finding and inter-ventricular interactions are well documented, a detailed characterization of arterial-ventricular coupling in subjects with isolated post-capillary (Ipc-PH) and combined pre- and post-capillary PH (Cpc-PH) has not been described. In recent times, diastolic pulmonary pressure gradient (DPG), a proposed measure to distinguish these two PH sub-groups, has come under scrutiny owing to the common occurrence of negative DPG values (DPGNEG). Further, the prognostic implications of DPGNEG are relatively obscure. Mitral Annular (MA) geometry in MS, and potential alterations associated with percutaneous transvenous mitral commissurotomy (PTMC) remain unclear. The studies in this thesis aim to provide insights into these understudied aspects of MS using novel hemodynamic and echocardiographic modalities.Methods and Results: In Study I, we assessed load-independent indices of LV performance using the single-beat method in 106 MS subjects employing simultaneous bi-ventricular catheterization and echocardiography. MS subjects showcased significantly elevated arterial load, LV contractility and stiffness as compared with controls. Afterload was inversely associated with the severity of stenosis. Both LV elastance (Ees) and arterial elastance (Ea) returned to more normal levels immediately after PTMC, while LV stiffness demonstrated a further rise. In Study II, we analysed systemic arterial-ventricular (AV) coupling in PH subjects among 106 MS patients. Compared with Ipc-PH subjects, the Cpc-PH group demonstrated elevated Ea and AV uncoupling, as expressed in an elevated Ea/Ees ratio. Further, Ea was associated with reduced LV deformation in both septal and lateral LV segments, whereas the impact of the RV on the LV was limited to the septum. In Study III, 316 subjects with left heart disease (LHD) due to primary myocardial dysfunction or valvular disorders were studied to clarify the physiological and prognostic implications of DPGNEG. DPGNEG was observed in 48% of 256 subjects with PH due to LHD. V-wave amplitude in the pulmonary artery wedge pressure (PAWP) curve was inversely associated with DPG at lower pulmonary vascular resistance (PVR), but not at higher levels. Subjects with DPGNEG showcased better prognosis as compared with positive, non-elevated (< 7mmHg) DPG. In Study IV, mitral annular geometry was studied in 57 MS subjects undergoing PTMC employing 3D echocardiography. MS subjects demonstrated a more circular and flatter annulus, with significantly larger orthogonal diameters, annular circumference and area. Annular non-planar angle and displacement demonstrated a tendency to normalize after PTMC. Subjects that developed higher grades of mitral regurgitation (MR) after intervention demonstrated larger baseline annular antero-posterior diameter and area.Conclusion: In summary, systemic AV coupling offers novel insights in the setting of MS, pre- and post-intervention, and between its PH subgroups. DPGNEG can be attributed to tall V-waves in the PAWP waveform. MA geometry is deformed in MS, demonstrates a tendency to normalize after PTMC, and may be associated with significant post-interventional MR.