Background Mixed valvular disease (MVD), mitral regurgitation (MR) from pre‐existing disease in conjunction with paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR), is one of the most important stimuli for left ventricle (LV) dysfunction, associated with cardiac mortality. Despite the prevalence of MVD, the quantitative understanding of the interplay between pre‐existing MVD, PVL, LV, and post‐TAVR recovery is meager. Methods and Results We quantified the effects of MVD on valvular‐ventricular hemodynamics using an image‐based patient‐specific computational framework in 72 MVD patients. Doppler pressure was reduced by TAVR (mean, 77%; N=72; P <0.05), but it was not always accompanied by improvements in LV workload. TAVR had no effect on LV workload in 22 patients, and LV workload post‐TAVR significantly rose in 32 other patients. TAVR reduced LV workload in only 18 patients (25%). PVL significantly alters LV flow and increases shear stress on transcatheter aortic valve leaflets. It interacts with mitral inflow and elevates shear stresses on mitral valve and is one of the main contributors in worsening of MR post‐TAVR. MR worsened in 32 patients post‐TAVR and did not improve in 18 other patients. Conclusions PVL limits the benefit of TAVR by increasing LV load and worsening of MR and heart failure. Post‐TAVR, most MVD patients (75% of N=72; P <0.05) showed no improvements or even worsening of LV workload, whereas the majority of patients with PVL, but without that pre‐existing MR condition (60% of N=48; P <0.05), showed improvements in LV workload. MR and its exacerbation by PVL may hinder the success of TAVR.
Aortic stenosis (AS) management is classically guided by symptoms and valvular metrics. However, the natural history of AS is dictated by coupling of the left ventricle, aortic valve, and vascular system. We investigated whether metrics of ventricular and vascular state add to the appreciation of AS state above valve gradient alone. Seventy patients with severe symptomatic AS were prospectively followed from baseline to 30 days after transcatheter aortic valve replacement (TAVR). Quality of life (QOL) was assessed using the Kansas City Cardiomyopathy Questionnaire. Left ventricular stroke work (SWLV) and vascular impedance spectrums were calculated noninvasively using in-house models based on central blood pressure waveforms, along with hemodynamic parameters from echocardiograms. Patients with higher preprocedural SWLV and lower vascular impedance were more likely to experience improved QOL after TAVR. Patients fell into two categories: those who did and those who did not exhibit increase in blood pressure after TAVR. In patients who developed hypertension (19%), vascular impedance increased and SWLV remained unchanged (impedance at zeroth harmonic: Z0, from 3964.4 to 4851.8 dyne·s/cm3, P = 0.039; characteristic impedance: Zc, from 376.2 to 603.2 dyne·s/cm3, P = 0.033). SWLV dropped only in patients who did not develop new hypertension after TAVR (from 1.58 to 1.26 J; P < 0.001). Reduction in valvular pressure gradient after TAVR did not predict change in SWLV (r = 0.213; P = 0.129). Reduction of SWLV after TAVR may be an important metric in management of AS, rather than relying solely on the elimination of transvalvular pressure gradients.
Objective Inflammation contributes to the development of peripheral artery disease (PAD) and may contribute to intermittent claudication by adversely affecting vascular and skeletal muscle function. We explored the association of inflammation to maximal walking time (MWT) in patients with claudication. Methods Circulating inflammatory biomarkers, including tumor necrosis factor α (TNFα), C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM) were measured in 75 subjects with intermittent claudication, as well as 43 healthy subjects. Real-time PCR was used to quantify mRNA expression of TNFα, IL-6, IFN gamma, and CD-36 from peripheral blood monocytes. Treadmill testing was performed in PAD subjects to assess MWT. Results Compared with healthy subjects, PAD subjects had higher levels of circulating TNFα (p<0.0001), CRP (p=0.003), sICAM (p<0.0001), and IL-6 (p<0.0001). Expression of both IL-6 (p=0.024) and CD36 (p=0.018) was greater in PAD than healthy subjects. Among subjects with PAD, higher gene expression of TNFα was associated inversely with MWT (p=0.01). MWT was also associated inversely with greater levels of circulating TNFα (p=0.028), CRP (p=0.024), IL-6 (p=0.03), and sICAM (p=0.018). Conclusions Systemic inflammation, as indicated by TNFα inflammatory gene expression in peripheral blood monocytes and by circulating biomarker levels, is associated with impairment in walking time in patients with PAD and intermittent claudication.
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