Mechanistic features associated with improvement in mitral regurgitation after cardiac resynchronization therapy and their relation to long-term patient outcome.

BACKGROUND: Mechanisms of mitral regurgitation (MR) reduction with cardiac resynchronization therapy (CRT) are complex, and their association with long-term outcome is unclear. We sought to elucidate mechanistic features of reduction in MR with CRT, which impact long-term patient survival. METHODS AND RESULTS: A prospective longitudinal study of 277 patients with heart failure with QRS width ≥ 120 ms and ejection fraction ≤ 35% for CRT was performed. Quantitative echocardiography, including dyssynchrony analysis, was performed at baseline. MR was quantified by color Doppler before and 6 months after CRT. Predefined end points of death, transplant, or left ventricular assist device were tracked during 4 years. There were 114 (48%) patients with CRT with significant MR (≥ moderate) at baseline; of whom 48 (42%) patients had MR improvement, and 24 (19%) patients had MR worsening after CRT. The 66 events (47 deaths, 10 transplantations, and 9 left ventricular assist devices) were strongly associated with significant MR after CRT (hazard ratio, 3.58; 95% confidence interval, 2.18-5.87; P<0.0001). Three echocardiographic features were independently associated with amelioration of significant MR after CRT by multivariable analysis: anteroseptal to posterior wall radial strain dyssynchrony >200 ms, lack of severe left ventricular dilatation (end-systolic dimension index <29 mm/m(2)), and lack of echocardiographic scar at papillary muscle insertion sites (all P<0.05) and, when combined, were additively associated with long-term survival (P=0.0001). CONCLUSIONS: Significant MR after CRT was strongly associated with less favorable long-term survival. Echocardiographic mechanistic features were identified that were associated with improvement in MR after CRT and favorable long-term survival.

Chaperonin containing T-complex polypeptide (CCT) subunit expression in oral mucosal wounds and fibroblasts.

Mucosal wound healing in adults has been reported to feature diminished scar formation compared to healing skin wounds. We sought to determine if the expression pattern of chaperonin containing T-complex polypeptide (CCT) subunits in mucosal wounds and fibroblasts is different from that observed in skin wounds and fibroblasts. We found that CCT-beta is the only subunit message to be reduced in wounded mucosa versus unwounded control, and this reduction was confirmed at the protein level. In contrast, mRNA levels of CCT-zeta, -delta, -eta, and -epsilon were significantly increased in mucosal wounds. The increase in CCT-eta was also confirmed at the protein level. Expression levels of CCT-alpha, -beta, -delta; -epsilon, and -theta mRNAs were significantly increased in adult mucosal fibroblasts in culture compared to skin-derived fibroblasts. Western blot analyses confirmed a modest increase in CCT-beta in adult mucosal fibroblasts relative to skin fibroblasts, but CCT-eta protein was unaffected. These differences may contribute to the reported difference in healing outcomes between these two tissue types.

Impact of scar burden by single-photon emission computed tomography myocardial perfusion imaging on patient outcomes following cardiac resynchronization therapy.

AIMS: Ischaemic heart disease negatively impacts response to cardiac resynchronization therapy (CRT), yet the impact of infarct scar burden on clinical outcomes and its interaction with mechanical dyssynchrony have not been well described. METHODS AND RESULTS: We studied 620 NYHA classes III-IV heart failure patients with ejection fraction (EF) ≤ 35% and QRS duration ≥120 ms referred for CRT. Included were 190 ischaemic cardiomyopathy (ICM) CRT recipients with scar burden quantified by rest-redistribution Tl(201) myocardial perfusion imaging using a 17-segment (0 = normal to 4 = absence of uptake) summed rest score (SRS). Non-ICM (NICM) CRT recipients (n = 380) and 50 patients referred for CRT with unsuccessful LV lead implant comprised the comparison groups. Echocardiographic dyssynchrony analysis was performed in a subgroup of 150 patients. Follow-up left ventricular EF (LVEF) and volumes were examined at 7 ± 3 months in 143 patients. The outcome of death, cardiac transplant, or mechanical circulatory support was assessed in all. Over 2.1 ± 1.6 years, ICM patients had significantly worse survival and less LVEF improvement than NICM patients (P < 0.01). Ischaemic cardiomyopathy patients with low scar burden (SRS < 27) had favourable survival and LVEF improvement, similar to NICM patients. A high scar burden (SRS ≥ 27) was associated with reduced survival and lack of LV functional improvement (P ≤ 0.01), similar to those with unsuccessful LV lead implant, whereas baseline dyssynchrony was not predictive of outcome in these patients. CONCLUSION: Extensive scar burden in ICM patients unfavourably affected clinical and LV functional outcomes after CRT, regardless of baseline dyssynchrony measures. Patients with ICM and lower scar burden had significantly better outcomes, similar to NICM patients.