Background-Numerous criteria believed to define a positive response to cardiac resynchronization therapy have been used in the literature. No study has investigated agreement among these response criteria. We hypothesized that the agreement among the various response criteria would be poor. Methods and Results-A literature search was conducted with the keywords "cardiac resynchronization" and "response." The 50 publications with the most citations were reviewed. After the exclusion of editorials and reviews, 17 different primary response criteria were identified from 26 relevant articles. The agreement among 15 of these 17 response criteria was assessed in 426 patients from the Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT) study with Cohen's -coefficient (2 response criteria were not calculable from PROSPECT data). The overall response rate ranged from 32% to 91% for the 15 response criteria. Ninety-nine percent of patients showed a positive response according to at least 1 of the 15 criteria, whereas 94% were classified as a nonresponder by at least 1 criterion.
Under the right conditions, some biological systems can maintain high viability after being frozen and thawed, but many others (e.g., organs and many mammalian cells) cannot. To increase the rates of post-thaw viability and widen the library of living cells and tissues that can be stored frozen, an improved understanding of the mode of action of polymeric cryoprotectants is required. Here, we present a polymeric cryoprotectant, poly(methyl glycidyl sulfoxide) (PMGS), that achieved higher post-thaw viability for fibroblast cells than its small-molecule analogue dimethyl sulfoxide. By limiting the amount of water that freezes and facilitating cellular dehydration after ice nucleation, PMGS mitigates the mechanical and osmotic stresses that the freezing of water imparts on cells and facilitates higher-temperature vitrification of the remaining unfrozen volume. The development of PMGS advances a fundamental physical understanding of polymer-mediated cryopreservation, which enables new material design for long-term preservation of complex cellular networks and tissue.
The acute adverse effects of left ventricular (LV) dyssynchrony on cardiac performance were first described in 1925 by Carl Wiggers 1 . In recent years, the accurate diagnosis of LV dyssynchrony has become the focus of a myriad of publications, driven by the advent of cardiac resynchronization therapy (CRT) to treat heart failure due to severe LV dysfunction in the setting of marked prolongation of the QRS interval 2-4 . In the initial large clinical trials of CRT, QRS duration was used as a measure of dyssynchrony to select patients for treatment 2, 3 . However, sensitivity 5 and specificity 6 of QRS duration to predict response to CRT were less than optimal. Subsequently, numerous "time-to-peak" parameters based directly on the motion of the LV walls were developed to diagnose LV mechanical dyssynchrony with echocardiography in an attempt to improve CRT selection criteria 7 .Echocardiographic mechanical dyssynchrony parameters initially showed promise in predicting response to CRT in single-center studies 8-12 . However, the multicenter Predictors of Response to CRT (PROSPECT) study recently reported that no echocardiographic dyssynchrony parameter could be recommended to improve patient selection for CRT beyond current guidelines 13 . In addition, the Resynchronization Therapy in Narrow QRS (RETHINQ) trial recently reported that patients with narrow QRS and evidence of mechanical dyssynchrony do not benefit from CRT 14 .So where do we go from here? Should selection of patients for CRT based on mechanical dyssynchrony be abandoned in the wake of the negative results from PROSPECT and RETHINQ? We believe that techniques to quantify LV mechanical dyssynchrony need to be refined, not forgotten, and will still play a role in improving CRT selection criteria in the future. This refinement of dyssynchrony quantification requires a paradigm shift. First, time-to-peak methods for quantifying dyssynchrony utilize only a single time point on the velocity or strain curves and should be replaced with more quantitatively sophisticated methods. Utilizing more data reduces variability and increases accuracy. Second, "response to CRT" should no longer
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