The Impact of Hospital Size on CMS Hospital Profiling.

Background: The Centers for Medicare & Medicaid Services (CMS) profile hospitals using a set of 30-day risk-standardized mortality and readmission rates as a basis for public reporting. These measures are affected by hospital patient volume, raising concerns about uniformity of standards applied to providers with different volumes.

Objectives: To quantitatively determine whether CMS uniformly profile hospitals that have equal performance levels but different volumes.

Impact of socioeconomic status measures on hospital profiling in New York City.

Background: Current 30-day readmission models used by the Center for Medicare and Medicaid Services for the purpose of hospital-level comparisons lack measures of socioeconomic status (SES). We examined whether the inclusion of an SES measure in 30-day congestive heart failure readmission models changed hospital risk-standardized readmission rates in New York City (NYC) hospitals.

Methods And Results: Using a Centers for Medicare & Medicaid Services (CMS)-like model, we estimated 30-day hospital-level risk-standardized readmission rates by adjusting for age, sex, and comorbid conditions.

Payer status and access to laparoscopic subtotal colectomy for ulcerative colitis.

Background: Medicaid populations have been shown to have inferior surgical outcomes, but less is known about their access to advanced surgical procedures.

Objective: The aim of this study was to evaluate if patients with Medicaid and ulcerative colitis who presented for subtotal colectomy would have reduced access to the laparoscopic approach in comparison with a similar population with private insurance.

Design/settings/patients: Using the Nationwide Inpatient Sample database from 2008 to 2010, we identified all patients who underwent subtotal colectomy for ulcerative colitis.

HCN2/SkM1 gene transfer into canine left bundle branch induces stable, autonomically responsive biological pacing at physiological heart rates.

Objectives: This study sought to test the hypothesis that hyperpolarization-activated cyclic nucleotide-gated (HCN)-based biological pacing might be improved significantly by hyperpolarizing the action potential (AP) threshold via coexpression of the skeletal muscle sodium channel 1 (SkM1).

Background: Gene-based biological pacemakers display effective in vivo pacemaker function. However, approaches used to date have failed to manifest optimal pacemaker properties, defined as basal beating rates of 60 to 90 beats/min, a brisk autonomic response achieving maximal rates of 130 to 160 beats/min, and low to absent electronic backup pacing.

pH (low) insertion peptide (pHLIP) targets ischemic myocardium.

The pH (low) insertion peptide (pHLIP) family enables targeting of cells in tissues with low extracellular pH. Here, we show that ischemic myocardium is targeted, potentially opening a new route to diagnosis and therapy. The experiments were performed using two murine ischemia models: regional ischemia induced by coronary artery occlusion and global low-flow ischemia in isolated hearts.

Effect of skeletal muscle Na(+) channel delivered via a cell platform on cardiac conduction and arrhythmia induction.

Background: In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel is largely inactivated, contributing to slow conduction and reentry. We have demonstrated that adenoviral delivery of the skeletal muscle Na(+) channel (SkM1) to epicardial border zones normalizes conduction and reduces induction of ventricular tachycardia/ventricular fibrillation. We now studied the impact of canine mesenchymal stem cells (cMSCs) in delivering SkM1.

Analysis of Florida and New York state hospital discharges suggests that carotid stenting in symptomatic women is associated with significant increase in mortality and perioperative morbidity compared with carotid endarterectomy.

Background: Although large randomized studies have established the efficacy and safety of carotid endarterectomy (CEA) and, recently, carotid artery stenting (CAS), the under-representation of women in these trials leaves the comparison of risks to benefits of performing these procedures on women an open question. To address this issue, we reviewed the hospital outcomes and delineated patient characteristics predicting outcome in women undergoing carotid interventions using New York and Florida statewide hospital discharge databases.

Methods: We analyzed in-hospital mortality, postoperative stroke, cardiac postoperative complications, and combined postoperative stoke and mortality in 20,613 CEA or CAS hospitalizations for the years 2007 to 2009.

Repolarization gradients in the intact heart: transmural or apico-basal?

Controversies regarding the genesis of the T wave in the electrocardiogram and the role of midmural M cells in the intact heart include: In normal, intact canine and human hearts there is no significant transmural gradient in repolarization times. The T wave results primarily from apico-basal differences in repolarization times. Also, in the intact heart there is no midmural region of prolonged action potential duration.

SkM1 and Cx32 improve conduction in canine myocardial infarcts yet only SkM1 is antiarrhythmic.

Aims: Reentry accounts for most life-threatening arrhythmias, complicating myocardial infarction, and therapies that consistently prevent reentry from occurring are lacking. In this study, we compare antiarrhythmic effects of gene transfer of green fluorescent protein (GFP; sham), the skeletal muscle sodium channel (SkM1), the liver-specific connexin (Cx32), and SkM1/Cx32 in the subacute canine infarct.

Methods And Results: Immediately after ligation of the left anterior descending artery, viral constructs were implanted in the epicardial border zone (EBZ).

Differential effects of ivabradine and ryanodine on pacemaker activity in canine sinus node and purkinje fibers.

Introduction: It is generally accepted that at least 2 major mechanisms contribute to sinus node (SN) pacemaking: a membrane voltage (mainly I(f) ) clock and a calcium (Ca) clock (localized submembrane sarcoplasmic reticulum Ca(2+) release during late diastolic depolarization). The aim of this study was to compare the contributions of each mechanism to pacemaker activity in SN and Purkinje fibers (PFs) exhibiting normal or abnormal automaticity.

Methods And Results: Conventional microelectrodes were used to record action potentials in isolated spontaneously beating canine SN and free running PF in control and in the presence of 0.

Increased Cell-Cell Coupling Increases Infarct Size and Does not Decrease Incidence of Ventricular Tachycardia in Mice.

Increasing connexin43 (Cx43) gap junctional conductance as a means to improve cardiac conduction has been proposed as a novel antiarrhythmic modality. Yet, transmission of molecules via gap junctions may be associated with increased infarct size. To determine whether maintaining open gap junction channels impacts on infarct size and induction of ventricular tachycardia (VT) following coronary occlusion, we expressed the pH- and voltage-independent connexin isoform connexin32 (Cx32) in ventricle and confirmed Cx32 expression.

Expression of skeletal muscle sodium channel (Nav1.4) or connexin32 prevents reperfusion arrhythmias in murine heart.

Aims: acute myocardial ischaemia induces a decrease in resting membrane potential [which leads to reduction of action potential (AP) V(max)] and intracellular acidification (which closes gap junctions). Both contribute to conduction slowing. We hypothesized that ventricular expression of the skeletal muscle Na(+) channel, Nav1.

Cardiac expression of skeletal muscle sodium channels increases longitudinal conduction velocity in the canine 1-week myocardial infarction.

Background: Skeletal muscle sodium channel (Nav1.4) expression in border zone myocardium increases action potential upstroke velocity in depolarized isolated tissue. Because resting membrane potential in the 1-week canine infarct is reduced, we hypothesized that conduction velocity (CV) is greater in Nav1.

Transcriptional and electrophysiological consequences of KChIP2-mediated regulation of CaV1.2.

Potassium channel interacting proteins (KChIP) are Ca(2+)-binding proteins that originally were identified as auxiliary subunits for K(V)4 channels. K(V)4 channels encode the voltage gated A-current (I(A)) in neuronal tissue and the fast, transient outward current (I(to,f)) in cardiac tissue. Recently, we have reported that KChIP2 functionally modulates the cardiac Ca(V)1.

Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration.

Background: Four voltage-gated potassium currents, I(to,f) (K(V)4.2), I(to,s) (K(V)1.4), I(K,slow) (K(V)1.

Epicardial border zone overexpression of skeletal muscle sodium channel SkM1 normalizes activation, preserves conduction, and suppresses ventricular arrhythmia: an in silico, in vivo, in vitro study.

Background: In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel (SCN5A) is largely inactivated, contributing to low action potential upstroke velocity (V(max)), slow conduction, and reentry. We hypothesized that a fast inward current such as the skeletal muscle sodium channel (SkM1) operating more effectively at depolarized membrane potentials might restore fast conduction in epicardial border zones and be antiarrhythmic.

Methods And Results: Computer simulations were done with a modified Hund-Rudy model.

Altered ventricular stretch contributes to initiation of cardiac memory.

Background: Cardiac memory is a change in T-wave morphology induced by ventricular pacing or arrhythmias that persist after resumption of normal AV conduction. Changing the pacemaker site from atrium to ventricle alters ventricular activation and the mechanical pattern of ventricular contraction. Either or both alterations affect T-wave configuration.

Early electrical remodeling in rabbit pulmonary vein results from trafficking of intracellular SK2 channels to membrane sites.

Objective: Atrial fibrillation is often initiated by bursts of ectopic activity arising in the pulmonary veins. We have previously shown that a 3-h intermittent burst pacing protocol (BPP), mimicking ectopic pulmonary vein foci, shortens action potential duration (APD) locally at the pulmonary vein-atrial interface (PV) while having no effect elsewhere in rabbit atrium. This shortening is Ca(2+) dependent and is prevented by apamin, which blocks small conductance Ca(2+)-activated K(+) channels (SK(Ca)).

Application of blebbistatin as an excitation-contraction uncoupler for electrophysiologic study of rat and rabbit hearts.

Background: Application of fluorescence imaging of cardiac electrical activity is limited by motion artifacts and/or side effects of currently available pharmacologic excitation-contraction uncoupling agents.

Objectives: The purpose of this study was to test whether blebbistatin, a recently discovered inhibitor of myosin II isoforms, can be used as an excitation-contraction uncoupler.

Methods: The specificity and potency of blebbistatin were examined by assaying the effects of blebbistatin on the contraction and basic cardiac electrophysiologic parameters of Langendorff-perfused rabbit hearts, isolated rabbit right ventricle and right atrium, and single rat ventricular myocytes using conventional ECG, surface electrograms, microelectrode recordings, and optical imaging with voltage-sensitive and Ca(2+)-sensitive dyes.

Ionic mechanisms underlying region-specific remodeling of rabbit atrial action potentials caused by intermittent burst stimulation.

Background: Pulmonary veins (PVs) and the coronary sinus (CS) play pivotal roles in triggering some episodes of atrial fibrillation. In isolated rabbit right or left atrial preparations, a 3-hour intermittent burst pacing protocol shortens action potential duration (APD) in CS and PV, but not in sinus node (SN) and left Bachmann bundle (BB) regions.

Objective: The purpose of this study was to use patch clamp techniques to study the rapidly inactivating (I(to)) and sustained (I(sus)) K(+) currents as well as Ca(2+) currents (I(Ca)) in cells dispersed from intermittent burst pacing and sham PV, BB, CS, and SN regions to determine whether changes in these currents contributed to APD shortening.

Long-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient.

Objective: The contribution of regional electrophysiologic heterogeneity to the T-wave changes of long-term cardiac memory (CM) is not known. We mapped activation and repolarization in dogs after induction of CM and in sham animals.

Methods And Results: CM was induced by three weeks of AV-sequential pacing at the anterior free wall of the left ventricle (LV), midway between apex and base in 5 dogs.

I(Kr) contributes to the altered ventricular repolarization that determines long-term cardiac memory.

Objective: Cardiac memory (CM) is characterized by an altered T-wave morphology, which reflects altered repolarization gradients. We hypothesized that the delayed rectifier currents, I(Kr) and I(Ks), might contribute to these repolarization changes.

Methods: We studied conscious, chronically instrumented dogs paced from the postero-lateral left ventricular (LV) wall at rates 5-10% faster than sinus rate for 3 weeks.

Repolarization gradients in the canine left ventricle before and after induction of short-term cardiac memory.

Background: Questions remain about the contributions of transmural versus apicobasal repolarization gradients to the configuration of the T wave in control settings and after the induction of short-term cardiac memory.

Methods And Results: Short-term cardiac memory is seen as T-wave changes induced by altered ventricular activation that persists after restoration of sinus rhythm. We studied cardiac memory in anesthetized, open-chest dogs paced from the ventricle for 2 hours.

Region-specific, pacing-induced changes in repolarization in rabbit atrium: an example of sensitivity to the rare.

Objective: In subsets of patients paroxysmal firing of ectopic foci in pulmonary veins or coronary sinus is an important cause of atrial fibrillation. This appears to represent a rare event overriding a dominant sinus mechanism to alter the rhythmic firing of the atrium. Hence, we tested the hypothesis that a rare stimulation pattern might alter the myocardial substrate, making it more susceptible to the initiation of arrhythmias.

Regional dispersion of L-type calcium current in ventricular myocytes of German shepherd dogs with lethal cardiac arrhythmias.

Objectives: The purpose of this study was to determine if regional differences in L-type Ca(2+) current (I(Ca,L)) are altered in a German shepherd model of sudden death.

Background: German shepherd dogs with inherited sudden cardiac death have reduced sympathetic innervation in the anteroseptal left ventricle that may contribute to arrhythmias in afflicted animals compared to control unafflicted animals. Differences in a number of repolarizing K(+) currents have been identified in this model, but I(Ca,L) has not been studied.