Use of a Pulmonary Artery Pressure Sensor to Manage Patients With Left Ventricular Assist Devices.

BACKGROUND: Hemodynamic-guided management with a pulmonary artery pressure sensor (CardioMEMS) is effective in reducing heart failure hospitalization in patients with chronic heart failure. This study aims to determine the feasibility and clinical utility of the CardioMEMS heart failure system to manage patients supported with left ventricular assist devices (LVADs). METHODS: In this multicenter prospective study, we followed patients with HeartMate II (n=52) or HeartMate 3 (n=49) LVADs and with CardioMEMS PA Sensors and measured pulmonary artery pressure, 6-minute walk distance, quality of life (EQ-5D-5 L scores), and heart failure hospitalization rates through 6 months. Patients were stratified as responders (R) and nonresponders to reductions in pulmonary artery diastolic pressure (PAD). RESULTS: There were significant reductions in PAD from baseline to 6 months in R (21.5-16.5 mm Hg; P<0.001), compared with an increase in NR (18.0-20.3; P=0.002), and there was a significant increase in 6-minute walk distance among R (266 versus 322 meters; P=0.025) compared with no change in nonresponder. Patients who maintained PAD <20 compared with PAD ≥20 mm Hg for more than half the time throughout the study (averaging 15.6 versus 23.3 mm Hg) had a statistically significant lower rate of heart failure hospitalization (12.0% versus 38.9%; P=0.005). CONCLUSIONS: Patients with LVAD managed with CardioMEMS with a significant reduction in PAD at 6 months showed improvements in 6-minute walk distance. Maintaining PAD <20 mm Hg was associated with fewer heart failure hospitalizations. Hemodynamic-guided management of patients with LVAD with CardioMEMS is feasible and may result in functional and clinical benefits. Prospective evaluation of ambulatory hemodynamic management in patients with LVAD is warranted. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03247829.

Transaxillary Stenting of LVAD Outflow Graft Obstruction.

An 82-year-old man with a HeartMate II left ventricular assist device presented with low-flow alarms and cardiogenic shock secondary to left ventricular assist device outflow graft obstruction. Given high risk for redo sternotomy, the heart team decided on percutaneous intervention with peripheral stents, a procedure that is currently limited to case reports. (Level of Difficulty: Advanced.).

Mortality differences among patients with in-hospital ST-elevation myocardial infarction.

BACKGROUND: In-hospital ST-elevation myocardial infarction (STEMI) is associated with a higher mortality rate than out-of-hospital STEMI. Quality measures and universal protocols for treatment of in-hospital STEMI do not exist, likely contributing to delays in recognition and treatment. HYPOTHESIS: To analyze differences in mortality among three subsets of patients who develop in-hospital STEMI. METHODS: This was a multicenter, retrospective observational study of patients who developed in-hospital STEMI at six United States medical centers between 2008 and 2017. Patients were stratified into three groups: (1) cardiac, (2) periprocedure, or (3) noncardiac/nonpostprocedure. Outcomes examined include time from electrocardiogram (ECG) acquisition to cardiac catheterization lab arrival (ECG-to-CCL) and survival to discharge. RESULTS: We identified 184 patients with in-hospital STEMI (mean age 68.7 years, 58.7% male). Group 1 (cardiac) patients had a shorter average ECG-to-CCL time (69 minutes) than group 2 (periprocedure, 215 minutes) and group 3 (noncardiac/nonpostprocedure, 199 minutes). Compared to group 1, survival to discharge was lower for group 2 (OR 0.33, P = .102) and group 3 (OR 0.20, P = .016). After adjusting for prespecified covariates, the relationship between group and survival showed a similar trend but did not reach statistical significance. CONCLUSIONS: Patients who develop in-hospital STEMI in the context of a preceding procedure or noncardiac illness appear to have longer reperfusion times and higher in-hospital mortality than patients admitted with cardiac diagnoses. Larger studies are warranted to further investigate these observations. Health systems should place an increased emphasis on developing quality metrics and implementing quality improvement initiatives to improve outcomes for in-hospital STEMI.

Recurrent Cardiogenic Shock Associated with Cannabis Use: Report of a Case and Review of the Literature.

BACKGROUND: The United States has recently undergone increases in the legalization and use of marijuana. There have been previous reports on the association of cannabis use and myocardial dysfunction, however, few on the association with acute stress cardiomyopathy and cardiogenic shock. CASE REPORT: This is a case of a 58-year-old female with a history of inhaled cannabis use, no history of diabetes, and no known history of cardiac disease, that illustrates an association between cannabis use and the recurrent development of stress cardiomyopathy and cardiogenic shock. A review of medical records was performed from two hospitalizations and subsequent outpatient follow-up for similar presentations 6 years apart and review of literature regarding cannabis use and its association with cardiac dysfunction. In separate hospitalizations, the patient presented with clinical findings of cardiogenic shock, severe left ventricular dysfunction with morphologic features of stress cardiomyopathy, and normal coronary angiography. Laboratory results included elevated cardiac biomarkers and urine tetrahydrocannabinol levels > 300 ng/mL. The patient required intensive cardiovascular support, but recovered with normal cardiac function after each event. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As use of cannabis becomes more prevalent, it will be important for physicians to recognize the potential association of cannabis use and acute myocardial dysfunction, and how early treatment may contribute to salutary outcomes.

In-Hospital ST-Segment Elevation Myocardial Infarction: Improving Diagnosis, Triage, and Treatment.

Importance: In-hospital ST-segment elevation myocardial infarction (STEMI) is a unique clinical entity with epidemiology, incidence, and outcomes distinct from that of out-of-hospital STEMI and has only within the past 10 years begun to receive increased attention and research. Patients with in-hospital STEMI are older, have more comorbidities, and more frequently have coagulopathies and contraindications for anticoagulation and fibrinolytic therapy. A standardized clinical definition of in-hospital STEMI is lacking. The objectives of this special communication are to (1) summarize the knowledge base regarding in-hospital STEMI; (2) review the challenges of diagnosis and treatment of patients with in-hospital STEMI; (3) present a standardized clinical definition for in-hospital STEMI; and (4) provide a quality improvement protocol to improve diagnosis, triage, and treatment of patients with in-hospital STEMI. Observations: Patients with in-hospital STEMI less frequently present with typical angina symptoms, and an electrocardiogram is often obtained owing to changes in clinical status, changes on telemetry, or a finding of elevated cardiac biomarker. The frequent nontypical presentations often lead to substantial delays in the diagnosis of STEMI. Only 34% to 71% of patients with in-hospital STEMI undergo diagnostic catheterization, and only 22% to 56% undergo percutaneous coronary intervention. Even in contemporary reports, some studies report in-hospital mortality in the range of 31% to 42%. Three areas of delay in the treatment of patients with in-hospital STEMI that merit particular attention are (1) delays in electrocardiogram acquisition, (2) delays in electrocardiogram interpretation, and (3) delays in activation of existing STEMI systems of care. Conclusions and Relevance: Treatment of patients with in-hospital STEMI is more complex and challenging than treatment of patients who develop out-of-hospital STEMI, leading to delays in diagnosis and triage and less frequent use of reperfusion therapy. Quality improvement programs targeted at decreasing delays and streamlining treatment of such patients may improve treatment and outcome.

Percutaneous Repair of Postoperative Mitral Regurgitation After Left Ventricular Assist Device Implant.

Mitral regurgitation commonly improves after implantation of a left ventricular assist device without concomitant valvular repair owing to the mechanical unloading of the left ventricle. However, the development (or persistence) of significant mitral regurgitation after implantation of a left ventricular assist device is associated with adverse clinical events. We present a case of a left ventricular assist device patient who successfully underwent a percutaneous MitraClip procedure for repair of persistent late postoperative mitral insufficiency with demonstrable clinical and hemodynamic improvement.

Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure: Current Status and Prospects for Further Research.

More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients' vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration.

Factors Associated With Ineligibility for PCI Differ Between Inpatient and Outpatient ST-Elevation Myocardial Infarction.

OBJECTIVES: Without early revascularization, both inpatient and outpatient STEMIs have poor outcomes. Reasons for denying PCI for STEMI, however, remain uncertain. This single-center retrospective cohort study compares factors and outcomes associated with ineligibility for PCI between inpatients and outpatients following ST-elevation myocardial infarction (STEMI). METHODS: A total of 1,759 STEMI patients between June 2009 and January 2015 were assessed. Individual medical records were reviewed to obtain reasons for PCI ineligibility for STEMI patients who did not receive reperfusion therapy. RESULTS: Compared to outpatients with STEMI (n = 1,688), inpatients (n = 71) were less likely to receive coronary angiography (60.6% vs 95.9%; P < 0.001) or PCI (50.7% vs 80.9%; P < 0.001), with longer ECG/door to first device activation times (97 [78, 131] vs 63 [49, 78] minutes; P < 0.001). When coronary angiography was performed, however, similar rates of PCI and procedural success were seen in both groups. Principal contraindication for PCI was risk of bleeding within the inpatient population and complex coronary artery disease within the outpatient population. Total in-hospital mortality was higher in inpatient STEMIs compared to outpatients (42.2% vs 10.0%; P < 0.001), but lower for patients eligible for PCI in both groups. CONCLUSIONS: Reasons for PCI ineligibility differ between inpatient and outpatient STEMIs. Inpatients have increased risks of bleeding, lower coronary angiography and PCI use, and higher in-hospital mortality. Especially for inpatients, specific PCI STEMI protocols that anticipate and overcome types of ineligibility and delay for cardiac catheterization may improve outcomes.

Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity is deficient in the failing heart. Correction of this abnormality by gene transfer might improve cardiac function. We aimed to investigate the clinical benefits and safety of gene therapy through infusion of adeno-associated virus 1 (AAV1)/SERCA2a in patients with heart failure and reduced ejection fraction. METHODS: We did this randomised, multinational, double-blind, placebo-controlled, phase 2b trial at 67 clinical centres and hospitals in the USA, Europe, and Israel. High-risk ambulatory patients with New York Heart Association class II-IV symptoms of heart failure and a left ventricular ejection fraction of 0·35 or less due to an ischaemic or non-ischaemic cause were randomly assigned (1:1), via an interactive voice and web-response system, to receive a single intracoronary infusion of 1 × 10(13) DNase-resistant particles of AAV1/SERCA2a or placebo. Randomisation was stratified by country and by 6 min walk test distance. All patients, physicians, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was time to recurrent events, defined as hospital admission because of heart failure or ambulatory treatment for worsening heart failure. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01643330. FINDINGS: Between July 9, 2012, and Feb 5, 2014, we randomly assigned 250 patients to receive either AAV1/SERCA2a (n=123) or placebo (n=127); 243 (97%) patients comprised the modified intention-to-treat population. Patients were followed up for at least 12 months; median follow-up was 17·5 months (range 1·8-29·4 months). AAV1/SERCA2a did not improve time to recurrent events compared with placebo (104 vs 128 events; hazard ratio 0·93, 95% CI 0·53-1·65; p=0·81). No safety signals were noted. 20 (16%) patients died in the placebo group and 25 (21%) patients died in the AAV1/SERCA2a group; 18 and 22 deaths, respectively, were adjudicated as being due to cardiovascular causes. INTERPRETATION: CUPID 2 is the largest gene transfer study done in patients with heart failure so far. Despite promising results from previous studies, AAV1/SERCA2a at the dose tested did not improve the clinical course of patients with heart failure and reduced ejection fraction. Although we did not find evidence of improved outcomes at the dose of AAV1/SERCA2a studied, our findings should stimulate further research into the use of gene therapy to treat patients with heart failure and help inform the design of future gene therapy trials. FUNDING: Celladon Corporation.

How B-Type Natriuretic Peptide (BNP) and Body Weight Changes Vary in Heart Failure With Preserved Ejection Fraction Compared With Reduced Ejection Fraction: Secondary Results of the HABIT (HF Assessment With BNP in the Home) Trial.

BACKGROUND: Heart failure is a common cause of hospitalization and can be divided into types with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). In this subanalysis of the HABIT (Heart Failure Assessment With BNP in the Home) trial, we examined the differences between home B-type natriuretic peptide (BNP) testing and weight monitoring in patients with HFpEF and with HFrEF before decompensation. METHODS AND RESULTS: This was a retrospective review of patients with HFpEF and HFrEF from the HABIT trial. The HFpEF patients compared with HFrEF patients were older and more obese and had lower baseline BNP values. Intra-individual BNP dispersion (spread of distribution over time) was greater in HFpEF than in HFrEF owing to rapid fluctuations (within 3 days). Slowly varying changes in BNP (estimated by a moving average) were equally predictive of ADHF risk in both HFpEF and HFrEF. However, in HFpEF, a rapid rise in BNP >200 pg/mL within 3 days was associated with an increased risk of acute decompensated heart failure (ADHF; hazard ratio 4.0), whereas a similar association was not observed in HFrEF. Weight gain ≥5 lb in 3 days had a high specificity but low sensitivity for ADHF in both HFpEF and HFrEF, whereas a lower threshold of ≥2 lb weight gain over 3 days in patients with HFpEF (but not HFrEF) was a moderately sensitive cutoff associated with decompensation (60% sensitivity). CONCLUSIONS: Patients with HFpEF and HFrEF have variations in their BNP and weight before decompensation. The rapid time scale behaves differently between the groups. In those with HFpEF, a 3-day period characterized by ≥2 lb weight gain and/or >200 pg/mL BNP rise was significantly associated with decompensation. Future prospective studies investigating different weight and BNP cutoffs for home monitoring of HFpEF and HFrEF patients should be performed to fully learn the value of BNP changes before clinical deompensation.

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure.

OBJECTIVES: The AVOID-HF (Aquapheresis versus Intravenous Diuretics and Hospitalization for Heart Failure) trial tested the hypothesis that patients hospitalized for HF treated with adjustable ultrafiltration (AUF) would have a longer time to first HF event within 90 days after hospital discharge than those receiving adjustable intravenous loop diuretics (ALD). BACKGROUND: Congestion in hospitalized heart failure (HF) patients portends unfavorable outcomes. METHODS: The AVOID-HF trial, designed as a multicenter, 1-to-1 randomized study of 810 hospitalized HF patients, was terminated unilaterally and prematurely by the sponsor (Baxter Healthcare, Deerfield, Illinois) after enrollment of 224 patients (27.5%). Aquadex FlexFlow System (Baxter Healthcare) was used for AUF. A Clinical Events Committee, blinded to the randomized treatment, adjudicated whether 90-day events were due to HF. RESULTS: A total of 110 patients were randomized to AUF and 114 to ALD. Baseline characteristics were similar. Estimated days to first HF event for the AUF and ALD group were, respectively, 62 and 34 (p = 0.106). At 30 days, compared with the ALD group, the AUF group had fewer HF and cardiovascular events. Renal function changes were similar. More AUF patients experienced an adverse effect of special interest (p = 0.018) and a serious study product-related adverse event (p = 0.026). The 90-day mortality was similar. CONCLUSIONS: Compared with the ALD group, the AUF group trended toward a longer time to first HF event within 90 days and fewer HF and cardiovascular events. More patients in the AUF group experienced special interest or serious product-related adverse event. Due to the trial's untimely termination, additional AUF investigation is warranted.

In-Hospital ST Elevation Myocardial Infarction: Clinical Characteristics, Management Challenges, and Outcome.

Timely reperfusion therapy reduces complications and improves survival in ST elevation myocardial infarction (STEMI). An effective chain of survival has been established for STEMIs occur in the community (outpatient STEMI). Recent studies have identified a subgroup of patients who develop STEMI while hospitalized for primary conditions, often not directly related to coronary artery disease (in-hospital STEMI or inpatient STEMI). This article summarizes current understanding of patient demographics, clinical characteristics, care delivery system and outcomes of in-hospital STEMI, comparing with outpatient STEMI. We also identified opportunities for quality improvement and proposed strategies and future directions to improve care for these patients.

Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial.

BACKGROUND: In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events. METHODS: The AVOID-HF trial seeks to determine if an early strategy of ultrafiltration in patients with acutely decompensated heart failure is associated with fewer heart failure events at 90 days compared with a strategy based on intravenous loop diuretics. Study subjects from 40 highly experienced institutions are randomized to either early ultrafiltration or intravenous loop diuretics. In both treatment arms, fluid removal therapies are adjusted according to the patients' hemodynamic condition and renal function. The study was unilaterally terminated by the sponsor in the absence of futility and safety concerns after the enrollment of 221 subjects, or 27% of the originally planned sample size of 810 patients. CONCLUSIONS: The AVOID-HF trial's principal aim is to compare the safety and efficacy of ultrafiltration vs that of intravenous loop diuretics in patients hospitalized with acutely decompensated heart failure. Because stepped treatment approaches are applied in both ultrafiltration and intravenous loop diuretics groups and the primary end point is time to first heart failure event within 90 days, it is hoped that the AVOID-HF trial, despite its untimely termination by the sponsor, will provide further insight on how to optimally decongest patients with fluid-overloaded heart failure.

Primary results of the HABIT Trial (heart failure assessment with BNP in the home).

OBJECTIVES: This study was a multicenter, single-arm, double-blinded observational prospective clinical trial designed to monitor daily concentrations of B-type natriuretic peptide (BNP) and to determine how these concentrations correlate with acute clinical heart failure decompensation (ADHF) and related adverse clinical outcomes in at-risk HF patients. BACKGROUND: Although BNP at discharge is predictive of 30-day outcomes, outpatient serial testing may improve the risk of detecting early decompensation. METHODS: A total of 163 patients with HF signs and symptoms of ADHF discharged from the hospital or in an outpatient setting measured their weight and BNP levels daily for 60 days with a finger-stick test. Patients and physicians were blinded to BNP levels. The composite outcome was ADHF events: cardiovascular death, admission for decompensated HF, or clinical HF decompensation requiring either parenteral HF therapy or changes in oral HF medications. RESULTS: A total of 6,934 daily BNP values were recorded, with a median of 46 measures per patient over a monitoring period of 65 days. Forty patients had 56 events. Correlations between BNP measures weakened over time, and the dispersion between BNP measures grew. During 10,035 patient-days, there were 494 (4.9%) days of weight gain (≥5 lbs). The hazard ratio per unit increase of ln BNP was 1.84, and the hazard ratio on a day of weight gain was 3.63. These effects retained significance when controlling for symptoms. When the monitoring period for each subject was broken into intervals based on ADHF events, there were 39 (18.4%) intervals of upward trending BNP corresponding to a risk increase of 59.8% and 64 (30.2%) downward trending intervals corresponding to a risk decrease of 39.0%. There were 94 (44.3%) intervals with 1 or more days of weight gain corresponding to a risk increase of 26.1%. CONCLUSIONS: This pilot study demonstrates that home BNP testing is feasible and that trials using home monitoring for guiding therapy are justifiable in high-risk patients. Daily weight monitoring is complementary to BNP, but BNP changes correspond to larger changes in risk, both upward and downward. (Heart Failure [HF] Assessment with B-type Natriuretic Peptide [BNP] In the Home [HABIT]; NCT00946231).

Predicting survival in patients receiving continuous flow left ventricular assist devices: the HeartMate II risk score.

OBJECTIVES: The aim of this study was to derive and validate a model to predict survival in candidates for HeartMate II (HMII) (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) support. BACKGROUND: LVAD mortality risk prediction is important for candidate selection and communicating expectations to patients and clinicians. With the evolution of LVAD support, prior risk prediction models have become less valid. METHODS: Patients enrolled into the HMII bridge to transplantation and destination therapy trials (N = 1,122) were randomly divided into derivation (DC) (n = 583) and validation cohorts (VC) (n = 539). Pre-operative candidate predictors of 90-day mortality were examined in the DC with logistic regression, from which the HMII Risk Score (HMRS) was derived. The HMRS was then applied to the VC. RESULTS: There were 149 (13%) deaths within 90 days. In the DC, mortality (n = 80) was higher in older patients (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1 to 1.7 per 10 years), those with greater hypoalbuminemia (OR: 0.49, 95% CI: 0.31 to 0.76 per mg/dl of albumin), renal dysfunction (OR: 2.1, 95% CI: 1.4 to 3.2 per mg/dl creatinine), coagulopathy (OR: 3.1, 95% CI: 1.7 to 5.8 per international normalized ratio unit), and in those receiving LVAD support at less experienced centers (OR: 2.2, 95% CI: 1.2 to 4.4 for <15 trial patients). Mortality in the DC low, medium, and high HMRS groups was 4%, 16%, and 29%, respectively (p < 0.001). In the VC, corresponding mortality was 8%, 11%, and 25%, respectively (p < 0.001). HMRS discrimination was good (area under the receiver-operating characteristic curve: 0.71, 95% CI: 0.66 to 0.75). CONCLUSIONS: The HMRS might be useful for mortality risk stratification in HMII candidates and may serve as an additional tool in the patient selection process.

Emergency department initiation of cardiopulmonary bypass: a case report and review of the literature.

BACKGROUND: Out-of-hospital cardiac arrest carries a dismal prognosis. Percutaneous extracorporeal membrane oxygenation (ECMO) has been used with success for in-hospital arrests, and some literature suggests improvement in long-term survival for out-of-hospital arrests as well. OBJECTIVES: This case highlights the use of ECMO in the emergency department. CASE REPORT: We report a case in which emergency physician-initiated ECMO was used as a bridge to definitive care in an out-of- hospital cardiac arrest in the United States. CONCLUSIONS: ECMO is a novel adjunct for patients in cardiac arrest in whom the usual advanced life support techniques have failed.

Emergency physician-initiated extracorporeal cardiopulmonary resuscitation.

CONTEXT: Extracorporeal cardiopulmonary resuscitation (ECPR) refers to emergent percutaneous veno-arterial cardiopulmonary bypass to stabilize and provide temporary support of patients who suffer cardiopulmonary arrest. Initiation of ECPR by emergency physicians with meaningful long-term patient survival has not been demonstrated. OBJECTIVE: To determine whether emergency physicians could successfully incorporate ECPR into the resuscitation of patients who present to the emergency department (ED) with cardiopulmonary collapse refractory to traditional resuscitative efforts. DESIGN: A three-stage algorithm was developed for ED ECPR in patients meeting inclusion/exclusion criteria. We report a case series describing our experience with this algorithm over a 1-year period. RESULTS: 42 patients presented to our ED with cardiopulmonary collapse over the 1-year study period. Of these, 18 patients met inclusion/exclusion criteria for the algorithm. 8 patients were admitted to the hospital after successful ED ECPR and 5 of those patients survived to hospital discharge neurologically intact. 10 patients were not started on bypass support because either their clinical conditions improved or resuscitative efforts were terminated. CONCLUSION: Emergency physicians can successfully incorporate ED ECPR in the resuscitation of patients who suffer acute cardiopulmonary collapse. More studies are necessary to determine the true efficacy of this therapy.

Neurocognitive function in destination therapy patients receiving continuous-flow vs pulsatile-flow left ventricular assist device support.

BACKGROUND: The HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow left ventricular assist device (LVAD) improved survival in destination therapy (DT) patients during a randomized trial compared with pulsatile-flow LVADs. This study documented changes in cognitive performance in DT patients from that trial to determine if there were differences between continuous-flow and pulsatile-flow support. METHODS: Data were collected in a sub-study from 96 HeartMate II continuous-flow and 30 HeartMate XVE pulsatile-flow LVAD patients from 12 of the 35 trial sites that followed the same serial neurocognitive (NC) testing protocol at 1, 3, 6, 12, and 24 months after LVAD implantation. Spatial perception, memory, language, executive functions, and processing speed were the domains assessed with 10 standard cognitive measures. Differences over time and between LVAD type were evaluated with linear mixed-effects modeling. RESULTS: From 1 to 24 months after LVAD implantation, changes in NC functions were stable or showed improvement in all domains, and there were no differences between the continuous-flow and pulsatile-flow groups. Data at 24 months were only available from patients with the continuous-flow LVAD due to the limited durability of the HeartMate XVE device. There was no decline in any NC domain over the time of LVAD support. Missing data not collected from patients who died could have resulted in a bias toward inflated study results. CONCLUSIONS: The NC performance of advanced heart failure patients supported with continuous-flow and pulsatile-flow LVADs shows stabilization or improvement during support for up to 24 months.

Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure.

BACKGROUND: Adeno-associated virus type 1/sarcoplasmic reticulum Ca(2+)-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. METHODS AND RESULTS: Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca(2+)-ATPase or placebo. Seven efficacy parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving efficacy at 6 months in the group-level (concordant improvement in 7 efficacy parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 efficacy parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P=0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P=0.05) on high-dose treatment versus placebo. There were no untoward safety findings. CONCLUSIONS: The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca(2+)-ATPase in advanced heart failure, supporting larger confirmatory trials. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00454818.