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Background The utility of convalescent coronavirus disease 2019 (COVID-19) plasma (CCP) in the current pandemic is not well defined. We sought to evaluate the safety and efficacy of CCP in severely or life threateningly ill COVID-19 patients when matched with a contemporaneous cohort. Methods Patients with severe or life-threatening COVID-19 were treated with CCP according to Food and Drug Administration criteria, prioritization by an interdisciplinary team, and based on CCP availability. Individual-level matched controls (1:1) were identified from patients admitted during the prior month when no CCP was available. The safety outcome was freedom from adverse transfusion reaction, and the efficacy outcome was a composite of death or worsening O2 support. Demographic, clinical, and laboratory data were analyzed by univariate and multivariable regression analyses accounting for matched design. Results Study patients (n = 94, 47 matched pairs) were 62% male with a mean age of 58, and 98% (90/94) were minorities (53% Hispanic, 45% Black, non-Hispanic) in our inner-city population. Seven-day composite and mortality outcomes suggested a nonsignificant benefit in CCP-treated patients (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.23–2.12; P = .52; aHR, 0.23; 95% CI, 0.04–1.51; P = .13, respectively). Stratification by pretransfusion mechanical ventilation status showed no differences between groups. No serious transfusion reactions occurred. Conclusions In this short-term matched cohort study, transfusion with CCP was safe and showed a nonsignificant association with study outcomes. Randomized and larger trials to identify appropriate timing and dosing of CCP in COVID-19 are warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04420988.

Aims This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF). Methods and results Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m2 received one 6-h i.v. infusion of BMS-986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS-986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time-averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS-986231 increased non-invasively measured time-averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug-related arrhythmia or symptomatic hypotension with BMS-986231. Analyses of adverse events throughout the 30-day follow-up did not identify any toxicities specific to BMS-986231, with the potential exception of infrequent mild-to-moderate headaches during infusion. There were no treatment-related serious adverse events. Conclusions BMS-986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS-986231 should be further assessed in patients with heart failure.

Aims This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS‐986231, a novel second‐generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF). Methods and results Forty‐six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose‐escalation cohorts in this double‐blind, randomized, placebo‐controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m2 received one 6‐h i.v. infusion of BMS‐986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS‐986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time‐averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS‐986231 increased non‐invasively measured time‐averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug‐related arrhythmia or symptomatic hypotension with BMS‐986231. Analyses of adverse events throughout the 30‐day follow‐up did not identify any toxicities specific to BMS‐986231, with the potential exception of infrequent mild‐to‐moderate headaches during infusion. There were no treatment‐related serious adverse events. Conclusions BMS‐986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS‐986231 should be further assessed in patients with heart failure.

Rationale: Despite direct immediate intervention and therapy, ST-segment–elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. Objective: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Methods and Results: Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months ( P P =0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. Conclusions: This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01495364.

Background Takotsubo cardiomyopathy (TCM) has been associated with repolarization abnormalities including QT prolongation and acquired long QT syndrome. However, the association between QT prolongation and clinical outcomes in patients with TCM remains unclear. The aim of this study is to examine the association between QT prolongation and ventricular arrhythmias, cardiogenic shock, and death in patients with TCM. Methods Forty-six patients with TCM met our inclusion criteria in an ongoing prospective cohort database from 2010 to May 2015. We assigned the patients to a long QT group or a normal QT group, and created a composite outcome consisting of ventricular arrhythmias, cardiogenic shock, or death. Results The mean age of the participants was 59.7 ± 16 years, 67% were women, and 63% had hypertension. Median follow-up time was 3.1 years (interquartile range: 2.0-3.8), with a total of 133.8 person-years. The mean left ventricular ejection fraction at diagnosis was 27.2% ± 1.4%. The mean QTc on diagnosis was 484 ms ± 10.2 ms for men, and 488 ms ± 8.6 ms for women. The long QT group had a 4.1-times higher odds of having the composite clinical outcome as compared to the normal QT group (95% confidence interval: 1.1, 16.1, P = 0.04) after adjusting for age and race in logistic regression. Conclusion Patients with TCM who have a long QT interval or develop acquired long QT syndrome due to TCM may be more likely to be intubated; require vasopressors; and develop shock, ventricular arrhythmias, and death than those with a normal QT interval.

Eptifibatide (Ep) induced profound thrombocytopenia (TP) has been rarely described. We report a case of acute profound TP after intravenous (IV) Ep. A 59 year old man with history of coronary artery disease and two vessel bypass was evaluated for a positive nuclear stress test. Coronary angiography

In exercise stress tests, a severe hypotensive response (SHR) is a predictor of poor outcomes. Hypotension during dobutamine stress echocardiography (DSE) has not been shown to predict adverse outcomes in the general population. However, whether SHR during DSE is predictive in patients undergoing

a Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, United States b Division of Cardiovascular Diseases, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, United States c Department of Psychiatry, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, United States

Stress-induced cardiomyopathy (SIC) is characterized by reversible left ventricular (LV) systolic dysfunction, which appears to be triggered by an intense, stressful event in the absence of signifi cant coronary artery disease. It manifests typically with transient left ventricular wall motion abnormalities (WMA) involving the apical and/or mid-ventricular myocardial segments, associated with minimal troponin rise (< 5 ng/ml), and typical EGG changes.Described are 3 cases of stress-induced cardiomyopathy with atypical distribution of wall motion abnormalities. Possible contributing mechanisms to the pathogenesis and the variability in WMA are discussed.

Objectives: To describe national trends in the incidence and outcomes of patients with chordae tendineae rupture (CTR).Methods: Patients who were diagnosed with CTR between 2000 and 2012 were identified in National (Nationwide) Inpatient Sample (NIS) registry. CTR was defined using validated International Classification of Diseases, 9th Edition, Clinical Modification diagnosis (ICD9-CM) codes. Results: A total of 37,287 (14,833 mitral valve repair, 7780 mitral valve replacement) CTR cases were identified. Overall, in-hospital mortality in CTR decreased by 3% from 2000 to 2012 (P < 0.001). From 2000 to 2012, the rate of mitral valve repair increased from 27.2% to 46.4%, (P < 0.001) with a concurrent decrease in the rate of mitral valve replacement (from 27.8 to 17.7%, P < 0.001). After multivariate adjustment, patient age (OR = 1.04, 95% CI 1.03-1.06, P < 0.001), congestive heart failure (CHF) (OR = 2.08, 95% CI 1.19-3.64, P = 0.01), myocardial infarction (MI) (OR = 3.58, 95% CI 2.10-6.11, P < 0.001), Deyo/Charlson comorbidity index (OR = 1.23, 95% CI 1.07-1.41, P < 0.003) and use of the intra aortic balloon pump (IABP) (OR = 4.81 95% CI 2.71-8.55, P < 0.001) were found to be independently associated with greater odds of mortality in these patients. Additionally, mitral valve replacement was significantly associated with higher costs of hospitalization (coefficient 15693, 95% CI 12638-18749, P < 0.001)Conclusion: Mitral valve repair is associated with reduced inpatient mortality and costs compared with mitral valve replacement. A substantial increase in the percentage of cases undergoing mitral valve repair with a concurrent decrease in cases undergoing mitral valve replacement were observed. Increasing age and comorbidity index, history of CHF and MI, and use of IABP were identified as factors that could increase the risk of mortality in patients with CTR.

To investigate the frequency and predictors of in-hospital complications among patients undergoing coronary artery bypass grafting (CABG) in the United States.Retrospective national database analysis SETTINGS: United States hospitals.A weighted sample of 1,910,236 patients undergoing CABG surgery identified from the National (Nationwide) Inpatient Sample from 2008 to 2012.CABG surgery MEASUREMENTS AND MAIN RESULTS: The number of CABG surgeries decreased from 436,275 in 2008 to 339,749 in 2012. The Deyo comorbidity index showed a steady increase from 2008 to 2012. The rate of in-hospital mortality decreased from 2.7% in 2008 to 2.2% in 2012 (p0.001). The most common in-hospital complication was postoperative hemorrhage (30.4%), followed by cardiac (11.34%) and respiratory complications (2.3%). During the 5-year period, the rates of in-hospital cardiac, respiratory and infectious complications decreased (p0.001), while the rate of postoperative hemorrhage showed a 35.8% relative increase in 2012 compared to 2008.The annual number of CABG surgeries is declining in the United States. While the burden of comorbidities is increasing, the rates of mortality and most in-hospital complications are improving. The increasing rate of postoperative bleeding necessitates the need to develop strategies to improve the risk of bleeding in this patient population.

Objectives The purpose of this study was to compare the efficacy and safety of intracoronary (IC) nitroprusside and intravenous adenosine (IVA) for assessing fractional flow reserve (FFR). Background IV infusion of adenosine is a standard method to achieve a coronary hyperemia for FFR measurement. However, adenosine is expensive, causes multiple side effects, and is contraindicated in patients with reactive airway disease. Sodium nitroprusside (NTP) is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not well established. Methods We compared FFR response and side effects profile of IC NTP and IVA. Bolus of NTP at a dose of 100 μg and IVA (140 μg/kg/min) were used to achieve coronary hyperemia. Results We evaluated 75 lesions in 53 patients (60% male) mean age 61.6 ± 13.9 years. Mean FFR after NTP was similar to FFR after adenosine (0.836 ± 0.107 vs. 0.856 ± 0.106; P = 0.26; r = 0.91, P < 0.001). NTP induced maximal stable hyperemia within 10 sec (mean: 6.4 ± 1) which lasted consistently between 38 and 60 sec (mean 51 ± 7.5). NTP caused significant (14%), but asymptomatic decrease in mean blood pressure which returned to baseline within 60 sec. Adenosine caused shortness of breath in 26%, headache and flushing in 19%, and transient second degree heart block in 6% of patients. No adverse symptoms were reported after NTP. Conclusions IC NTP is as effective as IVA for measuring FFR. NTP is better tolerated by patients. Since NTP is inexpensive, readily available, well tolerated, and safe, it may be a better choice for FFR assessment. © 2012 Wiley Periodicals, Inc.

Anteriorly displaced right coronary artery (RCA) and anomalous origin RCAs occur in ≈1% and 0.1% of adult patients, respectively, and are the leading cause of incomplete coronary angiography and prolonged procedure times. We present a case in which anteriorly displaced RCA occlusion resulted in an acute inferior–posterior–right ventricular myocardial infarction complicated by complete atrioventricular block and hypotension. Failure to image the RCA resulted in considerable delay in reperfusion time with fibrinolysis. The authors discuss the most frequent anatomic locations of ectopic RCAs and suggest an algorithm to be employed when an ectopic RCA cannot be imaged with conventional diagnostic catheters. Contrary to popular belief, the search for an ectopic RCA has b90° boundaries limited to the anterior third of the right sinus and anterior half of the left sinus. © 2011 Elsevier Inc. All rights reserved.

Osteopontin (OPN), also known as 44kDa bone phosphoprotein, sialoprotein I, secreted phosphoprotein I, 2ar, uropontin, and early T-lymphocyte activation-1 (Eta-1), is a multifunctional protein. OPN has been found to be expressed in various cell types and species with many physiologic and pathologic functions. OPN has emerged as a potential biomarker and mediator in cardiovascular disease. In this review, we will discuss the roles of OPN in cardiovascular disease, specifically in vascular and valvular heart disease, myocardial infarction and heart failure.

Aim To assess the effects of shortened door-to-intervention (DTI) time on appropriate clinical decisions regarding the four most critical and costly decisions during primary percutaneous coronary intervention (PCI): cath-lab activation (CLA), use of glycoprotein IIb/IIIa inhibitors (GPI), use of PCI, and deployment of drug-eluting stent (DES). Background STEMI PCI patients are frequently subject to decision making based on abbreviated medical encounter and limited medical information. Methods Clinical data were prospectively collected in a STEMI registry over 19 months. Retrospective chart reviews were conducted to determine the level of appropriateness of the above-mentioned decisions. Results Between June 2006 and December 2007, 200 EKGs with suspected STEMI were transmitted; 88 (44%) resulted in CLA. Compared to prior year, DTI times decreased from 145.7 to 69.9 min ( P =.00001). DTI was longer during nights and weekends (87.5 vs. 51.8 min, P =.001) and the initial 6 months of the registry (86.8 vs. 66.8 min, P =.07). Nineteen (21.6%) of the patients undergoing angiography did not require revascularization, 56 (63.6%) received GPIs, and 65 patients (73.8%) underwent at least one vessel PCI, and at least one DES was used in 39 patients (60% of PCI cohort). When assessed for appropriateness, CLA was appropriate in 81.8% of the time and rendered borderline or inappropriate in 5.7% and 12.5%, respectively. GPI use was appropriate in 66% of the patients but seemed borderline or inappropriate in 28.5% and 5.4%, respectively. PCI was appropriate in 90% of the lesions treated, and borderline or inappropriate in 7.1% and 2.9%, respectively. DES use was viewed appropriate in 38.4%, and borderline or inappropriate in 51% and 10.2% of the DES deployments, respectively. Conclusions (1) In view of expedited care, certain information required for decision-making process is either not available or ignored during primary PCI. (2) Appropriate use of resources in primary PCI needs to be better defined. (3) Measures of extracting patients' previous medical records and imaging studies along with in-lab immediate blood work and echocardiography and establishing new "time-out" protocols for STEMI patients may improve resource utilization and patient care and outcome.

Multiple reports have demonstrated superior outcomes at high-volume hospitals in patients undergoing heart transplant. However, comprehensive analyses on trends in hospital procedure numbers in recent years are lacking. We performed analysis of the Nationwide (National) Inpatient Sample (NIS) from

Percutaneous ventricular assist devices (PVAD) and intra-aortic balloon pump (IABP) provide mechanical support for patients in cardiogenic shock (CS). However, comparative outcomes of these therapies in a large real-world study remains unclear. Data was obtained from the National Inpatient Sample

Anemia is common in heart failure (HF) patients. A prespecified pooled analysis of 2 randomized, double-blind, placebo-controlled studies evaluated darbepoetin alfa (DA) in 475 anemic patients with HF (hemoglobin [Hb], 9.0-12.5 g/dL). DA was administered subcutaneously every 2 weeks and titrated to achieve and maintain a target Hb level of 14.0+/-1.0 g/dL. By week 27, mean (SD) Hb concentrations did not increase with placebo but increased with DA from 11.5 (0.7) to 13.3 (1.3) g/dL. Hazard ratios (HRs) for DA compared with placebo for all-cause death or first HF hospitalization (composite end point), all-cause death, and HF hospitalization by month 12 were 0.67 (95% confidence interval [CI], 0.44-1.03; P=.067), 0.76 (95% CI, 0.39-1.48; P=.419), and 0.66 (95% CI, 0.40-1.07; P=.093), respectively. Incidence of adverse events was similar in both groups. In post hoc analyses, improvement in the composite end point was significantly associated with the mean Hb change from baseline (adjusted HR, 0.40; P=.017) with DA treatment. There was no increased risk of all-cause mortality or first HF hospitalization with DA in patients with reduced renal function or elevated baseline B-type natriuretic peptide, a biomarker of worse HF. These results suggest that DA is well tolerated, corrects HF-associated anemia, and may have favorable effects on clinical outcomes.

Hypereosinophilic syndrome (HES) is a rare disorder of unregulated eosinophilia, which if untreated, may lead to systemic tissue infiltration and inflammation. Cardiac involvement is a common and serious associated complication. We describe a case of HES associated myocarditis mimicking a non-ST elevation MI (NSTEMI). Unlike myocarditis in general, our patient responded well to high dose methylprednisone, the standard of care in HES. We review the clinical presentation, pathophysiology, pathology and treatment of eosinophilic myocarditis related to HES.

Purpose: Patients with chronic fatigue syndrome (CFS) report that exertion produces dramatic symptom worsening. We hypothesized this might be due to the exacerbation of an underlying sleep disorder, which we have previously demonstrated to exist. Methods: Female patients with CFS and matched healthy controls with no evidence of major depressive disorder were studied with overnight polysomnography on a baseline night and on a night after their performance of a maximal exercise test. Results: CFS patients as a group had evidence for disturbed sleep compared with controls. Although exercise improved sleep for healthy subjects, it did not do this for the group as a whole. When we stratified the sample on the basis of self-reported sleepiness after a night's sleep, the patient group with reduced morning sleepiness showed improvement in sleep structure, whereas those with increased morning sleepiness continued to show evidence for sleep disruption. Conclusions: Sleep is disturbed in CFS patients as a group, but exercise does not exacerbate this sleep disturbance. Approximately half the patients studied actually sleep better after exercise. Therefore, activity-related symptom worsening is not caused by worsened sleep.

Aims To assess the safety and tolerability of darbepoetin alfa (DA) in the treatment of anaemia in heart failure (HF). Methods and results In this pooled analysis of three randomized, double-blind, placebo-controlled studies of anaemic [haemoglobin (Hb) ≤12.0 g/dL or ≤12.5 g/dL] symptomatic HF subjects, DA was administered subcutaneously once every 2 weeks and titrated to achieve and maintain a target Hb of 14.0 ± 1.0 g/dL. In total, 516 subjects were randomized; 231 (44.8%) to placebo, 285 (55.2%) to DA. Darbepoetin alfa was well tolerated, with an adverse event (AE) profile similar to placebo. Most subjects (placebo, 85%; DA, 87%) experienced at least one AE. There was a lower incidence of serious AEs in the DA group (placebo, 43%; DA, 37%) with the most frequent being worsening HF (placebo, 19%; DA, 11%). Treatment-related AEs were reported for 9% and 12% in placebo and DA subjects, respectively. Fewer deaths were reported in DA group (6%) vs. placebo (8%). Conclusion Darbepoetin alfa was well tolerated with an AE profile similar to placebo in HF subjects treated to a target Hb of 14.0 ± 1.0 g/dL. Contrary to recent data in other patient populations, there was no evidence of increased risk of mortality or cardiovascular events.

The 2005 American Heart Association/American College of Cardiology heart failure (HF) guidelines contributed to a renewed focus on "at-risk" patients and emphasized HF as a progressive disease. Patient categorization by stages focused attention on customization of therapy to achieve optimal, evidence-based treatments across the HF continuum. Therapy for risk factors that predispose patients to left ventricular dysfunction or other symptoms may help reduce HF development. beta-Blockers are valuable for treatment of HF; however, the class is heterogeneous, and proper beta-blocker selection for each HF stage is important. beta-Blockers have been used routinely to treat patients with stage A HF with hypertension. Recent controversy regarding the detrimental effects that some beta-blockers have on metabolic parameters has raised inappropriate concerns about the use of any beta-blocker for diabetes. beta-Blockade is standard therapy for the patient with stage B HF who has had a myocardial infarction, but few data are available concerning use in asymptomatic patients with left ventricular dysfunction. Additionally, beta-blockers are part of the core therapy for stage C HF and selected patients with stage D HF. This review examines the role and use of beta-blockers in each HF stage through an evidence-based approach to provide better understanding of their importance in this progressive disease. PubMed searches (1980-2008) identified large clinical trials that evaluated cardiovascular events and outcomes in any HF stage or hypertension. Search terms were heart failure, hypertension, beta-blocker, ACEI, ARB, and calcium channel blocker AND blood pressure coronary artery disease, diabetes, efficacy, left ventricular dysfunction, metabolism, mortality, myocardial infarction, or stroke.

Antidiuretic hormone, also known as arginine vasopressin, is a hormone with a multitude of physiologic activities including the control of urinary free water excretion. Antidiuretic hormone also plays a role in vasoconstriction and has 3 receptors that have been identified. Vasopressin analogs and antagonists have been extensively studied in animal models as well as in humans. Because heart failure is associated with a state of water retention, several vasopressin antagonists have been evaluated for their potential aquaretic effect. Diuretics remain the mainstay of treatment in acute and chronic volume overload but are not shown to improve survival. In fact, they are associated with numerous side effects including hypotension, electrolyte abnormalities, worsening renal function, and activation of renin-angiotensin-aldosternone system. Tolvaptan, conivaptan, and lixivaptan are some of the vasopressin antagonists that have been studied in heart failure. The results were initially encouraging with alleviation of symptoms and effective aquaresis without worsening of hyponatremia or renal function, but yet failed to show any effect on mortality in heart failure. With an increasing number of more selective orally active vasopressin antagonists, further studies are underway to establish the role of "Vaptans" in the treatment of heart failure and other disease states with volume overload and hyponatremia.

Background— Prior investigations suggest that superimposing continuous flow on aortic flow (continuous aortic flow augmentation) produces vasodilation, cardiac unloading, and improved cardiac performance. Methods and Results— We compared percutaneous continuous aortic flow augmentation (flow ≤1.5 L/min for up to 96 hours) plus medical therapy versus medical therapy alone by randomizing 168 patients (device, n=109; control, n=59) hospitalized with heart failure, reduced left ventricular ejection fraction and cardiac index, elevated pulmonary capillary wedge pressure, and renal impairment or substantial diuretic requirement despite intravenous inotropes/vasodilators. The primary composite efficacy end point included pulmonary capillary wedge pressure (72 to 96 hours) and days alive out of hospital off mechanical support over 35 days. The population’s illness severity posed unique challenges. Enrollment ended early because of an inability to demonstrate significant benefit on the primary composite end point (device, 17.4%; control, 13.6%; P =0.45) in the face of excess device group bleeding. Pulmonary capillary wedge pressure decreased from 28.8±6.3 mm Hg (mean±SD) to 24.9±7.2 mm Hg (average, 72 to 96 hours) and 28.9±7.1 to 26.5±6.2 mm Hg in the device and control groups, respectively (between-group P =0.074). Cardiac index progressively increased in the device (2.05±0.53 to 2.44±0.52 L · min −1 · m −2 ) but not the control (between-group P P =0.10). Through 65 days, device-to-control hazard ratios were as follows: all-cause mortality, 1.05 (95% confidence interval, 0.60 to 1.82); death or heart failure hospitalization, 0.87 (95% confidence interval, 0.57 to 1.33); and heart failure hospitalization, 0.66 (95% confidence interval, 0.38 to 1.13). Major bleeds occurred in 16.5% in the device (7.3% treatment related) and 5.1% in the control ( P =0.05) group. Conclusions— Continuous aortic flow augmentation improved cardiac performance, improving cardiac index and pulmonary capillary wedge pressure, but statistical significance for the primary efficacy end point was not attained. Hemodynamic and clinical observations provide direction toward additional studies to further investigate the clinical effects of this treatment.

Introduction and aim Post-percutaneous coronary intervention (PCI) length of hospital stay (LOHS) is one of the key modifiers of hospital cost and quality assessment. Commencing 2000, the cardiovascular services at our institution engaged in a continuous quality improvement program to reduce post-PCI LOHS. Methods All PCI patients were screened for potential early discharge. An expedited discharge protocol was applied to all suitable patients. Length of hospital stay and other outcomes were monitored daily. Data were compiled and reported monthly and quarterly by an independent chart review and data analysis team. Results Over the study period, PCI volume increased 4-fold. Annually, 61.8% to 78.4% of the patients were rendered suitable for abbreviated LOHS. Timely discharge of suitable candidates gradually improved from 77.6% (n = 116) discharged within 48 hours in 2000 to 95% (n = 480) discharged within 30 hours in 2006. Conclusion With the appropriate continuous quality improvement program, 30-hour post-PCI discharge is feasible in more than 95% of suitable cases.

Background Heart failure (HF) and cognitive impairment are both common in older adults. However, the association between the two has not been well studied. Methods and Results We explored the relationship between very probable HF, determined by self-reported symptoms, and cognitive impairment, defined as four or fewer correct on the Six-item Screener, in 14,089 participants of the Reasons for Geographic and Racial Differences in Stroke cohort. We determined the effect of adding demographic, socioeconomic status (SES), health behavior, and comorbidity covariates. In the univariate model, participants with very probable HF were 1.51 (95% confidence interval: 1.15–1.96) times more likely to have cognitive impairment than those without HF. As covariates were added to the model, the relationship between HF and cognitive impairment was attenuated and lost statistical significance after adjustment for depression. Demographic variables, Stroke Belt location (1.28 [1.11–1.48]), SES factors, prior stroke (1.43 [1.18–1.73]), and depression (1.66 [1.38–2.01]) remained significant in the multivariable model. Higher hemoglobin was associated (0.95 [0.9–1.00]) with modestly reduced odds of cognitive impairment. Conclusions The relationship between cognitive impairment and HF can be accounted for by multiple demographic and SES factors, and by comorbidities, some of which are modifiable. Persons with HF and cognitive impairment should be screened for anemia and depression.

MGuard is an ultra-thin polymer sleeve attached to the external surface stents. The polymer was designed to reduce distal embolization during coronary, renal, carotid, and vein graft stenting, and to potentially serve as a platform for uniform drug delivery. This report discusses the theoretical considerations that resulted in the conception of this device, and the scientific data that support the use of the innovation. With the encouraging initial feasibility and safety data, large-scale efficacy trials are currently in progress. Future applications of this platform for the treatment of cardiovascular disorders are discussed.

Glycoprotein inhibitors (GPI) are viewed as beneficial adjunctive pharmacotherapy agents for percutaneous coronary interventions (PCIs). The major benefit of GPI is derived from the reduction of ischemic events (mostly non-Q-wave myocardial infarctions) during PCI. There is no single randomized clinical trial demonstrating that any of these agents significantly reduces mortality in any clinical subset of patients. Studies of sustained oral GPI resulted in excessive death and myocardial infarctions. Reduction of ischemic end points was counteracted by excessive bleeding, vascular complications, and thrombocytopenia. These complications bear considerable medical and economic impact. The Acute Catheterization and Early Intervention Triage Strategy trial demonstrated that GPI, when added to heparin, enoxaparine, or bivalirudin, do not reduce mortality or ischemic events but significantly increase bleeding complications. Major bleeding resulted in threefold mortality at 1 year. In view of available data, the use of GPI should be limited to moderate-risk to high-risk PCI patients with low bleeding propensity. Protocols of abbreviated GPI administration and careful bleeding surveillance, in conjunction with lower doses of unfractionated heparin or new and possibly safer antithrombins, can potentially improve patient safety.

ObjectivesOur goal was to examine the effects of implementing a fully automated wireless network to reduce door-to-intervention times (D2I) in ST-segment elevation myocardial infarction (STEMI).BackgroundWireless technologies used to transmit prehospital electrocardiograms (ECGs) have helped to decrease D2I times but have unrealized potential.MethodsA fully automated wireless network that facilitates simultaneous 12-lead ECG transmission from emergency medical services (EMS) personnel in the field to the emergency department (ED) and offsite cardiologists via smartphones was developed. The system is composed of preconfigured Bluetooth devices, preprogrammed receiving/transmitting stations, dedicated e-mail servers, and smartphones. The network facilitates direct communication between offsite cardiologists and EMS personnel, allowing for patient triage directly to the cardiac catheterization laboratory from the field. Demographic, laboratory, and time interval data were prospectively collected and compared with calendar year 2005 data.ResultsFrom June to December 2006, 80 ECGs with suspected STEMI were transmitted via the network. Twenty patients with ECGs consistent with STEMI were triaged to the catheterization laboratory. Improvement was seen in mean door-to-cardiologist notification (−14.6 vs. 61.4 min, p < 0.001), door-to-arterial access (47.6 vs. 108.1 min, p < 0.001), time-to-first angiographic injection (52.8 vs. 119.2 min, p < 0.001), and D2I times (80.1 vs. 145.6 min, p < 0.001) compared with 2005 data.ConclusionsA fully automated wireless network that transmits ECGs simultaneously to the ED and offsite cardiologists for the early evaluation and triage of patients with suspected STEMI can decrease D2I times to

Background: Prior studies suggest an association between naturally high circulating levels of CD34+ cells (CD34) and better outcomes following ischemic events. Pts in the treatment arm of the PreSERVE-AMI study were infused with all CD34 yielded from their bone marrow harvest, resulting in pts with naturally higher CD34 cell counts being infused with a higher cell dose. To determine whether selection bias may have influenced results, we performed an analysis of the relationship between BM CD34 content and outcomes in PreSERVE-AMI. Methods: PreSERVE-AMI is a Phase 2, randomized, double-blind, placebo-controlled trial of autologous, BM derived CD34 (CLBS10) in pts with LV dysfunction (LVEF ≤48% by MRI) ≥4 days post-STEMI. All pts underwent mini BM harvest and were randomized 1:1 to intracoronary infusion of CD34 (minimum dose 10M±20% cells) or placebo (cell diluent). Primary safety endpoints included AEs, SAEs and MACE (CV mortality, HF hospitalization, reinfarction, revascularization). Secondary endpoints included LVEF change from baseline. Regression analyses were performed to assess the influence of BM CD34 content on outcomes. Results: 161 patients were randomized and received intracoronary infusion (Jan 2013-Dec 2014). Mean age was 57±10 and 82% were men. Mean follow-up time was 18 mo, and safety data are accruing. BM CD34 content was not associated with differences in baseline characteristics with the exception of diabetes prevalence being higher in those with higher BM CD34 count (p=0.03). In controls, regression analyses showed no association of BM CD34 content with rates of MACE (p=0.2), SAEs (p=0.4), or change in LVEF (p=0.9). However, in CD34 treated pts, there was a dose-dependent improvement in LV function (p=0.045) and dose-dependent trends in MACE and SAE reduction compared to controls. As previously reported SPECT perfusion improved to a similar degree in control and treated pts. Conclusions: These data suggest that intracoronary infusion of CD34 cells, rather than BM CD34 cell content, is responsible for the benefit observed in the CD34 treatment group. The finding of a dose-response relationship is an important advance for defining the CD34 as an active agent for tissue repair. Future studies will further define CD34 dosimetry.

Unicuspid aortic valve is a rare congenital malformation that usually presents in the 3rd to 5th decade of life—and usually with severe aortic stenosis or regurgitation. It often requires surgical correction. Diagnosis can be made with 2- or 3-dimensional transthoracic or transesophageal echocardiography, cardiac computed tomography, or cardiac magnetic resonance imaging. We report the case of a 31-year-old man who presented with dyspnea on exertion due to severe aortic stenosis secondary to a unicuspid unicommissural aortic valve. After aortic valve replacement, this patient experienced complete heart block that required the placement of a permanent pacemaker.

Background Daily measurements of left atrial pressure (LAP) may be useful for guiding adjustments in medical therapy that prevent clinical decompensation in patients with severe heart failure (HF). Study Design LAPTOP-HF is a prospective, multicenter, randomized, controlled clinical trial in ambulatory patients with advanced heart failure in which the safety and clinical effectiveness of a physician-directed patient self-management therapeutic strategy based on LAP measured twice daily by means of an implantable sensor will be compared with a control group receiving optimal medical therapy. The trial will enroll up to 730 patients with New York Heart Association functional class III symptoms and either a hospitalization for HF during the previous 12 months or an elevated B-type natriuretic peptide level, regardless of ejection fraction, at up to 75 investigational centers. Randomization to the treatment group or control group will be at a 1:1 ratio in 3 strata based on the ejection fraction (EF > or ≤35%) and the presence of a de novo CRT device indication. Summary LAPTOP-HF will provide essential information about the role of implantable LAP monitoring in conjunction with a new HF treatment paradigm across the spectrum of HF patients.

This was a multicenter, randomized, double-blind, placebo-controlled pilot study, evaluating the safety and efficacy of a standard care treatment regimen with the addition of either nesiritide or placebo (SCP) in 237 Emergency Department (ED)/Observation Unit (OU) patients with decompensated heart failure (HF). Efficacy measures included initial admission, length of hospital stay (LOS), and inpatient rehospitalization through 30 days. Compared to the standard care group, patients who also received nesiritide had 11% fewer inpatient hospital admissions at the index ED visit (55% SCP, 49% nesiritide, p = 0.436), and 57% fewer inpatient hospitalizations within 30 days after discharge from the index hospitalization (23% SCP, 10% nesiritide, p = 0.058). The duration of rehospitalization was shorter for nesiritide patients (median LOS 2.5 vs. 6.5 days, p = 0.032). The incidence of symptomatic hypotension was low and did not differ between the groups. This study showed that nesiritide is safe when used in the emergency department, observation units, or similar settings.

The onset of the clinical expression of rheumatic heart disease (RHD) is variable. Exercise or other states that necessitate increased cardiac output often precipitate symptoms. Mitral stenosis (MS) is present in 25% of patients with RHD, and 40% of patients have concomitant MS and mitral regurgitation. About two third of patients with MS have concurrent aortic insufficiency. Pulmonary and tricuspid insufficiency may occur from rheumatic involvement of these valves, or secondary to dilatation of valve annuli from pulmonary hypertension secondary to mitral and/or aortic valve disease. Pregnancy is associated with many hemodynamic changes including expanded intravascular volume, tachycardia, increased intracardiac dimensions, and valvular regurgitation. We report a case of a young female who developed flash pulmonary edema during parturition and was found to have abnormal rheumatic involvement of her aortic, mitral, and tricuspid valves. Successful triple valve repair was performed in a single operation. A review of rheumatic valvular abnormalities, and literature supporting multivalvular repair for rheumatic heart disease is provided.

Objectives We conducted a prospective multicenter registry in a large metropolitan area to define the clinical characteristics, hospital course, treatment, and factors precipitating decompensation in patients hospitalized for heart failure with a normal ejection fraction (HFNEF). Background The clinical profile of patients hospitalized for HFNEF has been characterized by retrospective analyses of hospital records and state data banks, with few prospective single-center studies. Methods Patients hospitalized for heart failure (HF) at 24 medical centers in the New York metropolitan area and found to have a left ventricular (LV) ejection fraction of ≥50% within seven days of admission were included in this registry. Patient demographics, signs and symptoms of HF, coexisting and exacerbating cardiovascular and medical conditions, treatment, laboratory tests, procedures, and hospital outcomes data were collected. Analysis by gender and race was prespecified. Results Of 619 patients, 73% were women, who were on average four years older than men (72.8 ± 14.1 years vs. 68.6 ± 13.8 years, p Conclusions Patients hospitalized for HFNEF are most often chronically incapacitated elderly women with a history of hypertension and increased LV mass. Reasons for clinical decompensation are identified in only one-half of patients.

Cardiac natriuretic peptides are a family of structurally related peptides that are important in sodium and volume homeostasis. They consist of atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide and are elevated in patients with left ventricular dysfunction. In contrast with vasoconstrictive hormones, such as norepinephrine, angiotensin II, and arginine vasopressin, which worsen the physiological milieu in patients with left ventricular dysfunction and heart failure, the natriuretic peptides ameliorate these effects by promoting natriuresis, diuresis, peripheral vasodilation, and by inhibiting the renin-angiotensin system. The serum levels of the natriuretic peptides correlate with the severity of heart failure and appear to have prognostic value. The present article reviews the biochemistry, molecular biology, and physiology of natriuretic peptides and their pathophysiological link to heart failure. The therapeutic uses of natriuretic peptides are also reviewed. This includes the use of intravenous nesiritide, a synthetic human brain natriuretic peptide, and the recently developed vasopeptidase inhibitors which are designed to inhibit the degradation of natriuretic peptides.

Background: The latest American Heart Association guidelines have recommended palliative/hospice care in selected patients with end-stage heart failure (HF). However, limited information exists regarding the trends in utilization of hospice care in this patient population. Methods: Data from the

Aim Concentric hypertrophy is thought to transition to left ventricular (LV) dilatation and systolic failure in the presence of long standing hypertension (HTN). Whether or not this transition routinely occurs in humans is unknown. Methods We consecutively enrolled African American patients hospitalized for acute decompensated volume overload heart failure (HF) in this retrospective study. All patients had a history of HTN and absence of obstructive coronary disease. Patients were divided into those with normal left ventricular ejection fraction (LVEF) and reduced LVEF. LV dimensions were measured according to standard ASE recommendations. LV mass was calculated using the ASE formula with Devereux correction. Results Patients with normal LVEF HF were significantly older, female and had a longer duration of HTN with higher systolic blood pressure on admission. LV wall thickness was similarly elevated in both groups. LV mass was elevated in both groups however was significantly greater in the reduced LVEF HF group compared to the normal LVEF HF group. Furthermore, gender was an independent predictor for LV wall thickness in normal LVEF HF group. Conclusion In African American patients with HF our study questions the paradigm that concentric hypertrophy transitions to LV dilatation and systolic failure in the presence of HTN. Genetics and gender likely play a role in an individual’s response to long standing hypertension.

Patients with end-stage liver disease (ESLD) may develop left ventricular diastolic dysfunction in the absence of coronary artery disease or hypertension. Prognostic value of the presence of diastolic dysfunction on post orthotopic liver transplant (OLT) survival is unknown. We report on the

We have previously reported from our institution outcomes in patients with ST-elevation myocardial infarction (STEMI) based on mode of arrival i.e., fully automated pathway for pre-hospital ECG transmission (STAT-MI pathway) versus other. We now report on the use of ECG Selvester score (SS) in

The purpose of this study was to determine the pharmacodynamics and pharmacokinetics of omapatrilat, administered orally (25 mg) or intravenously (10 mg) in 19 New York Heart Association class II and class III congestive heart failure (CHF) patients versus 17 healthy controls matched for age, race, gender, and weight. The plasma concentrations of atrial natriuretic peptide (ANP) increased by approximately 20% and 30% in CHF and control subjects, respectively, at 4 hours after intravenous or oral omapatrilat administration. Similar elevation in the cyclic guanosine monophosphate concentration (25% to 35%) and ANP urinary excretion (21 ng/24 h to 22 ng/24 h) was seen in all treatment groups after omapatrilat administration. Angiotensin-converting enzyme activity was > 90% inhibited at 4 hours after dosing and remained approximately 60% to 70% inhibited at 24 hours after dosing. The levels of endothelin-1 and endothelin-2 remained unchanged after oral or intravenous administration of omapatrilat. The maximal reduction in seated blood pressure compared with baseline was similar for CHF and control subjects. Clinical pharmacokinetic parameters were similar in both groups after intravenous dosing, but maximum concentration and area under the concentration-time curve were elevated in CHF patients compared with controls after oral dosing. Omapatrilat was well tolerated; differences in systemic exposure and metabolism between CHF patients and controls did not appear to be clinically significant.

Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fractionor = 40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by approximately 6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an approximately 2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.