PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI.

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<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose-dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (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.

In-Hospital Outcomes and Complications of Coronary Artery Bypass Grafting in the United States Between 2008 and 2012.

OBJECTIVE: To investigate the frequency and predictors of in-hospital complications among patients undergoing coronary artery bypass grafting (CABG) in the United States. DESIGN: Retrospective national database analysis SETTINGS: United States hospitals. PARTICIPANTS: A weighted sample of 1,910,236 patients undergoing CABG surgery identified from the National (Nationwide) Inpatient Sample from 2008 to 2012. INTERVENTIONS: 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 (p<0.001). 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 (p<0.001), while the rate of postoperative hemorrhage showed a 35.8% relative increase in 2012 compared to 2008. CONCLUSION: 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.

Chordae Tendineae Rupture in the United States: Trends of Outcomes, Costs and Surgical Interventions.

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.

QT Prolongation and Clinical Outcomes in Patients with Takotsubo Cardiomyopathy.

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.

Rationale and Design of the Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy Study (LAPTOP-HF).

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.

Comparison of efficacy and safety of intracoronary sodium nitroprusside and intravenous adenosine for assessing fractional flow reserve.

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.

Atypical stress-induced cardiomyopathy: a case series.

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 significant 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.

New index for assessing the chronotropic response in patients with end-stage liver disease who are undergoing dobutamine stress echocardiography.

The inability to achieve 85% of the maximum predicted heart rate (MPHR) on dobutamine stress echocardiography (DSE) is defined as chronotropic incompetence and is a predictor of major cardiac events after orthotopic liver transplantation (OLT). The majority of patients with end-stage liver disease (ESLD) receive beta-blockers for the prevention of variceal bleeding. In these patients, it is impossible to determine whether chronotropic incompetence is secondary to cirrhosis-related autonomic dysfunction or is merely a beta-blocker effect. We evaluated the usefulness of the maximum achieved heart rate (MAHR) and the heart rate reserve (HRR) in the detection of chronotropic incompetence in ESLD patients on beta-blocker therapy before DSE. We also evaluated the usefulness of a new index, the modified heart rate reserve (MHRR), in diagnosing chronotropic incompetence and predicting major cardiovascular adverse events after OLT. The study population consisted of 284 ESLD patients. The mean values of MAHR (expressed as a percentage of 85% of MPHR) and HRR were significantly lower for patients on beta-blockers versus patients off beta-blockers [97.1% versus 101.6% (t = 5.01, P < 0.001) and 71.7% versus 77.3% (t = 4.03, P < 0.001), respectively], whereas the values of MHRR were similar in patients on beta-blockers and patients off beta-blockers [102.3% versus 102.1% (t = 0.04, P = 0.97)]. A regression analysis showed a significant association of MAHR (P < 0.001) and HRR (P < 0.001) with beta-blockers, whereas MHRR was not associated with beta-blocker treatment (P = 0.92). MAHR and HRR were found to have no value for diagnosing chronotropic incompetence in ESLD patients. MHRR was not affected by beta-blocker therapy. Patients who developed heart failure (HF) and myocardial infarction (MI) after OLT had significantly lower MHRR values according to pretransplant DSE. MHRR was significantly associated with the subsequent development of HF (P = 0.01) and MI (P = 0.01) after OLT. MHRR may be useful for the determination of the target heart rate for stress testing, the diagnosis of chronotropic incompetence, and the prediction of adverse cardiac events after OLT.

Matched Cohort Study of Convalescent COVID-19 Plasma Treatment in Severely or Life Threateningly Ill COVID-19 Patients.

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.

HFSA 2010 Comprehensive Heart Failure Practice Guideline.

Heart failure (HF) is a syndrome characterized by high mortality, frequent hospitalization, reduced quality of life, and a complex therapeutic regimen. Knowledge about HF is accumulating so rapidly that individual clinicians may be unable to readily and adequately synthesize new information into effective strategies of care for patients with this syndrome. Trial data, though valuable, often do not give direction for individual patient management. These characteristics make HF an ideal candidate for practice guidelines. The 2010 Heart Failure Society of America comprehensive practice guideline addresses the full range of evaluation, care, and management of patients with HF.

An unusual combination of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) and a right coronary artery system with two separate ostia from the aorta in an adult.

We describe a patient with an infrequent combination of variants in both the right and the left coronary arterial ostia, namely a combination of two separate right coronary artery (RCA) ostia from the aorta, and an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). To our knowledge, such a combination has not been previously reported. Based on published statistics for individual variants, such a combination is expected to occur approximately once for every 500,000 to one million live births. ALCAPA and dual RCA anatomy was characterized in our patient by echocardiography, conventional angiography, and multidetector computed tomography before and after Takeuchi repair.

Effects of continuous aortic flow augmentation in patients with exacerbation of heart failure inadequately responsive to medical therapy: results of the Multicenter Trial of the Orqis Medical Cancion System for the Enhanced Treatment of Heart Failure Unresponsive to Medical Therapy (MOMENTUM).

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

Automated contrast injectors for angiography: devices, methodology, and safety.

Automated contrast injectors (ACIs) are widely employed in interventional cardiology, radiology and neurology. Information regarding the specifications of advanced ACIs and the appropriate injection settings of these devices is limited in the medical literature. This review describes the specifications of the most widely used ACIs and provides appropriate recommendations for injection settings for the various angiographic studies. These recommendations are based on expert consensus and commercial experience regarding characteristics of devices, catheters and contrast. The suggested settings were not subject to rigorous comparative clinical assessment. This review should increase the familiarity, comfort and appreciation of safety among ACI users.

Enormous right atrial hemangioma in an asymptomatic patient: a case report and literature review.

We report the case of an enormous right atrial hemangioma in an asymptomatic 42-year-old woman. The diagnosis was made by echocardiogram after the patient was found to have an abnormal EKG during a routine medical exam. The hemangioma is the largest described in English literature. The tumor was surgically resected and the patient did well postoperatively. In this case report, we discuss the discovery of the tumor and treatment of our patient. A brief discussion of cardiac hemangiomas follows.

Cardiac amyloidosis in a patient with multiple myeloma: a case report and review of literature.

We report a case of a 52-year-old man with multiple myeloma and rapidly progressive heart failure who died unexpectedly from a probable arrhythmia. Postmortem examination revealed infiltrative amyloid cardiomyopathy, a rare cause of predominantly diastolic myocardial disease. Cardiac amyloidosis should be considered in any patient presenting with congestive heart failure, preserved systolic function, and a discrepancy between a low QRS voltage on electrocardiography and an apparent left ventricular hypertrophy on sonogram. The pattern of left ventricular diastolic dysfunction changes during the course of amyloidosis and the classically described restrictive physiology occurs only in advanced stages of the disease.

Factors contributing to global cognitive impairment in heart failure: results from a population-based cohort.

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.

Length of hospital stay after percutaneous coronary interventions.

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.

Coronary stenting with MGuard: from conception to human trials.

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 IIb/IIIa inhibitors: questioning indications and treatment algorithms.

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.

Trends in Cardiac Tamponade Among Recipients of Permanent Pacemakers in the United States: From 2008 to 2012.

OBJECTIVES: The aim of this study was to describe the trends and predictors of cardiac tamponade among permanent pacemaker (PPM) recipients in the United States between 2008 and 2012. BACKGROUND: Limited data exist regarding the burden, trend, and predictors of tamponade in patients following PPM implantation. METHODS: The National (Nationwide) Inpatient Sample database was used to identify PPM implantations between 2008 and 2012. RESULTS: Among 922,549 patients who received PPM devices between 2008 and 2012, cardiac tamponade occurred in 2,595 patients (0.28%). Overall, in-hospital cardiac tamponade rates increased by 35% among recipients of PPMs. The incidence rate steadily increased from 0.26% in 2008 to 0.35% in 2012 (p < 0.0001). Although the mean age (p = 0.28) and sex distribution (p = 0.25) did not change over the years, the rate of in-hospital mortality increased among patients who developed tamponade from 2008 to 2012 (p = 0.014). After multivariate adjustment for patient and hospital characteristics, female sex (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.04 to 1.54; p = 0.011), dual-chamber pacemakers (OR: 1.68; 95% CI: 1.17 to 2.41; p < 0.004), and chronic liver disease (OR: 3.18; 95% CI: 1.92 to 5.64; p < 0.001) were found to be independently associated with a greater odds of cardiac tamponade. Conversely, hypertension (OR: 0.71; 95% CI: 0.45 to 0.94; p = 0.021) and atrial fibrillation (OR: 0.78; 95% CI; 0.61 to 0.96; p = 0.002) were associated with lower odds of tamponade. CONCLUSIONS: The burden of cardiac tamponade associated with PPM implantation has steadily increased in the United States. Specific patient factors were identified that could predict the risk for developing tamponade among PPM recipients.