Infectious complications after cardiac transplantation in patients bridged with mechanical circulatory support devices versus medical therapy.

BACKGROUND: Mechanical circulatory support (MCS) is increasingly used as a bridge to heart transplantation. It is not known whether patients who receive MCS as bridge to transplantation (BTT) have more frequent and severe infectious complications in the first transplant year. METHODS: Using a retrospective cohort in a single large transplant center from 2009 to 2014, we compared rates of post-transplant infections among patients bridged to transplantation with medical therapy (n = 134) or MCS (n = 178) over the first post-transplant year. Serious infections necessitated >14 days of continuous intravenous antibiotic therapy. RESULTS: Pre-transplant device infections were common in the MCS group (32.6%). The proportion of patients with any infection (74.2% vs 60.5%; p = 0.01, relative risk 1.23 [1.04 to 1.44]) or serious infections (45.5% vs 31.3%; p = 0.01, relative risk 1.45 [1.08 to 1.96]) in the first post-transplant year was significantly higher in the MCS group than in the medical therapy group, respectively. MCS patients but not medical therapy patients had significantly higher 1-year all-cause mortality in the presence of post-operative infections (16.7% vs 4.3%, p = 0.04). Device-related infections occurred in 67 (37.6%) MCS patients up to 337 days post-transplant, including 26 (14.6%) patients without a known or active pre-operative device infection. In multivariable analyses, age, intensive care unit length of stay, presence of pre-transplant device infection and use of an anti-thymocyte agent were associated with increased rates of infection. CONCLUSION: More infectious complications are experienced by patients who receive MCS as BTT, with a significant occurrence of device-related infections. MCS patients with post-transplant infections have higher mortality at 1 year compared with uninfected MCS patients.

Prognostic significance of left atrial appendage "sludge" in patients with atrial fibrillation: a new transesophageal echocardiographic thromboembolic risk factor.

BACKGROUND: When stratifying thromboembolic risk to patients with atrial fibrillation (AF), left atrial appendage (LAA) thrombus is currently the only echocardiographic index that absolutely contraindicates cardioversion. The aim of this study was to identify the predictors of LAA "sludge" and its impact on subsequent thromboembolism and survival in patients with AF. METHODS: A total of 340 patients (mean age, 66 ± 12 years; 75% men) who underwent transesophageal echocardiography to exclude LAA thrombus before electrical cardioversion or radiofrequency pulmonary vein isolation) for AF were retrospectively studied. LAA sludge was defined as a dynamic, viscid, layered echodensity without a discrete mass, visualized throughout the cardiac cycle. Follow-up was obtained after a mean of 6.7 ± 3.7 years, and patients were analyzed according to LAA thrombus (n = 62 [18%]), sludge (n = 47 [14%]), or spontaneous echocardiographic contrast (n = 84 [25%]). Patients without these transesophageal echocardiographic characteristics served as controls (n = 147 [43%]). RESULTS: LAA sludge was independently predicted by enlarged left atrial area (odds ratio, 4.54; 95% confidence interval [CI], 2.38-8.67; P < .001), reduced LAA emptying velocity (odds ratio, 12.7; 95% CI, 6.11-26.44; P < .001), and reduced left ventricular ejection fraction (odds ratio, 2.11; 95% CI, 1.03-4.32; P < .001). Thromboembolic event and all-cause mortality rates in patients with sludge were 23% and 57%, respectively. Multiple logistic regression analyses identified the presence of LAA sludge to be independently associated with thromboembolic complications (adjusted hazard ratio, 3.43; 95% CI, 1.42-8.28; P = .006) and all-cause mortality (adjusted hazard ratio, 2.02; 95% CI, 1.22-3.36; P = .007). CONCLUSION: Sludge within the LAA is independently associated with subsequent thromboembolic events and all-cause mortality in patients with AF.

Emerging role of serelaxin in the therapeutic armamentarium for heart failure.

Acute heart failure (AHF) remains a major cause of morbidity and mortality, with an increasing prevalence anticipated over the next few decades as the population ages, heightening already significant health and economic burdens to society. New therapies for AHF have stalled over the past decade for a multitude of reasons, principal among them the heterogeneous population of patients affected with potentially multiple operative pathophysiologic mechanisms making a single targeted therapy a challenge. Serelaxin, a recombinant form of human relaxin-2, mediates adaptive cardiovascular effects during pregnancy that could be beneficial in the AHF population, primarily through nitric oxide-mediated vasodilation. Serelaxin is a novel therapeutic agent that has shown promise in the treatment of AHF in predefined subpopulations, though studies powered for "hard" outcomes are still pending. In this review, we examine the clinical investigations to date involving serelaxin in patients with heart failure and its possible emerging role in the future therapy of AHF.

Efficacy of the CHADS2 scoring system to assess left atrial thrombogenic milieu risk before cardioversion of non-valvular atrial fibrillation.

The CHADS2 scoring system was found to be a good predictor for risk stratification of stroke in patients with atrial fibrillation. The effectiveness of this scoring system in assessing thrombogenic milieu before direct-current cardioversion has not yet fully been established on a large scale. In this study, data from 2,369 consecutive patients in whom transesophageal echocardiography was performed for screening before direct-current cardioversion from 1999 to 2008 were analyzed. Left atrial (LA) or LA appendage (LAA) thrombogenic milieu (spontaneous echo contrast, sludge, and thrombus) was investigated. The results were correlated with CHADS2 score findings. The mean age was 66 ± 13 years, and the ratio of men to women was 2.2:1. CHADS2 scores of 0, 1, 2, 3, 4, 5 and 6 were present in 11%, 25%, 30%, 22%, 8%, 3%, and 1% of the studies, respectively. The prevalence of LA or LAA sludge or thrombus increased with increasing CHADS2 scores (2.3%, 7%, 8.5%, 9.9%, 12.3%, and 14.1% for scores of 0, 1, 2, 3, 4, and 5 or 6, respectively, p = 0.01). In a multivariate model, an ejection fraction ≤20% was the best predictor of LA or LAA sludge or thrombus (odds ratio 2.99, p <0.001). In conclusion, transesophageal echocardiographic markers of thrombogenic milieu were highly correlated with increasing CHADS2 scores in patients who underwent transesophageal echocardiography-guided cardioversion. Giving more value to echocardiographic findings, such as the left ventricular ejection fraction, and its different levels (especially an ejection fraction ≤20%) might improve the precision of the CHADS2 scoring scheme to predict thrombogenic milieu in the left atrium or LAA as a surrogate to cardioembolic risk in patients with atrial fibrillation.

Indications for TEE before cardioversion for atrial fibrillation: implications for appropriateness criteria.

The purpose of this study was to evaluate appropriateness of transesophageal echocardiography (TEE) before direct current cardioversion (DCC), investigate indications for TEE, and analyze if indications are predictive of outcome. According to American College of Cardiology Foundation/American Society of Echocardiography 2011 Appropriateness Criteria, TEE is appropriate in the evaluation of patients with atrial fibrillation (AF) to facilitate clinical decision making with regards to anticoagulation and/or DCC. However, it is unclear in which instances physicians utilize TEE. We reviewed 671 TEE studies in 604 AF patients (age 66 ± 13 years, 67% male) in which TEE was performed before DCC for left atrial thrombus (LAT)/sludge. Studies were divided by the main indication for TEE into the following 8 categories: 1) congestive heart failure (CHF)/hemodynamic compromise; 2) symptomatic; 3) new onset AF; 4) hospitalized and symptomatic; 5) high stroke risk; 6) subtherapeutic anticoagulation; 7) miscellaneous; and 8) inappropriate for TEE. The main indications for TEE before DCC were symptomatic (26.4%) and CHF/hemodynamic compromise (26.1%). We deemed 2.7% of the studies as inappropriate. LAT/sludge was found in 8.2% of studies. Incidence of LAT/sludge differed significantly between indications (p = 0.0021) and the highest incidences occurred in the high stroke risk (17.6%) and hospitalized and symptomatic (14.1%) categories. No LAT/sludge was found in the miscellaneous or inappropriate groups. Stroke occurred in 2.5% (n = 15) of all patients and in all groups except for miscellaneous and inappropriate (p = 0.3). TEE is appropriately used prior to DCC for patients with the main indications of symptomatic and CHF/hemodynamic compromise. In a minority of studies, TEE utilization was inappropriate. Incidence of LAT/sludge differed between indications.

Role of CHADS2 score in evaluation of thromboembolic risk and mortality in patients with atrial fibrillation undergoing direct current cardioversion (from the ACUTE Trial Substudy).

The CHADS(2) (congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke or transient ischemic attack [2 points]) scoring scheme has been found to be a good predictor of stroke risk in patients with nonvalvular atrial fibrillation (AF). However, the value of the CHADS(2) scoring system in the risk stratification of patients with AF who undergo direct-current cardioversion has not yet been specifically investigated. In this study, a subgroup of 541 patients from the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study who had AF for >48 hours and planned to undergo transesophageal echocardiography before direct-current cardioversion were enrolled. Each patient had a CHADS(2) score calculated. Of the patients with CHADS(2) scores of 0, 14 (10%) were found to have left atrial appendage thrombi on transesophageal echocardiography. After 6 months of follow up, patients with CHADS(2) scores of 3 to 6 showed a significantly higher mortality rate in comparison with patients with lower CHADS(2) scores (4.3% vs 0.5%, p = 0.004), despite their similar prevalence of left atrial appendage thrombus and stroke (thrombus: 13.4% vs 11.6%, p = 0.60; stroke: 0% vs 0.3%, p = 0.70). In conclusion, the CHADS(2) scoring system may be useful for predicting short-term mortality risk in patients with AF receiving elective direct-current cardioversion. However, in the preprocedural risk assessment of these patients, the CHADS(2) scoring system is not reliable in predicting risk for left atrial appendage thrombus formation, especially in patients with low CHADS(2) scores.

Heart transplantation and cardiac amyloidosis: approach to screening and novel management strategies.

Limited data exist regarding screening methods and outcomes for orthotopic heart transplantation (OHT) in cardiac amyloidosis. As a result, uncertainty exists over the best approach to OHT for cardiac amyloidosis and for the timing of critical post-transplant therapies. This article reviews 6 patients who underwent OHT for cardiac amyloidosis at the Stanford University Amyloid Center from 2008 to present. All patients with light-chain amyloidosis received chemotherapy in the interval between OHT and autologous hematopoietic stem cell transplant. Five patients remain alive up to 25 months after OHT, without evidence of recurrent cardiac amyloid deposition. A novel strategy of OHT, followed by light-chain suppressive chemotherapy before autologous hematopoietic stem cell transplant, is feasible for patients with light-chain amyloidosis.

Role of the CHADS2 score in the evaluation of thromboembolic risk in patients with atrial fibrillation undergoing transesophageal echocardiography before pulmonary vein isolation.

OBJECTIVES: The goals of this study were to determine: 1) if low-risk patients assessed by a CHADS(2) score, a clinical scoring system quantifying a risk of stroke in patients with atrial fibrillation (AF), require a routine screening transesophageal echocardiogram (TEE) before pulmonary vein isolation (PVI); and 2) the relationship of a CHADS(2) score with left atrial (LA)/left atrial appendage (LAA) spontaneous echo contrast, sludge, and thrombus. BACKGROUND: There is no clear consensus of whether a screening TEE before catheter ablation of AF should be performed in every patient. METHODS: Initial TEEs for pre-PVI of 1,058 AF patients (age 57 +/- 11 years, 80% men) were reviewed and compared with a CHADS(2) score. RESULTS: CHADS(2) scores of 0, 1, 2, 3, 4, 5, and 6 were present in 47%, 33%, 14%, 5%, 1%, 0.3%, and 0% of patients, respectively. The prevalence of LA/LAA thrombus, sludge, and spontaneous echo contrast were present in 0.6%, 1.5%, and 35%. The prevalence of LA/LAA thrombus/sludge increased with ascending CHADS(2) score (scores 0 [0%], 1 [2%], 2 [5%], 3 [9%], and 4 to 6 [11%], p < 0.01). No patient with a CHADS(2) score of 0 had LA/LAA sludge/thrombus. In a multivariate model, history of congestive heart failure and left ventricular ejection fraction <35% were significantly associated with sludge/thrombus. CONCLUSIONS: The prevalence of LA/LAA sludge/thrombus in patients with AF undergoing a pre-PVI screening TEE is very low (<2%) and increases significantly with higher CHADS(2) scores. This suggests that a screening TEE before PVI should be performed in patients with a CHADS(2) score of >or=1, and in patients with a CHADS(2) score of 0 when the AF is persistent and therapeutic anticoagulation has not been maintained for 4 weeks before the procedure.