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Background Historically, there is perceived pressure to achieve therapeutic levels of tacrolimus quickly after heart transplant (HT). We evaluated the association between time within therapeutic tacrolimus range and time to therapeutic trough and rejection in the 30 days following HT. Methods This is a single-center retrospective cohort study of consecutive adult HT patients receiving immunosuppression. Goal trough tacrolimus levels were 10-15 ng/ml. Surveillance endomyocardial biopsies were performed weekly for 4 weeks. Outcomes included the effect of time to and time-in-therapeutic tacrolimus range (Rosendaal method) on 30-day clinical rejection, 1R/1B, and 2R or higher histologic occurrences. Results We reviewed 67 HT patients (median age 58.8 yrs). For clinical rejection versus no-rejection groups, the median (25th, 75th percentile) time to therapeutic tacrolimus levels was 9.5 (8, 12.3) days versus 9.0 (7, 13) days (p=0.623). The median time-in-therapeutic tacrolimus range was 34.1% (23.2, 42.2) versus 36.2% (19.9, 51.2), respectively (p=0.512). Similarly, we observed no significant differences in time to and time-in-therapeutic tacrolimus range in patients who developed grade 1R/1B (p=0.650 and p=0.725) or grade 2R or higher histology (p=0.632 and p=0.933). Conclusions Our small single-center analysis suggests that neither time to nor time in therapeutic tacrolimus range predicted acute rejection within 30 days of HT.

Right-sided heart failure is the most common cause of death in pulmonary hypertension (PH). Echocardiographic measurements of right atrial (RA) size are associated with worse outcome in PH, however the association between RA function and death in PH has not been well-described. 160 PH patients (World Health Organization groups 1-5) underwent cardiac magnetic resonance imaging (cMRI) and right heart catheterization (RHC) within 6 weeks of each other at a tertiary care academic medical center in the United States. We measured cMRI RA maximum and minimum volumes indexed to body surface area and calculated RA emptying fraction (RAEF). We evaluated the relationship between RAEF and clinical variables with death using Cox proportional hazard models. 57 deaths occurred during a median follow-up of 3.5 years (36 % died overall, 10 % per year). RAEF was directly correlated in univariate analyses with right ventricular (RV) ejection fraction, left ventricular (LV) ejection fraction, LV size, cardiac index, absence of tricuspid and pulmonic regurgitation, absence of pericardial effusion, estimated glomerular filtration rate, 6-minute walk distance, and pulmonary arterial oxygen saturation, whereas it was inversely correlated with death, BNP, heart rate, mean RA pressure, mean PA pressure, pulmonary and systemic vascular resistance, RV size, and RA size. Using multivariate analyses, RAEF had a robust inverse association with death after adjusting for measured risk factors (HR per 5 % change in RAEF: 0.83 [95 % CI 0.73-0.94], p = 0.003). In PH patients, decreased RAEF by cMRI is independently associated with worse survival after adjustment for other risk factors.

Objective: To evaluate the data supporting the approval of selexipag and discuss its potential place in therapy for managing pulmonary arterial hypertension (PAH). Data Sources: A systematic review of the literature for all relevant articles was performed through January 16, 2017, using MEDLINE and SCOPUS. A manual search of references from reports of clinical trials, review articles, and recent conference abstracts was performed to identify additional relevant studies. Study Selection and Data Extraction: Eligible citations included in vitro or in vivo evaluations of selexipag, with no restrictions on patient population or indication. Data related to the patient populations and outcomes of interest were extracted from each citation. Data Synthesis: Single phase II and phase III trials have been published evaluating selexipag in patients with PAH. In 43 patients, the phase II trial showed that selexipag significantly reduced pulmonary vascular resistance by 30% versus placebo ( P = 0.0045) and improved 6-minute walk distance by 24 m ( P < 0.05). The larger phase III trial enrolled 1156 patients with PAH, showing that selexipag lowered the incidence of death or PAH-related complications by 40% versus placebo ( P < 0.001). Selexipag also improved 6-minute walk distance and lowered hospitalization risk. Common adverse events included headache, diarrhea, nausea, and jaw pain. Conclusions: The specific role of selexipag for managing PAH patients is unclear because of its modest efficacy, lack of mortality reduction, and cost similar to intravenous prostacyclins. Additional clinical trials exploring combination therapy as well as its role in other types of pulmonary hypertension are needed.

In the last decade, the role of the right ventricle (RV) has been increasingly recognized in a variety of conditions, contributing to the pathophysiology of disease and the prediction of outcomes. Recent echocardiography guidelines focused on the RV have been published by the American Society of Echocardiography to encourage a standardized approach in assessing RV size and function. In this article, we review the recently published echocardiog- raphy guidelines for assessing RV size and function, and their importance in clinical practice. We discuss advantages and disadvantages of currently available imaging techni- ques for evaluating the RV morphology, size, and systolic function. Basic methods such as TAPSE, tissue Doppler, RIMP, and fractional area change are discussed, as are more emerging techniques such as strain and strain rate. Additional insights are provided into upcoming uses of echocardiography in the areas or RV dyssynchrony and three-dimensional echocardiography.

Purpose Calcineurin inhibitors are a cornerstone of immunosuppression post-orthotopic heart transplantation (OHT). The relationship of tacrolimus exposure, measured by time within therapeutic range (TTR), and level variability, measured by standard deviation (SD) of trough blood levels, to post-OHT acute rejection is unclear. We evaluated if tacrolimus TTR or variability in the 1-year post OHT impacted rejection. Methods This was a single-center, retrospective cohort study of consecutive adult OHT patients receiving standard immunosuppression with tacrolimus, MMF, and prednisone. Tacrolimus TTR was calculated up to 1 year using protocol goal ranges (10-15 ng/mL for months 0-2, 8-12 ng/mL for months 2-6 and 5-10 ng/mL for months 6-12) using the Rosendaal method. The primary outcomes included the association of TTR and level variability with 1-year clinical rejection (defined as any patient receiving ≥ 125 mg of IV methylprednisolone from post-op day 7-365). We analyzed categorical and continuous variables using chi-square and Mann Whitney-U respectively. Time-to-event analysis was conducted for 1-yr clinical rejection using both Kaplan-Meier and Cox Proportional Hazards methods, whereby TTR was calculated until event or censor date and reported using hazard ratio (HR) and 95% confidence interval (CI). Results 78 patients underwent OHT (age, 56.2 ± 12.7 years) with a median 1-yr TTR of 50.2%. Clinical rejection occurred in 31 (39.7%) patients. Those with clinical rejection had a significantly lower median TTR (45.9%) and higher level variability (5.8) than those without rejection (TTR 56.5%, variability 4.9; p=0.021 and p=0.005, respectively) (Figure A&B) . Time to therapeutic tacrolimus level (median 9 days) did not predict 1-year clinical rejection (p=0.274). In a univariable Cox Proportional Hazards Model (median TTR=40%), TTR Figure C ). Five (6.4%) patients died in the first year after OHT. TTR 50% (p=0.018, Figure D ). Conclusions Lower tacrolimus TTR and/or greater level variability predicts clinical rejection and death in the first year after OHT. TTR and and level variability should be monitored in addition absolute levels.

Chronic Thromboembolic Pulmonary Hypertension(CTEPH) is the only pulmonary hypertension group with a cure. 50-year-old male presented with disabling dyspnea. Right heart catheterization(RHC) showed pulmonary artery pressure(PAP) 90/30 mm Hg (mean 51 mm Hg), pulmonary capillary wedge pressure(PCWP)

Background Effective closure performance for patent foramen ovale (PFO) has been suggested to be one of the factors that plays a relevant role in future clinical outcomes after stroke or transient ischemic attack. Methods Between January 2009 and June 2012, all consecutive patients undergoing transcatheter PFO closure in our institution using the Amplatzer PFO Occluder (APO) (St Jude Medical, St Paul, MN), BioSTAR (NMT Medical Inc, Boston, MA), GORE HELEX (HELEX) (W.L. Gore & Associates, Newark, DE), and GORE Septal Occluder (GSO) (W.L. Gore & Associates) were included. Closure performance was assessed using transesophageal echocardiography 4 months after the index procedure. Results One hundred ninety-three patients were included in the study. Patient distribution was as follows: (1) 48 GSO (24.8%); (2) 34 HELEX (17.6%); (3) 74 APO (38.3%); and (4) 37 BioSTAR (19.1%). No complications occurred during device implantation. During clinical follow-up (20.8 ± 13.2 months), 2 (1.1%) patients had a stroke, 3 (1.7%) patients had a peripheral embolism, and 8 (4.7%) patients presented with a documented atrial arrhythmia. There were no significant differences in clinical outcomes among the devices. Transesophageal echocardiography follow-up revealed higher closure rates with GSO (92.6%) and BioSTAR (93.7%) compared with HELEX (74.2%; P = 0.031 and P = 0.034, respectively) and APO (76.4%; P = 0.036 and P = 0.041, respectively). Conclusions The GSO and BioSTAR showed better closure rates than HELEX and APO at 4 months. PFO closure is a safe procedure with a low rate of clinical events at follow-up.