EmPHasis-10 as a measure of health-related quality of life in pulmonary arterial hypertension: data from PHAR.

INTRODUCTION: While the performance of the emPHasis-10 (e10) score has been evaluated against limited patient characteristics within the United Kingdom, there is an unmet need for exploring the performance of the e10 score among pulmonary arterial hypertension (PAH) patients in the United States. METHODS: Using the Pulmonary Hypertension Association Registry, we evaluated relationships between the e10 score and demographic, functional, haemodynamic and additional clinical characteristics at baseline and over time. Furthermore, we derived a minimally important difference (MID) estimate for the e10 score. RESULTS: We analysed data from 565 PAH (75% female) adults aged mean±sd 55.6±16.0 years. At baseline, the e10 score had notable correlation with factors expected to impact quality of life in the general population, including age, education level, income, smoking status and body mass index. Clinically important parameters including 6-min walk distance and B-type natriuretic peptide (BNP)/N-terminal proBNP were also significantly associated with e10 score at baseline and over time. We generated a MID estimate for the e10 score of -6.0 points (range -5.0--7.6 points). CONCLUSIONS: The e10 score was associated with demographic and clinical patient characteristics, suggesting that health-related quality of life in PAH is influenced by both social factors and indicators of disease severity. Future studies are needed to demonstrate the impact of the e10 score on clinical decision-making and its potential utility for assessing clinically important interventions.

Disseminated Acanthamoeba infection in a heart transplant recipient treated successfully with a miltefosine-containing regimen: Case report and review of the literature.

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Endothelin-1 Pathway Polymorphisms and Outcomes in Pulmonary Arterial Hypertension.

RATIONALE: Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Variable response and tolerability to PAH therapeutics suggests that genetic differences may influence outcomes. The endothelin pathway is central to pulmonary vascular function, and several polymorphisms and/or mutations in the genes coding for endothelin (ET)-1 and its receptors correlate with the clinical manifestations of other diseases. OBJECTIVES: To examine the interaction of ET-1 pathway polymorphisms and treatment responses of patients with PAH treated with ET receptor antagonists (ERAs). METHODS: A total of 1,198 patients with PAH were prospectively enrolled from 45 U.S. and Canadian pulmonary hypertension centers or retrospectively from global sites participating in the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials. Comprehensive objective measures including a 6-minute-walk test, Borg dyspnea score, functional class, and laboratory studies were completed at baseline, before the initiation of ERAs, and repeated serially. Single-nucleotide polymorphisms from ET-1 pathway candidate genes were selected from a completed genome-wide association study performed on the study cohort. MEASUREMENTS AND MAIN RESULTS: Patient efficacy outcomes were analyzed for a relationship between ET-1 pathway polymorphisms and clinical efficacy using predefined, composite positive and negative outcome measures in 715 European descent samples. A single-nucleotide polymorphism (rs11157866) in the G-protein alpha and gamma subunits gene was significantly associated, accounting for multiple testing, with a combined improvement in functional class and 6-minute-walk distance at 12 and 18 months and marginally significant at 24 months. CONCLUSIONS: ET-1 pathway associated polymorphisms may influence the clinical efficacy of ERA therapy for PAH. Further prospective studies are needed.

Center-level self-study identifies opportunities to advance equity in cystic fibrosis clinical trial participation.

Clinical trials are a necessary tool for evaluating the effectiveness of newly developed treatments and interventions for cystic fibrosis (CF). Prior work demonstrated a proportional underrepresentation of people with CF (pwCF) identifying as part of a minoritized racial or ethnic group in clinical trials. In order to establish a baseline for improvement efforts, we undertook a center-level self-study to evaluate if the racial and ethnic backgrounds of pwCF participating in clinical trials at our CF Center in New York City reflect our overall patient diversity (N = 200; 55 pwCF identifying as part of a minoritized racial or ethnic group and 145 pwCF identifying as non-Hispanic White). A smaller proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a clinical trial as compared to pwCF identifying as non-Hispanic White (21.8% vs. 35.9%, P = 0.06). A similar trend was present for pharmaceutical clinical trials (9.1% vs. 16.6%, P = 0.3). When limiting the study population to the pwCF most likely to be eligible for a CF pharmaceutical clinical trial, a larger proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a pharmaceutical clinical trial as compared to pwCF identifying as non-Hispanic White (36.4% vs. 19.6%, P = 0.2). No pwCF identifying as part of a minoritized racial or ethnic group participated in an offsite clinical trial. Efforts to improve the racial and ethnic diversity of pwCF in clinical trials, both onsite and offsite, will require a shift in how recruitment opportunities are identified and communicated to pwCF.

Randomized controlled trial of ventricular elastic support therapy in the treatment of symptomatic heart failure: rationale and design.

BACKGROUND: Despite the current drug and device therapies, heart failure remains associated with high rates of disability, morbidity, and mortality. There is a need for newer therapies. One investigational approach is the use of ventricular support devices. These devices reduce ventricular wall stress leading to decreases in left ventricular (LV) volumes, dimensions, and mass. Ventricular support devices have been shown to reverse pathological ventricular remodeling, improve systolic function, and improve symptoms of heart failure. The Prospective Evaluation of Elastic Restraint to LESSen the effects of Heart Failure (PEERLESS-HF) trial was designed to further evaluate the safety and efficacy of one such device, the HeartNet (Paracor Medical, Sunnyvale, CA). METHODS: The HeartNet is an elastic ventricular restraint device formed from nitinol and covered in silicone, implanted using a minimally invasive approach. The aim of this randomized controlled trial is to compare optimal heart failure drug and device therapy plus the HeartNet (treatment group) to optimal drug and device therapy alone (control group) in patients with advanced systolic heart failure (LV ejection fraction ≤35% and LV end diastolic diameter <85 mm). Primary efficacy end points include the change in peak VO(2), quality of life score, and 6-minute hall walk distance from baseline to 6 months. The primary safety objective is to demonstrate noninferiority for all-cause mortality at 12 months. Planned enrollment is for 272 patients at approximately 35 centers in North America. CONCLUSIONS: The PEERLESS-HF trial will evaluate the safety and efficacy of ventricular elastic support in advanced systolic heart failure, advancing our knowledge of this investigational approach to heart failure therapy.

Prospective evaluation of elastic restraint to lessen the effects of heart failure (PEERLESS-HF) trial.

BACKGROUND: Left ventricular (LV) remodeling predicts poor outcomes in heart failure (HF) patients. The HeartNet(®) cardiac restraint device (Paracor Medical Inc., Sunnyvale, CA) may reduce LV remodeling and improve functional capacity, quality of life, and outcomes in HF patients. To evaluate the safety and efficacy of the HeartNet Ventricular Support System in HF patients receiving optimal medical therapy. METHODS AND RESULTS: Prospective, randomized, controlled, multicenter trial in patients with symptomatic HF and LV ejection fraction ≤35% on optimal medical and device therapy. The primary efficacy end points were changes in peak VO(2), 6-minute walk (6MW) distance, and Minnesota Living with Heart Failure (MLWHF) quality of life score at 6 months. The primary safety end point was all-cause mortality at 12 months. Because the planned adaptive interim analysis of the first 122 subjects with a completed 6-month follow-up indicated futility to reach the peak VO(2) end point, trial enrollment was suspended. Hence, the results on the 96 treatment and 114 control subjects are reported. Groups were similar at baseline. At 6 months, responder frequency for a prespecified improvement was similar between groups for peak VO(2) (P = .502) and MLWHF score (P = .184) but borderline higher for improvement in 6MW distance in the treatment compared with the control group (33 [38%] vs. 25 [25%]; P = .044). At 6 months, the treatment group had a significantly greater improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) (P < .001) and decrease in LV mass (P = .032), LV end-diastolic diameter (P = .015), LV end-systolic diameter (P = .032), and LV end-diastolic volume (P = .031) as compared with controls. At 12 months, all-cause mortality and responder rates were similar in the 2 groups. Success rate for the HeartNet implantation was 99%. CONCLUSION: Enrollment in the trial was stopped because an interim analysis showed futility of reaching the peak VO(2) end point. However, because of the device safety and favorable signals for LV remodeling and quality of life, further investigation of this device is warranted.

Prediction of patient outcomes through social determinants of health: The Pulmonary Hypertension Association Registry (PHAR) evaluation.

Outcomes of patients with pulmonary arterial hypertension (PAH) may be associated with social determinants of health (SDOH) and other baseline patient characteristics. At present, there is no prognostic model to predict important patient outcomes in PAH based on SDOH. Utilizing information from the Pulmonary Hypertension Association Registry (PHAR), we derive a model (PHAR Evaluation or PHARE) to predict an important composite patient outcomes based on SDOH and other patient characteristics. Baseline data regarding SDOH from adult patients with PAH enrolled in the PHAR between 2015 and March 23, 2020, were included for analysis. We performed repeated measures logistic regression modeling with dichotomous outcome data (0 for no events, 1 for one or more events) to derive the PHARE. Here, 1275 consecutive adult patients enrolled in the PHAR from 47 participating centers were included. Variables included in our model are race, gender, ethnicity, household income, level of education, age, body mass index, drug use, alcohol use, marital status, and type of health insurance. Interaction effect between variables was analyzed and several interactions were also included in the PHARE. The PHARE shows a c-statistic of 0.608 (p < 0.0001) with 95% confidence intervals (0.583, 0.632). Using SDOH and baseline characteristics from the PHAR, the PHARE correlates with our composite patient outcome. Further work evaluating the role of SDOH in prognostic modeling of PAH is indicated.

Special Considerations in the Care of Women With Advanced Heart Failure.

Advanced heart failure (AHF) is associated with increased morbidity and mortality, and greater healthcare utilization. Recognition requires a thorough clinical assessment and appropriate risk stratification. There are persisting inequities in the allocation of AHF therapies. Women are less likely to be referred for evaluation of candidacy for heart transplantation or left ventricular assist device despite facing a higher risk of AHF-related mortality. Sex-specific risk factors influence progression to advanced disease and should be considered when evaluating women for advanced therapies. The purpose of this review is to discuss the role of sex hormones on the pathophysiology of AHF, describe the clinical presentation, diagnostic evaluation and definitive therapies of AHF in women with special attention to pregnancy, lactation, contraception and menopause. Future studies are needed to address areas of equipoise in the care of women with AHF.

Echocardiographic assessment of pulmonary arterial capacitance predicts mortality in pulmonary hypertension.

BACKGROUND: Pulmonary arterial capacitance (PAC) is one of the strongest predictors of clinical outcomes in patients with pulmonary hypertension (PH). We examined the value of an echocardiographic surrogate for PAC (ePAC) as a predictor of mortality in patients with PH. METHODS: We performed a retrospective study of 302 patients with PH managed at a PH comprehensive care center over a cumulative follow-up time of 858 patient-years. Charts from 2004 to 2018 were reviewed to identify patients in whom a right heart catheterization (RHC) was performed within two months of an echocardiogram. Standard invasive, non-invasive, functional, and biochemical prognostic markers were extracted from the time of RHC. The primary outcome was all-cause mortality. Cox proportional hazards models were used to model the time from RHC to the primary outcome or last medical contact. RESULTS: Variables associated with all-cause mortality included ePAC [standardized hazard ratio (HR) 0.68, 95% CI 0.48-0.98, p = 0.036], RHC-PAC (HR 0.68, 95% CI 0.48-0.96, p = 0.027), echocardiographic pulmonary vascular resistance (HR 1.29, 95% CI 1.05-1.60, p = 0.017), six-minute walk distance (HR 0.43, 95% CI 0.23-0.82, p = 0.01), and B-type natriuretic peptide (HR 1.29, 95% CI 1.03-1.62, p = 0.027). In multivariable-adjusted Cox analysis, ePAC predicted all-cause mortality independently of age, gender, and multiple comorbidities. There was a graded and stepwise association between low (<0.15 cm/mmHg), medium (0.15-0.25 cm/mmHg), and high (>0.25 cm/mmHg) tertiles of ePAC and all-cause mortality. CONCLUSIONS: We have demonstrated that ePAC is a readily available echocardiographic marker that independently predicts mortality in PH, and have provided clinically relevant ranges by which to risk-stratify patients and predict mortality.

Assessment of late-term progression of cardiac allograft vasculopathy in patients with orthotopic heart transplantation using quantitative cardiac 82Rb PET.

The risk stratification and long-term survival of patients with orthotopic heart transplantation (OHT) is impacted by the complication of cardiac allograft vasculopathy (CAV). This study evaluates changes in myocardial blood flow (MBF) and myocardial coronary flow reserve (CFR) in a group of long-term OHT patients using quantitative cardiac 82Rb-positron emission tomography (PET). Twenty patients (7 females and 13 males, mean age = 72.7 ± 12.2 years with CAV and 62.9 ± 7.2 years without CAV and post-OHT mean time = 13.9 years), were evaluated retrospectively using dynamic cardiac 82Rb-PET at rest and regadenoson-induced stress. The patients also underwent selective coronary angiography (SCA) for diagnosis and risk stratification. CAV was diagnosed based on SCA findings and maximal intimal thickness greater than 0.5 mm, as defined by International Society of Heart and Lung Transplantation (ISHLT). Global and regional MBFs were estimated in three vascular territories using the standard 1-tissue compartment model for dynamic 82Rb-PET. The myocardial CFR was also calculated as the ratio of peak stress MBF to rest MBF. Among twenty patients, seven had CAV in, at least, one major coronary artery (ISHLT CAV grade 1 or higher) while 13 patients did not have CAV (NonCAV). Mean rate-pressure products (RPP) at rest were significantly elevated in CAV patients compared to those without CAV (P = 0.002) but it was insignificant at stress (P = NS). There was no significant difference in the stress MBFs between CAV and NonCAV patients (P = NS). However, the difference in RPP-normalized stress MBFs was significant (P = 0.045), while RPP-normalized MBFs at rest was not significant (P = NS). Both CFR and RPP-normalized CFR were significantly lower in CAV compared to NonCAV patients (P < 0.001). There were significant correlations between MBFs and RPPs at rest for both CAV (ρ = 0.764, P = 0.047) and NonCAV patients (ρ = 0.641, P = 0.017), while there were no correlations at stress for CAV (ρ = 0.232, P = NS) and NonCAV patients (ρ = 0.068, P = NS). This study indicates that the resting MBF is higher in late-term post-OHT patients. The high resting MBF and reduced CFR suggest an unprecedented demand of blood flow and blunted response to stress due to impaired vasodilatory capacity that is exacerbated by the presence of CAV.

Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association class IV heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) alone or combined with an implantable defibrillator (CRT-D) has been shown to improve exercise capacity and quality of life and to reduce heart failure (HF) hospitalizations and mortality in patients with New York Heart Association (NYHA) class III and IV HF. There is concern that the device procedure may destabilize these very ill class IV patients. We sought to examine the outcomes of NYHA class IV patients enrolled in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial to assess the potential benefits of CRT and CRT-D. METHODS AND RESULTS: The COMPANION trial randomized 1520 patients with NYHA class III and IV HF to optimal medical therapy, CRT, or CRT-D. In the class IV patients (n=217), the primary end point of time to death or hospitalization for any cause was significantly improved by both CRT (hazard ratio [HR], 0.64; 95% CI, 0.43 to 0.94; P=0.02) and CRT-D (HR, 0.62; 95% CI, 0.42 to 0.90; P=0.01). Time to all-cause death and HF hospitalization was also significantly improved in both CRT (HR, 0.57; 95% CI, 0.37 to 0.87; P=0.01) and CRT-D (HR, 0.49; 95% CI, 0.32 to 0.75; P=0.001) Time to all-cause death trended to an improvement in both CRT (HR, 0.67; 95% CI, 0.41 to 1.10; P=0.11) and CRT-D (HR, 0.63; 95% CI, 0.39 to 1.03; P=0.06). Time to sudden death appeared to be significantly reduced in the CRT-D group (HR, 0.27; 95% CI, 0.08 to 0.90; P=0.03). There was a nonsignificant reduction in time to HF deaths for both CRT (HR, 0.68; 95% CI, 0.34 to 1.37; P=0.28) and CRT-D (HR, 0.79; 95% CI, 0.41 to 1.52; P=0.48). CONCLUSIONS: CRT and CRT-D significantly improve time to all-cause mortality and hospitalizations in NYHA class IV patients, with a trend for improved mortality. These devices should be considered in ambulatory NYHA class IV HF patients similar to those enrolled in COMPANION.

Characterization and prognostic value of persistent hyponatremia in patients with severe heart failure in the ESCAPE Trial.

BACKGROUND: Mild hyponatremia is relatively common in patients hospitalized with heart failure (HF). To our knowledge, the association of hyponatremia with outcomes has not been evaluated in the context of in-hospital clinical course including central hemodynamics and changes in serum sodium level. METHODS: The ESCAPE trial (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) was a randomized, controlled study designed to evaluate the utility of a pulmonary artery catheter plus clinical assessment vs clinical assessment alone in guiding therapy in patients hospitalized with New York Heart Association class IV HF due to systolic dysfunction (left ventricular ejection fraction <30%). A Cox proportional hazards model with baseline serum sodium level as a continuous variable was used to examine the association of serum sodium level with 6-month postdischarge mortality, HF rehospitalization, and death or rehospitalization. A categorical analysis was also performed comparing persistent and corrected hyponatremia. RESULTS: A total of 433 hospitalized patients with HF were enrolled in ESCAPE. Hyponatremia (serum sodium level < or = 134 mEq/L) was present in 103 patients (23.8%). (To convert serum sodium to millimoles per liter, multiply by 1.0.) Of these, 71 had persistent hyponatremia (68.9%). Hyponatremia was associated with higher 6-month mortality after covariate adjustment (hazard ratio [HR] for each 3-mEq/L decrease in sodium level, 1.23; 95% confidence interval [CI], 1.05-1.43) (P = .01). After controlling for baseline variables and clinical response, we found that patients with persistent hyponatremia had an increased risk of all-cause mortality (31% vs 16%; HR, 1.82) (P = .04), HF rehospitalization (62% vs 43%; HR, 1.52) (P = .03), and death or rehospitalization (73% vs 50%; HR, 1.54) (P = .01) compared with normonatremic patients. CONCLUSION: Persistent hyponatremia was an independent predictor of mortality, HF hospitalization, and death or rehospitalization despite clinical and hemodynamic improvements that were similar to those in patients without hyponatremia.

Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure.

BACKGROUND: Treatment of decompensated heart failure often includes the use of intravenous vasoactive medications, but the effect on outcome has not been clearly defined. METHODS: Data from 433 patients enrolled in the ESCAPE trial were analyzed to determine 6-month risks of all-cause mortality and all-cause mortality plus rehospitalization associated with the use of vasodilators, inotropes, and their combination. Patients had a mean left ventricular ejection fraction of 19%, 6-minute walk distance of 414 ft, and systolic blood pressure of 106 mm Hg. The main outcome measure was multivariable risk-adjusted 6-month hazard ratios (HRs). RESULTS: Overall 6-month mortality was 19%. Risk-adjusted HRs were not statistically significant for vasodilators (1.39, 95% CI 0.64-3.00), but were significant for inotropes (2.14, 95% CI 1.10-4.15) and the combination (4.81, 95% CI 2.34-9.90). Risk-adjusted 6-month mortality plus rehospitalization HRs were not significant for vasodilators (1.20, 95% CI 0.81-1.78, P = .37), but were significant for inotropes (1.96, 95% CI 1.37-2.82, P < .001) and their combination (2.90, 95% CI 1.88-4.48, P = .001). The decision to use vasodilators or inotropes was determined by hemodynamic parameters and renal function, but the main factor was treatment site. CONCLUSIONS: In ESCAPE, the choice of medications was mainly determined by the treatment site. Use of inotropic agents was associated with adverse outcomes, whereas the use of vasodilators was not. Inotropes in combination with vasodilators identified a group with the highest mortality. Prospective studies are needed to establish the appropriate use of vasoactive medications in this population.

Influence of diabetes on cardiac resynchronization therapy with or without defibrillator in patients with advanced heart failure.

OBJECTIVES: We performed a post hoc analysis to determine the influence of cardiac resynchronization therapy with a defibrillator (CRT-D) or without a defibrillator (CRT-P) on outcomes among diabetic patients with advanced heart failure (HF). BACKGROUND: In patients with systolic HF, diabetes is an independent predictor of morbidity and mortality. No data are available on its impact on CRT-D or CRT-P in advanced HF. METHODS: The database of the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure trial was examined to determine the influence of CRT (CRT-D and CRT-P) on outcomes among diabetic patients. All-cause mortality or hospitalization, all-cause mortality or cardiovascular hospitalization, all-cause mortality or HF hospitalization, and all-cause mortality were analyzed among diabetic patients (n = 622). A Cox proportional hazard model, adjusting for age, gender, New York Heart Association, ischemic status, body mass index, left ventricular ejection fraction, heart rate, QRS, left or right bundle branch block, blood pressure, comorbidities (renal failure, carotid artery disease, peripheral vascular disease, hypertension, coronary artery bypass grafting, and atrial fibrillation), medications, and device (with or without defibrillator), was used to estimate hazard ratios (HRs) and significance. RESULTS: The overall outcome of diabetic patients was similar to that of nondiabetic patients in the optimal pharmacologic therapy arm. With CRT, diabetic patients experienced a substantial reduction in all-cause mortality or all-cause hospitalization (HR = 0.77, 95% confidence interval [CI] 62-0.97), all-cause mortality or cardiovascular hospitalization (HR = 0.67, 95% CI 0.53-0.85), all-cause mortality or HF hospitalization (HR = 0.52, 95% CI 0.40-0.69), and all-cause mortality (HR = 0.67, 95% CI 0.45-0.99) compared with optimal pharmacologic therapy. Procedure-related complications and length of stay were identical in diabetic and nondiabetic patients. CONCLUSION: In diabetic patients with advanced HF, there is a substantial benefit from device therapy with significant improvement in all end points.

Gender differences in in-hospital management and outcomes in patients with decompensated heart failure: analysis from the Acute Decompensated Heart Failure National Registry (ADHERE).

BACKGROUND: The impact of gender differences has not been well described in patients hospitalized with acute decompensated heart failure (ADHF). METHODS AND RESULTS: Through review of medical records, data on characteristics, treatments, and outcomes were analyzed on 105,388 patient records according to gender. Women accounted for 52% of these admissions and were older than men (74.5 versus 70.1 years,) and more commonly had preserved left ventricular function (51% versus 28%). Based on history, women were less likely to have coronary artery disease (51% versus 64%) and its risk factors, but more commonly had hypertension (76% versus 70%). Both genders received similar intravenous diuretic regimens, but fewer women received vasoactive therapy (24% vs 31%). Evidence-based oral therapies were underused in both genders. Women consistently received less procedure-oriented therapy. Mean length of stay (women 5.9, men 5.8 days) and the risk-adjusted in-hospital mortality (adjusted odds ratio 0.974 [0.910-1.042], P = .4390) were similar in both genders. CONCLUSION: More women than men are hospitalized with ADHF. Heart failure with preserved left ventricular function predominates in women. Though women are treated less aggressively, treatment gaps exists in both sexes. Despite these differences, length of stay and in-hospital mortality rates are similar.

Use of bivalirudin, a direct thrombin inhibitor, and its reversal with modified ultrafiltration during heart transplantation in a patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an increasingly common clinical finding in patients presenting for cardiac transplantation. Bivalrudin, a reversible direct thrombin inhibitor, is a molecular anti-coagulant with short half-life and the potential for removal by intraoperative hemofiltration. Herein we describe the dosing and intraoperative management of bivalrudin anti-coagulation in a patient undergoing urgent cardiac transplantation in the context of recently diagnosed HIT.

World Health Organization Pulmonary Hypertension group 2: pulmonary hypertension due to left heart disease in the adult--a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation.

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension encountered in clinical practice today. Although frequently a target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of worse prognosis and disease severity, but whether its primary treatment is beneficial or harmful is unknown. An important step to the future study of this important clinical problem will be to standardize definitions across disciplines to facilitate an evidence base that is interpretable and applicable to clinical practice. In this current statement, we provide an extensive review and interpretation of the current available literature to guide current practice and future investigation. At the request of the Pulmonary Hypertension (PH) Council of the International Society for Heart and Lung Transplantation (ISHLT), a writing group was assembled and tasked to put forth this document as described above. The review process was facilitated through the peer review process of the Journal of Heart and Lung Transplantation and ultimately endorsed by the leadership of the ISHLT PH Council.