COVID-19 associated development of antibody mediated rejection in orthotopic heart transplantation patients.

Solid organ transplant candidates encountered increased wait times and mortality rates during the coronavirus 2019 (COVID-19) pandemic. Despite improvement in medical management and vaccination efficacy, this patient population remains at increased risk for complications post COVID-19 including organ rejection. We describe the development of antibody mediated rejection with or without cellular rejection in heart transplant (HT) recipients and previous COVID-19 infection or vaccination. Although centers have changed their management of outpatient follow-up for orthotopic heart transplant patients, little is known on surveillance of rejection and management of HT recipients after COVID-19 infection. We recommend frequent surveillance for rejection or allograft dysfunction after COVID-19 infection. We have adopted a transplant surveillance protocol for HT recipients with COVID-19 infection, given our recent experience with transplanted patients affected of COVID-19.

Incidence of acute rejection and patient survival in combined heart-liver transplantation.

Combined heart-liver transplantation (CHLT) is indicated for patients with concomitant end-stage heart and liver disease or patients with amyloid heart disease where liver transplantation mitigates progression. Limited data suggest that the liver allograft provides immunoprotection for heart and kidney allografts in combined transplantation from the same donor. We hypothesized that CHLT reduces the incidence of acute cellular rejection (ACR) and the development of de novo donor-specific antibodies (DSAs) compared with heart-alone transplantation (HA). We conducted a retrospective analysis of 32 CHLT and 280 HA recipients in a single-center experience. The primary outcome was incidence of ACR based on protocol and for-cause myocardial biopsy. Rejection was graded by the International Society of Heart and Lung Transplantation guidelines with Grade 2R and higher considered significant. Secondary outcomes included the development of new DSAs, cardiac function, and patient and cardiac graft survival rates. Of CHLT patients, 9.7% had ACR compared with 45.3% of HA patients (p < 0.01). Mean pretransplant calculated panel reactive antibody (cPRA) levels were similar between groups (CHLT 9.4% vs. HA 9.5%; p = 0.97). Among patients who underwent testing, 26.9% of the CHLT and 16.7% of HA developed DSA (p = 0.19). Despite the difference in ACR, patient and cardiac graft survival rates were similar at 5 years (CHLT 82.1% vs. HA 80.9% [p = 0.73]; CHLT 82.1% vs. HA 80.9% [p = 0.73]). CHLT reduced the incidence of ACR in the cardiac allograft, suggesting that the liver offers immunoprotection against cellular mechanisms of rejection without significant impacts on patient and cardiac graft survival rates. CHLT did not reduce the incidence of de novo DSA, possibly portending similar long-term survival among cardiac allografts in CHLT and HA.

Pulmonary vasodilator use in continuous-flow left ventricular assist device management.

Pulmonary hypertension (PH) due to left heart disease is the most common etiology for PH. PH in patients with heart failure with reduced fraction (HFrEF) is associated with reduced functional capacity and increased mortality. PH-HFrEF can be isolated post-capillary or combined pre- and post-capillary PH. Chronic elevation of left-sided filling pressures may lead to reverse remodeling of the pulmonary vasculature with development of precapillary component of PH. Untreated PH in patients with HFrEF results in predominant right heart failure (RHF) with irreversible end-organ dysfunction. Management of PH-HFrEF includes diuretics, vasodilators like angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers or angiotensin-receptor blocker-neprilysin inhibitors, hydralazine and nitrates. There is no role for pulmonary vasodilator use in patients with PH-HFrEF due to increased mortality in clinical trials. In patients with end-stage HFrEF and fixed PH unresponsive to vasodilator challenge, implantation of continuous-flow left ventricular assist device (cfLVAD) results in marked improvement in pulmonary artery pressures within 6 months due to left ventricular (LV) mechanical unloading. The role of pulmonary vasodilators in management of precapillary component of PH after cfLVAD is not well-defined. The purpose of this review is to discuss the pharmacologic management of PH after cfLVAD implantation.

The impact of peripheral arterial disease on left ventricular assist device implantation: A propensity-matched analysis of the nationwide inpatient sample database.

Left ventricular assist device (LVAD) candidacy screening includes evaluation for peripheral arterial disease (PAD). However, given current evidence, the impact of PAD on post-LVAD complications remains unknown. The National Inpatient Sample (NIS) database (2002-2017) was utilized to identify all LVAD cases. The in-hospital safety endpoints included major cardiovascular adverse events and its components. A propensity-matched analysis was used to obtain adjusted odds ratios (aOR). A subgroup analysis of patients with diabetes mellitus (DM) with PAD was also performed. A total of 27 424 patients with LVAD implantation (PAD: 516 [1.8%] and no-PAD 26 908 [98.2%]) were included. There were significant intergroup differences in the demographics and baseline comorbidities. A weighted sample of 1053 (no-PAD 537, PAD 516) propensity-matched population was selected. The adjusted odds for in-hospital mortality (aOR 1.7; 95% CI, 1.2-2.44, P = .004) were found to be significantly higher for LVAD-patients with PAD. There was no significant difference in the adjusted odds of MACE (aOR 1.16, 95% CI 0.87-1.5), postprocedure bleeding (aOR 0.88, 95% CI 0.62-1.26, P = .54) and risk of pneumonia (aOR 0.67, 95% CI 0.44-1.15, P = .63) between the two groups. A selected cohort of DM-only population (7339) consistently showed a higher adjusted mortality rate in PAD patients with LVAD implantation (aOR 2.3, 95% CI 1.2-4.47, P = .01). The rate of MACE (P = .17), myocardial infarction (P = .12), stroke (P = .60), postprocedural (0.10), and major bleeding (P = .51) remained identical between patients with PAD and those with no-PAD. PAD confers an increased risk of in-hospital all-cause mortality in patients undergoing LVAD implantation. This risk increases further in patients with a concomitant diagnosis of DM.

Proposal for a trial of early left ventricular venting during venoarterial extracorporeal membrane oxygenation for cardiogenic shock.

Objective: Patients with profound cardiogenic shock may require venoarterial (VA) extracorporeal membrane oxygenation (ECMO) for circulatory support most commonly via the femoral vessels. The rate of cardiac recovery in this population remains low, possibly because peripheral VA-ECMO increases ventricular afterload. Whether direct ventricular unloading in peripheral VA-ECMO enhances cardiac recovery is unknown, but is being more frequently utilized. A randomized trial is warranted to evaluate the clinical effectiveness of percutaneous left ventricle venting to enhance cardiac recovery in the setting of VA-ECMO. Methods: We describe the rationale, design, and initial testing of a randomized controlled trial of VA-ECMO with and without percutaneous left ventricle venting using a percutaneous micro-axial ventricular assist device. Results: This is an ongoing prospective randomized controlled trial in adult patients with primary cardiac failure presenting in cardiogenic shock requiring peripheral VA-ECMO, designed to test the safety and effectiveness of percutaneous left ventricle venting in improving the rate of cardiac recovery. Conclusions: The results of this nonindustry-sponsored trial will provide critical information on whether left ventricle unloading in peripheral VA-ECMO is safe and effective.

Predictors of in-hospital mortality and midterm outcomes of patients successfully weaned from venoarterial extracorporeal membrane oxygenation.

OBJECTIVES: There is limited evidence to guide the decision to proceed with weaning from venoarterial extracorporeal membrane oxygenation, and approximately 30% of patients weaned "successfully" do not survive to hospital discharge. We evaluated predictors of in-hospital mortality and midterm outcomes of patients successfully weaned from venoarterial extracorporeal membrane oxygenation after support for cardiogenic shock, surviving more than 24 hours after weaning, with the aim of improving patient selection for durable weaning. METHODS: We performed a retrospective analysis of 92 patients supported on venoarterial extracorporeal membrane oxygenation and successfully weaned between January 2013 and February 2018. Survival was estimated by the Kaplan-Meier method. Predictors of in-hospital mortality were identified using a Cox proportional hazards model and an Akaike information criterion-selected multivariate model. RESULTS: Overall survival at hospital discharge was 64.2%; survival was 54.6% 1 year after support and 51.4% 3 years after support. A history of diabetes, previous myocardial infarction, prolonged extracorporeal membrane oxygenation support, and hypoxemia at extracorporeal membrane oxygenation weaning were independent predictors of in-hospital mortality. At midterm follow-up, New York Heart Association class I heart function was observed in 53% of patients, class II in 19%, class III in 16%, and class IV in 12%. Average left ventricular ejection fraction was 46.5% ± 18.2%, and 50% of the patients had been readmitted to the hospital because of heart failure. CONCLUSIONS: Durable extracorporeal membrane oxygenation weaning with acceptable midterm functional status is obtainable in well-selected patients. Previous myocardial infarction, diabetes, prolonged extracorporeal membrane oxygenation support, and pulmonary dysfunction strongly predicted in-hospital mortality after venoarterial extracorporeal membrane oxygenation weaning. In this high-risk situation, other heart replacement therapies should be considered.

Effects of left ventricular assist device on pulmonary functions and pulmonary hemodynamics: A meta-analysis. waqasullah.dr@gmail.com.

BACKGROUND: Given current evidence, the effect of left ventricular assist device (LVAD) implantation on pulmonary function tests remains controversial. AIM: To better understand the factors contributing to the changes seen on pulmonary function testing and the correlation with pulmonary hemodynamics after LVAD implantation. METHODS: Electronic databases were queried to identify relevant articles. The summary effect size was estimated as a difference of overall means and standard deviation on a random-effects model. RESULTS: A total of four studies comprising 219 patients were included. The overall mean forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion lung capacity of carbon monoxide (DLCO) after LVAD implantation were significantly lower by 0.23 L (95%CI: 0.11-0.34, P = 00002), 0.18 L (95%CI: 0.03-0.34, P = 0.02), and 3.16 mmol/min (95%CI: 2.17-4.14, P < 0.00001), respectively. The net post-LVAD mean value of the cardiac index was significantly higher by 0.49 L/min/m2 (95%CI: 0.31-0.66, P < 0.00001) compared to pre-LVAD value. The pulmonary capillary wedge pressure and pulmonary vascular resistance were significantly reduced after LVAD implantation by 8.56 mmHg (95%CI: 3.78-13.35, P = 0.0004), and 0.83 Woods U (95%CI: 0.11-1.55, P = 0.02), respectively. There was no significant difference observed in the right atrial pressure after LVAD implantation (0.61 mmHg, 95%CI: -2.00 to 3.32, P = 0.65). Overall findings appear to be driven by studies using HeartMateII devices. CONCLUSION: LVAD implantation might be associated with a significant reduction of the spirometric measures, including FEV1, FVC, and DLCO, and an overall improvement of pulmonary hemodynamics.

Safety and efficacy of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis.

BACKGROUND: The utility of novel oral soluble guanylate cyclase (sGC) stimulators (vericiguat and riociguat), in patients with reduced or preserved ejection fraction heart failure (HFrEF/HFpEF) is currently unclear. AIM: To determine the efficacy and safety of sGC stimulators in HF patients. METHODS: Multiple databases were searched to identify relevant randomized controlled trials (RCTs). Data on the safety and efficacy of sGC stimulators were compared using relative risk ratio (RR) on a random effect model. RESULTS: Six RCTs, comprising 5604 patients (2801 in sGC stimulator group and 2803 placebo group) were included. The primary endpoint (a composite of cardiovascular mortality and first HF-related hospitalization) was significantly reduced in patients receiving sGC stimulators compared to placebo [RR 0.92, 95% confidence interval (CI): 0.85-0.99, P = 0.02]. The incidence of total HF-related hospitalizations were also lower in sGC group (RR 0.91, 95%CI: 0.86-0.96, P = 0.0009), however, sGC stimulators had no impact on all-cause mortality (RR 0.96, 95%CI: 0.86-1.07, P = 0.45) or cardiovascular mortality (RR 0.94, 95%CI: 0.83-1.06, P = 0.29). The overall safety endpoint (a composite of hypotension and syncope) was also similar between the two groups (RR 1.50, 95%CI: 0.93-2.42, P = 0.10). By contrast, a stratified subgroup analysis adjusted by type of sGC stimulator and HF (vericiguat vs riociguat and HFrEF vs HFpEF) showed near identical rates for all safety and efficacy endpoints between the two groups at a mean follow-up of 19 wk. For the primary composite endpoint, the number needed to treat was 35, the number needed to harm was 44. CONCLUSION: The use of vericiguat and riociguat in conjunction with standard HF therapy, shows no benefit in terms of decreasing HF-related hospitalizations or mortality.

Mid-term outcomes with the use of extracorporeal membrane oxygenation for cardiopulmonary failure secondary to massive pulmonary embolism.

OBJECTIVES: There has been increasing interest in using extracorporeal membrane oxygenation (ECMO) to rescue patients with pulmonary embolism (PE) in the advanced stages of respiratory or haemodynamic decompensation. We examined mid-term outcomes and risk factors for in-hospital mortality. METHODS: We conducted a retrospective study of 36 patients who required ECMO placement (32 veno-arterial ECMO, 4 veno-venous) following acute PE. Survival curves were estimated using the Kaplan-Meier method. Risk factors for in-hospital mortality were assessed by logistic regression analysis. Functional status and quality of life were assessed by phone questionnaire. RESULTS: Overall survival to hospital discharge was 44.4% (16/36). Two-year survival conditional to discharge was 94% (15/16). Two-year survival after veno-arterial ECMO was 39% (13/32). In patients supported with veno-venous ECMO, survival to discharge was 50%, and both patients were alive at follow-up. In univariable analysis, a history of recent surgery (P = 0.064), low left ventricular ejection fraction (P = 0.029), right ventricular dysfunction ≥ moderate at weaning (P = 0.083), on-going cardiopulmonary resuscitation at ECMO placement (P = 0.053) and elevated lactate at weaning (P = 0.002) were risk factors for in-hospital mortality. In multivariable analysis, recent surgery (P = 0.018) and low left ventricular ejection fraction at weaning (P = 0.013) were independent factors associated with in-hospital mortality. At a median follow-up of 23 months, 10 patients responded to our phone survey; all had acceptable functional status and quality of life. CONCLUSIONS: Massive acute PE requiring ECMO support is associated with high early mortality, but patients surviving to hospital discharge have excellent mid-term outcomes with acceptable functional status and quality of life. ECMO can provide a stable platform to administer other intervention with the potential to improve outcomes. Risk factors for in-hospital mortality after PE and veno-arterial ECMO support were identified.

Pulmonary arterial hypertension in adults with systemic right ventricles referred for cardiac transplantation.

BACKGROUND: Systemic right ventricular (RV) failure may progress necessitating referral for orthotropic heart transplantation (OHT). Pulmonary hypertension (PH) frequently coexists in adult congenital heart disease and can complicate the assessment for OHT. METHODS: Single-center case series of six patients (median age 34.9 years [IQR, 31.9-42.4]) with systemic RV physiology with PH referred for OHT evaluation from 2008 to 2017. RESULTS: One-third (n = 6) of 18 patients with systemic RV physiology referred for OHT evaluation had pulmonary arterial hypertension (PAH) defined as mean pulmonary artery pressure (mPAP) > 25 mm Hg and pulmonary vascular resistance (PVR) > 3 Wood Units. Two of the six patients were considered OHT-ineligible due to PH and comorbidities. Of the remaining four, two had pre-capillary PH and underwent heart-lung transplant (HLTx). The other two demonstrated reversibility of PVR with vasodilator testing and underwent OHT alone, one of whom died post-transplant from PH crisis. CONCLUSIONS: Pulmonary arterial hypertension is common in systemic RV patients referred for OHT. Systemic RV dysfunction places these patients at risk for post-capillary PH but pre-capillary PH can exist. Despite management with selective pulmonary vasodilators and afterload reduction, criteria for listing patients for HLTx vs OHT are not known and need further elucidation.

Prognostic Implications of Changes in Albumin Following Left Ventricular Assist Device Implantation in Patients With Severe Heart Failure.

Mechanical assist devices have emerged as an established therapeutic option for patients with end-stage heart failure. Because preimplant hypoalbuminemia is a known risk factor for adverse outcomes, we hypothesized that change in albumin may be a prognostic indicator in patients with continuous-flow left ventricular assist devices (cfLVADs). This is a retrospective single-center study of patients who underwent cfLVAD implantation (HeartMate II and HeartWare HVAD) at an academic center from 2008 to 2014. After excluding those who died, were transplanted, or hospitalized during the first 3 months post-implant, albumin values were obtained and stratified by an increase or a decrease from pre-implant to 3 months post-implant on 171 (81% male, mean age 57 ± 16 years) patients (139 for the survival analysis and 90 for the hospitalization analysis). Decrease in albumin from pre-implant to 3 months after implant correlated with increased mortality (hazard ratio 2.93, confidence interval 1.57 to 5.44, p <0.01) and reduced time to next hospitalization (hazard ratio 1.70, confidence interval 1.03 to 2.81, p = 0.04). The Kaplan-Meier survival curve estimated a 49.43% 2-year survival rate in those whose albumin decreased versus 83.62% in those whose albumin increased over 3 months (p <0.01). Improved outcomes were seen in patients whose albumin normalized versus patients whose albumin remained normal over 3 months. In conclusion, our study is the first to demonstrate the importance of change in albumin from pre- to postimplant on the prognosis of cfLVAD patients. Future studies are needed to determine whether therapeutic intervention to improve albumin post-implant will prevent hospitalizations and improve outcomes.

Lower-extremity complications with femoral extracorporeal life support.

OBJECTIVE: Patients undergoing emergency peripheral arteriovenous extracorporeal life support were evaluated for lower-extremity complications on the basis of the ipsilateral limb perfusion strategy. METHODS: In a retrospective review of patients receiving extracorporeal life support (2008-2013), 105 of 250 underwent femoral extracorporeal life support. For ipsilateral lower-extremity perfusion, patients underwent no superficial femoral artery cannulation (n = 35), percutaneous superficial femoral artery cannulation (n = 23), or open superficial femoral artery cannulation (n = 47). RESULTS: Patients' mean age was 50 ± 16 years, and 63% (n = 67) were male. A total of 92 patients (88%) had primary cardiac emergency, and 13 patients (12%) had cardiopulmonary emergency. The 30-day in-hospital mortality was 65% (n = 68), with an overall lower-extremity complication rate of 13% (n = 14). Lower-extremity complications were highest in the percutaneous superficial femoral artery (n = 6, 26%) and no superficial femoral artery (n = 7, 20%) groups (n = 1 [2%] in open superficial femoral artery group). In 2 group comparisons, the open superficial femoral artery group had significantly lower lower-extremity complications than the no superficial femoral artery (P = .02) and percutaneous superficial femoral artery (P = .004) groups. There was no difference between the no superficial femoral artery and percutaneous superficial femoral artery groups (P = .7). In the no superficial femoral artery group, emergency thromboembolectomy (n = 2), fasciotomy (n = 3), and emergency superficial femoral artery cannula placement (n = 2) were required. In the percutaneous superficial femoral artery group, thromboembolectomy with superficial femoral artery repair (n = 2), fasciotomy (n = 1), below-knee amputation (n = 1), open superficial femoral artery cannula revision (n = 1), and loss of distal signals from multiorgan failure (n = 1) were noted. In the open superficial femoral artery group, 1 patient had loss of signals from multiorgan failure. CONCLUSIONS: No superficial femoral artery perfusion strategy is associated with a high lower-extremity complication rate. If percutaneous cannulation is performed, then angiographic confirmation of superficial femoral artery run-off is highly recommended. The open superficial femoral artery approach remains a safe alternative to the other strategies.

The HVAD Left Ventricular Assist Device: Risk Factors for Neurological Events and Risk Mitigation Strategies.

OBJECTIVES: The purpose of this study was to determine the risk factors for ischemic in hemorrhage cerebrovascular events in patients supported by the HeartWare ventricular assist device (HVAD). BACKGROUND: Patients supported with left ventricular assist devices are at risk for both ischemic and hemorrhagic cerebrovascular events. METHODS: Patients undergoing implantation with a HVAD as part of the bridge-to-transplant trial and subsequent continued access protocol were included. Neurological events (ischemic cerebrovascular accidents [ICVAs] and hemorrhagic cerebrovascular accidents [HCVAs]) were assessed, and the risk factors for these events were evaluated in a multivariable model. RESULTS: A total of 382 patients were included: 140 bridge-to-transplant patients from the ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) clinical trial and 242 patients from the continued access protocol. Patients had a mean age of 53.2 years; 71.2% were male, and 68.1% were white. Thirty-eight percent had ischemic heart disease, and the mean duration of support was 422.7 days. The overall prevalence of ICVA was 6.8% (26 of 382); for HCVA, it was 8.4% (32 of 382). Pump design modifications and a protocol-driven change in the antiplatelet therapy reduced the prevalence of ICVA from 6.3% (17 of 272) to 2.7% (3 of 110; p = 0.21) but had a negligible effect on the prevalence of HVCA (8.8% [24 of 272] vs. 6.4% [7 of 110]; p = 0.69). Multivariable predictors of ICVA were aspirin ≤81 mg and atrial fibrillation; predictors of HCVA were mean arterial pressure >90 mm Hg, aspirin ≤81 mg, and an international normalized ratio >3.0. Eight of the 30 participating sites had established improved blood pressure management (IBPM) protocols. Although the prevalence of ICVA for those with and without IBPM protocols was similar (5.3% [6 of 114] vs. 5.2% [14 of 268]; p = 0.99), those with IBPM protocols had a significantly lower prevalence of HCVA (1.8% [2 of 114] vs. 10.8% [29 of 268]; p = 0.0078). CONCLUSIONS: Anticoagulation, antiplatelet therapy, and blood pressure management affected the prevalence of cerebrovascular events after implantation of the HVAD. Attention to these clinical parameters can have a substantial impact on the occurrence of serious neurological events. (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE]; NCT00751972).

Extracorporeal life support as rescue strategy for out-of-hospital and emergency department cardiac arrest.

BACKGROUND: Extracorporeal life support (ECLS) has been utilized as a rescue strategy for patients with cardiac arrest unresponsive to conventional cardiopulmonary resuscitation. OBJECTIVE: We sought to describe our institution's experience with implementation of ECLS for out-of-hospital and emergency department (ED) cardiac arrests. Our primary outcome was survival to hospital discharge. METHODS: Consecutive patients placed on ECLS in the ED or within one hour of admission after out-of-hospital or ED cardiac arrest were enrolled at two urban academic medical centers in the United States from July 2007-April 2014. RESULTS: During the study period, 26 patients were included. Average age was 40±15 years, 54% were male, and 42% were white. Initial cardiac rhythms were ventricular fibrillation or pulseless ventricular tachycardia in 42%. The average time from initial cardiac arrest to initiation of ECLS was 77 ± 51 min (range 12-180 min). ECLS cannulation was unsuccessful in two patients. Eighteen (69%) had complications related to ECLS, most commonly bleeding and ischemic events. Four patients (15%) survived to discharge, three of whom were neurologically intact at 6 months. CONCLUSION: ECLS shows promise as a rescue strategy for refractory out-of-hospital or ED cardiac arrest but is not without challenges. Further investigations are necessary to refine the technique, patient selection, and ancillary therapeutics.

Hypertrophic cardiomyopathy with restrictive phenotype and myocardial crypts.

This report describes a 22-year-old woman who has clinical and physiologic features of a restrictive cardiomyopathy. Magnetic resonance imaging showed myocardial delayed enhancement and interventricular septal crypts characteristic of hypertrophic cardiomyopathy (HCM). Transcatheter biopsy confirmed the diagnosis, revealing marked myocyte hypertrophy, interstitial fibrosis, and fiber disarray, which are findings consistent with HCM. A review of the literature suggests that this is the first case of HCM reported with a restrictive pattern and myocardial crypts.

Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension.

RATIONALE: Circulating microparticles (MPs) are submicron membrane fragments shed from damaged or activated vascular cells. Endothelial MPs are a biological marker of dysfunctional endothelium. Vascular remodeling and endothelial dysfunction are involved in pulmonary hypertension (PH). OBJECTIVES: We tested the hypothesis that circulating MPs are increased in patients with PH and that identifiable subgroups of MPs predict the hemodynamic severity of this condition progression. METHODS: Patients (n = 24; age, 54 +/- 4 yr) undergoing right heart catheterization for precapillary PH without any endothelium-active vasodilator therapy participated in the study. Age- and sex-matched healthy control subjects (n = 20) were included. Endothelial (PECAM(+) [CD31(+)]/ CD41(-), VE-cadherin(+) [CD144(+)], and E-selectin(+) [CD62e(+)]), platelet (CD41(+)), leukocyte-derived (CD45(+)), and annexin V(+) MPs were measured by flow cytometry in platelet-free plasma from venous blood. MEASUREMENTS AND MAIN RESULTS: Levels of circulating endothelial PECAM(+), VE-cadherin(+), E-selectin(+), and leukocyte-derived MPs, but not platelet and annexin V(+) MPs, were increased in subjects with PH compared with control subjects (P < 0.01 each). PECAM(+) and VE-cadherin(+) MP levels significantly correlated with mean pulmonary artery pressure (r = 0.92 and r = 0.87, respectively), pulmonary vascular resistance (r = 0.78 and r = 0.73), and mean right atrial pressure (r = 0.43, and r = 0.46) and correlated inversely with cardiac index (r = -0.59 and r = -0.52). These relationships were not observed for other MP subgroups, and persisted in multivariate analysis after adjustment for confounding factors. CONCLUSIONS: In subjects with precapillary PH, levels of circulating endothelial and leukocyte MPs were increased compared with control subjects. In addition, levels of PECAM(+) and VE-cadherin(+), but not E-selectin(+), endothelial MPs predicted hemodynamic severity of the disease.