NT-pro-BNP is predictive of morbidity and mortality after pulmonary thromboendarterectomy and is independent of preoperative hemodynamics.

Current predictors of clinical outcomes after pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are largely limited to preoperative clinical characteristics. N-terminal-pro-brain natriuretic peptide (NT-pro-BNP), a biomarker of right ventricular dysfunction, has not yet been well described as one such predictor. From 2017 to 2021, 816 patients with CTEPH referred to the University of California, San Diego for PTE were reviewed for differences in NT-pro-BNP to predict preoperative characteristics and postoperative outcomes up to 30 days post-PTE. For analysis, NT-pro-BNP was dichotomized to less than/equal to or greater than 1000 pg/mL based on the mean of the study population. Mean NT-pro-BNP was 1095.9 ±1783.4 pg/mL and median was 402.5 pg/mL (interquartile range: 119.5-1410.8). Of the 816 patients included, 250 had NT-pro-BNP > 1000 pg/mL. Those with NT-pro-BNP > 1000 pg/mL were significantly more likely to have worse preoperative functional class (III-IV) and worse preoperative hemodynamics. Patients with NT-pro-BNP > 1000 pg/mL also tended to have more postoperative complications including reperfusion pulmonary edema (22% vs. 5.1%, p < 0.001), airway hemorrhage (8.4% vs. 4.9%, p = 0.075), residual pulmonary hypertension (11.9% vs. 3.1%, p < 0.001), and 30-day mortality (4.8% vs. 1.1%, p = 0.001). Even after adjusting for confounders, patients with NT-pro-BNP > 1000 pg/mL had a 2.48 times higher odds (95% confidence interval: 1.45-4.00) of reaching a combined endpoint that included the above complications. Preoperative NT-pro-BNP > 1000 pg/mL is a strong predictor of more severe preoperative hemodynamics and identifies patients at higher risk for postoperative complications.

Cardiopulmonary exercise test to detect cardiac dysfunction from pulmonary vascular disease.

BACKGROUND: Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease. METHODS: We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT). We correlated CPET-determined O2·pulseAT/O2·pulserest with RHC-determined SVAT/SVrest. We evaluated the sensitivity and specificity of O2·pulseAT/O2·pulserest to detect SVAT/SVrest below the lower limit of normal (LLN). For comparison, we performed similar analyses comparing echocardiographically-measured peak tricuspid regurgitant velocity (TRVpeak) with SVAT/SVrest. RESULTS: From July 2018 through February 2023, 83 simultaneous RHC and CPET were performed. Thirty-six studies measured O2·pulse and SV at rest and at AT. O2·pulseAT/O2·pulserest correlated highly with SVAT/SVrest (r = 0.72, 95% CI 0.52, 0.85; p < 0.0001), whereas TRVpeak did not (r = -0.09, 95% CI -0.47, 0.33; p = 0.69). The AUROC to detect SVAT/SVrest below the LLN was significantly higher for O2·pulseAT/O2·pulserest (0.92, SE 0.04; p = 0.0002) than for TRVpeak (0.69, SE 0.10; p = 0.12). O2·pulseAT/O2·pulserest of less than 2.6 was 92.6% sensitive (95% CI 76.6%, 98.7%) and 66.7% specific (95% CI 35.2%, 87.9%) for deficient SVAT/SVrest. CONCLUSIONS: CPET detected deficient SV augmentation more accurately than echocardiography. CPET-determined O2·pulseAT/O2·pulserest may have a prominent role for noninvasive screening of patients at risk for pulmonary vascular disease, such as patients with persistent dyspnea after pulmonary embolism.

Balloon pulmonary angioplasty in the current era of CTEPH treatment: How did we get here?

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by persistent organized thromboembolic obstruction of the pulmonary arteries from incompletely resolved pulmonary embolism. The treatment of choice is pulmonary thromboendarterectomy (PTE) surgery and all patients should be evaluated for operability candidacy. Despite advancements in PTE technique allowing more segmental-subsegmental surgeries, up to a third of patients with CTEPH may still be considered inoperable. Over the past decade, there have been increasing treatment options for these inoperable CTEPH patients. Balloon pulmonary angioplasty (BPA) is a percutaneous-based interventional treatment option for select CTEPH cases. Early BPA experiences were plagued by high complication rates, but further refinements in technique and equipment pioneered by Japan led to the worldwide spread and adoption of BPA. Multiple centers have shown that patients experience significant improvements in hemodynamics, quality of life, exercise capacity, and survival with BPA treatment. There remain many questions on best practices, but BPA has evolved into a pivotal cornerstone of CTEPH treatment.

Repeat pulmonary thromboendarterectomy outcomes: A 15-year single-center retrospective review.

OBJECTIVE: Chronic thromboembolic pulmonary hypertension is potentially curable via pulmonary thromboendarterectomy. A minority of patients experience recurrence of their symptoms and are eligible for repeat pulmonary thromboendarterectomy. However, little data exist regarding risk factors and outcomes for this patient population. METHODS: We performed a retrospective review of the University of California San Diego chronic thromboembolic pulmonary hypertension quality improvement database, including all patients who underwent pulmonary thromboendarterectomy from December 2005 to December 2020. Of the 2019 cases performed during this period, 46 were repeat pulmonary thromboendarterectomy procedures. Demographics, preoperative and postoperative hemodynamics, and surgical complications were compared between the repeat pulmonary thromboendarterectomy group and 1008 first pulmonary thromboendarterectomy group. RESULTS: Repeat pulmonary thromboendarterectomy recipients were more likely to be younger, to have an identified hypercoagulable state, and to have higher preoperative right atrial pressure. Etiologies of recurrent disease include incomplete initial endarterectomy, discontinuation of anticoagulation (noncompliance or for medical reasons), and anticoagulation treatment failure. Patients who received repeat pulmonary thromboendarterectomy had significant hemodynamic improvement, but less pronounced compared with patients who received first pulmonary thromboendarterectomy. Repeat pulmonary thromboendarterectomy was associated with an increased risk of postoperative bleeding, reperfusion lung injury, residual pulmonary hypertension, and increased ventilator, intensive care unit, and hospital days. However, hospital mortality was similar between the groups (2.2% vs 1.9%). CONCLUSIONS: This is the largest reported series of repeat pulmonary thromboendarterectomy surgery. Despite an increase in postoperative complications, this study demonstrates that repeat pulmonary thromboendarterectomy surgery can result in significant hemodynamic improvement with acceptable surgical mortality in an experienced center.

Airway Hemorrhage Complicating Pulmonary Thromboendarterectomy: Risk Factors and Outcomes.

BACKGROUND: Airway hemorrhage is a known complication of pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension. Predisposing factors for postoperative airway hemorrhage have not been well described. The aims of this study were to determine the incidence and outcomes of airway hemorrhage after PTE and to identify potential risk factors. METHODS: This was a retrospective chart review of subjects undergoing PTE between 2015 and 2019. Postoperative airway hemorrhage was defined as significant endobronchial bleeding requiring withholding anticoagulation, bronchial blocker placement, and/or extracorporeal membrane oxygenation (ECMO). RESULTS: Of 877 subjects who underwent PTE, 58 subjects (6.6%) developed postoperative airway hemorrhage. Subjects with hemorrhage were more likely to be women (60% vs 45%, P = .03), to be older (57.8 vs 54.0 years, P = .04), and to have a higher incidence of preoperative hemoptysis (19.0% vs 7.6%, P = .006) compared with control subjects (subjects without airway hemorrhage). Those with hemorrhage had significantly higher preoperative right atrial pressure (P = .002) and pulmonary vascular resistance (P < .001) and a higher incidence of residual pulmonary hypertension (P = .005). Airway hemorrhage management included ECMO with bronchial blocker (n = 2), bronchial blocker without ECMO (n = 26), or withholding anticoagulation alone until bleeding subsided (n = 30). Mortality was significantly higher in those with airway hemorrhage compared with control subjects (13.8% vs 1.2%, P < .001). CONCLUSIONS: The incidence of postoperative airway hemorrhage is low but associated with significant mortality. Older age, female sex, preoperative hemoptysis, and worse preoperative pulmonary hypertension were associated with an increased risk of developing postoperative airway hemorrhage.

Drug-Drug Interactions in the Management of Patients With Pulmonary Arterial Hypertension.

The management of pulmonary arterial hypertension (PAH) has become more complex in recent years because of increased pharmacotherapy options and longer patient survival with increasing numbers of comorbidities. As such, more opportunities exist for drug-drug interactions between PAH-targeted medications and medications potentially used to treat comorbid conditions. In this review, we provide an overview of pharmaceutical metabolism by cytochrome P450 and discuss important drug-drug interactions for the 14 Food and Drug Administration-approved medications for PAH in the nitric oxide (NO), endothelin, and prostacyclin pathways. Among the targets in the NO pathway (sildenafil, tadalafil, and riociguat), important interactions with nitrates, protease inhibitors, and other phosphodiesterase inhibitors can cause profound hypotension. In the endothelin pathway, bosentan is associated with more drug interactions via CYP3A4 inhibition; macitentan and ambrisentan have fewer interactions of note. Although the parenteral therapies in the prostacyclin pathway bypass significant liver metabolism and avoid drug interactions, selexipag and oral treprostinil may exhibit interactions with CYP2C8 inhibitors such as gemfibrozil and clopidogrel, which can raise drug levels. Finally, we provide a framework for identifying potential drug-drug interactions and avoiding errors.

Outcomes of cardiopulmonary resuscitation in patients with pulmonary arterial hypertension.

Over the past 20 years, despite significant advancements in pulmonary arterial hypertension (PAH) medical therapy, many patients require admission to the hospital and are at risk for in-hospital cardiac arrest (IHCA). Prior data found poor survival in PAH patients after cardiac arrest. The purpose of this study was to explore post-IHCA outcomes in PAH patients receiving advanced medical therapies. This is a single-center retrospective study of PAH patients who underwent cardiopulmonary resuscitation for IHCA between July 2005 and May 2021. Patients were identified through an internal cardiac arrest database. Twenty six patients were included. Half of the cohort had idiopathic PAH, with 54% of patients on combination therapy, 27% on monotherapy, and 19% of patients on no therapy. Mean right atrial pressure, mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance were 13 ± 6 mmHg, 57 ± 13 mmHg, 2.0 ± 0.7 L/min/m2, and 14.5 ± 7.6 Wood units, respectively. Most common etiology of cardiac arrest was circulatory collapse. Initial arrest rhythm in all but one patient was pulseless electrical activity. Six patients (23%) achieved return of spontaneous circulation (ROSC) and one patient (4%) survived to hospital discharge. Rates of ROSC and survival to discharge after IHCA are poor in patients with PAH. Even patients with mild hemodynamics had low likelihood of survival. In patients who are lung transplant candidates, there should be early consideration of extracorporeal support before cardiac arrest.

Carfilzomib-associated pulmonary arterial hypertension in multiple myeloma.

Drug-induced pulmonary arterial hypertension (PAH) is constantly evolving as new drugs are developed. Carfilzomib is a recently approved therapy for relapsed and refractory multiple myeloma. While it has been associated with cardiovascular adverse events, such as ischemic heart disease and heart failure, PAH has not been a well-described side effect. We present two patients who developed PAH associated with initiation of carfilzomib. They both initially presented with severe dyspnea, had elevated right ventricular systolic pressure on transthoracic echocardiography and ultimately underwent right heart catheterization. With discontinuation of carfilzomib, both patients had improvement in hemodynamics. However, one patient required initiation of PAH-targeted therapies and has had worsening right ventricular function again despite permanent discontinuation of carfilzomib. It is important to recognize the association between carfilzomib and PAH. Echocardiography can be an important initial screening tool. PAH from carfilzomib therapy may be reversible, especially if diagnosed early; however, extended follow-up is essential.

Pregnancy and pulmonary arterial hypertension: a case series and literature review.

BACKGROUND: Despite the development of advanced therapies for pulmonary arterial hypertension, pregnancy remains contraindicated in these patients owing to high maternal and fetal morbidity and mortality. Limited data exist regarding pregnancy management and outcome in this unique patient population. We describe a series of pregnant patients diagnosed as having pulmonary arterial hypertension before or during pregnancy who delivered at a tertiary center with a comprehensive and established pulmonary vascular disease program. OBJECTIVE: This study aimed to describe a single institution's experience and review the existing literature for pregnancy management and outcomes in patients with pulmonary arterial hypertension. STUDY DESIGN: A review of all patients with pulmonary arterial hypertension who were admitted for delivery between 2005 and 2019 at our institution was performed. All data were extracted from the electronic health record and included patient demographics, pulmonary arterial hypertension subtype, pulmonary arterial hypertension-targeted therapies, and mode of delivery and anesthesia. RESULTS: A total of 7 patients were identified; 5 patients had a prepartum diagnosis of pulmonary arterial hypertension, whereas 2 patients were diagnosed as having pulmonary arterial hypertension during the third trimester. All patients were started on prostacyclins and the majority were on combination pulmonary arterial hypertension-targeted therapy. The maternal mortality rate was 29%. Elective cesarean delivery was performed in more than 70% of cases, whereas 1 patient required an urgent cesarean delivery and 1 patient had a successful vaginal delivery. Most patients had epidural anesthesia. Notably, 2 patients required extracorporeal membrane oxygenation after delivery and both died. There were no cases of neonatal mortality. CONCLUSION: Our cases series and the published literature to date show that pregnancy in pulmonary arterial hypertension remains poorly tolerated despite marked advancements in pulmonary arterial hypertension-targeted therapies and postpartum care. A multidisciplinary team approach remains essential for the management of these patients.

Incorporating baseline functional status to improve validity of neurological outcome assessments following cardiac arrest.

BACKGROUND: Neurological status at hospital discharge is routinely used to assess patient outcome after cardiac arrest. However, attribution of impairment to the arrest is valid only if baseline neurological status is known. This study evaluated whether incorporating baseline neurological status improves performance of a widely employed neurological outcome scale for quantifying arrest-attributable morbidity. METHODS: Retrospective cohort study of two U.S. hospitals. Neurological function was assessed via Cerebral performance category (CPC), an ordinal five-point scale with 1 indicating sufficient cognition to lead an independent life and 5 representing brain death. Hospitalized adult patients who suffered in-hospital cardiac arrest for which cardiopulmonary resuscitation was attempted between 2011-2015 were included. Patients were identified through a quality improvement registry that captures all inpatient arrests in the two hospitals. RESULTS: Of 486 patients who suffered in-hospital cardiac arrest, 124 (25.5%) had baseline abnormal neurological function (pre-hospitalization CPC>1). Although 54 patients had a normal discharge CPC of 1, 80 patients had no change in CPC from their prior baseline (11.1% vs. 16.5% met criterion for "normal" outcome defined as CPC of 1 vs. change-in-CPC of 0; McNemar p < .01; kappa for agreement: .78, 95% CI .69-.86). Across several formulations of criteria for "good" neurological outcome, similar discordance existed between conventional definitions considering only discharge CPC and modified definitions that included change-in-CPC from baseline. CONCLUSIONS: Incorporating change-in-CPC into criteria for "good" neurological outcome post-arrest yields discordant results from traditional approaches that consider discharge CPC only and increases face validity of reporting arrest-related morbidity.