BACKGROUND: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability. RESULTS: The median age of the study population was 66 (56–77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%–87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST–elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively. CONCLUSIONS: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites.

BACKGROUND:There are limited data on how patients with cardiogenic shock (CS) die. METHODS:The Critical Care Cardiology Trials Network is a research network of cardiac intensive care units coordinated by the Thrombolysis In Myocardial Infarction (TIMI) Study Group (Boston, MA). Using standardized definitions, site investigators classified direct modes of in-hospital death for CS admissions (October 2021 to September 2022). Mutually exclusive categories included 4 modes of cardiovascular death and 4 modes of noncardiovascular death. Subgroups defined by CS type, preceding cardiac arrest (CA), use of temporary mechanical circulatory support (tMCS), and transition to comfort measures were evaluated. RESULTS:Among 1068 CS cases, 337 (31.6%) died during the index hospitalization. Overall, the mode of death was cardiovascular in 82.2%. Persistent CS was the dominant specific mode of death (66.5%), followed by arrhythmia (12.8%), anoxic brain injury (6.2%), and respiratory failure (4.5%). Patients with preceding CA were more likely to die from anoxic brain injury (17.1% vs 0.9%; P < .001) or arrhythmia (21.6% vs 8.4%; P < .001). Patients managed with tMCS were more likely to die from persistent shock (P < .01), both cardiogenic (73.5% vs 62.0%) and noncardiogenic (6.1% vs 2.9%). CONCLUSIONS:Most deaths in CS are related to direct cardiovascular causes, particularly persistent CS. However, there is important heterogeneity across subgroups defined by preceding CA and the use of tMCS.

Background Previous studies have suggested that there is wide variability in cardiac intensive care unit (CICU) length of stay (LOS); however, these studies are limited by the absence of detailed risk assessment at the time of admission. Thus, we evaluated inter -hospital differences in CICU LOS, and the association between LOS and in -hospital mortality. Methods Using data from the Critical Care Cardiology Trials Network (CCCTN) registry, we included 22,862 admissions between 2017 and 2022 from 35 primarily tertiary and quaternary CICUs that captured consecutive admissions in annual 2 -month snapshots. The primary analysis compared inter -hospital differences in CICU LOS, as well as the association between CICU LOS and all -cause in -hospital mortality using a Fine and Gray competing risk model. Results The overall median CICU LOS was 2.2 (1.1-4.8) days, and the median hospital LOS was 5.9 (2.8-12.3) days. Admissions in the longest tertile of LOS tended to be younger with higher rates of pre-existing comorbidities, and had higher Sequential Organ Failure Assessment (SOFA) scores, as well as higher rates of mechanical ventilation, intravenous vasopressor use, mechanical circulatory support, and renal replacement therapy. Unadjusted all -cause in -hospital mortality was 9.3%, 6.7%, and 13.4% in the lowest, intermediate, and highest CICU LOS tertiles. In a competing risk analysis, individual patient CICU LOS was correlated (r2 = 0.31) with a higher risk of 30 -day in -hospital mortality. The relationship remained significant in admissions with heart failure, ST -elevation myocardial infarction and non -ST segment elevation myocardial infarction. Conclusions In a large registry of academic CICUs, we observed significant variation in CICU LOS and report that LOS is independently associated with all -cause in -hospital mortality. These findings could potentially be used to improve CICU resource utilization planning and refine risk prognostication in critically ill cardiovascular patients. (Am Heart J 2024;271:28- 37.)

PURPOSE: Interstitial lung abnormalities (ILAs) are an increasingly recognized finding on lung computed tomography (CT) scans, with a prevalence ranging from 3-17%.These findings have been identified in elderly or smoking populations via noncontrasted CT scans.Individuals with ILAs have increased morbidity and a subset of individuals will have progression of disease to interstitial lung disease (ILD).To our knowledge no data exists in contrasted CT scan cohorts.Scant data exists in which the Fleischner criteria has been used to identify ILAs.The purpose of this study is to identify the incidence of ILAs on CTPAs in a cohort of patients across two urban Emergency Departments.METHODS: This is a single-center retrospective review of computed tomography wit pulmonary angiography (CTPA) scans obtained between May 2009 and July 2010.Reviewer (RG) identified scans with presumed ILAs, which were then reviewed by an ILD Pulmonologist (PC).If there were discrepancies, then the scan in question was reviewed by a chest radiologist (ZK). RESULTS:We reviewed 990 charts and identified patients who had follow-up chest CT scans with or without contrast at least 1 year after the original.We identified 383 charts with follow-up imaging.31/383 (8.1%) had an ILA on the initial scan.The mean age of those with ILAs was 68.1 years and mean time to follow-up imaging was 6.8 years.Follow-up imaging revealed progression to ILD in 4/31 (12.9%), resolution of ILA in 3/31 (9.7%) and stable scan in 24/31 (77.4%).Of the 4 with progression, one was diagnosed with sarcoid, one with eGPA, one with probable chronic HP, and one that was lost to follow-up.Mean time to followup imaging in these 4 patients was 11.6 years.More than half of patients with ILAs did not have Pulmonary Function Tests (PFTs) nor pulmonology follow-up (16/31, 51.6%) despite abnormal imaging. CONCLUSIONS:In this retrospective study, we demonstrate a similar incidence of ILAs as that of published literature (8.1%).To our knowledge, this is the first study in which contrasted scans were used to identify ILAs.The ability to detect early interstitial changes on contrasted scans could allow for early recognition of at-risk individuals.51.6% of patients with ILAs were not referred to a pulmonologist, nor were PFTS obtained.This suggests that at the time of image acquisition, many practitioners may have been unaware of ILAs and their significance.CLINICAL IMPLICATIONS: This is, to our knowledge, the first study to identify ILAs via contrasted imaging.The incidence of ILAs in our cohort aligns with previously published data.The use of CTPAs, in combination with increasing awareness of ILAs and advancements in imaging analytics, may allow for the early diagnosis and monitoring of radiographic abnormalities that have the possibility of progressing to ILD.

PURPOSE: An enlarged pulmonary artery (PA) on CT imaging has been associated with mortality risk in several cohorts.Two measures of abnormal PA size have been defined based on the distribution of sizes in healthy individuals: PA diameter (PAd; abnormal >27mm [female], >29mm [male]) and PAd ratio to the ascending aorta (PA:AA; abnormal > 0.9).It is not known if these thresholds correspond to the PA size beyond which risk of adverse outcomes increases.We hypothesized that mortality risk would increase in a size-dependent manner for both metrics.The average AA diameter increases faster with age; thus we also hypothesized that higher PA:AA ratios would be needed to confer excess mortality risk in younger patients. METHODS:We reviewed 1000 randomly-selected CTPAs completed in 2009-2010 in two EDs within an integrated healthcare system in Utah.Patients with acute pulmonary emboli and duplicate scans were excluded.We measured the PAd and AA at the same level on each CTPA.Mortality status was obtained from the EHR and death registries.Restricted cubic splines were used to model the association of PA:AA and PAd with death in Cox regression models that also control for age and sex.Hazard Ratios (HR) are compared to the healthy population median value (PA:AA 0.77; PAd 25.1mm). RESULTS:The median age (n¼912 included) was 51y (interquartile range [IQR] 37-67) and 36.5% were male.28.8% died during follow-up (median 7 years).The median age of the n¼318 patients with high PA:AA was 41.5 (IQR.30-61).Patients with enlarged PAd were older (n¼ 258, median age 62 IQR 46-77).The PA:AA ratio associated with the lowest mortality risk was higher in younger patients.For the entire sample, all ratios below 0.75 predicted equivalent and minimized risk, while patients <50y had mortality risk nadir at PA:AA of 0.83.Similarly, the PA:AA conferring a HR of 1.5 was higher in younger patients (PA:AA ratio of 0.96 entire sample; PA:AA 1.05 under age 50y) with near log-linear increase for further size increase in all ages.The PAd associated with lowest risk of death was also smaller in the entire cohort (PAd of 22.1 mm [F] and 24.1 mm [M]) than in patients <50y (25.6 mm [F] and 27.6 mm [M]).The size associated with HR 1.5 was also larger in younger patients (entire cohort: PAd of 28.8 mm [F] and 30.8 mm [M]; under 50y: 30.7 mm [F] and 32.7 mm [M]) CONCLUSIONS: We found that both enlarged PAd and elevated PA:AA confer excess mortality risk in a dose-dependent manner for patients receiving CTPAs in the ED.Therefore, dichotomization as "normal or abnormal" may discard prognostic information.For both PAd and PA:AA, a larger PA size was required in younger patients before mortality risk increased.Whether this is due to differing timelines of mortality risk, increased vascular compliance in younger adults, or other mechanisms warrants further investigation.CLINICAL IMPLICATIONS: Dichotomized classification of pulmonary artery size on CTPA has previously been shown to predict mortality risk, but we show that age adjustment and accounting for the degree of enlargement may improve predictive performance.

Findings of an enlarged pulmonary artery diameter (PAd) and increased pulmonary artery to ascending aorta ratio (PA:AA) on contrast-enhanced computed tomography pulmonary angiography (CTPA) are associated with increased mortality in particular groups of patients with cardiopulmonary disease. However, the frequency and prognostic significance of these incidental findings has not been studied in unselected patients evaluated in the Emergency Department (ED). This study aims to determine the prevalence and associated prognosis of enlarged pulmonary artery measurements in an ED cohort. We measured PA and AA diameters on 990 CTPA studies performed in the ED. An enlarged PA diameter was defined as >27 mm in females and >29 mm in males, while an increased PA:AA was defined as >0.9. Poisson regression was performed to calculate prevalence ratios for relevant comorbidities, and multivariable Cox regression was performed to calculate hazard ratios (HR) for mortality of patients with enlarged pulmonary artery measurements. An enlarged PAd was observed in 27.9% of 990 patients and was more commonly observed in older patients and in patients with obesity or heart failure. Conversely, PA:AA was increased in 34.2% of subjects, and was more common in younger patients and those with peripheral vascular disease or obesity. After controlling for age, sex, and comorbidities, both enlarged PAd (HR 1.29, 95% CI 1.00-1.68, p = 0.05) and PA:AA (HR 1.70, 95% CI 1.31-2.22 p < 0.01) were independently associated with mortality. In sum, enlarged PAd and increased PA:AA are common in patients undergoing CTPAs in the ED setting and both are independently associated with mortality.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious complication of acute pulmonary embolism (PE) which remains underdiagnosed. A better understanding of risk factors for CTEPH would improve our ability to predict which PE survivors are at risk. Several medical conditions-including malignancy, splenectomy, thyroid hormone supplementation, the presence of an intravascular device, inflammatory bowel disease, osteomyelitis, and non-O blood group-have been associated with increased risk of CTEPH, primarily in studies comparing patients with CTEPH to individuals with non-thrombotic conditions. Because many of these conditions increase thrombosis risk, it remains unclear whether their association with CTEPH reflects a general effect on thrombosis risk, or a specific effect on the risk of developing CTEPH as an outcome of thrombosis. We performed a case-control study comparing the frequencies of these conditions in patients with CTEPH versus patients with acute PE who did not develop CTEPH. The conditions studied were equally frequent in the CTEPH and PE cohorts, although there was a trend towards an increased frequency of splenectomy and non-O blood group among the CTEPH cohort. Thus, other than the possible exceptions of splenectomy and non-O blood group, the investigated medical conditions do not appear likely to increase the risk of CTEPH as an outcome of acute PE, and thus are unlikely to be useful in predicting CTEPH risk among PE survivors.

Chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (PE) are related phenotypes, however, previous reports have suggested that genetic risk factors for CTEPH and PE differ. Here we report that a family history of VTE is equally frequent in individuals with CTEPH and PE, suggesting that shared genetic variants may influence risk of both phenotypes. We also provide the first estimate of the frequency of familial CTEPH, which we identified in 2.2% of CTEPH patients in our cohort.

"The CTEPH Trajectories Study: Assessment of Follow-Up after Acute Pulmonary Embolism to Identify Missed Opportunities for Chronic Thromboembolic Pulmonary Hypertension Diagnosis." Annals of the American Thoracic Society, 19(8), pp. 1428–1432

The Factor V Leiden variant is identified significantly less frequently among CTEPH patients who had their first venous thromboembolism prior to 50 years of age than among similar patients with acute pulmonary embolism who did not develop CTEPHhttps://bit.ly/2W6qoLK

Group 1 pulmonary hypertension (pulmonary arterial hypertension; PAH) is a rare disease characterized by remodeling of the small pulmonary arteries leading to progressive elevation of pulmonary vascular resistance, ultimately leading to right ventricular failure and death. Deleterious mutations in the serine-threonine receptor bone morphogenetic protein receptor 2 (BMPR2; a central mediator of bone morphogenetic protein (BMP) signaling) and female sex are known risk factors for the development of PAH in humans. In this narrative review, we explore the complex interplay between the BMP and estrogen signaling pathways, and the potentially synergistic mechanisms by which these signaling cascades increase the risk of developing PAH. A comprehensive understanding of these tangled pathways may reveal therapeutic targets to prevent or slow the progression of PAH.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious sequela of pulmonary embolism (PE) and occurs in about 3% of acute PE survivors. Common inherited thrombophilias, including the Factor V Leiden mutation, are not associated with increased risk of CTEPH, even though they increase the risk for VTE. Whether other inherited genetic factors contribute to the risk of developing CTEPH remains unknown. Familial clustering of a disease can indicate inherited genetic risk for that disease. In this study, the Utah Population Database (UPDB), a unique genealogy resource, was used to assess whether CTEPH cases cluster in families. METHODS: Prevalent CTEPH patients in Utah were identified and were then matched to control subjects. Using the UPDB, the Genealogical Index of Familiality (a statistical measure of relatedness of individuals with a given phenotype) was calculated. The UPDB was also used to calculate the relative risk of CTEPH and VTE in the family members of patients with CTEPH. RESULTS: This study found that Utah patients with CTEPH are significantly more related than would be expected by chance, with both close and distant relationships identified. We also found that the relative risk of VTE was significantly increased among first-degree relatives of CTEPH probands. CONCLUSIONS: The study data suggest that heritable genetic factors influence an individual's risk of developing CTEPH, providing the strongest evidence to date for a genetic contribution to CTEPH risk. Although our data suggest that these inherited genetic factors likely also increase the risk for VTE, they are likely to be distinct from the common inherited thrombophilias.

This article provides an overview of pulmonary arterial hypertension (PAH), beginning with the initial pathologic recognition of pulmonary hypertension more than 100 years ago and progressing to the current diagnostic categorization of PAH. It reviews the epidemiology, pathophysiology, genetics, and modern treatment of PAH. The article discusses several important recent studies that have highlighted the importance of new management strategies, including serial risk assessment and combination pharmacotherapy.

This article provides an overview of pulmonary arterial hypertension (PAH), beginning with the initial pathologic recognition of pulmonary hypertension more than 100 years ago and progressing to the current diagnostic categorization of PAH. It reviews the epidemiology, pathophysiology, genetics, and modern treatment of PAH. The article discusses several important recent studies that have highlighted the importance of new management strategies, including serial risk assessment and combination pharmacotherapy.

BACKGROUND: Differentiating pulmonary venoocclusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) from idiopathic pulmonary arterial hypertension (IPAH) or heritable pulmonary arterial hypertension (HPAH) is important clinically. Mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) cause heritable PVOD and PCH, whereas mutations in other genes cause HPAH. The aim of this study was to describe the frequency of pathogenic EIF2AK4 mutations in patients diagnosed clinically with IPAH or HPAH.METHODS: Sanger sequencing and deletion/duplication analysis were performed to detect mutations in the bone morphogenetic protein receptor type II (BMPR2) gene in 81 patients diagnosed at 30 North American medical centers with IPAH (n = 72) or HPAH (n = 9). BMPR2 mutation-negative patients (n = 67) were sequenced for mutations in four other genes (ACVRL1, ENG, CAV1, and KCNK3) known to cause HPAH. Patients negative for mutations in all known PAH genes (n = 66) were then sequenced for mutations in EIF2AK4. We assessed the pathogenicity of EIF2AK4 mutations and reviewed clinical characteristics of patients with pathogenic EIF2AK4 mutations.RESULTS: Pathogenic BMPR2 mutations were identified in 8 of 72 (11.1%) patients with IPAH and 6 of 9 (66.7%) patients with HPAH. A novel homozygous EIF2AK4 mutation (c.257+A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations.CONCLUSIONS: Pathogenic biallelic EIF2AK4 mutations are rarely identified in patients diagnosed with HPAH. Identification of pathogenic biallelic EIF2AK4 mutations can aid clinicians in differentiating HPAH from heritable PVOD or PCH.

This article provides an overview of pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH), two disorders that challenge clinicians, radiologists, and pathologists because they often mimic pulmonary arterial hypertension (PAH). The article reviews the features that differentiate PVOD and PCH from PAH. The article also describes the overlap of PVOD and PCH, highlighted by recent reports of families diagnosed with PVOD or PCH caused by EIF2AK4 mutations. In addition, the article outlines current approaches to the diagnosis and treatment of PVOD and PCH.