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Septic shock is a severe form of sepsis that has a high mortality rate, and a substantial proportion of these patients will develop cardiac dysfunction, often termed septic cardiomyopathy (SCM). Some SCM patients may develop frank cardiac failure, termed sepsis-related cardiogenic shock (SeRCS). Little is known of SeRCS. This study describes baseline characteristics of patients with SCM and SeRCS compared to patients with septic shock without cardiac dysfunction. We compare clinical outcomes among SCM, SeRCS, and septic shock, and identify risk factors for the development of SCM and SeRCS. Septic patients admitted to the ICU with an echocardiogram obtained within 72 hours were included. Left ventricular ejection fraction of ≤55% was used to define SCM, and cardiac index ≤2.1 L/min/m2 among patients with SCM defined SeRCS. Machine learning was used to identify risk factors for development of SCM and SeRCS. Logistic regression was used to compare mortality among groups. Among 1229 patients, 977 patients had septic shock without cardiac dysfunction, 207 had SCM, and 45 had SeRCS. In patients with septic shock, the strongest predictor for developing SCM and SeRCs was a prior history of cardiac dysfunction. Mortality did not significantly differ among the three groups. SCM and SeRCS affect a minority of patients with septic shock, disproportionately affecting individuals with a history of cardiac disease. We did not identify a mortality difference associated with SCM or SeRCS. Additional work is needed to define further subtypes and treatment options for this patient population.

Arrhythmias are increasingly recognized as serious, end-stage complications of pre-capillary pulmonary hypertension, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Although arrhythmias contribute to symptoms, morbidity, in-hospital mortality, and possibly sudden death in PAH/CTEPH, there remains a paucity of epidemiologic, pathophysiologic, and outcome data to guide management of these patients. This review summarizes the most current evidence on the topic: from the molecular mechanisms driving arrhythmia in the hypertrophied or failing right heart, to the clinical aspects of epidemiology, diagnosis, and management.

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.

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.

The use of electronic cigarettes has been associated with pulmonary injury, one feature of which has been lipid-laden macrophages in pulmonary-lavage fluid. Six cases in Utah are reported.

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.

Background Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis. Results In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > − 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5–67.0) years and admission APACHE II score of 21.0 (16.0–32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p  < 10 −5 ). Conclusions In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM.

Chronic thromboembolic pulmonary hypertension (CTEPH) is due to unresolved pulmonary embolism (PE), however the pathophysiology of how PE evolves into CTEPH is unclear. Study of populations of acute PE patients at increased risk for CTEPH, such as those with prior splenectomy, may clarify the mechanisms driving transition from acute PE to CTEPH. In this study, we examined the relationship between acute PE, CTEPH and splenectomy in two observational cohorts. In the first, we compared the frequency of splenectomy among groups of patients with CTEPH, PE, and no PE. In the second, we compare clinical features of acute PE presentation in hospitalized patients with or without a prior splenectomy. We find that a history of splenectomy is significantly more frequent in patients with CTEPH than in patients with PE (OR 4.3, 95% CI 1.5–12.6). This association remained when we compared CTEPH patients to PE patients without a provoking factor for PE (OR 5.3, 95% CI 1.7–16.9), a population that is at increased risk of developing CTEPH. Patients with acute PE and prior splenectomy were more likely to present with subacute symptoms, more likely to have a distal location of PE, and less likely to have deep venous thrombosis (DVT) than were non‐splenectomized acute PE patients. Thus, prior splenectomy appears to modify some clinical features of acute PE. We hypothesize that the difference in clinical features of PE that are observed in the context of prior splenectomy are relevant to the increased risk of CTEPH observed in this population.

e-Cigarette, or vaping, product use-associated lung injury (EVALI) has caused more than 2800 illnesses and 68 deaths in the United States. Better characterization of this novel illness is needed to inform diagnosis and management. To describe the clinical features, bronchoscopic findings, imaging patterns, and outcomes of EVALI. This case series of 31 adult patients diagnosed with EVALI between June 24 and December 10, 2019, took place at an academic medical center in Salt Lake City, Utah. e-Cigarette use, also known as vaping. Symptoms, laboratory findings, bronchoscopic results, imaging patterns, and clinical outcomes. Data from 31 patients (median [interquartile range] age, 24 [21-31] years) were included in the study. Patients were primarily men (24 [77%]) and White individuals (27 [87%]) who used e-cigarette products containing tetrahydrocannabinol (THC) (29 [94%]). Patients presented with respiratory (30 [97%]), constitutional (28 [90%]), and gastrointestinal (28 [90%]) symptoms. Serum inflammatory markers were elevated in all patients. Bronchoscopy was performed in 23 of 28 inpatients (82%) and bronchoalveolar lavage (BAL) revealed the presence of lipid-laden macrophages (LLMs) in 22 of 24 cases (91%). BAL samples tested positive for Pneumocystis jirovecii (3 patients [13%]), rhinovirus (2 patients [8%]), human metapneumovirus and Aspergillus (1 patient each [4%]); all except human metapneumovirus were determined to be false-positives or clinically inconsequential. The exclusive or dominant computed tomography (CT) pattern was organizing pneumonia in 23 of 26 cases (89%). Patients received antibiotics (26 [84%]) and corticosteroids (24 [77%]), and all survived; 20 patients (65%) seen in follow-up showed marked improvement, but residual symptoms (13 [65%]), radiographic opacities (8 [40%]), and abnormal pulmonary function tests (8 of 18 [44%]) were common. In this case series, patients with EVALI characteristically presented with a flu-like illness with elevated inflammatory markers, LLMs on BAL samples, and an organizing pneumonia pattern on CT imaging. Bronchoscopic testing for infection had a high incidence of false-positive results. Patients had substantial residual abnormal results at early follow-up. These data suggest a limited role for bronchoscopy in typical presentations of EVALI without risk factors for alternative diagnoses and the need for careful longitudinal follow-up.

An elevated RV/LV ratio predicts poor short- and long-term outcomes in patients with pulmonary hypertension and acute pulmonary embolism [3,4]; we investigated whether this parameter would perform similarly in a more heterogenous population of sepsis patients with a focus on 30-day mortality. Interestingly, visually estimated parameters of RV function (semi-quantitative size and function) did not predict in-hospital mortality and were no different between survivors and non-survivors at 1 year. [...]the manuscript by Vallabhajosyula and colleagues is more similar than different to our work, as an observed increase in semi-quantitative RV size may be equivalent to increased RV/LV ratio (at least in the patients with isolated RV dysfunction). Dr. Liou is supported by funding for other projects from NHLBI/NIH (R01 HL125520), the US Cystic Fibrosis Foundation (LIOU13A0, LIOU14Y4, CC132-16AD, LIOU14Y0, LIOU14P0), the Ben B. And Iris M. Margolis Family Foundation of Utah and the Claudia Ruth Goodrich Stevens Endowment Fund and received support during the current study for performing clinical trials from Abbvie, Gilead, Nivalis, Novartis, Proteostasis, Inc., Savara and Vertex.