The effects of oxygenation on acute vasodilator challenge in pulmonary arterial hypertension.

Identification of long-term calcium channel blocker (CCB) responders with acute vasodilator challenge is critical in the evaluation of patients with pulmonary arterial hypertension. Currently there is no standardized approach for use of supplemental oxygen during acute vasodilator challenge. In this retrospective analysis of patients identified as acute vasoresponders, treated with CCBs, all patients had hemodynamic measurements in three steps: (1) at baseline; (2) with 100% fractional inspired oxygen; and (3) with 100% fractional inspired oxygen plus inhaled nitric oxide (iNO). Those meeting the definition of acute vasoresponsiveness only after first normalizing for the effects of oxygen in step 2 were labeled "iNO Responders." Those who met the definition of acute vasoresponsiveness from a combination of the effects of 100% FiO2 and iNO were labeled "oxygen responders." Survival, hospitalization for decompensated right heart failure, duration of CCB monotherapy, and functional data were collected. iNO responders, when compared to oxygen responders, had superior survival (100% vs. 50.1% 5-year survival, respectively), fewer hospitalizations for acute decompensated right heart failure (0% vs. 30.4% at 1 year, respectively), longer duration of CCB monotherapy (80% vs. 52% at 1 year, respectively), and superior 6-min walk distance. Current guidelines for acute vasodilator testing do not standardize oxygen coadministration with iNO. This study demonstrates that adjusting for the effects of supplemental oxygen before assessing for acute vasoresponsiveness identifies a cohort with superior functional status, tolerance of CCB monotherapy, and survival while on long-term CCB therapy.

Reduced mortality associated with pulmonary embolism response team consultation for intermediate and high-risk pulmonary embolism: a retrospective cohort study.

BACKGROUND: The management of acute pulmonary embolism (PE) has become increasingly complex with the expansion of advanced therapeutic options, resulting in the development and widespread adoption of multidisciplinary Pulmonary Embolism Response Teams (PERTs). Much of the literature evaluating the impact of PERTs has been limited by pre- postimplementation study design, leading to confounding by changes in global practice patterns over time, and has yielded mixed results. To address this ambiguity, we conducted a retrospective cohort study to evaluate the impact of the distinct exposures of PERT availability and direct PERT consultation. METHODS: At a single tertiary center, we conducted propensity-matched analyses of hospitalized patients with intermediate or high-risk PE. To assess the impact of PERT availability, we evaluated the changes in 30-day mortality, hospital length of stay (HLOS), time to therapeutic anticoagulation (TAC), in-hospital bleeding complications, and use of advanced therapies between the two years preceding and following PERT implementation. To evaluate the impact of direct PERT consultation, we conducted the same analyses in the post-PERT era, comparing patients who did and did not receive PERT consultation. RESULTS: Six hundred eighty four patients were included, of which 315 were pre-PERT patients. Of the 367 postPERT patients, 201 received PERT consultation. For patients who received PERT consultation, we observed a significant reduction in 30-day mortality (5% vs 20%, OR 0.38, p = 0.0024), HLOS. (-5.4 days, p < 0.001), TAC (-0.25 h, p = 0.041), and in-hospital bleeding (OR 0.28, p = 0.011). These differences were not observed evaluating the impact of PERT presence in pre-vs postimplementation eras. CONCLUSIONS: We observed a significant reduction in 30-day mortality, hospital LOS, TAC, and in-hospital bleeding complications for patients who received PERT consultation without an observed difference in these metrics when comparing the pre- vs post-implementation eras. This suggests the benefits stem from direct PERT involvement rather than the mere existence of PERT. Our data supports that PERT consultation may provide benefit to patients with acute intermediate or high-risk PE and can be achieved without a concomitant increase in advanced therapies.

A case of pulmonary tumor embolism syndrome with thrombus in transit.

The incidence of pulmonary tumor embolism in patients with solid tumors is estimated to be between 3% and 26% yet is rarely diagnosed. In this case, a 74-year-old male with sarcomatoid variant of urothelial carcinoma and recently diagnosed left renal vein thrombus treated with low-molecular-weight-heparin, presented to the emergency department with acute syncope and dyspnea. He was found to have CT imaging of segmental and subsegmental arterial filling defects, a right atrial filling defect concerning for thrombus in transit and was diagnosed with pulmonary tumor embolism syndrome. The patient was treated with aspiration thrombectomy, with pathology demonstrating sarcomatoid urothelial carcinoma cells. He was initiated on a combination of gemcitabine plus carboplatin to decrease the tumor burden. While pulmonary tumor embolism syndrome is associated with a poor prognosis, prompt diagnosis and initiation of cancer-specific therapies can significantly improve survival.

Impact of the COVID-19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry.

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly-sponsored insurance during the COVID-19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly-sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID-19 pandemic. The relatively small impact of the COVID-19 pandemic on pulmonary hypertension-related outcomes was unexpected but may be due to pre-established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID-19 pandemic, patients who were on publicly-sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness.

A Case of High-Output Heart Failure.

CASE PRESENTATION: A 55-year-old woman with a medical history of hereditary hemorrhagic telangiectasia (HHT) complicated by recurrent nosebleeds, severe blood loss anemia, hepatic arterial-venous malformation (AVM), pulmonary hypertension, and severe tricuspid regurgitation presented to the HHT specialty clinic with acute hypoxic respiratory failure (new 3-L O2 requirement), weight gain, and volume overload. She was directly admitted to the pulmonary hypertension unit of our hospital. She had two recent admissions for similar symptoms thought to be due to worsening pulmonary arterial hypertension. In prior admissions, she had undergone right heart catheterization demonstrating mild pulmonary hypertension (pulmonary arterial pressure, 29 mm Hg, cardiac output by Fick 5.76, and cardiac index 3.22, mildly elevated pulmonary vascular resistance to 5.5 woods units). She would undergo diuresis with symptomatic improvement; however, after discharge she would rapidly develop recurrent heart failure symptoms. She reported compliance with guideline-directed medications, diuretics, and dietary restrictions and was still suffering severe symptoms. Notably she had previously elevated liver enzymes concerning for cirrhosis and had begun a workup to evaluate for causes of cirrhosis; she had a history of mild alcohol use, negative hepatitis viral serology, and no known history of liver disease.

A 65-Year-Old Man With Weight Loss, Peripheral Neuropathy, and Lower Extremity Swelling.

CASE PRESENTATION: A 65-year-old man with no past medical history sought treatment at the hospital with lower extremity swelling, pain, tingling in a stocking-glove distribution, and syncope. He reported a 23-pound unintentional weight loss. He felt unsteady walking with a couple of falls, and his exercise tolerance was limited to several hundred feet. He did not report vision changes, dysphagia, bowel or bladder problems, tremor, orthopnea, lightheadedness, or chest pain. He did not report any history of substance misuse, high-risk sexual behavior, or concerning exposures. The patient was admitted for further workup.

Pragmatic Use of Catheter-Directed Thrombolysis in Venous Thromboembolism and a Comparative Evaluation With Traditional Therapies in Submassive Pulmonary Embolism.

BACKGROUND: Catheter-directed thrombolysis (CDT) is a novel treatment for venous thromboembolism (VTE). Limited data describe pragmatic use of CDT and compare CDT to other VTE therapies. OBJECTIVE: Assess the use of CDT and comparatively evaluate CDT, anticoagulation, and systemic thrombolysis in submassive pulmonary embolism (PE). METHODS: Retrospective, single-center, chart audit. Part 1 described all patients who received CDT for VTE. Part 2 matched patients with submassive PE who received CDT, heparin, or systemic thrombolysis and assessed length of stay (LOS), bleeding, all cause in-hospital mortality, and escalation of care. RESULTS: For part 1, 70 CDT patients were identified; 42 with DVT and 28 with PE. ICU LOS was longer (2.5 ± 2.9 vs. 4.9 ± 8.4 days, p = 0.07), escalation of care more frequent (0% vs. 35.7%, p < 0.0001), and hospital mortality greater (2.4% vs. 21.4%, p = 0.014) in the PE group. For part 2, 21 CDT patients were matched to 21 heparin and 21 systemic thrombolysis patients. All CDT and tPA patients were admitted to the ICU versus only 6 (28.6%, p < 0.001) heparin patients. ICU LOS was significantly longer in the CDT group versus systemic tPA and systemic anticoagulation (80.7 ± 64.1 vs. 48.2 ± 27.7 vs. 24.9 ± 59.1 hours; p = 0.0048). More IVC filters and thrombectomies were performed in the CDT group. CONCLUSIONS: CDT is frequently used for both DVT and PE and requires ICU admission. Escalation of care is common when CDT is used for PE. For submassive PE, CDT is associated with prolonged ICU LOS compared to heparin or systemic thrombolysis. Resource utilization with CDT requires further evaluation.

Residence at moderately high altitude and its relationship with WHO Group 1 pulmonary arterial hypertension symptom severity and clinical characteristics: the Pulmonary Hypertension Association Registry.

BACKGROUND: WHO Group 1 pulmonary arterial hypertension is a progressive and potentially fatal disease. Individuals living at higher altitude are exposed to lower barometric pressure and hypobaric hypoxemia. This may result in pulmonary vasoconstriction and contribute to disease progression. We sought to examine the relationship between living at moderately high altitude and pulmonary arterial hypertension characteristics. METHODS: Forty-two US centers participating in the Pulmonary Hypertension Association Registry enrolled patients who met the definition of WHO Group 1 pulmonary arterial hypertension. We utilized baseline data and patient questionnaire responses. Patients were divided into two groups: moderately high altitude residence (home ≥4000 ft) and low altitude residence (home <4000 ft) based on zip-code. Clinical characteristics, hemodynamic data, patient demographics, and patient reported quality of life metrics were compared. RESULTS: Controlling for potential confounders (age, sex at birth, body mass index, supplemental oxygen use, race, 100-day cigarette use, alcohol use, and pulmonary arterial hypertension medication use), subjects residing at moderately high altitude had a 6-min walk distance 32 m greater than those at low altitude, despite having a pulmonary vascular resistance that was 2.2 Wood units higher. Additionally, those residing at moderately high altitude had 3.7 times greater odds of using supplemental oxygen. CONCLUSION: Patients with pulmonary arterial hypertension who live at moderately high altitude have a higher pulmonary vascular resistance and are more likely to need supplemental oxygen. Despite these findings, moderately high altitude Pulmonary Hypertension Association Registry patients have better functional tolerance as measured by 6-min walk distance. It is possible that a "high-altitude phenotype" of pulmonary arterial hypertension may exist. These findings warrant further study.

A 44-Year-Old Woman With Chest Pain and Dyspnea.

CASE PRESENTATION: A 44-year-old woman with a medical history of anti-phospholipid antibody syndrome complicated by recurrent pulmonary emboli with subsequent chronic hypoxic respiratory failure (3 L/min oxygen baseline) presented to the ED with 2 to 3 weeks of shortness of breath and pleuritic chest pain that radiated to the center of her back. These symptoms were accompanied by an increase in her oxygen requirement from 3 L/min to 6 L/min. She also reported nausea, vomiting, lightheadedness, and dizziness for the same period. The patient had two prior pulmonary emboli in the same year, which prompted a hypercoagulable workup, ultimately revealing a diagnosis of antiphospholipid antibody syndrome. The second pulmonary embolus occurred while the patient was on coumadin, though achieving a therapeutic international normalized ratio was challenging. At the recommendation of the Hematology Department, she was transitioned to systemic anticoagulation with low-molecular-weight heparin (LMWH) at a dose of 1.5 mg/kg twice daily, which was her regimen at the time of admission. The patient confirmed total compliance with her anticoagulation therapy, and she denied any recent travel or long periods of being sedentary. She was up to date on her age-appropriate cancer screening, without any evidence of active malignancy.

Inferior Vena Cava Filters: Past, Present, and Future.

Inferior vena cava (IVC) filters have existed as a treatment option for VTE for decades. Advances in medical technology have provided physicians with several options for devices that can be placed on either a permanent or temporary basis; however, there are limited data from randomized, controlled trials on the appropriate use of IVC filters. This contemporary review summarizes the history of IVC filters and the types that are available in clinical practice. It reviews the literature on the use of IVC filters and discusses the indications that professional societies have endorsed for their use. In addition, it outlines the complications of IVC filter placement and future research directions.

Advanced therapies for pulmonary embolism.

PURPOSE OF REVIEW: Treatment options for managing patients with acute pulmonary embolism are rapidly evolving. In this review, we discuss the supporting evidence and implementation strategies for these advanced therapeutic modalities. RECENT FINDINGS: We review the recent data supporting systemic and catheter directed thrombolytic therapies, mechanical embolectomy, use of extracorporeal membrane oxygen support, and pulmonary embolism response teams in managing patients with acute pulmonary embolism. We discuss the major professional society recommendations regarding their implementation. SUMMARY: A review of advanced therapies for pulmonary embolism.

Detection of respiratory pathogens in clinical samples using metagenomic shotgun sequencing.

PURPOSE: In this pilot study, we used shotgun metagenome sequencing (SMS) strategy on bronchoalveolar lavage (BAL) samples from hospitalized patients with suspected ventilate-associated pneumonia (VAP) in order to explore its potential for improving detection of ventilator-associated-pneumonia (VAP) etiology. METHODOLOGY: In total, 67BAL samples from patients with VAP were tested with SMS strategy for detection of respiratory pathogens. Results of SMS and routine respiratory culture were compared. RESULTS: SMS detected all pathogens recovered by cultivation approaches. In addition, putative pathogens other than the organisms recovered by culture were detected by SMS in culture-positive samples. In 40 of 45 (89  %) culture-negative samples, a potential pathogen was detected by SMS. CONCLUSION: This proof-of-concept study demonstrates that SMS is able to detect bacterial, fungal and viral organisms in BAL, including culture-negative cases.

A 49-Year-Old Woman With Chest Pain, Cough, and Hypoxemia After a Seizure.

CASE PRESENTATION: A 49-year-old woman with a medical history of epilepsy presented to the ED 1 h after a single, 15-min, witnessed, tonic-clonic seizure. Over the preceding 6 months, she had experienced five similar seizures of shorter duration. There were no recent changes to her phenytoin dose nor had she started any new medications. The patient had traveled to Jamaica 3 weeks before presentation, where she smoked marijuana once but otherwise had not used illicit substances nor had she used tobacco or alcohol. She states she felt well during and after the trip until this presentation. While being evaluated by the neurology service, the patient complained of sudden-onset chest pain and cough with associated hypoxemia. She denied changes in her sleep habits, she had not experienced any fevers, and she had no changes in her exercise tolerance. The patient was admitted to the general medicine floor for further workup.

Multidimensional Assessment of the Host Response in Mechanically Ventilated Patients with Suspected Pneumonia.

Rationale: The identification of informative elements of the host response to infection may improve the diagnosis and management of bacterial pneumonia. Objectives: To determine whether the absence of alveolar neutrophilia can exclude bacterial pneumonia in critically ill patients with suspected infection and to test whether signatures of bacterial pneumonia can be identified in the alveolar macrophage transcriptome. Methods: We determined the test characteristics of alveolar neutrophilia for the diagnosis of bacterial pneumonia in three cohorts of mechanically ventilated patients. In one cohort, we also isolated macrophages from alveolar lavage fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: An alveolar neutrophil percentage less than 50% had a negative predictive value of greater than 90% for bacterial pneumonia in both the retrospective (n = 851) and validation cohorts (n = 76 and n = 79). A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to alveolar neutrophilia. Conclusions: The absence of alveolar neutrophilia has a high negative predictive value for bacterial pneumonia in critically ill patients with suspected infection. Macrophages can be isolated from alveolar lavage fluid obtained during routine care and used for RNA-Seq analysis. This novel approach may facilitate a longitudinal and multidimensional assessment of the host response to bacterial pneumonia.

A 62-Year-Old Woman With Wheezing, Respiratory Failure, and an Abnormal CT Scan.

CASE PRESENTATION: A previously healthy 62-year-old woman was transferred to the ICU from the medical ward with acute bronchospastic respiratory failure requiring intubation and mechanical ventilation. Four weeks before, the patient was vacationing in Arizona and acquired a mildly productive cough as well as mild dyspnea. She presented to an urgent care facility and was diagnosed with community-acquired pneumonia. She received a 5-day course of azithromycin, with partial improvement of her symptoms. The patient returned home 1 week prior to admission, reporting worsening dyspnea, chest pressure, cough, and fever. The patient was admitted to the medical ward, and treatment for unresolved pneumonia was begun with levofloxacin, an inhaled short-acting beta agonist, and oral prednisone. Despite this treatment, the patient experienced severe respiratory distress with audible wheezing as well as increased work of breathing. She was intubated for acute hypoxemic respiratory failure and transferred to the ICU.

The microbiome in mechanically ventilated patients.

PURPOSE OF REVIEW: Discovery of a normal lung microbiome requires reassessment of our concepts of HAP/VAP pathogenesis and has important implications for clinical diagnosis and management. RECENT FINDINGS: Changes in the microbiome of dental plaque are associated with increased risk of HAP/VAP. A transition to a lung microbiome enriched with gut flora is found in ARDS with an increased inflammatory response in patients with this change in microbial flora. A characteristic microbiome pattern of higher amounts of bacterial DNA, lower community diversity, and greater relative abundance of a single species characterize pneumonia and occasionally identify bacteria not found in culture. The influence of the microbiome makes probiotics a logical strategy to prevent or ameliorate HAP/VAP but so far clinical support is unclear. SUMMARY: The presence of a normal lung microbiome and the interaction of that microbiome with other microbiota have an important but previously overlooked impact on the pathogenesis of HAP/VAP. Deep sequencing suggests that the repertoire of microorganisms and the pattern of bacterial communities associated with HAP/VAP remains incompletely understood but recent studies are adding greater clarity.