Left atrial reservoir pressure-volume relations during exercise in healthy older adults.

The left atrium (LA) mediates cardiopulmonary interactions. During ventricular systole, the LA functions as a compliant reservoir that is coupled to the left ventricle (LV) and offloads volume from the pulmonary vasculature. We aimed to describe LA reservoir function using phasic relationships between pulmonary artery wedge pressure (PAWP) and LA volume events. We included healthy adults (7 M/6 F, 56 ± 8 yr) who were studied at rest and during semirecumbent cycle ergometry at a target of 100 beats/min heart rate. Right heart catheterization was performed to record the PAWP and two-dimensional (2-D) echocardiography was used to measure LA and LV volumes. We manually measured A-wave, x-trough, V-wave, and y-trough PAWP beat-by-beat, as well as minimal, maximal, and precontraction biplane LA volumes. Heart rate increased by 40 ± 7 beats/min with exercise; stroke volume and cardiac output also rose. Although all phasic PAWP measurements increased with exercise, the x-V pressure pulse during LA filling doubled from 4 ± 2 to 8 ± 4 mmHg (P = 0.001). LA minimal volume was unchanged but maximal volume increased from 39 ± 9 to 48 ± 9 mL (P < 0.001) with exercise, and so reservoir volume increased from 24 ± 5 to 32 ± 8 mL (P < 0.001). As such, calculated LA compliance decreased from 6.8 ± 3.4 to 4.8 ± 2.6 mL/mmHg (P = 0.029). The product of V-wave PAWP and LA maximal volume, a surrogate for LA wall stress, increased from 486 ± 193 to 953 ± 457 mmHg·mL (P < 0.001). In healthy older adults during submaximal exercise, the PAWP waveform shifts upward and its amplitude widens, LA filling increases, LA compliance decreases modestly, and LA wall stress may augment substantially.NEW & NOTEWORTHY We combined invasive estimates of left atrial pressure with noninvasive left atrial volume measurements made at rest and during exercise in healthy humans. Left atrial pressure and volume both increased with exercise, though the pressure increase was relatively greater, and calculated compliance decreased modestly while estimated peak wall stress nearly doubled. Our results demonstrate left atrial loading during exercise in healthy older adults and provide insight into how the left atrium mediates cardiopulmonary interactions.

Exercise and pulsatile pulmonary vascular loading in chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty-five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p < 0.001). ExABN patients had lower PA compliance and higher pulmonary vascular resistance at rest and exercise and prolonged resistance-compliance time product at rest. The physiological relationship between changes in PA pressures relative to PAWP was disrupted in the ExABN group. In CTEPD without PH, exercise RHC revealed latent pulmonary vascular afterload elevations in 58% of patients with more frequent augmentation of pulsatile than resistive pulmonary vascular afterload.

Unlocking the potential of RNA-based therapeutics in the lung: current status and future directions.

Awareness of RNA-based therapies has increased after the widespread adoption of mRNA vaccines against SARS-CoV-2 during the COVID-19 pandemic. These mRNA vaccines had a significant impact on reducing lung disease and mortality. They highlighted the potential for rapid development of RNA-based therapies and advances in nanoparticle delivery systems. Along with the rapid advancement in RNA biology, including the description of noncoding RNAs as major products of the genome, this success presents an opportunity to highlight the potential of RNA as a therapeutic modality. Here, we review the expanding compendium of RNA-based therapies, their mechanisms of action and examples of application in the lung. The airways provide a convenient conduit for drug delivery to the lungs with decreased systemic exposure. This review will also describe other delivery methods, including local delivery to the pleura and delivery vehicles that can target the lung after systemic administration, each providing access options that are advantageous for a specific application. We present clinical trials of RNA-based therapy in lung disease and potential areas for future directions. This review aims to provide an overview that will bring together researchers and clinicians to advance this burgeoning field.

Overnight staffing in Canadian neonatal and pediatric intensive care units.

Aim: Infants and children who require specialized medical attention are admitted to neonatal and pediatric intensive care units (ICUs) for continuous and closely supervised care. Overnight in-house physician coverage is frequently considered the ideal staffing model. It remains unclear how often this is achieved in both pediatric and neonatal ICUs in Canada. The aim of this study is to describe overnight in-house physician staffing in Canadian pediatric and level-3 neonatal ICUs (NICUs) in the pre-COVID-19 era. Methods: A national cross-sectional survey was conducted in 34 NICUs and 19 pediatric ICUs (PICUs). ICU directors or their delegates completed a 29-question survey describing overnight staffing by resident physicians, fellow physicians, nurse practitioners, and attending physicians. A comparative analysis was conducted between ICUs with and without in-house physicians. Results: We obtained responses from all 34 NICUs and 19 PICUs included in this study. A total of 44 ICUs (83%) with in-house overnight physician coverage provided advanced technologies, such as extracorporeal life support, and included all ICUs that catered to patients with cardiac, transplant, or trauma conditions. Residents provided the majority of overnight coverage, followed by the Critical Care Medicine fellows. An attending physician was in-house overnight in eight (15%) out of the 53 ICUs, seven of which were NICUs. Residents participating in rotations in the ICU would often have rotation durations of less than 6 weeks and were often responsible for providing care during shifts lasting 20-24 h. Conclusion: Most PICUs and level-3 NICUs in Canada have a dedicated in-house physician overnight. These physicians are mainly residents or fellows, but a notable variation exists in this arrangement. The potential effects on patient outcomes, resident learning, and physician satisfaction remain unclear and warrant further investigation.

Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study.

Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will develop septic shock and certainly a need to develop targeted treatments to prevent septic shock and its high mortality. Herein, we explore metabolic alterations due to mesenchymal stromal cell (MSC) treatment of septic shock. The clinical findings for this study were already reported; MSC therapy was well-tolerated and safe in patients in this phase I clinical trial. In this exploratory metabolomics study, 9 out of 30 patients received an escalating dose of MSC treatment, while 21 patients were without MSC treatment. Serum metabolomics profiling was performed to detect and characterize metabolite changes due to MSC treatment and to help determine the sample size needed for a phase II clinical trial and to define a metabolomic response to MSC treatment. Serum metabolites were measured using 1H-NMR and HILIC-MS at times 0, 24 and 72 h after MSC infusion. The results demonstrated the significant impact of MSC treatment on serum metabolic changes in a dose- and time-dependent manner compared to non-MSC-treated septic shock patients. This study suggests that plasma metabolomics can be used to assess the response to MSC therapy and that treatment-related metabolomics effects can be used to help determine the sample size needed in a phase II trial. As this study was not powered to detect outcome, how the treatment-induced metabolomic changes described in this study of MSC-treated septic shock patients are related to outcomes of septic shock in the short and long term will need to be explored in a larger adequately powered phase II clinical trial.

Outcomes of Patients Transported in the Prone Position to a Regional Extracorporeal Membrane Oxygenation Center: A Retrospective Cohort Study.

Prone positioning is associated with improved mortality in patients with moderate/severe acute respiratory distress syndrome (ARDS) and has been increasingly used throughout the COVID-19 pandemic. In patients with refractory hypoxemia, transfer to an extracorporeal membrane oxygenation (ECMO) center may improve outcome but may be challenging due to severely compromised gas exchange. Transport of these patients in prone position may be advantageous; however, there is a paucity of data on their outcomes. OBJECTIVES: The primary objective of this retrospective cohort study was to describe the early outcomes of ARDS patients transported in prone position for evaluation at a regional ECMO center. A secondary objective was to examine the safety of their transport in the prone position. DESIGN: Retrospective cohort study. SETTING: This study used patient charts from Ornge and Toronto General Hospital in Ontario, Canada, between February 1, 2020, and November 31, 2021. PARTICIPANTS: Patient with ARDS transported in the prone position for ECMO evaluation to Toronto General Hospital. MAIN OUTCOMES AND MEASURES: Descriptive analysis of patients transported in the prone position and their outcomes. RESULTS: One hundred fifteen patients were included. Seventy-two received ECMO (63%) and 51 died (44%) with ARDS and sepsis as the most common listed causes of death. Patients were transported primarily for COVID-related indications (93%). Few patients required additional analgesia (8%), vasopressors (4%), or experienced clinically relevant desaturation during transport (2%). CONCLUSIONS AND RELEVANCE: This cohort of patients with severe ARDS transported in prone position had outcomes ranging from similar to better compared with existing literature. Prone transport was performed safely with few complications or escalation in treatments. Prone transport to an ECMO center should be regarded as safe and potentially beneficial for patients with ARDS and refractory hypoxemia.

Impact of sex on outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

BACKGROUND: The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (PH) remains unclear. We therefore examined the early and long-term outcome after PEA to determine whether sex had an impact on the risk of residual PH and need for targeted PH medical therapy. METHODS: Retrospective study of 401 consecutive patients undergoing PEA at our institution between August 2005 and March 2020 was performed. Primary outcome was the need for targeted PH medical therapy postoperatively. Secondary outcomes included survival and measures of hemodynamic improvement. RESULTS: Females (N = 203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p < 0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p < 0.01). Despite similar preoperative values, females had higher postoperative pulmonary vascular resistance (final total pulmonary vascular resistance after PEA, 437 Dynes∙s∙cm-5 vs 324 Dynes∙s∙cm-5 in males, p < 0.01). Although survival at 10 years was not significantly different between sexes (73% in females vs 84% in males, p = 0.08), freedom from targeted PH medical therapy was lower in females (72.9% vs 89.9% in males at 5 years, p < 0.001). Female sex remained an independent factor affecting the need for targeted PH medical therapy after PEA in multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p = 0.04). CONCLUSIONS: Although outcomes are excellent for both sexes, females had greater need for targeted PH medical therapy in the long-term. Early reassessment and long-term follow-up of these patients are important. Further investigations into possible mechanisms to explain the differences are warranted.

Outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation: a prospective observational study.

PURPOSE: Descriptive information on referral patterns and short-term outcomes of patients with respiratory failure declined for extracorporeal membrane oxygenation (ECMO) is lacking. METHODS: We conducted a prospective single-centre observational cohort study of ECMO referrals to Toronto General Hospital (receiving hospital) for severe respiratory failure (COVID-19 and non-COVID-19), between 1 December 2019 and 30 November 2020. Data related to the referral, the referral decision, and reasons for refusal were collected. Reasons for refusal were grouped into three mutually exclusive categories selected a priori: "too sick now," "too sick before," and "not sick enough." In declined referrals, referring physicians were surveyed to collect patient outcome on day 7 after the referral. The primary study endpoints were referral outcome (accepted/declined) and patient outcome (alive/deceased). RESULTS: A total of 193 referrals were included; 73% were declined for transfer. Referral outcome was influenced by age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95 to 0.96; P < 0.01) and involvement of other members of the ECMO team in the discussion (OR, 4.42; 95% CI, 1.28 to 15.2; P < 0.01). Patient outcomes were missing in 46 (24%) referrals (inability to locate the referring physician or the referring physician being unable to recall the outcome). Using available data (95 declined and 52 accepted referrals; n = 147), survival to day 7 was 49% for declined referrals (35% for patients deemed "too sick now," 53% for "too sick before," 100% for "not sick enough," and 50% for reason for refusal not reported) and 98% for transferred patients. Sensitivity analysis setting missing outcomes to directional extreme values retained robustness of survival probabilities. CONCLUSION: Nearly half of the patients declined for ECMO consideration were alive on day 7. More information on patient trajectory and long-term outcomes in declined referrals is needed to refine selection criteria.

RéSUMé: OBJECTIF: On manque d'informations descriptives sur les schémas de références et les devenirs à court terme des patient·es atteint·es d'insuffisance respiratoire n'ayant pas pu recevoir une oxygénation par membrane extracorporelle (ECMO). MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective monocentrique sur les références vers l'ECMO à l'Hôpital général de Toronto (hôpital d'accueil) pour insuffisance respiratoire grave (COVID-19 et non-COVID-19), entre le 1er décembre 2019 et le 30 novembre 2020. Les données relatives à la référence, à la décision de référence et aux motifs du refus ont été recueillies. Les motifs de refus ont été regroupés en trois catégories mutuellement exclusives sélectionnées a priori : « Trop malade maintenant ¼, « Trop malade avant ¼ et « Pas assez malade ¼. En ce qui concerne les références refusées, un sondage envoyé aux médecins traitant·es avait pour objectif de recueillir les devenirs des patient·es le jour 7 suivant la référence. Les critères d'évaluation principaux de l'étude étaient le résultat de la référence (accepté/refusé) et le devenir des patient·es (vivant·e/décédé·e). RéSULTATS: Au total, 193 références ont été incluses; le transfert a été refusé dans 73 % des cas. L'acceptation ou le refus de la référence était influencé par l'âge (rapport de cotes [RC], 0,97; intervalle de confiance [IC] à 95 %, 0,95 à 0,96; P < 0,01) et la participation d'autres membres de l'équipe ECMO à la discussion (RC, 4,42; IC 95 %, 1,28 à 15,2; P < 0,01). Les devenirs des patient·es étaient manquants pour 46 (24 %) des personnes référées (incapacité de localiser les médecins traitant·es ou incapacité des médecins de se souvenir du devenir). À l'aide des données disponibles (95 références refusées et 52 références acceptées; n = 147), la survie jusqu'au jour 7 était de 49 % pour les références refusées (35 % pour la patientèle jugée « trop malade maintenant ¼, 53 % pour celle « trop malade avant ¼, 100 % pour celle « pas assez malade ¼ et 50 % pour les cas où la raison du refus n'était pas déclarée) et 98 % pour les patient·es transféré·es. L'analyse de sensibilité établissant les résultats manquants à des valeurs extrêmes directionnelles a conservé la robustesse des probabilités de survie. CONCLUSION: Près de la moitié des patient·es pour lesquel·les un traitement sous ECMO a été refusé étaient en vie au jour 7. Davantage d'informations concernant la trajectoire et les devenirs à long terme des patient·es refusé·es sont nécessaires pour parfaire les critères de sélection.

Point-of-Care Ultrasonography in a Pulmonary Hypertension Clinic: A Randomized Pilot Study.

Pulmonary arterial hypertension (PAH) is a rare condition with the potential to progress to right heart failure. Point-of-Care Ultrasonography (POCUS), used and interpreted in real time at the bedside to further the cardiopulmonary assessment, has the potential to improve the longitudinal care of PAH patients in the ambulatory setting. Patients from PAH clinics at two academic medical centers were randomized to either a POCUS assessment cohort or non-POCUS standard care (ClinicalTrials.gov identifier NCT05332847). The POCUS group received blinded heart, lung, and vascular ultrasound assessments. Thirty-six patients were randomized to the study and followed over time. Mean age was 65 in both groups and majority female (76.5% and 88.9% females in POCUS and control, respectively). Median time for POCUS assessment was 11 min (range 8-16). There were significantly more changes in management in the POCUS group than control (73% vs. 27%, p-value < 0.001). Multivariate analysis revealed that management changes were more likely to occur with a POCUS assessment, with an odds ratio (OR) of 12 when POCUS was added to physical exam vs. OR of 4.6 compared to physical examination alone (p < 0.001). POCUS in the PAH clinic is feasible and, when combined with physical examination, increases the number of findings and results in changes in management without significantly prolonging visit encounters. POCUS may help support clinical evaluation and decision making in ambulatory PAH clinics.

Secondary infections in critically ill patients with viral pneumonia due to COVID-19 and influenza: a historical cohort study.

PURPOSE: To compare the incidence and nature of secondary infections (SI) between critically ill patients with viral pneumonia due to COVID-19 and seasonal influenza and explore the association between SI and clinical outcomes. METHODS: We conducted a historical cohort study of patients admitted to the intensive care unit (ICU) at two tertiary care centers during the first wave of the COVID-19 pandemic and patients admitted with influenza during the 2018-2019 season. The primary outcome was the rate of SI. Secondary outcomes included rates of ICU and in-hospital mortality, organ-support-dependent disease, and length of ICU and hospital stay. RESULTS: Secondary infections developed in 55% of 95 COVID-19 patients and 51% of 47 influenza patients (unadjusted odds ratio [OR], 1.16; 95% confidence interval [CI], 0.57 to 2.33). After adjusting for baseline differences between cohorts, there were no significant differences between the COVID-19 cohort and the influenza cohort (adjusted OR, 1.00; 95% CI, 0.41 to 2.44). COVID-19 patients with SI had longer ICU and hospital stays and duration of mechanical ventilation. The SI incidence was higher in COVID-19 patients treated with steroids than in those not treated with steroids (15/20, 75% vs 37/75, 49%). CONCLUSION: Secondary infections were common among critically ill patients with viral pneumonia including COVID-19. We found no difference in the incidence of SI between COVID-19 and influenza in our cohort study, but SI in patients with COVID-19 were associated with worse clinical outcomes and increased healthcare resource use. The small cohort size precludes any causal inferences but may provide a basis for future research.

RéSUMé: OBJECTIF: Comparer l'incidence et la nature des infections secondaires entre les patients gravement malades atteints de pneumonie virale due à la COVID-19 et ceux atteints de la grippe saisonnière et explorer l'association entre les infections secondaires et les issues cliniques. MéTHODE: Nous avons réalisé une étude de cohorte historique de patients admis à l'unité de soins intensifs (USI) dans deux centres de soins tertiaires pendant la première vague de la pandémie de COVID-19 et de patients admis pour la grippe au cours de la saison 2018-2019. Le critère d'évaluation principal était le taux d'infections secondaires. Les critères d'évaluation secondaires comprenaient les taux de mortalité à l'USI et à l'hôpital, les maladies nécessitant un support d'organes et la durée du séjour à l'USI et à l'hôpital. RéSULTATS: Des infections secondaires se sont développées chez 55 % des 95 patients atteints de COVID-19 et 51 % des 47 patients grippaux (rapport des cotes [RC] non ajusté, 1,16; intervalle de confiance [IC] à 95 %, 0,57 à 2,33). Après ajustement pour tenir compte des différences initiales entre les cohortes, aucune différence significative n'a été observée entre la cohorte de COVID-19 et la cohorte de grippe (RC ajusté, 1,00; IC 95 %, 0,41 à 2,44). Les patients atteints de COVID-19 atteints d'infections secondaires ont séjourné plus longtemps aux soins intensifs et à l'hôpital et la durée de la ventilation mécanique était plus longue pour ces patients. L'incidence d'infections secondaires était plus élevée chez les patients atteints de COVID-19 traités par stéroïdes que chez ceux non traités par stéroïdes (15/20, 75 % vs 37/75, 49 %). CONCLUSION: Les infections secondaires étaient fréquentes chez les patients gravement malades atteints de pneumonie virale, y compris de COVID-19. Nous n'avons observé aucune différence dans l'incidence d'infections secondaires entre les patients atteints de COVID-19 et ceux atteints de grippe dans notre étude de cohorte, mais les infections secondaires chez les patients atteints de COVID-19 étaient associées à de moins bonnes issues cliniques et à une utilisation accrue des ressources de soins de santé. La petite taille de la cohorte exclut toute inférence causale, mais peut fournir une base pour les recherches futures.

Pharmacokinetic Alterations Associated with Critical Illness.

Haemodynamic, metabolic, and biochemical derangements in critically ill patients affect drug pharmacokinetics and pharmacodynamics making dose optimisation particularly challenging. Appropriate therapeutic dosing depends on the knowledge of the physiologic changes caused by the patient's comorbidities, underlying disease, resuscitation strategies, and polypharmacy. Critical illness will result in altered drug protein binding, ionisation, and volume of distribution; it will also decrease oral drug absorption, intestinal and hepatic metabolism, and renal clearance. In contrast, the resuscitation strategies and the use of vasoactive drugs may oppose these effects by leading to a hyperdynamic state that will increase blood flow towards the major organs including the brain, heart, kidneys, and liver, with the subsequent increase of drug hepatic metabolism and renal excretion. Metabolism is the main mechanism for drug clearance and is one of the main pharmacokinetic processes affected; it is influenced by patient-specific factors, such as comorbidities and genetics; therapeutic-specific factors, including drug characteristics and interactions; and disease-specific factors, like organ dysfunction. Moreover, organ support such as mechanical ventilation, renal replacement therapy, and extracorporeal membrane oxygenation may contribute to both inter- and intra-patient variability of drug pharmacokinetics. The combination of these competing factors makes it difficult to predict drug response in critically ill patients. Pharmacotherapy targeted to therapeutic goals and therapeutic drug monitoring is currently the best option for the safe care of the critically ill. The aim of this paper is to review the alterations in drug pharmacokinetics associated with critical illness and to summarise the available evidence.

Alterations of pulmonary vascular afterload in exercise-induced pre- and post-capillary pulmonary hypertension.

Exercise imposes increased pulmonary vascular afterload based on rises in pulmonary artery (PA) wedge pressure, declines in PA compliance, and resistance-compliance time. In health, afterload stress stabilizes during steady-state exercise. Our objective was to examine alterations of these exercise-associated stresses in states of pre- and post-capillary pulmonary hypertension (PH). PA hemodynamics were evaluated at rest, 2 and 7 min of steady-state exercise at moderate intensity in patients who exhibited Pre-capillary (n = 22) and post-capillary PH (n = 22). Patients with normal exercise hemodynamics (NOR-HD) (n = 32) were also studied. During exercise in all groups, PA wedge pressure increased at 2 min, with no further change at 7 min. In post-capillary PH and NOR-HD, increases in PA diastolic pressure and diastolic pressure gradient remained stable at 2 and 7 min of exercise, while in pre-capillary PH, both continued to increase at 7 min. The behavior of the diastolic pressure gradient was linearly related to the duration of resistance-compliance time at rest (r2  = 0.843) and exercise (r2  = 0.760). Exercise resistance-compliance time was longer in pre-capillary PH associated with larger increases in diastolic pressure gradient. Conversely, resistance-compliance time was shortest in post-capillary PH compared to pre-capillary PH and NOR-HD and associated with limited increases in exercise diastolic pressure gradient. During steady-state, modest-intensity exercise-specific patterns of pulmonary vascular afterload responses were observed in pre- and post-capillary PH relative to NOR-HD. Longer resistance-compliance time related to greater increases in PA diastolic pressure and diastolic pressure gradients in pre-capillary PH, while shorter resistance-compliance time appeared to limit these increases in post-capillary PH.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Meta-analysis.

PURPOSE: To perform a systematic review and meta-analysis assessing the safety and efficacy of balloon pulmonary angioplasty (BPA) in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). MATERIALS AND METHODS: Systematic literature searches were performed from inception to June 2022 to identify studies assessing BPA for CTEPH. Outcomes of interest included the following functional and hemodynamic measures: (a) six-minute walk distance (6MWD), (b) New York Heart Association (NYHA) status, (c) World Health Organization (WHO)-Functional Class status, (d) cardiac index (CI), (e) mean pulmonary artery pressure (mPAP), (f) mean right atrial pressure (mRAP), and (g) pulmonary vascular resistance (PVR). Subgroup analysis was also performed for BPA in post-pulmonary endarterectomy (PEA) patients. All reported BPA-related complications were also recorded. Forty unique studies with a total of 1763 patients were identified for meta-analysis. RESULTS: All functional and hemodynamic parameters improved significantly following BPA; 6MWD increased 70 m (95% CI 58-82; P < 0.001), NYHA class improved by - 0.9 classes (95% CI - 1.0 to - 0.8; P < 0.001), WHO-FC class improved by - 1 classes ((95% CI - 1.2 to - 0.9; P < 0.001), CI increased 0.26 L/min/m2 (95% CI 0.17-0.35; P < 0.001), mPAP decreased - 13.2 mmHg (95% CI - 14.7 to - 11.8; P < 0.001), mRAP decreased - 2.2 mmHg (95% CI - 2.8 to - 1.6; P < 0.001), and PVR decreased - 311 dyne/cm/s-5 (95% CI - 350 to - 271; P < 0.001). Meta-analysis of patients who underwent BPA for persistent pulmonary hypertension post-PEA demonstrated significant improvements in 6MWD, WHO-FC, PVR and mPAP. Most common complications included lung injury (8.16%), hemoptysis (7.07%) and vessel injury (5.05%). CONCLUSION: BPA represents a safe and effective treatment option for select individuals with CTEPH with significant improvements in hemodynamic parameters, improved exercise tolerance and a relatively low risk of major complications.

Hospital outbreak of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) delta variant in partially and fully vaccinated patients and healthcare workers in Toronto, Canada.

The severe acute respiratory coronavirus virus 2 (SARS-CoV-2) delta variant is highly transmissible, and current vaccines may have reduced effectiveness in preventing symptomatic infection. Using epidemiological and genomic analyses, we investigated an outbreak of the variant in an acute-care setting among partially and fully vaccinated individuals. Effective outbreak control was achieved using standard measures.

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.