Study protocol for IMPRoVE: a multicentre prospective observational cohort study of the incidence, impact and mechanisms of perioperative right ventricular dysfunction in non-cardiac surgery.

INTRODUCTION: Perioperative myocardial injury evidenced by elevated cardiac biomarkers (both natriuretic peptides and troponin) is common after major non-cardiac surgery. However, it is unclear if the rise in cardiac biomarkers represents global or more localised cardiac injury. We have previously shown isolated right ventricular (RV) dysfunction in patients following lung resection surgery, with no change in left ventricular (LV) function. Given that perioperative RV dysfunction (RVD) can manifest insidiously, we hypothesise there may be a substantial burden of covert yet clinically important perioperative RVD in other major non-cardiac surgical groups. The Incidence, impact and Mechanisms of Perioperative Right VEntricular dysfunction (IMPRoVE) study has been designed to address this knowledge gap. METHODS AND ANALYSIS: A multicentre prospective observational cohort study across four centres in the West of Scotland and London. One hundred and seventy-five patients will be recruited from five surgical specialties: thoracic, upper gastrointestinal, vascular, colorectal and orthopaedic surgery (35 patients from each group). All patients will undergo preoperative and postoperative (day 2-4) echocardiography, with contemporaneous cardiac biomarker testing. Ten patients from each surgical specialty (50 patients in total) will undergo T1-cardiovascular magnetic resonance (CMR) imaging preoperatively and postoperatively. The coprimary outcomes are the incidence of perioperative RVD (diagnosed by RV speckle tracking echocardiography) and the effect that RVD has on days alive and at home at 30 days postoperatively. Secondary outcomes include LV dysfunction and clinical outcomes informed by Standardised Endpoints in Perioperative Medicine consensus definitions. T1 CMR will be used to investigate for imaging correlates of myocardial inflammation as a possible mechanism driving perioperative RVD. ETHICS AND DISSEMINATION: Approval was gained from Oxford C Research Ethics Committee (REC reference 22/SC/0442). Findings will be disseminated by various methods including social media, international presentations and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05827315.

Feasibility of 2-dimensional speckle tracking echocardiography strain analysis of the right ventricle with trans-thoracic echocardiography in intensive care: a literature review and meta-analysis.

OBJECTIVES: To identify variables that affect the feasibility of 2-dimensional right ventricular speckle tracking echocardiography (RV-STE) in the intensive care unit. BACKGROUND: Trans-thoracic echocardiography (TTE) of the right ventricle is challenging. RV-STE is a novel echocardiography method thought to measure global RV function more fully than conventional TTE parameters. The feasibility of RV-STE in ICU populations has not been well described, and variables influencing RV-STE in ICU have not been investigated. This study aimed to address this. METHODS: A literature review using Ovid MEDLINE(R) was undertaken. We performed meta-analysis with subgroup analysis of; RV-STE type (RV free-wall [RVFWLS] versus RV global longitudinal strain [RVGLS]), study design (prospective versus retrospective), coronavirus disease-19 (COVID-19) study or not, and strain software used. This was followed by meta-regression of proportion of invasive mechanical ventilation (IMV), with and without COVID-19 studies as a co-variate. RESULTS: Eleven relevant studies from the literature search were identified, reporting an overall feasibility of RV-STE of 83.3% (95%CI 74.6-89.4%). Prospective study design was associated with higher feasibility compared with retrospective studies (p = 0.02). There were no statistical differences on univariate analysis between RVFWLS versus RVGLS, COVID-19 study or not, or strain software used. Meta-regression with COVID-19 study as a covariate demonstrated that higher proportions of IMV were significantly associated with worse feasibility (p = 0.04), as were COVID-19 studies (p < 0.01). CONCLUSIONS: We have identified three variables associated with poor feasibility; retrospective study design, COVID-19 studies, and proportion of IMV. A prospective study design should be viewed as gold standard to maximise RV-STE feasibility.

L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults.

Introduction: Millions of people worldwide take medications such as L-DOPA that increase dopamine to treat Parkinson's disease. Yet, we do not fully understand how L-DOPA affects sleep and memory. Our earlier research in Parkinson's disease revealed that the timing of L-DOPA relative to sleep affects dopamine's impact on long-term memory. Dopamine projections between the midbrain and hippocampus potentially support memory processes during slow wave sleep. In this study, we aimed to test the hypothesis that L-DOPA enhances memory consolidation by modulating NREM sleep. Methods: We conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65-79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning. Results: The single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1-4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects. Discussion: Our results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slow-wave sleep and long-term memory may have clinical implications. Clinical trial registration: Eudract number: 2015-002027-26; https://doi.org/10.1186/ISRCTN90897064, ISRCTN90897064.

Perioperative cardiovascular pathophysiology in patients undergoing lung resection surgery: a narrative review.

Although thoracic surgery is understood to confer a high risk of postoperative respiratory complications, the substantial haemodynamic challenges posed are less well appreciated. This review highlights the influence of cardiovascular comorbidity on outcome, reviews the complex pathophysiological changes inherent in one-lung ventilation and lung resection, and examines their influence on cardiovascular complications and postoperative functional limitation. There is now good evidence for the presence of right ventricular dysfunction postoperatively, a finding that persists to at least 3 months. This dysfunction results from increased right ventricular afterload occurring both intraoperatively and persisting postoperatively. Although many patients adapt well, those with reduced right ventricular contractile reserve and reduced pulmonary vascular flow reserve might struggle. Postoperative right ventricular dysfunction has been implicated in the aetiology of postoperative atrial fibrillation and perioperative myocardial injury, both common cardiovascular complications which are increasingly being appreciated to have impact long into the postoperative period. In response to the physiological demands of critical illness or exercise, contractile reserve, flow reserve, or both can be overwhelmed resulting in acute decompensation or impaired long-term functional capacity. Aiding adaptation to the unique perioperative physiology seen in patients undergoing thoracic surgery could provide a novel therapeutic avenue to prevent cardiovascular complications and improve long-term functional capacity after surgery.

Right ventricular free wall longitudinal strain is independently associated with mortality in mechanically ventilated patients with COVID-19.

BACKGROUND: Right ventricular (RV) dysfunction has been commonly reported in patients with Coronavirus disease 2019 (COVID-19), and is associated with mortality in mixed cohorts of patients requiring and not requiring invasive mechanical ventilation (IMV). Using RV-speckle tracking echocardiography (STE) strain analysis, we aimed to identify the prevalence of RV dysfunction (diagnosed by abnormal RV-STE) in patients with COVID-19 that are exclusively undergoing IMV, and assess association between RV dysfunction and 30 day mortality. We performed a prospective multicentre study across 10 ICUs in Scotland from 2/9/20 to 22/3/21. One-hundred-and-four echocardiography scans were obtained from adult patients at a single timepoint between 48 h after intubation, and day 14 of intensive care unit admission. We analysed RV-STE using RV free-wall longitudinal strain (RVFWLS), with an abnormal cutoff of > -20%. We performed survival analysis using Kaplan-Meier, log rank, and multivariate cox-regression (prespecified covariates were age, gender, ethnicity, severity of illness, and time since intubation). RESULTS: Ninety-four/one-hundred-and-four (90.4%) scans had images adequate for RVFWLS. Mean RVFWLS was -23.0% (5.2), 27/94 (28.7%) of patients had abnormal RVFWLS. Univariate analysis with Kaplan-Meier plot and log-rank demonstrated that patients with abnormal RVFWLS have a significant association with 30-day mortality (p = 0.047). Multivariate cox-regression demonstrated that abnormal RVFWLS is independently associated with 30-day mortality (Hazard-Ratio 2.22 [1.14-4.39], p = 0.020). CONCLUSIONS: Abnormal RVFWLS (> -20%) is independently associated with 30-day mortality in patients with COVID-19 undergoing IMV. Strategies to prevent RV dysfunction, and treatment when identified by RVFWLS, may be of therapeutic benefit to these patients. TRIAL REGISTRATION: Retrospectively registered 21st Feb 2021. CLINICALTRIALS: gov Identifier: NCT04764032.