Cardiac Failure

This study aims to develop and refine a microRNA (miR) biomarker panel that can be used to phenotype net immune state after heart transplantation using circulating miRs (associated with drug doses and levels). These miRs will be used to characterize the overall immune state in adult heart transplant patients and predict patients that will go on to develop infection and rejection. MicroRNAs (miRs) are small, non-coding RNA molecules that regulate gene expression and serve as molecular biomarkers found in the circulation.

This study aims to discover circulating microRNAs (associated with drug doses and levels) that can be used to characterize the overall immune state in pediatric heart transplant patients and predict patients that will go on to develop infection and rejection. MicroRNAs (miRs) are small, non-coding RNA molecules that regulate gene expression and serve as molecular biomarkers found in the circulation.

Background: Heart Failure (HF) is the second most common cause of hospitalizations for women in North America. Non-adherence to guideline-directed medical therapy (GDMT) is associated with 50% of all treatment failures and high rates of hospitalizations and death. A recent Canadian study showed that adherence to three or more GDMT medications occurred in only 20% of Canadian HF patients. Despite clear guidelines on the pharmacologic management of HF and the introduction of new and effective drugs, adherence to GDMT in women with HF is low. Furthermore, the rates of hospitalizations have not improved in Canada over the last decade, and mortality in Canadian women with HF remains high. One explanation may be that social determinants of health (SDOH), which are known to be strong predictors of both adherence and adverse outcomes in HF, have not specifically been targeted to improve either adherence or outcomes in HF. Social prescribing (SP) is an innovative, non-medical intervention that aims to improve health by addressing SDOH. However, whether using SP to LINK clinical and social services for the benefit of socially vulnerable HF women can improve outcome is unknown. By targeting SDOH, which are strong predictors of adherence and outcomes in HF, and which have been shown to disproportionately disfavor women, SP has the potential to significantly improve medication adherence, quality of life and outcomes in women with HF. Objectives: The overall aim of this study is to assess whether SP, through individualized, SDOH-targeted interventions, can improve adherence and quality of life in Canadian women with HF and at high risk for no adherence. Primary objective: To determine whether SP can improve adherence to GDMT. Secondary objective: To determine whether SP can improve quality of life. Methods: This is an intention to treat, multicenter (five centers), and open-labeled, randomized clinical trial. Women with HF with two or more points on a weighted SDOH questionnaire (SPARK tool) will be randomly assigned to either SP or control group. Women in the SP group will meet with a link worker (LW) who will perform SP. SP will consist of personalized referrals to non-medical supports or services based on women's specific SDOH-related vulnerabilities and social needs. SP will address social needs such as issues with income, unemployment, transportation, mobility, dependents, housing, loneliness, mental health, health literacy, medication management and medical appointment schedules. Social prescriptions will be based on the interview conducted by the LW and will prioritize SDOH-related vulnerabilities identified on the SPARK questionnaire. Participants in the control group will receive standard care as is typically offered in the current specialized HF clinic in the participating centers. Controls will not meet with a LW, but, as usual, their physician or treating team may refer them to any specialists or services deemed necessary. Outcome measures: The primary outcome will be adherence to GDMT measured with PDC obtained from provincial administrative databases and the secondary outcome will be quality of life measures including physical limitations, social limitations, as measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sample size Calculations: The sample size was calculated using the primary outcome of adherence to GDMT measured with PDC as a continuous variable. In one observational study on adherence to HF medications which compared women and males adherence using PDCs, adherence in women was 63% with a SD of 23%. The impact of an absolute increase of 10% in PDC on clinical end points was considered significant. Using an alpha of 0.05 and a power of 0.80, a minimum of 166 participants would be needed to detect a statistically significant difference. Based on pilot data, the proportion of women followed in heart failure clinics is 28% and the proportion of eligible women (i.e. 1 point or more on the SPARK questionnaire) is about 30%. Considering a 30% refusal rate and a 5% dropout rate (intention to treat with registry based outcome), the five chosen centers should totalize 188 participants. The secondary outcome, the KCCQ, is a continuous variable for which a change of five points or more (5%) is considered clinically significant. Using an alpha of 0.05 and a power of 0.80, 126 patients would be required to detect such a difference. Significance: SP holds immense potential for women with HF by addressing critical gaps in care. SP may help bridge the gap between healthcare providers and community resources, providing tailored support addressing SDOH that disproportionately affect women with HF. SP has the potential to significantly enhance adherence to GDMT, which has been shown to greatly, reduce hospitalizations and mortality in this vulnerable population.

To assess the effects of endovascular aortic repair on cardiac morphology and function

To observe and identify determinants of recovery from intensive care unit-acquired weakness (ICUAW) following a severe cardiorespiratory failure requiring extra-corporeal membrane oxygenation (ECMO). Additionally, to discover the effects of ICUAW on physical function and health-related quality of life (HRQoL) after critical illness. CLEVERER is a clinical observational pilot study.

Advances in flow cytometry techniques have led to a better understanding of platelet phenotypes and have revealed the existence of four major platelet populations with distinct functional properties (native, proaggregating, procoagulating, or apoptotic). These phenotypes have a significant impact on the hemostatic capacity of blood platelets, and a proportional change in these populations during ECMO treatment could, at least in part, contribute to the observed complications.

Chronic mitral regurgitation is the most common valvular abnormality worldwide, it occurs in 10% of the general population and its prevalence increases with age. When left untreated, it can lead to left ventricular dysfunction and cause disabling symptoms (e.g., fatigue and dyspnea), life-threatening complications (e.g., ventricular dilation, congestive heart failure) and death. Surgical correction of chronic mitral regurgitation before irreversible changes happen can be curative. Open surgical valve repair or replacement are accomplished through cardiopulmonary bypass and cardioplegic arrest. Myocardial protection is essential to guarantee an uneventful perioperative course since a not-well protected heart may lead to postoperative low-cardiac output syndrome. This occurs in 30% of high-risk patients who undergo elective cardiac surgery and is associated with 20% mortality. Cardioplegia preserves the heart during ischemic arrest by reducing its metabolic demand. The most effective cardioplegia for protection in adult cardiac surgery remains unknown and improving the protection of the heart during the ischemic arrest may potentially improve patients' postoperative outcomes. Pharmacological adjuvants to the cardioplegic solutions have been tested to mitigate the ischaemic-reperfusion injury following cardiac surgery. Ultra-short acting beta-blockers (e.g., esmolol, landiolol) decrease intraoperative myocardial metabolic demand and suppress the sympathetic response to surgical stimuli while exhibiting limited adverse effects. Few studies with limited sample size investigated the role of ultra-short acting beta-blockers in reducing perioperative ischaemia and arrhythmia after cardiac surgery. When ultra-short acting beta-blockers were administered before aortic cross-clamping and as cardioplegia adjuvant we observed a trend towards a reduction in postoperative low-cardiac output syndrome (13/98 vs 6/102; p=0.08) and in the rate of hospital re-admission at one year (26/95 v 16/96, p=0.08) with an increase in the number of patients with ejection fraction \>60% at hospital discharge (4/95 vs 11/92, p=0.06) (Zangrillo 2021). However, despite a growing body of literature exploring the role of ultra-short acting beta-blockers in enhancing myocardial protection during on-pump cardiac surgery, further high-quality evidence is needed before this practice can be established as standard routine care. Hence, we designed a randomized, placebo-controlled trial involving 1500 patients undergoing open mitral valve surgery to assess the effect of administering landiolol as cardioplegia adjuvant to reduce the occurrence of postoperative low-cardiac output syndrome. Successful results would have a significant impact on short and long-term complications.

Unexpected deaths and unplanned intensive care unit (ICU) admissions are common during hospital stay and are often preceded by warning abnormalities in patients' vital signs. These abnormalities trigger Medical Emergency Team (MET) activation and up to 15% of patients visited by the MET is admitted to the ICU with an overall hospital stay after the MET intervention of approximately 2 weeks. Phosphocreatine (PCr) is a natural energy-buffering molecule associated with signals of mortality reduction in patients with acute cardiac conditions (according to meta-analytic finding from our group) and with encouraging beneficial effects on other acute organ failures (e.g. brain). The investigators designed a multi-center, randomized, placebo-controlled trial to confirm the promising beneficial effects of PCr in hospitalized patients. The investigators expects a reduction in hospital stay (measured as an increase in days alive and out of hospital at 30 days) when PCr is added to standard treatment in patients requiring MET intervention.

The purpose of this study is to evaluate prospectively the safety and performance of the MOBYBOX System in the veno-arterial configuration in patients with cardiorespiratory failure or in the veno-venous configuration in patients with severe respiratory failure.

An investigator-initiated clinical drug study Main Objective: To explore neuroprotective properties of xenon in patients after aneurysmal subarachnoid hemorrhage (SAH). Primary endpoint: Global fractional anisotropy of white matter of diffusion tensor imaging (DTI). Hypothesis: White matter damage is less severe in xenon treated patients, i.e. global fractional anisotropy is significantly higher in the xenon group than in the control group as assessed with the 1st magnetic resonance imaging (MRI). After confirmation of aSAH and obtaining a signed assent subjects will be randomized to the following groups: Control group: Standard of Care (SOC) group: Air/oxygen and Normothermia 36.5-37.5°C; Xenon group: Normothermia 36.5-37.5°C +Xenon inhalation in air/oxygen for 24 hours. Brain magnetic resonance imaging techniques will be undertaken to evaluate the effects of the intervention on white and grey matter damage and neuronal loss. Neurological outcome will be evaluated at 3, 12 and 24 months after onset of aSAH symptoms Investigational drug/treatment, dose and mode of administration: 50±2 % end tidal concentration of inhaled xenon in oxygen/air. Comparative drug(s)/placebo/treatment, dose and mode of administration: Standard of care treatment according to local and international consensus reports. Duration of treatment: 24 hours Assessments: Baseline data Information that characterizes the participant's condition prior to initiation of experimental treatment is obtained as soon as is clinically reasonable. These include participant demographics, medical history, vital signs, oxygen saturation, and concentration of oxygen administered. Acute data The collected information will contain quantitative and qualitative data of aSAH patients, as recommended by recent recommendations of the working group on subject characteristics, and including all relevant Common Data Elements (CDE) can be applied. Specific definitions, measurements tools, and references regarding each SAH CDE can be found on the weblink here: https://www.commondataelements.ninds.nih.gov/SAH.aspx#tab=Data\_Standards.

The objective of this study is to compare the accuracy and correlation of the capnodynamic method for measuring mixed venous oxygen saturation (SvO2) with the standard reference method (pulmonary artery catheter), with the potential for the capnodynamic method to replace the traditional method in selected cases.