Atherosclerotic Coronary Plaque Regression and Risk of Adverse Cardiovascular Events: A Systematic Review and Updated Meta-Regression Analysis.

Importance: The association between changes in atherosclerotic plaque induced by lipid-lowering therapies (LLTs) and reduction in major adverse cardiovascular events (MACEs) remains controversial. Objective: To evaluate the association between coronary plaque regression assessed by intravascular ultrasound (IVUS) and MACEs. Data Sources: A comprehensive, systematic search of publications in PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science was performed. Study Selection: Clinical prospective studies of LLTs reporting change in percent atheroma volume (PAV) assessed by IVUS and describing MACE components were selected. Data Extraction and Synthesis: Reporting was performed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The association between mean change in PAV and MACEs was analyzed by meta-regression using mixed-effects, 2-level binomial logistic regression models, unadjusted and adjusted for clinical covariates, including mean age, baseline PAV, baseline low-density lipoprotein cholesterol level, and study duration. Main Outcome and Measures: Mean PAV change and MACE in intervention and comparator arms were assessed in an updated systematic review and meta-regression analysis of IVUS trials of LLTs that also reported MACEs. Results: This meta-analysis included 23 studies published between July 2001 and July 2022, including 7407 patients and trial durations ranging from 11 to 104 weeks. Mean (SD) patient age ranged from 55.8 (9.8) to 70.2 (7.6) years, and the number of male patients from 245 of 507 (48.3%) to 24 of 26 (92.3%). Change in PAV across 46 study arms ranged from -5.6% to 3.1%. The number of MACEs ranged from 0 to 72 per study arm (17 groups [37%] reported no events, 9 [20%] reported 1-2 events, and 20 [43%] reported ≥3 events). In unadjusted analysis, a 1% decrease in mean PAV was associated with 17% reduced odds of MACEs (unadjusted OR, 0.83; 95% CI, 0.71-0.98; P = .03), and with a 14% reduction in MACEs in adjusted analysis (adjusted OR, 0.86; 95% CI, 0.75-1.00; P = .050). Further adjustment for cardiovascular risk factors showed a 19% reduced risk (adjusted OR, 0.81; 95% CI, 0.68-0.96; P = .01) per 1% decrease in PAV. A 1% reduction of PAV change between intervention and comparator arms within studies was also associated with a significant 25% reduction in MACEs (OR, 0.75; 95% CI, 0.56-1.00; P = .046). Conclusions and Relevance: In this meta-analysis, regression of atherosclerotic plaque by 1% was associated with a 25% reduction in the odds of MACEs. These findings suggest that change in PAV could be a surrogate marker for MACEs, but given the heterogeneity in the outcomes, additional data are needed.

Attitudes towards people who use substances: a survey of mental health clinicians from an urban hospital in British Columbia.

Stigma and other barriers limit harm reduction practice integration by clinicians within acute psychiatric settings. The objective of our study was to explore mental health clinician attitudes towards substance use and associations with clinical experience and education level. The Brief Substance Abuse Attitudes Survey was completed among a convenience sample of mental health clinicians in Vancouver, British Columbia. Five predefined attitude subgroups were evaluated. Respondents' attitudes towards substance use were associated with level of education on questions from two (non-stereotyping [p = 0.012] and treatment optimism [p = 0.008]) subscales. In pairwise comparisons, postgraduate education was associated with more positive attitudes towards relapse risk (p = 0.004) when compared to diploma-educated respondents. No significant associations were observed between years of clinical experience and participant responses. Our findings highlight important aspects of clinician attitudes that could improve harm reduction education and integration into clinical practice.

The association of duration of resuscitation and long-term survival and functional outcomes after out-of-hospital cardiac arrest.

AIM: Longer emergency medical system cardiopulmonary-resuscitation-to-return of-spontaneous-circulation (EMS CPR-to-ROSC) interval has been associated with worse hospital discharge outcomes after out-of-hospital cardiac arrest (OHCA). We hypothesized that this association extends post-discharge in hospital survivors. We investigated whether pre-arrest co-morbidities influence the duration of resuscitation. METHODS: We included EMS-treated adult OHCA (January 2009 - December 2016) from British Columbia Cardiac Arrest Registry linked to provincial databases. Pre-OHCA characteristics were compared by ≤10, 10-20, and >20 min interval categories. Outcomes included survival and functional outcomes at hospital discharge and 1- and 3-year survival. We examined the relationship between CPR-to-ROSC intervals and survival using Kaplan-Meier. We examined the relationship between the CPR-to-ROSC interval (continuous variable) with all outcomes using regression models. RESULTS: Among 10,241 OHCA, 4604 (45%) achieved ROSC, with a median CPR-to-ROSC interval of 15.5 (IQR 9.0-22.9) minutes. Diabetes, chronic kidney disease, and prior myocardial infarction were associated with longer CPR-to-ROSC intervals. 1245 (12.2%) survived to hospital discharge. Among hospital survivors, Kaplan-Meier survival at 1- and 3-years were 92% [95% CI 90-93%] and 84% [95% CI 82-86%] respectively; survival curves stratified by CPR-to-ROSC intervals were not statistically different. Longer CPR-to-ROSC interval was non-linearly associated with lower survival and functional outcomes at hospital discharge but not with post-discharge outcomes. CONCLUSION: Longer CPR-to-ROSC interval was associated with lower survival at hospital discharge and was influenced by pre-arrest co-morbidities. However, these intervals were not associated with long-term survival or functional outcome among hospital survivors, suggesting early risk of longer CPR-to-ROSC intervals does not persist.

Long-term Mortality, Readmission, and Resource Utilization Among Hospital Survivors of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Among patients with out-of-hospital cardiac arrest (OHCA), the influence of pre- and in-hospital factors on long-term survival, readmission, and resource utilization is ill-defined, mainly related to challenges combining disparate data sources. METHODS: Adult nontraumatic OHCA from the British Columbia Cardiac Arrest Registry (January 2009 to December 2016) were linked to provincial datasets comprising comorbidities, medications, cardiac procedures, mortality, and hospital admission and discharge. Among hospital-discharge survivors, the 3-year end point of mortality or mortality and all-cause readmission was examined with the use of the Kaplan-Meier method and multivariable Cox regression model for predictors. The use of publicly funded home care and community services within 1 year after discharge also was evaluated. RESULTS: Of the 10,674 linked, emergency medical services-treated adult OHCAs, 3230 were admitted to hospital and 1325 survived to hospital discharge. At 3 years after discharge, the estimated Kaplan-Meier survival rate was 84.1% (95% CI 81.7%-86.1%) and freedom from death or all-cause readmission was 31.8% (29.0%-34.7%). After exclusions, 26.6% (n = 315/1186) accessed residential or home care services within 1 year. Independent predictors of long-term outcomes included age and comorbidities, but also favourable arrest characteristics and in-hospital factors such as revascularization or receipt of an intracardiac defibrillator before discharge. CONCLUSIONS: Among OHCA hospital survivors, the long-term death or readmission risk persists and is modulated by both pre- and in-hospital factors. However, only 1 in 4 survivors required residential or home care after discharge. These results support efforts to improve care processes to increase survival to hospital discharge.

Coronary atheroma regression and adverse cardiac events: A systematic review and meta-regression analysis.

BACKGROUND AND AIMS: The relationship between plaque regression induced by dyslipidemia therapies and occurrence of major adverse cardiovascular events (MACE) is controversial. We performed a systematic review and meta-regression of dyslipidemia therapy studies reporting MACE and intravascular ultrasound (IVUS) measures of change in coronary atheroma. METHODS: Prospective studies of dyslipidemia therapies reporting percent atheroma volume (PAV) measured by IVUS and reporting death, myocardial infarction, stroke, unstable angina or transient ischemic attack (MACE) were included. The association between mean change in PAV and MACE was examined using meta-regression via mixed-effects binomial logistic regression models, unadjusted and adjusted for mean age, baseline PAV, baseline low density lipoprotein-cholesterol and study duration. RESULTS: The study included 17 prospective studies published between 2001 and 2018 totaling 6333 patients. Study duration varied from 11 to 104 weeks. Mean change in PAV, across the study arms, ranged from -5.6% to 3.1%. MACE ranged from 0 to 72 events per study arm: 13 study arms (38%) reported no events, 8 (24%) reported 1-2 events and 13 (38%) reported 3 or more events. Meta-regression demonstrated a decline in the odds of MACE associated with reduction in mean PAV: unadjusted odds ratio (OR): 0.78, 95% Confidence Interval (CI): [0.63, 0.96], p = 0.018; adjusted OR: 0.82, 95% CI: [0.70, 0.95], p = 0.011, per 1% decrease in mean PAV. CONCLUSIONS: A 1% reduction in mean PAV as induced by dyslipidemia therapies was associated with a 20% reduction in the odds of MACE.

Effect of Lowering Diastolic Pressure in Patients With and Without Cardiovascular Disease: Analysis of the SPRINT (Systolic Blood Pressure Intervention Trial).

Systolic and diastolic blood pressure thresholds, below which cardiovascular events increase, are widely debated. Using data from the SPRINT (Systolic Blood Pressure Intervention Trial), we evaluated the relation between systolic and diastolic pressure and cardiovascular events among 1519 participants with or 7574 without prior cardiovascular disease. Using Cox regression, we examined the composite risk of myocardial infarction, other acute coronary syndrome, stroke, heart failure, or cardiovascular death, and follow-up systolic and diastolic pressure were analyzed as time-dependent covariates for a median of 3.1 years. Models were adjusted for age, sex, baseline systolic pressure, body mass index, 10-year Framingham risk score, and estimated glomerular filtration rate. A J-shaped relationship with diastolic pressure was observed in both treatment arms in patients with or without cardiovascular disease (P nonlinearity≤0.002). When diastolic pressure fell <55 mm Hg, the hazards were at least 25% higher relative to 70 mm Hg (P=0.29). The hazard ratios (95% CI) of diastolic pressure <55 mm Hg versus 55 to 90 mm Hg were 1.68 (1.16-2.43), P value 0.006 and 1.52 (0.99-2.34), P value 0.06 in patients without and with prior cardiovascular disease, respectively. After adjusting for follow-up diastolic pressure, follow-up systolic pressure was not associated with the outcome in those without prior cardiovascular disease (P=0.64). In those with cardiovascular disease, adjusting for diastolic pressure, follow-up systolic pressure was associated with the risk in the intensive arm (hazard ratio per 10 mm Hg decrease, 0.86; 95% CI, 0.75-0.99; P interaction=0.02). Although the observed J-shaped relationship may be because of reverse causality in the SPRINT population, we advise caution in aggressively lowering diastolic pressure.

Meta-Analysis of the Effectiveness of Heart Transplantation in Patients With a Failing Fontan.

The Fontan procedure is increasingly being used to palliate univentricular physiology. It is a complex anatomic and physiologic repair that can fail at any age, often leaving heart transplantation as the only remaining solution. A meta-analysis was performed to achieve the aim of systematically evaluating the existing evidence for survival after heart transplantation in patients who have undergone a Fontan palliation. MEDLINE, Embase, PubMed, and Web of Science were searched for original research studies. The primary outcome was mortality at 1 and 5 years after transplantation. Five hundred eighty-two records were screened, after the removal of duplicates, 12 retrospective observational studies were selected for inclusion in our meta-analysis. This encompassed a total of 351 Fontan patients undergoing heart transplantation. Mean age was 14 years (range 7 to 24 years) and 65% were men. One- and 5-year survival rates after heart transplantation were found to be 80.3% (95% CI 75.9% to 84.2%) and 71.2% (95% CI 66.3% to 75.7%), respectively. No significant association was found between age, gender, and pulmonary pressures and 1-year mortality. In conclusion, in the largest analysis to date, we found that heart transplantation in younger patients after Fontan procedure has an acceptable early and mid-term mortality. It is comparable to published mortality data of heart transplantation for other forms of congenital heart disease. Heart transplantation in the younger failing Fontan population appears to be a reasonable option when all other avenues have been exhausted and appropriate screening has taken place.