Management of cardiogenic shock: a narrative review.

Cardiogenic shock (CS) is characterized by low cardiac output and sustained tissue hypoperfusion that may result in end-organ dysfunction and death. CS is associated with high short-term mortality, and its management remains challenging despite recent advances in therapeutic options. Timely diagnosis and multidisciplinary team-based management have demonstrated favourable effects on outcomes. We aimed to review evidence-based practices for managing patients with ischemic and non-ischemic CS, detailing the multi-organ supports needed in this critically ill patient population.

Inflammation in heart failure: pathophysiology and therapeutic strategies.

A role for inflammation in the development and progression of heart failure (HF) has been proposed for decades. Multiple studies have demonstrated the potential involvement of several groups of cytokines and chemokines in acute and chronic HF, though targeting these pathways in early therapeutic trials have produced mixed results. These studies served to highlight the complexity and nuances of how pro-inflammatory pathways contribute to the pathogenesis of HF. More recent investigations have highlighted how inflammation may play distinct roles based on HF syndrome phenotypes, findings that may guide the development of novel therapies. In this review, we propose a contemporary update on the role of inflammation mediated by the innate and adaptive immune systems with HF, highlighting differences that exist across the ejection fraction spectrum. This will specifically be looked at through the lens of established and novel biomarkers of inflammation. Subsequently, we review how improvements in inflammatory pathways may mediate clinical benefits of existing guideline-directed medical therapies for HF, as well as future therapies in the pipeline targeting HF and inflammation.

Low-Dose Colchicine in Patients With Type 2 Diabetes and Recent Myocardial Infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).

OBJECTIVE: The cardiovascular benefits of low-dose colchicine have been demonstrated in patients with coronary disease. Its effects were evaluated in this prespecified analysis in patients with type 2 diabetes (T2D) from the Colchicine Cardiovascular Outcomes Trial (COLCOT). RESEARCH DESIGN AND METHODS: COLCOT was a randomized, double-blinded trial of colchicine, 0.5 mg daily, versus placebo initiated within 30 days after a myocardial infarction. RESULTS: There were 959 patients with T2D enrolled and monitored for a median of 22.6 months. A primary end point event occurred in 8.7% of patients in the colchicine group and in 13.1% in the placebo group (hazard ratio 0.65; 95% CI 0.44-0.96; P = 0.03). Nausea was reported in 2.7% and 0.8% in the study groups (P = 0.03), and pneumonia occurred in 2.4% and 0.4% (P = 0.008). CONCLUSIONS: Among patients with T2D and a recent myocardial infarction, colchicine, 0.5 mg daily, leads to a large reduction of cardiovascular events. These results support the conduct of the COLCOT-T2D trial in primary prevention.

Mediterranean diet and time-restricted eating as a cardiac rehabilitation approach for patients with coronary heart disease and pre-diabetes: the DIABEPIC-1 protocol of a feasibility trial.

INTRODUCTION: Despite proven programmes, implementing lifestyle interventions for pre-diabetes and type 2 diabetes is challenging. Cardiac rehabilitation, provide a valuable opportunity to promote the adoption of healthy lifestyle behaviours for patients with atherosclerotic cardiovascular disease (ASCVD). However, only a limited number of studies have explored the potential for reversing the underlying causes of ASCVD in this setting. OBJECTIVES: The DIABEPIC1 study is an ongoing single-arm lifestyle clinical trial to assess the feasibility of an upgraded 6-month intensive cardiac rehabilitation programme combining an innovative diet assignment with exercise training to reverse newly onset pre-diabetes (glycated haemoglobin 5.7%-6.4%) to normal glucose concentrations in patients with coronary heart disease. METHODS AND ANALYSIS: 36 patients referred from the Montreal Heart Institute for cardiac rehabilitation, aged ≥40 years with a recent diagnosis of pre-diabetes in the last 6 months, will be offered to participate in the upgraded programme. Interventions will include four sessions of nutritional counselling on ultra-processed foods intake reduction and a moderate-carbohydrate (<40%) ad libitum Mediterranean diet coupled with 36 1-hour sessions of supervised exercise training (continuous and interval aerobic training, and resistance training) and educational intervention. Phase 2 will continue the same interventions adding 8:16 hour time-restricting eating (TRE) at least 5 days per week. During this second phase, exercise training will be performed with autonomy. The primary objectives will be to evaluate the recruitment rate, the completion rates at 3 and 6 months, and the compliance of participants. The secondary objectives will be to assess the proportion of prediabetic participants in remission of pre-diabetes at the programme's end and to characterise the factors associated with remission. ETHICS AND DISSEMINATION: The DIABEPIC1 feasibility study is approved by the Research Ethics Board of the Montreal Heart Institute (Project Number ICM 2022-3005). Written informed consent will be obtained from each participant prior to inclusion. Results will be available through research articles and conferences. CONCLUSIONS: The DIABEPIC1 trial will examine the feasibility and effectiveness of an enhanced cardiac rehabilitation programme combining exercise training with an ultra-processed food reduction intervention, a Mediterranean diet, and TRE counselling to remit pre-diabetes to normal glucose concentrations. TRIAL REGISTRATION NUMBER: NCT05459987.

Extracorporeal membrane oxygenation and microaxial left ventricular assist device in cardiogenic shock: Choosing the right mechanical circulatory support to improve outcomes.

Objective: To evaluate the outcomes of patients supported with Impella (CP/5.0) or venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock according to shock phenotype. The primary end point was 30-day survival. Methods: A retrospective study of patients supported with Impella (CP/5.0) or VA-ECMO between 2010 and 2020 was performed. Patients were grouped according to 1 of 2 shock phenotypes: isolated left ventricular (LV) dysfunction versus biventricular dysfunction or multiple organ failure (MOF). The local practice favors Impella for isolated LV dysfunction and VA-ECMO for biventricular dysfunction or MOF. Results: Among the 75 patients included, 17 (23%) had isolated LV dysfunction. Patients with biventricular dysfunction or MOF had a greater median lactate level compared with those with isolated LV dysfunction (7.9 [2.9-11.8] vs 3.8 [1.1-5.8] mmol/L, respectively). Among patients with isolated LV dysfunction, 30-day survival was 46% for the Impella group (n = 13) and 75% for VA-ECMO (n = 4). Among patients with biventricular dysfunction or MOF, 30-day survival was 9% for the Impella group (n = 11) and 28% for VA-ECMO (n = 47). Patients supported with Impella 5.0 had better 30-day survival compared with those supported with Impella CP, for both shock phenotypes (83% vs 14% and 14% vs 0%, respectively). Conclusions: In this small cohort, patients supported with Impella for isolated LV dysfunction and VA-ECMO for biventricular dysfunction or MOF had acceptable survival at 30 days. Patients with biventricular dysfunction or MOF who were supported by Impella had the lowest survival rates. Patients with isolated LV dysfunction who were supported with VA-ECMO had good 30-day survival.

Cardiorespiratory Fitness Moderates the Age-Related Association Between Executive Functioning and Mobility: Evidence From Remote Assessments.

Background and Objectives: In older adults, executive functions are important for daily-life function and mobility. Evidence suggests that the relationship between cognition and mobility is dynamic and could vary according to individual factors, but whether cardiorespiratory fitness reduces the age-related increase of interdependence between mobility and cognition remains unexplored. Research Design and Methods: One hundred eighty-nine participants (aged 50-87) were divided into 3 groups according to their age: middle-aged (MA; <65), young older adults (YOA; 65-74), and old older adults (OOA; ≥75). Participants performed Timed Up and Go and executive functioning assessments (Oral Trail Making Test and Phonologic verbal fluency) remotely by videoconference. Participants completed the Matthews questionnaire to estimate their cardiorespiratory fitness (VO2 max in ml/min/kg). A 3-way moderation was used to address whether cardiorespiratory fitness interacts with age to moderate the relationship between cognition and mobility. Results: Results showed that the cardiorespiratory fitness × age interaction moderated the association between executive functioning and mobility (ß = -0.05; p = .048; R 2 = 17.6; p < .001). At lower levels of physical fitness (<19.16 ml/min/kg), executive functioning significantly influenced YOA's mobility (ß = -0.48, p = .004) and to a greater extent OOA's mobility (ß = -0.96, p = .002). Discussion and Implications: Our results support the idea of a dynamic relationship between mobility and executive functioning during aging and suggest that physical fitness could play a significant role in reducing their interdependency.

Optimization of pharmacotherapies for ambulatory patients with heart failure and reduced ejection fraction is associated with improved outcomes.

BACKGROUND: In heart failure, specific target doses for each drug are recommended, but some patients receive suboptimal dosing, others are undertreated or remain chronically in a titration phase, despite having no apparent contraindication or intolerance. We assessed the association of different levels of adherence to guidelines with outcomes in patients with heart failure and reduced ejection fraction (HFrEF). METHODS: Medical records of patients with HFrEF followed at our heart failure (HF) clinic for at least 6 months (n = 511) were reviewed and patients categorized as: 1) optimized (25.4%); 2) in-titration (29.0%); 3) undertreated (32.7%); and 4) intolerant/contraindicated (12.9%). Risk of mortality or HF events (hospitalization, emergency visit or ambulatory administration of intravenous diuretics) within one year was assessed using Cox regression models and Kaplan-Meier curves. RESULTS: Compared to optimized patients, those intolerant (HR: 4.60 [95%CI: 2.23-9.48]; p < 0.0001) had the highest risk of outcomes, followed by those undertreated (3.45 [1.78-6.67]; p = 0.0002) and in-titration (1.99 [0.97-4.06]; p = 0.0588). Overall predictors of outcomes included loop diuretics' use (4.54 [2.39-8.60]), undertreatment (2.38 [1.22-4.67]), intolerance/ contraindication to triple therapy (3.08 [1.47-6.42]), peripheral vascular disease (2.13 [1.29-3.50]) and NYHA class III-IV (1.89 [1.25-2.85]); all p < 0.05. CONCLUSION: Level of adherence to guidelines is associated with outcomes, with intolerant/contraindicated patients having the worst prognosis and those undertreated and in-titration at intermediate risk compared to those optimized. Up-titration of therapy should be attempted whenever possible, considering patients' limitations, to potentially improve outcomes.

Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure.

AIMS: Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin-angiotensin-aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non-absorbed intestinal potassium binder proven to lower serum potassium concentrations. METHODS AND RESULTS: PRIORITIZE-HF was an international, multicentre, parallel-group, randomized, double-blind, placebo-controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID-19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. CONCLUSIONS: PRIORITIZE-HF was terminated prematurely due to COVID-19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium-reducing agent SZC compared with placebo.

Metabolic Improvements and Remission of Prediabetes and Type 2 Diabetes: Results From a Multidomain Lifestyle Intervention Clinic.

OBJECTIVES: Although lifestyle interventions are first-line treatment for individuals living with prediabetes and type 2 diabetes (T2D), they are rarely implemented effectively in routine clinical care. METHODS: We present a retrospective analysis of a 12-month, single-centre, structured multidomain lifestyle intervention clinic offered to individuals living with prediabetes and type 2 diabetes. The intervention consisted of expert-guided educational and nutritional counselling combined with a personalized physical exercise prescription, with the main goal of improving metabolic health and reaching remission. Anthropometric parameters, glucose, basal insulin, glycated hemoglobin (A1C), and lipid levels were measured at baseline and at 3, 6, and 12 months after the lifestyle intervention initiation. Remission of prediabetes and T2D were defined as a return of A1C at 6 months to <6.5% (or <5.7% for prediabetes) and persisting for at least 3 months in the absence of glucose-lowering pharmacotherapy. RESULTS: After a multidomain, expert-guided lifestyle intervention, 117 individuals living with prediabetes and T2D had significantly improved metabolic profiles: Mean weight change at 12 months was -4.9 kg (95% confidence interval [CI], -4.0 to -5.7; p<0.001), and mean change in A1C at 12 months was -0.6% (95% CI, -0.4 to -0.7; p<0.001). A substantial proportion of individuals reached the criteria for remission (20% among participants with prediabetes and 12% among those with T2D). CONCLUSIONS: The results of this study suggest that prioritizing lifestyle changes in a multifaceted, progressive, 12-month intervention in this population improves anthropometric and insulin resistance measures, and has the potential to normalize metabolic values, even to the point of reaching the criteria of remission.

Growth Differentiation Factor-15 as a Predictor of Functional Capacity, Frailty, and Ventricular Dysfunction in Patients With Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

In aortic stenosis (AS), left ventricular (LV) remodeling often occurs before symptom onset, and early intervention may be beneficial. Risk stratification remains challenging and identification of biomarkers may be useful. We evaluated the association between growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity 2 (sST2) and known markers of poor prognosis in AS. Baseline plasma GDF-15 and sST2 levels were measured in 70 patients with moderate-severe AS (aortic valve area <1.5 cm2) and preserved LV ejection fraction (>45%). Patients were categorized into "low GDF-15" versus "high GDF-15" and "low sST2" versus "high sST2" groups. Groups were compared for differences in cardiovascular risk factors, 6-minute walk test, 5 m gait speed, cognitive function (Montreal Cognitive Assessment), and echocardiographic parameters. Overall, 44% of patients were deemed asymptomatic by New York Heart Association class, 61% had severe AS (aortic valve area <1 cm2) and all patients had preserved LV ejection fraction. GDF-15 levels were not predictive of AS severity. However, high GDF-15 (>1,050 pg/ml) was associated with LV dysfunction as shown by lower indexed stroke volume (p <0.01), worse LV global longitudinal strain (p = 0.04), greater mean E/e' (p = 0.02) and indexed left atrial volume (p <0.01). It was also associated with decreased functional capacity with shorter 6-minute walk test (p = 0.01) and slower 5 m gait speed (p = 0.02). Associations between sST2 levels and markers of poor prognosis were less compelling. In this study of patients with moderate to severe AS, elevated GDF-15 levels are associated with impaired functional capacity, poorer performance on fragility testing, and LV dysfunction. In conclusion, GDF-15 may integrate these markers of adverse outcomes into a single biomarker of poor prognosis.

Videoconference version of the Montreal Cognitive Assessment: normative data for Quebec-French people aged 50 years and older.

BACKGROUND: The COVID-19 pandemic forced health professionals to rapidly develop and implement telepractice and remote assessments. Recent reviews appear to confirm the validity of a wide range of neuropsychological tests for teleneuropsychology and among these, the Montreal Cognitive Assessment (MoCA), a cognitive screening test widely used in clinical settings. The normative data specific to the context of videoconference administration is essential, particularly that consider sociodemographic characteristics. AIMS: This study had for objective to develop French-Quebec normative data for videoconference-administration of the MoCA that consider sociodemographic characteristics. METHODS: A total of 230 community-dwelling adults aged 50 years and older taking part in clinical trials completed the MoCA by videoconference. Regression analyses were run with sex, education, and age as predictors of the total MoCA scores, based on previously published norms. As an exploratory analysis, a second regression analysis was also run with cardiovascular disease as a predictor. RESULTS: Regression analyses revealed that older age and lower education were associated with poorer total MoCA scores, for medium effect size (p < 0.001, R2 = 0.17). Neither sex nor cardiovascular disease, were significant predictors in our analyses. For clinicians, a regression equation was proposed to calculate Z scores. DISCUSSION: This study provides normative data for the MoCA administered via videoconference in Quebec-French individuals aged 50 years and over. CONCLUSIONS: The present normative data will not only allow clinicians to continue to perform assessments remotely in this pandemic period but will also allow them to perform cognitive assessments to patients located in remote areas.

Predictive risk factors for hospitalization and response to colchicine in patients with COVID-19.

OBJECTIVE: A predictive model for hospitalization due to COVID-19 or death was developed in the placebo group (N=2,084) from a large clinical trial of colchicine in COVID-19 patients (N = 4,159). RESULTS: The 7 variables retained in the predictive model were age, gender, body-mass index, history of respiratory disease, use of diabetes drugs, use of anticoagulants, and use of oral steroids at the time of randomization. An optimal threshold value identified from the predictive model was used to classify high-risk patients (those with a predicted probability above the optimal threshold) and low-risk patients (those with a predicted probability below the optimal threshold). The number needed to treat to prevent 1 hospitalization or death with colchicine treatment decreased from 71 in the whole study population (N = 4,159) to 29 in the high-risk subgroup (N=1,692). CONCLUSION: This model could serve to identify high-risk subjects who will particularly benefit from early colchicine therapy.

Right ventricular function and its coupling to pulmonary circulation predicts exercise tolerance in systolic heart failure.

AIMS: Right ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We investigated how RV function alone and its coupling with pulmonary circulation (RV-PA) predict cardio-respiratory fitness in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: The Evaluation of Resynchronization Therapy for Heart Failure (EARTH) study included 205 HFrEF patients with narrow (n = 85) and prolonged (n = 120) QRS duration undergoing implantable cardioverter defibrillator implantation. All patients underwent a comprehensive evaluation with exercise tolerance tests and echocardiography. We investigated the correlations at baseline between RV parameters {size, function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV-FAC), and RV myocardial performance index (RV-MPI)], pulmonary artery systolic pressure (PASP), and tricuspid regurgitation}; left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi), and left atrial volume index (LAVi); and cardiopulmonary exercise test (CPET) [peak VO2 , minute ventilation/carbon dioxide production (VE/VCO2 ), 6 min walk distance (6MWD), and submaximal exercise duration (SED)]. We also studied the relationship between RV-PA coupling (TAPSE/PASP ratio) and echocardiographic parameters in patients with both data available. Univariate and multivariate linear regression models were used. Patients enrolled in EARTH (overall population) were mostly male (73.2%), mean age 61.0 ± 9.8 years, New York Heart Association class II-III (87.8%), mean LVEF of 26.6 ± 7.7%, and reduced peak VO2 (15.1 ± 4.6 mL/kg/min). Of these, 100 had both TAPSE and PASP available (TAPSE/PASP population): they exhibited higher BNP, wider QRS duration, larger LVEDVi, with more having tricuspid regurgitation compared with the 105 patients for whom these values were not available (all P < 0.05). RV-FAC (ß = 7.5), LAVi (ß = -0.1), and sex (female, ß = -1.9) predicted peak VO2 in the overall population (all P = 0.01). When available, TAPSE/PASP ratio was the only echocardiographic parameter associated with peak VO2 (ß = 6.8; P < 0.01), a threshold ≤0.45 predicting a peak VO2  ≤ 14 mL/kg/min (0.39 for VO2  ≤ 12). RV-MPI was the only echocardiographic parameter associated with ventilatory inefficiency (VE/VCO2 ) and 6MWD (ß = 21.9 and ß = -69.3, respectively, both P ≤ 0.01) in the overall population. In presence of TAPSE/PASP, it became an important predictor for those two CPET (ß = -18.0 and ß = 72.4, respectively, both P < 0.01), together with RV-MPI (ß = 18.5, P < 0.01) for VE/VCO2 . Tricuspid regurgitation predicted SED (ß = -3.2, P = 0.03). CONCLUSIONS: Right ventricular function assessed by echocardiography (RV-MPI and RV-FAC) is closely associated with exercise tolerance in patients with HFrEF. When the TAPSE/PASP ratio is available, this marker of RV-PA coupling becomes the stronger echocardiographic predictor of exercise capacity in this population, highlighting its potential role as a screening tool to identify patients with reduced exercise capacity and potentially triage them to formal peak VO2 and/or evaluation for advanced HF therapies.

Performances on the Montreal Cognitive Assessment Along the Cardiovascular Disease Continuum.

Cardiovascular diseases involve a continuum starting with risk factors, which can progress to coronary heart disease and eventually, to heart failure. Cognitive impairment (CI) is observed as early as cardiovascular risk factors, and in up to 50% of patients with heart failure. Because CI in cardiovascular disease is linked to poorer clinical outcomes, early detection is essential. The Montreal Cognitive Assessment (MoCA) is a screening tool widely used in clinical setting. To date, little is known about MoCA scores along the cardiovascular disease continuum. OBJECTIVE: This study compared performances of different cardiovascular disease profiles on the MoCA and its subscores. METHOD: Eighty participants (>50 years) from two studies conducted at the Montreal Heart Institute were separated into four groups: low cardiovascular risk factors (<2), high cardiovascular risk factors (>2), coronary heart disease, and stable heart failure. ANCOVAs were performed on the total score and on subscores, with sex, age, and education as covariates. RESULTS: Group differences were observed on the MoCA total score (heart failure < low cardiovascular risk), verbal fluency (heart failure < low cardiovascular risk), memory (coronary heart disease < low cardiovascular risk), and orientation (coronary heart disease < low and high cardiovascular risk) subscores. CONCLUSION: Results suggest that the MoCA, particularly verbal fluency and memory subscores, can detect cognitive changes in later stages of the cardiovascular disease continuum, such as heart failure. Detecting cognitive changes earlier on the cardiovascular disease continuum may require more in depth neuropsychological assessments.

Repurposing Colchicine for Heart Disease.

Colchicine is one of the most ancient medications still prescribed. It is extracted from the Colchicum autumnale plant and is routinely used because of its broad anti-inflammatory properties to treat gout and familial Mediterranean fever. Colchicine has shown efficacy in various clinical settings in which inflammation is a key component, and it has become first-line therapy for acute and recurrent pericarditis. Two landmark clinical trials have recently shown that colchicine significantly improves cardiovascular outcomes on background statin and antiplatelet therapy in patients with coronary artery disease, supporting its role for the prevention of atherothrombotic events. Favorable results have also emerged in atrial fibrillation. We herein briefly review the most recent data related to the multiple cardiovascular conditions for which colchicine has been successfully repurposed.

Investigation of the Effects of Home-Based Exercise and Cognitive Training on Cognitive and Physical Functions in Cardiac Patients: The COVEPICARDIO Study Protocol of a Randomized Clinical Trial.

Introduction: During the COVID-19 pandemic, confinement measures are likely to produce collateral damage to health (stress, confusion, anxiety), especially in frail individuals and those living with cardiovascular disease (CVD). In cardiac patients in particular, these measures dramatically increase the level of physical inactivity and sedentary lifestyle, which can decrease cardiorespiratory capacity and increase the risk of acute events, rehospitalization, and depressive syndromes. Maintaining a minimum level of physical activity and cognitive stimulation during the COVID-19 crisis is essential for cardiac patients. This study is designed to document the effects of 6 months of home-based physical exercise alone or combined with cognitive training on cognitive and physical functions in patients with CVD over 50 years old. Methods and Analysis: 122 patients (>50 years old) with stable CVD and no contraindication to perform physical exercise training will be recruited and randomly assigned to one of the 2 following arms: (1) Home-based physical exercise alone, (2) Home-based physical exercise combined with cognitive training. The intervention lasts 6 months, with remote assessments performed prior to, mid and post-training. A follow-up 6 months after the end of the intervention (12 month) is also proposed. The primary outcome is cognition, including general functioning (Montreal Cognitive Assessment (MoCA) score), as well as performances on measures of executive functions, processing speed, and episodic memory. The secondary outcome is physical performance, including balance, gait and mobility, leg muscle strength and estimated cardiorespiratory fitness. Tertiary outcomes include mood, anxiety, and health-related quality of life as assessed by self-reported online questionnaires. Discussion: With the COVID-19 crisis, there is a critical need for remote exercise and cognitive training, and to further investigate this topic, in particular for cardiac patients. The present context can be viewed as an opportunity to perform a major shift from center-based programs to home-based physical exercise. This is especially important to reach out to older adults living in remote areas, where access to such interventions is limited. ClinicalTrials.gov: [https://clinicaltrials.gov/ct2/show/NCT04661189], NCT04661189.

Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease.

AIMS: Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the 'smoker's paradox' suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease. METHODS: The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers. RESULTS: Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p < 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p < 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p < 0.05). CONCLUSION: In contrast to the 'smoker's paradox', current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564).

Colchicine in the Management of Acute and Chronic Coronary Artery Disease.

PURPOSE OF REVIEW: Inflammation is involved in the initiation, progression, and destabilization of atherosclerosis. Anti-inflammatory strategies aimed at reducing residual cardiovascular (CV) risk have gained increasing interest in addition to the traditional management of risk factors. Colchicine is a potent anti-inflammatory therapy that affects the inflammasome and other targets. We will herein review the most recent evidence regarding the usefulness of colchicine in patients with coronary artery disease (CAD). RECENT FINDINGS: Colchicine has recently been repurposed from its traditional use to a number of CV indications. The landmark COLCOT and LoDoCo2 trials have demonstrated that long-term use of colchicine was associated with a reduced rate of CV events in both acute and chronic presentations of CAD, with an overall good safety profile. Colchicine is emerging as a valuable, safe, and cost-effective therapy in addition to standard of care for the prevention of atherothrombotic events in CAD.

COVEPIC (Cognitive and spOrt Virtual EPIC training) investigating the effects of home-based physical exercise and cognitive training on cognitive and physical functions in community-dwelling older adults: study protocol of a randomized single-blinded clinical trial.

BACKGROUND: In the context of the COVID-19 pandemic, lockdown and social distancing measures are applied to prevent the spread of the virus. It is well known that confinement and social isolation can have a negative impact on physical and mental health, including cognition. Physical activity and cognitive training can help enhance older adults' cognitive and physical health and prevent the negative collateral impacts of social isolation and physical inactivity. The COVEPIC study aims to document the effects of 6 months of home-based physical exercise alone versus home-based physical exercise combined with cognitive training on cognitive and physical functions in adults 50 years and older. METHODS: One hundred twenty-two healthy older adults (> 50 years old) will be recruited from the community and randomized to one of the two arms for 6 months: (1) home-based physical exercises monitoring alone and (2) combined physical exercises monitoring with home-based cognitive training. The primary outcome is cognition, including general functioning (Montreal Cognitive Assessment (MoCA) score), as well as executive functions, processing speed, and episodic memory (composite Z-scores based on validated neuropsychological tests and computerized tasks). The secondary outcome is physical functions, including balance (one-leg stance test), gait and mobility performance (Timed Up and Go, 4-meter walk test), leg muscle strength (5-time sit-to-stand), and estimated cardiorespiratory fitness (Matthews' questionnaire). Exploratory outcomes include mood, anxiety, and health-related quality of life as assessed by self-reported questionnaires (i.e., Geriatric depression scale-30 items, Perceived stress scale, State-trait anxiety inventory-36 items, Perseverative thinking questionnaire, Connor-Davidson Resilience Scale 10, and 12-item Short Form Survey). DISCUSSION: This trial will document the remote monitoring of home-based physical exercise alone and home-based physical combined with cognitive training to enhance cognitive and physical health of older adults during the COVID-19 pandemic period. Remote interventions represent a promising strategy to help maintain or enhance health and cognition in seniors, and potentially an opportunity to reach older adults in remote areas, where access to such interventions is limited. TRIAL REGISTRATION: Clinical trial Identifier NCT04635462 . COVEPIC was retrospectively registered on November 19, 2020.