Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction (MI). However, it remains unclear whether and in which extent the different angiographic types of SCAD (type 1-3) impact patients´ outcome. We analyzed data from all patients included in our national SCAD study. For this analysis, only patients with angiographically classified type of SCAD and complete follow-up were eligible. Patients with different types of SCAD during their index event were excluded. Cumulative rate of recurrent MI was the primary endpoint and assessed by Kaplan-Meier curves. Of 684 eligible patients, SCAD type 2 during index event was the most common diagnosis affecting 478 (69.8%) patients. SCAD type 1 was more common than SCAD type 3 (150 patients (22.0%) versus 56 patients (8.2%), respectively). Within the long-term follow-up of 1800 days, 57 patients (7.9%) had a recurrent MI of which 22 patients (38.6%) had recurrent SCAD. Assessment of cumulative rate of recurrent MI showed a significant gradient within 1800 days of long-term follow-up over the 3 predefined types of SCAD (p=0.04, Figure 1). Patients with type 1 SCAD during their index event had the highest rate of recurrent MI when compared to patients with type 2 and type 3 SCAD (12.0% versus 6.7% versus 5.3%, respectively). There was a statistically significant difference when comparing the cumulative rate of recurrent MI in patients with type 1 and type 2 SCAD during 1800 days of follow-up (p=0.01). The angiographic type of SCAD had a significant impact on the cumulative rate of recurrent MI during long-term follow-up. Patients with initial type 1 SCAD had the highest event rate when compared to patients with type 2 and 3 SCAD.Cumulative event rate over 1800 days for

Medication regimen complexity may be an important risk factor for adverse outcomes in older adults with heart failure. However, increasing complexity is often necessary when prescribing guideline-directed medical therapy at the time of a heart failure hospitalization. We sought to determine whether increased medication regimen complexity following a heart failure hospitalization was associated with worse post-hospitalization outcomes. This retrospective cohort study included Reasons for Geographic and Racial Differences in Stroke (REGARDS) participants aged at least 65 years hospitalized for heart failure between 2003 and 2014. We calculated changes between hospital admission and discharge in medication count (Δcount) and in the validated Medication Regimen Complexity Index (ΔMRCI), which incorporates each medication’s dosage formulation, frequency, timing, and special instructions. The primary outcome was a composite of 90-day all-cause readmission and all-cause mortality post-discharge. We calculated ΔMRCI and Δcount, identified their predictors, and examined their association with the primary outcome. Among 725 patients hospitalized for heart failure, the mean (SD) age was 77 (7.2) years, 46

Background Physician underprescribing and patient nonadherence are major barriers to the benefits of guideline‐directed medical therapy. An important contributor to both underprescribing and patient nonadherence is concern about medication‐related side effects. Yet, there are few to no data on approaches used by physicians to: (1) elicit medication‐related side effects, (2) attribute these side effects to specific medications, and (3) take appropriate action. Methods and Results The authors conducted semistructured interviews with physicians to identify facilitators and barriers to each critical step of heart failure medication management: elicitation of side effects, attribution of side effects to a medication, and action in response to attributed side effects. Interviews were transcribed and coded using directed content analysis. For elicitation of potential side effects, limited patient communication and family discordance in reporting were key barriers, whereas guiding questions, measurement, and open channels of communication were key facilitators. For attribution of side effects, confounding from other medications, limited time for clinical encounters, and nonspecific symptoms were key barriers, whereas time‐limited medication discontinuation trials and medication rechallenges were key facilitators. For taking action, challenges with weighing risks and benefits and physician fear about causing harm or interfering with other clinicians were barriers, whereas patient‐physician communication and the results of a medication discontinuation trials and medication rechallenge were facilitators. Conclusions This study generated key facilitators and barriers to 3 key aspects of heart failure medication management related to side effects that should drive future work to improve heart failure medication management.

Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice.

Background and aims: Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.Methods: Patients were grouped into two pools: 1) atherosclerotic cardiovascular disease (ASCVD) and/or het-erozygous familial hypercholesterolemia (HeFH) "on statins" and 2) "low-dose or no statin". Percent changes from baseline to at least week 12 in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex.Results: Overall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acid vs. placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools (p <= 0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (-21.2% vs.-17.4%; p = 0.044), non-HDL-C (-17.3% vs.-12.1%; p = 0.003), TC (-13.8% vs.-10.5%; p = 0.012), and Apo B (-16.0% vs.-11.3%; p = 0.004) in the ASCVD and/or HeFH on statins pool. Women had similar reductions to men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was com-parable between sexes.Conclusions: In this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid.

Antiplatelet therapy (APT) is the foundation of treatment and prevention of atherothrombotic events in patients with atherosclerotic cardiovascular disease. Selecting the optimal APT strategies to reduce major adverse cardiovascular events, while balancing bleeding risk, requires ongoing review of clinical trials. Appended, the focused update of the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the use of APT provides recommendations on the following topics: (1) use of acetylsalicylic acid in primary prevention of atherosclerotic cardiovascular disease; (2) dual APT (DAPT) duration after percutaneous coronary intervention (PCI) in patients at high bleeding risk; (3) potent DAPT (P2Y12 inhibitor) choice in patients who present with an acute coronary syndrome (ACS) and possible DAPT de-escalation strategies after PCI; (4) choice and duration of DAPT in ACS patients who are medically treated without revascularization; (5) pretreatment with DAPT (P2Y12 inhibitor) before elective or nonelective coronary angiography; (6) perioperative and longer-term APT management in patients who require coronary artery bypass grafting surgery; and (7) use of APT in patients with atrial fibrillation who require oral anticoagulation after PCI or medically managed ACS. These recommendations are all on the basis of systematic reviews and meta-analyses conducted as part of the development of these guidelines, provided in the Supplementary Material.

Background/Objectives: Cardiac Resynchronization Therapy (CRT) is a treatment option for many adults with heart failure with reduced ejection fraction (HFrEF). While the benefits of CRT are well-established, the downstream implications of adverse events are not well-characterized. We sought to better understand the ramifications of CRT-related adverse events on length of hospital stay (LOS) and mortality—information relevant for patients and clinicians to make informed decisions about pursuing CRT. Design: Scoping Review Methods: We conducted an initial PubMed search using terms including “Congestive Heart Failure” or “Heart Failure” and "Cardiac resynchronization" or "Cardiac re-synchronization" or "Biventricular pacing.” We reviewed resulting articles that were written in English, studied CRT devices, and outlined adverse events related to CRT device placement. We separately searched PubMed for additional articles outlining individual adverse events identified using search terms “event name,” “mortality,” and “hospital stay.” We read articles and summarized data regarding the impact of reported adverse events on hospital LOS and mortality. Results: Our search identified 18 full length articles with relevant data. The most common adverse events included device implant failure/non-response, lead dislodgment, coronary sinus dissection, and pocket hematoma. The LOS and mortality rates of each event are shown in Table 1. Of note, LOS for implantation in the ambulatory setting is up to 1 day; LOS for uncomplicated implantation during hospitalization is 4.6 days. Implantation during hospitalization with complication is mean 13.6 days. Conclusion: While absolute risks for adverse events associated with CRT implantation are low, several have important implications on hospital LOS and mortality. These findings warrant inclusion in discussion regarding the risks of CRT when clinicians and patients engage in informed decision making related to CRT.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease.The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Multiple randomized clinical trials and observational studies in patients with chronic coronary artery disease have evaluated whether revascularization, in particular PCI, can reduce the incidence of future cardiovascular events and relieve angina. Perhaps the two most widely quoted trials are COURAGE and ISCHEMIA. In both trials revascularization did not reduce the incidence of cardiovascular death or non-fatal events. In both, revascularization did relieve angina, particularly in patients with severe pain. From the time of COURAGE to ISCHEMIA there were also multiple developments. In particular improved stent technology with second and third generation drug eluting stents in ISCHEMIA compared to bare metal stents in COURAGE. There was also the development of new methods to evaluate ischemia, in particular the potential surrogate fractional flow reserve. This period also saw improvement and maturation of coronary computed tomography angiography to assess coronary anatomy non-invasively. There was also greater emphasis on more intensive, guideline directed medical therapy to treat dyslipidemia and hypertension. There has also been greater recognition that not all angina is due to epicardial obstructive disease. Microvascular disease and coronary spasm are responsible for much of the symptom burden of ischemia. These data have led to a paradigm shift toward a more nuanced approach to treating stable ischemic heart disease, with less need for revascularization except in cases of particularly severe anatomic disease or unremitting symptoms while on optimal medial therapy. In recognition of the importance of disparities in cardiovascular health, it is crucial to implement preventive strategies with optimal medical therapy in the community.

The REDUCE-IT trial demonstrated that icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, lowers cardiovascular (CV) events and CV death in statin-treated individuals with mild-moderate hypertriglyceridemia, relatively well-controlled low-density lipoprotein cholesterol (LDL-C) levels and with either known CV disease or diabetes with other risk factors. Inasmuch as over 90% of the REDUCE-IT cohort were White, the generalization of its results to non-White populations is unclear. Compared with White individuals and other races/ethnicities, people of South Asian (SA) descent have higher levels of triglycerides and are at a markedly higher risk of developing atherosclerotic cardiovascular disease (ASCVD). Given that SAs represent the largest visible minority in Canada, the overarching goal of the REDUCE-IT Canada SA study was to determine eligibility for use of IPE for residual CV risk reduction in SAs in Canada who have ASCVD. The REDUCE-IT Canada SA study enrolled 200 SA individuals (≥45 years) with ASCVD on stable statin therapy from 4 community cardiology (65%) and 2 family practice (35%) clinics across the Greater Toronto Area. Race/ethnicity and medical coverage status were self-reported; all other variables were extracted from medical records. Most (82%) were men; 57% had known diabetes. The median [IQR] age, body mass index, A1C, LDL-C, high-density lipoprotein cholesterol, and triglyceride levels for the cohort were 67 years (59.8, 74.0), 26.0 kg/m2 (23.8, 28.4), 6.5% (5.9, 7.3), 1.5 mmol/L (1.1, 2.0), 1.1 mmol/L (1.0, 1.3), and 1.2 mmol/L (0.9, 1.7), respectively. Despite most being on guideline-recommended lipid-lowering therapies - 75% on a high-intensity statin, 18% on ezetimibe, and 4% on a proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) inhibitor - 33% of the REDUCE-IT Canada SA cohort fulfilled the Health Canada and 2021 Canadian Cardiovascular Society (CCS) Dyslipidemia Guidelines eligibility criteria for IPE therapy. Less than one-quarter (22%) of this contemporary cohort of SAs reported having access to private health insurance, while 33% described challenges covering the cost of medication. Even though the lipid levels of the REDUCE-IT Canada SA participants were generally well managed, our data suggest that approximately one-third of this ASCVD cohort would be eligible for IPE according to Health Canada and the 2021 CCS Dyslipidemia Guidelines. Strategies aimed at improving access to IPE may offer additional opportunities to reduce vascular events in SAs who are recognized as a high-risk population.

Background Homozygous familial hypercholesterolaemia (HoFH) is a rare and life-threatening genetic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels, important xanthomatosis and increased risk of premature atherosclerotic cardiovascular disease. Management of HoFH at an early stage is recommended but conventional lipid-lowering therapies (LLTs) dependent on the LDL-receptor for clearance of LDL particles, are usually not sufficient. However, agents acting independently of the LDL-receptor, such as inhibitors of microsomal triglyceride transfer protein (MTP) or angiopoietin-like protein 3 (ANGPTL3), administered in combination, on top of standard-of-care LLT constitute a promising therapy for HoFH. Case summary The present case describes a long-term (>10 years) follow-up of a 52-year-old woman with severe HoFH, who was treated with conventional lipid-lowering medications (i.e. statins and ezetimibe) for several years before experiencing the risks and benefits that were encountered with the use of LDL-receptor-independent agents (MTP and ANGPTL3 inhibitors). This combination therapy demonstrated a good long-term safety and efficacy profile, while continuous monitoring of hepatic enzymes (sometimes requiring dose adjustments) and fat accumulation is recommended when using lomitapide. Discussion Treating this HoFH patient with an LLT involving the combination of MTP and ANGPTL3 LDL-receptor-independent inhibitors (lomitapide and evinacumab, respectively) showed remarkable improvement in LDL-C levels, disappearance of xanthomatosis and regression in atherosclerotic plaques. In addition to safety and efficacy, one should question the affordability and access hurdle that emerging combination of expensive therapies might constitute in the future for the payers. These challenges could eventually limit the clinical use of those innovative treatments despite their clinical benefit.

BACKGROUND: Optimal management for ischemic mitral regurgitation (IMR) is controversial.Current evidence supports replacement over repair due to improved durability however the latter often involves undersizing with a complete ring and does not include edge-to-edge approximation.METHODS AND RESULTS: This is a single-center retrospective study of patients undergoing mitral surgery at the time of revascularization for moderate to severe (3+) or greater IMR between 2004-2020, with either mitral valve replacement (MVR), mitral valve repair with edge-to-edge approximation and mild-undersized annuloplasty (MVr) or undersized ring annuloplasty alone (URA).Freedom from all-cause mortality was analyzed using Cox proportional hazards and recurrence of MR and reoperation were analyzed as cumulative incidence with death as a competing risk.Follow-up echos were assessed for changes in ejection fraction (EF) and LV size using a mixed model.There were 121, 93, and 98 patients in the MVR, MVr and URA groups respectively.Follow-up was significantly longer in the MVr group (5.9 years) compared to the MVR (2.7 years) and URA (3.7 years) groups (p¼0.0001).Survival was significantly better after MVr than after MVR (p¼0.021) or URA (p¼0.003)(94.5% (95%CI [87.3,97.7])vs 86.6% (95% CI[78.7,91.7])and 88.7% (95% CI [78.7,94.2])at 2 years respectively).Rate of recurrent moderate (2-3+) or greater MR was similar between MVr and MVR group (p¼0.726)but significantly higher after URA (p¼ 0 < 0.0001) at latest follow up.There was no difference in the rate of reoperation amongst the groups.CONCLUSION: Alfieri repair in addition to mild-undersizing annuloplasty with an incomplete band offers similar durability as compared to replacement and may confer a survival advantage.

Introduction: Some patients cannot tolerate statins mainly because of statin-associated muscle symptoms (SAMS). Bempedoic acid (BA) is a prodrug activated in the liver and not in skeletal muscle. BA has been shown to significantly lower LDL-C by a mean of ~18% in patients receiving background maximally tolerated statins and a mean of ~25% in patients with statin intolerance. Objective: Determine efficacy and safety of BA in statin-intolerant patients receiving no background statin therapy across 4 phase 3 clinical trials. Methods: Data were pooled from 4 randomized (2:1), placebo-controlled studies evaluating oral BA 180 mg once daily vs placebo for 12 to 52 weeks. Primary efficacy endpoint was LDL-C % change from baseline to week 12. Safety assessments included treatment-emergent adverse events (TEAEs), adverse events of special interest (AESI), and laboratory values. For patients who reported SAMs, additional information around etiology and location were collected. Results: Of 3621 patients, 586 (394 BA; 192 placebo) reported intolerance to multiple statins because of SAMS or other AEs and received no statins during the studies. Mean baseline LDL-C was 148.7 mg/dL. After 12 weeks, BA significantly lowered LDL-C vs placebo (placebo-corrected, -26.5%; P < 0.001). Myalgia was the top reason for drug discontinuation, but was less common in the BA arm (17.7%) vs placebo (43.5%). CK > 5 х ULN was uncommon in both groups. Among AESIs (Table) , muscle disorders were reported by 12.7% (BA) vs 14.1% (placebo). Myalgia was less common with BA (4.6%) vs placebo (7.3%). Muscle spasms (4.1% vs 3.6%) and pain in extremity (3.3% vs 2.1%) were comparable between treatment groups. Muscular weakness was rare (0.5% BA, 1% placebo). Conclusion: Among the population of patients unable to use statins, BA significantly lowered LDL-C vs placebo without increasing muscle-related TEAEs. BA may be an appropriate lipid-lowering therapy for patients with hyperlipidemia who are statin intolerant.

BACKGROUND:Lipoprotein(a) is an atherogenic low-density lipoprotein-like particle and circulating levels are largely determined by genetics. Patients with familial hypercholesterolemia (FH) have elevated lipoprotein(a); however, it remains unclear why. OBJECTIVES:This study compared the levels of lipoprotein(a) and associated genetic factors between individuals that were ascertained for FH clinically versus genetically. METHODS:We investigated causes of elevated lipoprotein(a) in individuals with clinically diagnosed FH (FH cohort, n = 391) and in individuals with genetically diagnosed FH from the general population (UK Biobank; n = 37,486). RESULTS:Patients in the FH cohort had significantly greater lipoprotein(a) levels than either the general population or non-FH dyslipidemic patients. This was accounted for by increased frequency of the rs10455872-G LPA risk allele (15.1% vs. 8.8%; p < 0.05). However, within the FH cohort, lipoprotein(a) levels did not differ based on the presence or absence of an FH-causing variant (means = 1.43 log mg/dl vs. 1.42 log mg/dl; p = 0.97). Lipoprotein(a) levels were also not statistically different between individuals with and without an FH-causing variant in the UK Biobank cohort, which represents a population sample not biased to cardiovascular ascertainment (n = 221 vs. 37,486). We performed a phenome-wide association study between LPA genotypes and 19,202 phenotypes to demonstrate that elevated lipoprotein(a) is associated with increased low-density lipoprotein cholesterol, a family history of cardiovascular disease, premature coronary artery disease, and a diagnosis of FH. CONCLUSIONS:These results suggest that FH does not cause elevated lipoprotein(a), but that elevated lipoprotein(a) increases the likelihood that an individual with genetic FH will be clinically recognized.

Several risk scores in acute coronary syndromes are available, but few models exist for stable coronary artery disease to guide decision-making and prognosis. A multivariate model was developed using 23 baseline candidate variables from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Therapy EvaluationTrial (n = 2,287 patients). Discrimination of the model was evaluated by the concordance c-index. The procedure was validated using 100 random half samples. We identified 9 independent predictors of death or myocardial infarction (MI) during a 5-year follow-up. The following predictors and points contributing to the risk score were: heart failure (3), number of diseased coronary arteries (1 for each vessel), diabetes (1), age (1 for each 15 years >= age 45), previous revascularization (1), current smoking (1), female (1), previous MI (1), and high-density lipoprotein cholesterol (1: 31 to 40 mg/dL; 2: <30 mg/dL). The risk tool had a potential range from 0 to 15, corresponding to 5-year event rates of 5.8% to 56%. C-indices ranged from 0.67 for the full data set to 0.62 for the validating subsamples. Respective observed versus predicted 5-year event rates for 3 predefined risk strata revealed: 30% had a low-risk score of 0 to 3 (9.3% vs 9.3%, or 1.9%/year); 59% had an intermediate-risk score of 4-6 (18.0% vs 18.1%, or 3.6%/year); and 11% had a high-risk score of 7-11 (36% vs 36.5%, or 7.2%/year). This stable coronary artery disease risk score permitted a prognostic assessment of 5-year probability of death or MI with an approximate 4-fold range in event rates from the lowest (9.3%) to the highest (36%) terciles, thus enabling better clinical practice decisions that allow physicians to tailor the intensity of treatment to the level of risk. (C) 2020 Elsevier Inc. All rights reserved.

Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (<= 3, 3.1-5 or > 5 mg/day), follow-up (> 12 or <= 12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65). Moreover, we showed reduced risk of Non-MuD (OR = 0.59, 95%CI 0.50, 0.69) and SAE (OR = 0.54, 95%CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01). Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects.

• Une cardiopathie est plus susceptible de survenir, et plus tôt dans la vie, chez les personnes atteintes de diabète de type 1 et 2 (surtout les femmes) que chez les personnes non diabétiques. Malheureusement, dans une forte proportion des cas, il n’y a pas de symptômes avant un infarctus du myocarde mortel ou non. Il est donc souhaitable de reconnaître les personnes présentant un risque élevé d’événements cardiovasculaires, en particulier celles qui présentent une coronaropathie grave avérée inconnue.