Can We Eliminate Low-Density Lipoprotein Cholesterol-Related Cardiovascular Events Through More Aggressive Primary Prevention Therapy?

Intravascular levels of low-density lipoprotein cholesterol (LDL-C) at approximately ≤ 0.6 mmol/L are likely to minimize, and perhaps eliminate, LDL-C-related vascular toxicity while having no effect on essential, intracellular cholesterol homeostatic pathways, according to accumulated knowledge from basic science. Randomized clinical trials, observational reports, and Mendelian randomization trials are also forcing a reconsideration of what “normal” LDL-C means. Recent trials of secondary prevention have substantiated that such levels are safe and associated with a decreased risk of cardiovascular events (CVEs) compared with patients with higher levels of LDL-C. Similarly, treatment to this low range is associated with regression and stabilization of established atherosclerosis. Primary prevention trials also show that low levels of LDL-C are safe and associated with decreased risk of CVEs through cholesterol-lowering in adults with LDL-C ≥ 3.5 mmol/L or when levels are < 3.5 mmol/L in association with other cardiovascular risks. Although there are no randomized clinical outcome trials of familial hypercholesterolemia patients, such patients have very high, lifetime risk of CVE, and registry studies show that LDL-C reduction has nearly normalized their CVE rates. The possibility of familial hypercholesterolemia should be considered if LDL-C is > 4.5 and > 4.0 mmol/L at ages 18-39 years and younger than 18 years, respectively. On the basis of these convergent and internally consistent lines of evidence, in this article we speculate on a translational paradigm aimed at eliminating LDL-C-related CVEs through aggressive primary prevention strategies that are already proven and well accepted in principle.     

Antithrombotic Therapy for Atrial Fibrillation and Coronary Disease Demystified

Atrial fibrillation (AF) is a progressive chronic disease characterized by exacerbations and periods of remission. It is estimated that up to 20% to 30% of those with AF also have coronary artery disease (CAD), and 5% to 15% will require percutaneous coronary intervention (PCI). In patients with concomitant AF and CAD, management remains challenging and requires a careful and balanced assessment of the risk of bleeding against the anticipated impact on ischemic outcomes (AF-related stroke and systemic embolism, as well as ischemic coronary events). Oral anticoagulation (OAC) is indicated for the prevention of AF-related stroke and systemic embolism, whereas antiplatelet therapy is indicated for the prevention of coronary events. Each offers a relative efficacy benefit (dual antiplatelet therapy [DAPT] is more effective than OAC alone in reducing cardiovascular death, myocardial infarction, stent thrombosis, and ischemic coronary events in a population with acute coronary syndromes [ACS]), but with a relative compromise (DAPT is significantly inferior to OAC for the prevention of stroke/systemic embolism in an AF population at increased risk of stroke). The purpose of this review is to explore the current evidence and rationale for antithrombotic treatment strategies in patients with both AF and CAD. Specifically, there is a focus on how to best tailor the therapeutic choices (OAC and antiplatelet therapy) to individual patients based on their underlying coronary presentation.     

Quality of Cardiac Care in Canada: Recommendations for Building a Sustainable Future

Cardiovascular (CV) disease continues to present a significant disease and economic burden in Canada. To improve the quality of care and ensure sustainability of services, a national quality improvement initiative is required. The purpose of this analysis was to review the evidence for public reporting (PR) and external benchmarking (EB) to improve patient outcomes, and to recommend a strategy to improve CV care in Canada. To incorporate recent literature, the Canadian Cardiovascular Society (CCS) commissioned the Institute of Health Economics to provide a rapid update on the literature of PR and EB. The review showed that EB is more likely to promote positive effects, such as improved mortality, morbidity, and evidence-based clinical practice, and to limit negative effects, such as access restrictions or unintended provider behaviour associated with some forms of “top-down” PR. On the basis of these findings, this we recommend the following: (1) secure funding for the provincial collection of CV quality indicators and the creation of annual National CV Quality Reports; (2) enhance the culture of using CV quality indicator data for continuous quality improvement and opportunities for national or regional EB and sharing best practices; and (3) implement ongoing evaluation and revision of CCS clinical practice guidelines incorporating key quality indicators. This is already under way to a limited extent by the CCS with its Quality Project, but intentional, sustained support needs to be secured to enhance this ongoing effort and improve the quality of CV care for all Canadians.     

Canadian Cardiovascular Society Cardiovascular Screening of Competitive Athletes: The Utility of the Screening Electrocardiogram to Predict Sudden Cardiac Death

Prevention of sudden cardiac arrest/death (SCA/D) among athletes is a universal goal, although the optimal strategy for its achievement is controversial, with the inclusion of the 12-lead electrocardiogram (ECG) at the center of the debate. The ECG exhibits superior sensitivity over history and physical examination to detect conditions associated with SCA/D. However, the identification of disease does not necessarily lead to a significant reduction in SCA/D. The “Canadian Cardiovascular Society/Canadian Heart Rhythm Society Joint Position Statement on the Cardiovascular Screening of Competitive Athletes” recommended against the routine performance of an ECG for the initial cardiovascular screening of competitive athletes. The incidence of SCA/D among athletes (<35 years of age), the risk of SCA/D during sport participation among individuals with abnormalities found on screening ECG, the efficacy of the ECG to identify conditions associated with SCA/D, and the positive predictive value of an abnormal ECG to predict SCA/D are critically examined. This review presents the evidence informing the panel’s recommendation.     

The Atherogenic Dyslipidemia Complex and Novel Approaches to Cardiovascular Disease Prevention in Diabetes

Despite the effectiveness of low-density lipoprotein (LDL)-lowering strategies for the treatment of diabetic dyslipidemia, significant residual risk of atherosclerotic cardiovascular disease remains. Residual risk might in part be explained by lipid abnormalities that go beyond LDL cholesterol elevation, collectively termed the “atherogenic dyslipidemia complex (ADC),” consisting of hypertriglyceridemia, elevated small dense LDL particles, reduced high-density lipoprotein cholesterol, and high-density lipoprotein particle numbers, increased remnant lipoproteins, and postprandial hyperlipidemia. In this review, we briefly discuss the pathophysiology of the typical dyslipidemia that occurs in insulin-resistant states including obesity, the metabolic syndrome, and type 2 diabetes. Lipid-modifying strategies including lifestyle modification, ezetimibe, statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors in treating ADC are discussed. With the advent of novel therapies involving antisense oligonucleotides and monoclonal antibodies, new targets can be specifically downregulated to potentially promote lipoprotein clearance or suppress production. We review novel approaches currently undergoing clinical testing and we speculate on their suitability for use in treating ADC for the prevention of atherosclerotic cardiovascular disease. In addition, future targets that might be considered for therapeutic development are discussed.     

Sex Differences in Atrial Fibrillation

Atrial fibrillation (AF) is a chronic progressive disease characterized by exacerbations and remissions. It remains the most common sustained arrhythmia seen in clinical practice, and represents a major burden to health care systems. Similar to other cardiovascular conditions, significant sex-specific differences have been observed in the epidemiology (lower rate of prevalence in women, women present at a later age), pathophysiology (sex-related differences in AF triggers and substrate), clinical presentation (women are more likely symptomatic, with relatively more severe symptoms), and natural history. Moreover, similar to other cardiovascular conditions there are substantial sex-specific differences in the management of AF, with women being significantly less likely to receive therapeutic anticoagulation, attempts at rhythm control, or undergo invasive cardiovascular procedures. The purpose of this review is to explore these sex-specific differences.     

Change in Proteinuria or Albuminuria as a Surrogate for Cardiovascular and Other Major Clinical Outcomes: A Systematic Review and Meta-analysis

Background

There is ongoing controversy around the surrogacy of proteinuria or albuminuria, particularly for cardiovascular (CV) outcomes, which remain the leading cause of morbidity and mortality among patients with chronic kidney disease. We performed a systematic review and meta-analysis of the literature to assess the surrogacy of changing proteinuria or albuminuria for CV events, end-stage renal disease (ESRD), and all-cause mortality.

Coronary Vasospasm Following Heart Transplantation: Rapid Progression to Aggressive Cardiac Allograft Vasculopathy

Coronary artery vasospasm (CVS) has been described in orthotopic heart transplant patients but is rare in the post-transplanted, denervated heart. Severe CVS has been associated with accelerated cardiac allograft vasculopathy (CAV) and allograft rejection. Allograft vasculopathy is the leading cause of decreased long-term survival in orthotopic heart transplant. The prognostic significance and relationship of the presence and severity of CVS with CAV are not well understood. We present a case of severe symptomatic CVS with rapid development of severe CAV. Our case emphasizes the need for close angiographic surveillance and intracoronary imaging for early detection of CAV in the presence of vasospasm.     

Remote Monitoring of Cardiac Implantable Electronic Devices

Over the past decade, technological advancements have transformed the delivery of care for arrhythmia patients. From early transtelephonic monitoring to new devices capable of wireless and cellular transmission, remote monitoring has revolutionized device care. In this article, we review the current evolution and evidence for remote monitoring in patients with cardiac implantable electronic devices. From passive transmission of device diagnostics, to active transmission of patient- and device-triggered alerts, remote monitoring can shorten the time to diagnosis and treatment. Studies have shown that remote monitoring can reduce hospitalization and emergency room visits, and improve survival. Remote monitoring can also reduce the health care costs, while providing increased access to patients living in rural or marginalized communities. Unfortunately, as many as two-thirds of patients with remote monitoring-capable devices do not use, or are not offered, this feature. Current guidelines recommend remote monitoring and interrogation, combined with annual in-person evaluation in all cardiac device patients. Remote monitoring should be considered in all eligible device patients and should be considered standard of care.     

Variability in Non–Vitamin K Antagonist Oral Anticoagulants Dose Adjustment in Atrial Fibrillation Patients With Renal Dysfunction: The Influence of Renal Function Estimation Formulae

Background

Non–vitamin K antagonist oral anticoagulants (NOACs) require renal dose adjustment. The most common estimates of renal function in clinical practice are derived from estimated glomerular filtration rate (eGFR; Modified Diet in Renal Disease [MDRD] or the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). However, the landmark stroke prevention trials and product monographs recommend the use of the Cockcroft-Gault creatinine clearance equation (eCrCl) for drug eligibility and dose adjustment. We sought to evaluate the agreement in NOAC dosing between these 3 equations in a large population of patients with atrial fibrillation and moderate chronic kidney disease.

Switching Between β-Blockers: An Empiric Tool for the Cardiovascular Practitioner

β-Blockers are a cornerstone of therapy for cardiovascular disease, but their clinical benefits are not consistent across the class and specific agents are preferred for certain indications. Further, when prescribed, a patient’s clinical status might change, requiring the cardiologist to switch to an alternate agent. Examples of such scenarios include the development or a worsening of chronic noncardiac diseases (eg, hyperthyroidism, renal failure), new cardiac-related disease (eg, heart failure, atrial fibrillation), or practical/safety issues (eg, pregnancy, cost, side effects). However, guidelines on how to best switch to a different β-blocker are lacking. Additionally, most hospital-based formularies and guidelines do not provide recommendations around common challenges, like medication intolerance or adjustments for acute illness. We present a practical approach to switching between commonly prescribed β-blockers, which considers drug interchangeability for various indications, rationale for switching, necessary initial adjustments to dose/frequency, and differences in target/maximal doses.     

Fontan-Associated Liver Disease: Evidence for Early Surveillance of Liver Health in Pediatric Fontan Patients

The growing awareness of Fontan-associated liver disease (FALD) in adults with Fontan physiology has provided the impetus to better understand the natural history of FALD and develop a reliable noninvasive method to diagnose and monitor liver health in this population. Biochemical and imaging tests have been investigated to determine their association with liver pathology. The congestive hepatopathy that develops after the Fontan procedure has made interpreting these tests challenging. We have reviewed and summarized the current understanding and ongoing challenges with respect noninvasive measures of liver health in Fontan patients including biochemical tests, elastography, hepatic ultrasound, cross-sectional imaging, and hemodynamics and how they relate to liver pathology. It has been demonstrated from biopsy data that liver disease is universal and progressive in Fontan patients. Traditional biochemical tests, elastography, and imaging methods are often abnormal in Fontan patients but do not reliably indicate significant liver pathology. Although a reliable means for surveillance of FALD remains elusive, this continues to be an active area of investigation, with promising recent developments. Therapeutic options for FALD are limited, with cardiac transplant as the only option that can stabilize FALD pathology and improve symptomatology. Given the limited therapeutic options and the prevalence of liver disease in Fontan patients, there is a compelling case for early routine surveillance of liver health and promotion of global liver health.     

Blood Pressure–Lowering Targets in Patients With Diabetes Mellitus

Diabetes is a highly prevalent medical condition that commonly coexists with hypertension. The presence of diabetes and hypertension significantly increases the risk of adverse cardiovascular events. Although compelling evidence exists from randomized controlled trials demonstrating that blood pressure (BP) reduction effectively prevents cardiovascular complications, optimal BP targets remain uncertain and continue to be the subject of ongoing controversy. Until recently, most major clinical practice guidelines recommended a BP target of < 130/80 mm Hg, but some expert panels have raised their recommended treatment targets in recent years. The primary benefit of more intensive BP reduction appears to be prevention of stroke, but this is balanced against an increase in treatment burden, side effects, and cost. The purpose of this review is to summarize the global body of evidence evaluating BP targets as well as to compare the recommendations from different clinical practice guidelines, which inform the treatment of patients with hypertension and diabetes.     

Atherosclerotic Heart Disease in Women With Autoimmune Rheumatologic Inflammatory Conditions

Women have a higher prevalence of several inflammatory rheumatologic conditions. These include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) to name a few. These conditions are all associated with higher rates of cardiovascular (CV) morbidity and mortality, which is driven primarily by atherosclerotic heart disease. Traditional risk factors are important considerations in the assessment of CV risk in the rheumatologic patient; however, these factors do not appear to impart a similar weight of risk in women with inflammatory autoimmune rheumatologic conditions. In addition, even when controlling for traditional risk factors, patients with RA or SLE continue to have a higher risk of CV events, which has been linked to the burden of systemic inflammation. Currently, the CV risk scoring systems available for the general population underestimate the burden of the problem in these complex patients. The increased CV risk in patients with rheumatologic diseases has been reported in the literature for years but remains underrecognized by internists and cardiologists. Although these conditions themselves are relatively rare, the further study of inflammation and its treatment in CV disease will be beneficial to the general population.     

Radiotherapy for Patients with Cardiovascular Implantable Electronic Devices: A Review

Because cardiovascular implantable electronic devices are increasingly indicated in older patients, and the burden of cancer is rising with the growth and aging of the world population, the management of patients with cardiac devices who require radiotherapy for cancer treatment is a timely concern. Device malfunctions might occur in as high as 3% of radiotherapy courses, posing a substantial issue in clinical practice. A nonsystematic comprehensive review was undertaken. We searched PubMed and the MEDLINE database for randomized controlled trials, meta-analyses, systematic reviews, observational studies, in vitro/in vivo studies, and case reports. Articles were selected by 2 independent reviewers, and emphasis was given to information of interest to a general medical readership. The pathophysiology and predictors of cardiovascular implantable electronic device malfunction due to radiotherapy are reviewed, recommendations for the management of patients with such devices undergoing radiotherapy are summarized, and the clinical significance and future directions of this field are discussed. Radiotherapy-induced device malfunctions are rare, but because of the potential complications, the development of evidence-based guidelines for the management of patients with cardiovascular implantable electronic devices undergoing radiotherapy is a timely concern.     

Diabetes,Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms

Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes.     

The Potential Effects of New Stent Platforms for Coronary Revascularization in Patients With Diabetes

Coronary artery disease in patients with diabetes mellitus (DM) is characterized by extensive atherosclerosis, longer lesions, and diffuse distal disease. Consequently, these patients have worse outcomes after coronary revascularization, regardless of the modality used. Traditionally, coronary artery bypass grafting (CABG) has been regarded as more effective than percutaneous coronary intervention (PCI) in patients with DM, likely because of more complete revascularization and protection against disease progression in the bypass segment. Revascularization with balloon angioplasty, bare-metal stents, and first-generation drug-eluting stents have all been shown to be inferior to CABG in patients with DM. Current professional society guidelines reflect these findings, strongly recommending CABG over PCI in this setting. Newer stent platforms, however, have challenged this notion. The use of thinner struts, biocompatible polymer coating, and newer antiproliferative agents have improved the rates of cardiovascular events in patients with DM revascularized percutaneously. Since the publication of current guidelines, new studies suggested acceptable outcomes in patients with DM revascularized with second-generation drug-eluting stents, even though these conclusions are drawn from small subgroup analyses or nonrandomized studies. Robust registry data suggest similar mortality with lower rates of stroke after PCI compared with surgery, at the expense of increased rates of repeat revascularization. If complete revascularization can be achieved, similar rates of myocardial infarction are also observed. Therefore, contemporary revascularization in patients with DM with multivessel coronary artery disease should involve a multidisciplinary approach, in which interventional cardiologists and cardiac surgeons involve their patients to individualize treatment choices, and balance the risks and effectiveness of each modality.     

Atrial Fibrillation Clinics in Canada: A Nationwide Project Report

The increased prevalence of atrial fibrillation (AF) has led to specialized AF clinics (AFCs) to facilitate management of AF patients. In this article we report on outpatient AFCs in Canada, which is essential to health policies required to standardize the performance of existing AFCs and help design new AFCs. We surveyed 14 clinics in 5 provinces; 100% provided responses to a detailed questionnaire on clinic processes and care practices. Fourteen care maps were analyzed, and 5 models of care were identified; 4 were specific to AFCs. An online survey with 49 questions included items on: (1) process before visit; (2) process at visit; (3) patient education provided; (4) outreach; and (5) specific clinic information. Clinicians’ advice to patients on self-care items such as: (1) amount of alcohol and (2) caffeine intake; (3) exercise activity; (4) stressful events; (5) “when to go to the emergency department”; and (6) lifestyle changes, were evaluated to assess consistency in practice. There were moderate variances in clinicians’ advice to patients in 5 of 6 self-care items. The 1 item that had 100% consistent practice recommendation was when to go to the emergency department. A guideline-based clinical assessment checklist (CAC) was piloted to obtain feedback on its usability in real-world practice; revisions finalized the “simplified CAC” for AF care encompassing 35 data points with rationale. There was 100% positive feedback on its ability to provide baseline elements in AF care. When validated, a “simplified CAC” can facilitate a standardized clinical assessment tool in clinical practice.     

Abnormal Myocardial Dietary Fatty Acid Metabolism and Diabetic Cardiomyopathy

Patients with diabetes are at very high risk of hospitalization and death from heart failure. Increased prevalence of coronary heart disease, hypertension, autonomic neuropathy, and kidney failure all play a role in this increased risk. However, cardiac metabolic abnormalities are now recognized to play a role in this increased risk. Increased reliance on fatty acids to produce energy might predispose the diabetic heart to oxidative stress and ischemic damage. Intramyocellular accumulation of toxic lipid metabolites leads to a number of cellular abnormalities that might also contribute to cardiac remodelling and cardiac dysfunction. However, fatty acid availability from circulation and from intracellular lipid droplets to fuel the heart is critical to maintain its function. Fatty acids delivery to the heart is very complex and includes plasma nonesterified fatty acid flux as well as triglyceride-rich lipoprotein-mediated transport. Although many studies have shown a cross-sectional association between enhanced fatty acid delivery to the heart and reduction in left ventricular function in subjects with prediabetes and diabetes, these mechanisms change very rapidly during type 2 diabetes treatment. The present review focuses on the role of fatty acids in cardiac function, with particular emphasis on the possible role of early abnormalities of dietary fatty acid metabolism in the development of diabetic cardiomyopathy.