Sex Considerations in Aneurysm Formation,Progression, and Outcomes

Aneurysm formation is a complex multifactorial process with both genetic and environmental influences. Over recent years, there has been increasing recognition of sex-specific differences regarding the prevalence and natural history of cardiovascular diseases in the population. In particular, there is a growing body of evidence showing that aneurysm behaviour differs based on sex. Although most types of aneurysms are more common in men, their growth rates and outcomes are worse in women. This fact raises attention about potential underlying differences in the arteries of men and women that may contribute to differences in aneurysm prevalence and outcomes. There are complex biochemical and mechanical mechanisms at play that contribute to vascular health. Furthermore, many studies have suggested potential differences in the hormonal milieu and underlying arterial anatomy between men and women. Based on the data reviewed in this article, assessment of the underlying pathophysiology of aneurysms in women might prove clinically useful regarding prevention, early detection, and management of aneurysms in women. Sex-specific research, screening, and treatment guidelines for aneurysm disease should be introduced to reflect the differing natural history of these diseases in men and women.     

The State of Affairs for Cardiovascular Health Research in Indigenous Women in Canada: A Scoping Review

Cardiovascular disease (CVD) is the leading cause of death among Indigenous peoples in Canada. As rates of CVD rise, the impacts among the growing population of Indigenous women will emerge as an important health issue. The objective of this scoping review was to advance the state of knowledge about cardiovascular health research in Indigenous women in Canada. Five databases and grey literature (non–peer reviewed works) were searched to identify all studies that reported on the prevalence, pathophysiology, diagnosis, treatment, or interventions for CVD among adult Indigenous women in Canada, including First Nations, Métis, and Inuit. Searching identified 3194 potential articles; 61 of which were included. The most commonly researched topics were the prevalence of CVD, hypertension, and dyslipidemia. Rates of CVD and associated mortality among Indigenous women appear to have surpassed those of their nonindigenous counterparts. Very little research has examined the pathophysiology, diagnosis, and treatment of CVD. Gaps in the research identified the need for sex-based analyses, comparison with nonindigenous women, comprehensive longitudinal data, assessment of diagnosis criteria, development and evaluation of cardiovascular health interventions, and a better understanding of the role of culture and traditions in the prevention and treatment of CVD among Indigenous women. Although comprehensive CVD data are lacking, rates of CVD among Indigenous women in Canada are rising and are nearing or surpassing those of nonindigenous women. This review serves as a call to action to seek further research on the pathophysiology, diagnosis, and treatment of CVD among Indigenous women from across Canada.     

Profound Vasoplegia During Sacubitril/Valsartan Treatment After Heart Transplantation

Vasoplegia occurs in up to 16% of patients who undergo heart transplantation (HT) and is associated with significant morbidity and mortality. We present a case of a 61-year-old man with ischemic cardiomyopathy receiving sacubitril/valsartan (Entresto; Novartis, Cambridge, MA) who developed profound hypotension after HT. He was treated with intravenous methylene blue and high-dose vasopressors, but developed acute kidney injury requiring dialysis and a prolonged stay in the intensive care unit. This case supports a potent vasodilatory effect of sacubitril/valsartan, and if confirmed by other studies, might warrant consideration for withholding treatment while awaiting HT, particularly in patients with risk factors for vasoplegia.     

Optimizing Risk Stratification and Noninvasive Diagnosis of Ischemic Heart Disease in Women

Ischemic heart disease (IHD) is an important and previously underappreciated cause of significant morbidity and mortality in women. Key differences exist in the pathophysiology, sex-specific risk factors, and clinical presentation in women compared with men, which influence diagnostic accuracy and utility of pretest risk assessments and noninvasive testing. Women are disproportionately affected by ischemia from microvascular dysfunction as evidenced by having less obstructive coronary artery disease on angiography, contributing to the challenge in diagnosis and prognosis of IHD in women via conventional methods, which tend to emphasize detection of epicardial stenoses. In this article, we review the utility, evidence for, and challenges of currently available risk assessments and noninvasive cardiac diagnostic tests in women. We propose an approach to investigation of the symptomatic woman with suspected IHD and selection of the appropriate testing modality. Finally, we explore opportunities for future research and highlight the urgent need for updated, evidence-based, Canadian guidelines specific to women with IHD.     

Characterization of Low-Voltage Areas in Patients With Atrial Fibrillation: Insights From High-Density Intracardiac Mapping

Background

There is limited data on the scar burden in patients with atrial fibrillation (AF). In this study, we sought to evaluate the presence and extent of an abnormal left atrial (LA) substrate in patients with paroxysmal or persistent AF.

Decision Support Tools,Systems, and Artificial Intelligence in Cardiac Imaging

Noninvasive cardiac imaging is widely used for the diagnosis and management of cardiac patients. The increasing demand for cardiac imaging begins to exceed the number of available interpreting physicians, leaving less time to interpret studies. In addition, the busy clinician is facing the increasingly daunting task of keeping abreast of current medical advancements and the ongoing changes in disease diagnosis and therapy. Committing to memory and recalling such large volumes of information is challenging and is responsible for difficulties in adopting the rapid changes in imaging practice, and is likely partially responsible for errors in patient diagnosis and management. Diagnostic errors rank high in the cause of death in the United States, and are more common than any other medical error and are responsible for most malpractice claims. Most of these errors are related to cognitive errors. The use of artificial intelligence systems that can serve as complementary methods to assist humans with decision making can potentially prevent these errors. The past decades witnessed the development and integration of these tools, which can assist physicians with image interpretation. These tools work to optimize image quality for better visualization and accompany all imaging modalities, starting from patient selection for the appropriate test, patient preparation, image acquisition, processing, and finally interpretation. Current and future directions for technologies that support cardiac imaging physicians are discussed in this review.     

Diffuse Subepicardial Late Gadolinium Enhancement After Heart Transplant: A Potentially Ominous Finding

Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging has prognostic utility in populations with cardiac disease, including heart transplant (HT) recipients. The etiology of specific LGE patterns and their correlation with outcomes after HT are unclear. Antibody-mediated rejection and cardiac allograft vasculopathy are major causes of death, and their evaluation remains challenging. We report identical diffuse subepicardial LGE in 2 highly allosensitized HT recipients who developed allograft failure. We postulate this LGE pattern may be related to antibody-mediated rejection and cardiac allograft vasculopathy, and portends poor outcomes. These cases illustrate a potential role of cardiac magnetic resonance for antibody-mediated rejection evaluation and risk stratification.     

Double-Valve Surgery After Cardiac Retransplantation

We provide an update on Canada’s first neonatal heart transplant recipient who, after cardiac retransplantation, underwent a mitral valve replacement and tricuspid valve repair. Twenty-seven years after his initial heart surgery and 13 years after his most recent transplant, this patient developed heart failure with severe mitral regurgitation secondary to a calcified mitral valve. The patient was highly sensitized with no evidence of allograft rejection; therefore, mitral and tricuspid surgery was performed. The patient did well perioperatively and remains well 18 months after surgery. To our knowledge, this novel case represents the first double-valve surgery in a patient who underwent cardiac retransplantation.     

The Impact of Cardiac Rehabilitation on Mental and Physical Health in Patients With Atrial Fibrillation: A Matched Case-Control Study

Background

Patients with atrial fibrillation (AF) experience symptom burden, exercise intolerance, weight gain, poor mental health, and diminished quality of life (QoL). Cardiac rehabilitation (CR) is recommended for patients with heart disease, and its benefits are well established, yet clinical guidelines for patients with AF do not include the referral to CR.

Effects of Riociguat on Right Ventricular Remodelling in Chronic Thromboembolic Pulmonary Hypertension Patients: A Prospective Study

Background

The effects of riociguat treatment on right ventricular (RV) metabolism, perfusion, and output in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are unknown. In this study, RV changes associated with riociguat therapy were investigated.

Coronary Surgery in Women and the Challenges We Face

This review was undertaken to understand the dynamics that have shaped our current treatment of women who undergo coronary artery bypass grafting (CABG) and summarize the current literature on surgical revascularization in women. There has been improved access to CABG over the past several decades. Despite this, compared with men, CABG in women involves fewer grafts and less frequent use of arterial grafts, the latter having improved long-term patency compared with saphenous vein grafts. We attempt to determine whether the adverse clinical profile of women, when referred for CABG is responsible for this finding. Female coronary anatomy and pathophysiology are reviewed and an attempt is made to understand how this might affect decisions of selection and outcome measures post CABG. We review the short-term, long-term, and quality of life outcomes in women. These data are taken from large databases, as well as from more recent publications. Randomized controlled trial data and meta-analytic data are used when available. Differential use of and outcomes of surgical strategies, including off-pump CABG and total arterial revascularization, are contrasted with those in men. This review shows that there continues to be widespread differences in surgical approach to coronary artery disease in female vs male patients. We provide evidence suggestive of the existence of issues specific to women that affect selection for surgical procedures and outcomes in women. More work is required to understand the reason for these differences and how to optimize sex-specific outcomes.     

Feasibility and Reliability of Nonexpert POCUS for Cardiovascular Preparticipation Screening of Varsity Athletes: The SHARP Protocol

Background

Point of care ultrasound (POCUS) is a potential adjunctive cardiovascular preparticipation screening modality for young competitive athletes. A novel cardiac POCUS screening protocol, Screening the Heart of the Athlete Research Program (SHARP), was developed for nonexpert examiners to assess common structural etiologies associated with sudden cardiac arrest/death (SCA/D).

Simplified Canadian Definition for Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal codominant lipoprotein disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease. Definitions for FH rely on complex algorithms that are on the basis of levels of total or LDL-C, clinical features, family history, and DNA analysis that are often difficult to obtain. We propose a novel simplified definition for FH. Definite FH includes: (1) elevated LDL-C (≥ 8.50 mmol/L); or (2) LDL-C ≥ 5.0 mmol/L (for age 40 years or older; ≥ 4.0 mmol/L if age younger than 18 years; and ≥ 4.5 mmol/L if age is between 18 and 39 years) when associated with at least 1 of: (1) tendon xanthomas; or (2) causal DNA mutation in the LDLR, APOB, or PCSK9 genes in the proband or first-degree relative. Probable FH is defined as subjects with an elevated LDL-C (≥ 5.0 mmol/L) and the presence of premature atherosclerotic cardiovascular disease in the patient or a first-degree relative or an elevated LDL-C in a first-degree relative. LDL-C cut points were determined from a large database comprising > 3.3 million subjects. To compare the proposed definition with currently used algorithms (ie, the Simon Broome Register and Dutch Lipid Clinic Network), we performed concordance analyses in 5987 individuals from Canada. The new FH definition showed very good agreement compared with the Simon Broome Register and Dutch Lipid Clinic Network criteria (κ = 0.969 and 0.966, respectively). In conclusion, the proposed FH definition has diagnostic performance comparable to existing criteria, but adapted to the Canadian population, and will facilitate the diagnosis of FH patients.     

The Next Generation of Physician-Scientists: Adapting to Academic Cardiology in the 21st Century

More than 3 decades ago, Wyngaarden and Gill first warned of the challenges facing physician-scientists in their seminal papers “The Clinical Investigator as an Endangered Species” and “The End of the Physician-Scientist.” In the years since these papers were published, there has been expansion of stage I-II preclinical research focusing on discovery and exploratory studies. Expansion has often come at the expense of physician-scientists whose traditional role has been to bridge the gap between early preclinical research (stage I-II) and clinical trials (stage IV). Consequently, a paradigm shift has occurred, and increasing pressure has been placed on physician-scientists to choose between clinical practice and fundamental research. This shift is particularly concerning in the field of cardiovascular medicine, where the ubiquitous nature and clinical significance of cardiovascular disease make the role of the translational scientist essential. The challenges facing academic cardiologists have then further been amplified by the necessity not only to maintain clinical competence but also to maintain competence in highly technical fields with rapidly advancing technology. Potential solutions to these problems include increasing support from postgraduate training programs, increased participation of trainees in physician-scientist development programs, and recognition of the pivotal role physician-scientists play in translational research by funding agencies. Although the physician-scientist remains an endangered species, multifaceted solutions with a focus on collaboration among institutions, training programs, and funding agencies have the potential to maximize efficiency in biomedical research and successfully translate scientific discoveries from bench to bedside.