A systematic review of present and future pharmaco-structural therapies for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.

Transient left bundle branch block associated with very high coronary artery calcium: a case report.

Coronary artery calcium (CAC) is the measure of subclinical coronary artery atherosclerosis most strongly associated with atherosclerotic cardiovascular disease (ASCVD) risk. However, CAC is rarely reported in the inpatient setting to guide chest pain management. We present a case of very high CAC in a 64-year-old woman with hypertension, type 2 diabetes, and hyperlipidemia presenting with dyspnea. Initial electrocardiogram (ECG) demonstrated normal conduction with a heart rate of 76 beats/min, but new T-wave inversions in V1-V4 and a high-sensitivity troponin-I (hsTnI) value of 6 ng/L (normal < 6 ng/L). Repeat ECG in the emergency department showed normal sinus rhythm (heart rate of 80 beats/min); however, it subsequently demonstrated a left bundle branch block (LBBB) with a repeat hsTnI of 7 ng/L. Stress testing with pharmacologic single-photon emission computerized tomography did not show scintigraphic evidence of ischemia but noted extensive CAC and a concern for balanced ischemia. Subsequent coronary computed tomography angiography (CCTA) showed nonobstructive disease and a total Agatston CAC score of 1262. Invasive evaluation with left heart catheterization was deferred given the patient's unchanged symptoms and CCTA findings. Statin therapy was intensified and aspirin, metoprolol succinate, and antihypertension therapies were continued. Initiation of glucose-lowering therapy and lipoprotein(a) testing was strongly recommended on follow-up. Our case suggests that CAC ⩾ 1000 may be incidentally associated with transient LBBB during the workup of coronary artery disease. Here, we specifically show that functional testing that incorporates measurement of CAC burden can help to improve ASCVD-preventive pharmacotherapy initiation and intensification beyond the identification of obstructive disease alone.

Cardiovascular Disease in Women Update: Ischemia, Diagnostic Testing, and Menopause Hormone Therapy.

OBJECTIVE: This update will address 3 areas specifically that are essential to improving cardiovascular outcomes for women. METHODS: The current literature has been reviewed and three important areas of cardiovascular care in women are highlighted. First is that even though women and men share many traditional risk factors for ischemic heart disease, several of these risk factors affect women disproportionately when it comes to CVD risk and events. There are also unique sex-specific risk factors for women and risk factors that are more common in women than in men. Adverse outcomes of pregnancy and hypertensive disorders of pregnancy are associated with an increased long-term risk of CVD and events. At menopause, cardiovascular risks increase, and lipids become unfavorable. Second is that diagnostic testing for ischemic heart disease presents different specificities and sensitivities between men and women and testing should be determined according to what is best and safest for women. Third is that currently, menopause hormone therapy is approved by the U.S. Food and Drug Administration for the treatment of vasomotor and genitourinary symptoms, prevention of osteoporosis, and estrogen replacement in the setting of surgical menopause, hypogonadism, or premature ovarian insufficiency. It is not recommended for the primary or secondary prevention of CVD and not recommended for women with high atherosclerotic CVD risk. RESULTS: Cardiovascular disease (CVD) remains the most common cause of death in women in the United States despite tremendous improvements in cardiovascular care for men and women. The prevention of CVD in women with early detection and implementation of preventive therapies before atherosclerotic CVD develops is critical to improving outcomes for women.

Cardiovascular risk in menopausal women and our evolving understanding of menopausal hormone therapy: risks, benefits, and current guidelines for use.

Women are at increased risk for cardiovascular disease (CVD) compared with men. While traditional risk factors for CVD seem to disproportionately affect women and contribute to this disparity, increased prevalence of CVD at midlife calls into question the contribution of menopause. Given the potential role that declining hormone levels play in this transition, menopause hormone therapies (MHT) have been proposed as a strategy for risk factor reduction. Unfortunately, trials have not consistently shown cardiovascular benefit with use, and several describe significant risks. Notably, the timing of hormone administration seems to play a role in its relative risks and benefits. At present, MHT is not recommended for primary or secondary prevention of CVD. For women who may benefit from the associated vasomotor, genitourinary, and/or bone health properties of MHT, CVD risks should be taken into account prior to administration. Further research is needed to assess routes, dosing, and formulations of MHT in order to elucidate appropriate timing for administration. Here, we aim to review both traditional and sex-specific risk factors contributing to increased CVD risk in women with a focus on menopause, understand cardiovascular effects of MHT through a review of several landmark clinical trials, summarize guidelines for appropriate MHT use, and discuss a comprehensive strategy for reducing CV risk in women.

Atrial Fibrillation in Women: Risks and Management.

Atrial fibrillation (AF) is one of the most commonly occurring arrhythmias and a major modifiable risk factor for stroke, especially in women. While its prevalence is similar in both men and women, women unfortunately face a greater intrinsic AF-related risk of stroke than men do. This is likely one of the reasons that more women than men die from strokes, in addition to experiencing more new and recurrent strokes. Therefore, in women especially, it is imperative to diagnose and treat AF as early as possible. While its unreliable symptom profile and possible intermittent nature can make AF difficult to detect, proactive identification of risk factors and improved detection methods can help. Additionally, the use of risk stratification schemes for anticoagulant therapy, along with the efficacy of nonvitamin K antagonist anticoagulants can enable appropriate therapy to prevent stroke occurrence.