Coronary artery disease remains a leading cause of morbidity and mortality globally, with chronic total occlusions (CTOs) representing a particularly challenging subset. Percutaneous coronary intervention (PCI) for CTOs has evolved significantly over the years, driven by advancements in equipment, techniques, and operator expertise. However, women have historically been underrepresented in clinical trials and guidelines, leading to a gap in an evidence-based management tailored to their specific needs, including in CTO-PCI. This review aims to explore the nuances of CTO-PCI in women, including anatomic considerations, procedural strategies, and clinical outcomes, with the goal of optimizing their care.

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.

Ischemic heart disease is a major cause of morbidity and mortality in the US, affecting both men and women significantly. The presentation of chest pain is largely similar in female and male patients, but additional non-chest pain symptoms can confound timely diagnosis in women. Management, diagnostic evaluation, and clinical outcomes for patients admitted with chest pain differ significantly between men and women, and understanding of these discrepancies is limited. The objective of this review is to familiarize readers with gender- and sex-specific differences in the presentation, diagnosis, and management of chest pain.

The intestinal microbiome has emerged as a potential contributor to the severity of sickle cell disease (SCD). We sought to determine whether SCD mice exhibit intestinal barrier dysfunction, inflammation, and dysbiosis. Using the Townes humanized sickle cell mouse model, we found a 3‐fold increase in intestinal permeability as assessed via FITC‐dextran (4 kDa) assay in SS (SCD) mice compared to AA (wild type) mice (n = 4, p < 0.05). This was associated with 25 to 50% decreases in claudin‐1, 3, and 15 and zonula occludens‐1 gene expression (n = 8–10, p < 0.05) in the small intestine. Increased Ly6G staining demonstrated more neutrophils in the SS small intestine (3‐fold, n = 5, p < 0.05) associated with increased expression of TNFα, IL‐17A, CXCL1, and CD68 (2.5 to 5‐fold, n = 7–10, p < 0.05). In addition, we observed 30 to 55% decreases in superoxide dismutase‐1, glutathione peroxidase‐1, and catalase antioxidant enzyme expression (n = 7–8, p < 0.05) concomitant to an increase in superoxide (2‐fold, n = 4, p < 0.05). Importantly, all significant observations of a leaky gut phenotype and inflammation were limited to the small intestine and not observed in the colon. Finally, characterization of the composition of the microbiome within the small intestine revealed dysbiosis in SS mice compared to their AA littermates with 47 phyla to species‐level significant alterations in amplicon sequence variants. We conclude that the intestinal barrier is compromised in SCD, associated with decreased gene expression of tight junction proteins, enhanced inflammation, oxidative stress, and gut microbiome dysbiosis, all specific to the small intestine.

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.

This review summarizes current data supporting a minimalist TAVR approach and identifies the need for additional study to optimize TAVR care. The authors discuss future directions of the TAVR landscape and how this necessitates evolution of minimalist care pathways. Transcatheter aortic valve replacement (TAVR) has become a mainstay in the treatment of aortic stenosis since the initial procedure in 2002. Recently, attention has shifted to TAVR optimization and the minimalist approach with a focus on minimizing procedural sedation, protocolization of perioperative management, and prioritization on early discharge. This approach has been shown to be safe and reduce procedure time, length of stay, and overall cost for hospital systems. The minimalist care pathway avoids general anesthesia, shortens procedure time and length of stay, and reduces cost without changing mortality or readmission rates at 30 days. A variety of protocols have been proposed without a clear consensus on specific components or patient eligibility. There is a continued need for data regarding patient risk stratification, valve selection, and discharge strategy as TAVR becomes increasingly common.

Cardiac rehabilitation(CR) has known proven benefits in reducing mortality related to cardiovascular disease (CVD), improving quality of life (QoL), and preventing CVD-related readmissions. Despite these known benefits, CR remains underutilized among women relative to men. Disparities exist at the level of referral, enrollment, and program completion. Much is left to be understood regarding the utility of CR in female-predominant CVD such as postpartum cardiomyopathy and Spontaneous Coronary Artery Dissection. This review identifies the benefits of CR for specific populations of women and elucidates on the barriers to CR. We also describe current recommendations to overcome barriers to CR in women.

Background Statins have anti-inflammatory and immunomodulatory effects that may reduce the severity of coronavirus disease 2019 (COVID-19), in which organ dysfunction is mediated by severe inflammation. Large studies with diverse populations evaluating statin use and outcomes in COVID-19 are lacking. Methods and results We used data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease (CVD) Registry to evaluate the associations between statin use and outcomes. Prior to admission, 42% of subjects (n = 4,449) used statins (7% on statins alone, 35% on statins plus anti-hypertensives). Death (or discharge to hospice) occurred in 2,212 subjects (21%). Outpatient use of statins, either alone or with anti-hypertensives, was associated with a reduced risk of death (adjusted odds ratio [aOR] 0.59, 95% CI 0.50-0.69), adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications by logistic regression. In propensity-matched analyses, use of statins and/or anti-hypertensives was associated with a reduced risk of death among those with a history of CVD and/or hypertension (aOR 0.68, 95% CI 0.58-0.81). An observed 16% reduction in odds of death among those without CVD and/or hypertension was not statistically significant. Conclusions Patients taking statins prior to hospitalization for COVID-19 had substantially lower odds of death, primarily among individuals with a history of CVD and/or hypertension. These observations support the continuation and aggressive initiation of statin and anti-hypertensive therapies among patients at risk for COVID-19, if these treatments are indicated based upon underlying medical conditions.

Significant residual mitral regurgitation (MR) after left ventricular assist device (LVAD) implantation has been associated with increased morbidity and mortality. The effect of cannula position on improvement of preexisting MR has yet to be evaluated. Consecutive patients who underwent centrifugal LVAD implantation with >mild preoperative MR and without concomitant mitral repair were reviewed. Left ventricular assist device position was determined by the angle between actual and ideal inflow cannula on computed tomography. The magnitudes of angles (anterior and lateral angle) were added to form an LVAD position assessment (LVADpa). Mitral regurgitation was numerically classified, and improvement in MR was determined by difference in MR preoperatively to MR >1 month postoperatively with a median of 162 (interquartile range: 78-218) days. The primary analysis examined the relationship between LVADpa and postoperative MR. Forty-one patients were identified with >mild preoperative functional MR. Mean age was 51 ± 13 years with an ejection fraction of 16 ± 4%. Overall, MR improved from moderate-severe preoperatively to mild postoperatively (p < 0.001). On multivariable analysis, higher LVADpa deviation was associated with greater postoperative MR (odds ratio [OR] = 2.29, p = 0.005) and higher 1-month pulsatility index was associated with lower postoperative MR (OR = 0.47, p = 0.011). Inflow cannula position during centrifugal LVAD implantation is an important determinant of postoperative MR.

OBJECTIVE:Despite improvement in outcomes after left ventricular assist device (LVAD) implantation over the past 2 decades, high-risk recipients continue to have a prohibitive rate of morbidity and mortality. We hypothesized that a less invasive approach to LVAD implantation would be associated with improved survival compared to a conventional approach in this high-risk cohort.METHODS:All consecutive LVAD recipients (2013 to 2017) that underwent centrifugal LVAD implantation were retrospectively reviewed. Patients were classified as high-risk if INTERMACS 1 or required temporary VAD/venoarterial extracorporeal membrane oxygenation prior to durable VAD implantation. Patients were stratified into 3 groups: left thoracotomy with hemi-sternotomy (LTHS) high-risk, conventional sternotomy (CS) high-risk, and non-high-risk. The primary outcome was 1-year survival.RESULTS:A total of 57 patients (LTHS high-risk: 11, CS high-risk: 12, non-high-risk: 34) were identified. Preoperative right ventricular failure scores, HeartMate-II mortality scores, and end-organ dysfunction were similar between the 2 high-risk groups. While operative time was similar between the 3 groups, cardiopulmonary bypass time was significantly shorter in the LTHS high-risk group compared to other groups. There was a trend toward decreased intensive care unit length of stay and ventilator time in LTHS high-risk compared to CS high-risk patients. Moreover, between these 2 groups, there was a significant decrease in temporary right VAD support (50% vs 0%, P = 0.014), and 1-year survival was significantly higher in the LTHS group (42% vs 91%, P = 0.025).CONCLUSIONS:Less invasive LVAD implantation appears to be associated with improved survival compared to conventional LVAD implantation in high-risk patients.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of cardiovascular morbidity and mortality. Impaired left ventricular (LV) global longitudinal strain (GLS) can be a sign of subclinical cardiac dysfunction even in patients with otherwise preserved ejection fraction (EF). Transmitral early filling velocity to early diastolic strain rate (E/SRe) is a novel measure of LV filling pressure, which is often affected early in cardiac disease. A total of 110 ADPKD patients not on dialysis were included in this prospective study. All patients underwent an extensive echocardiographic examination including two-dimensional speckle tracking. GLS and strain rates were measured. The distribution of GLS and E/SRe was determined and patient characteristics were compared by median levels of GLS (− 17.8%) and E/SRe (91.4 cm). Twenty healthy participants were included as control group. There was a significantly worse GLS in the ADPKD patients (mean: − 17.8 ± 2.5%) compared to the healthy controls (mean: − 21.9 ± 1.9%), p < 0.001. The same was true for E/SRe (mean: 10.0 ± 0.3 cm) compared to the control group (mean: 6.5 ± 0.3 cm), p < 0.001. In simple logistic regression, male gender (OR: 4.74 [2.10–10.71], p < 0.001), fasting glucose (odds ratio (OR) 1.05 [1.01–1.10], p = 0.024), htTKV (OR: 1.07 [1.01–1.13], p = 0.013), HDL cholesterol (OR: 0.97 [0.94, 0.996], p = 0.025), triglycerides (OR: 1.01 [1.00–1.02], p = 0.039), hemoglobin (OR: 1.50 [1.11–2.04], p = 0.009), and β-blocker use (OR: 1.07 [1.01, 1.13], p = 0.013) were all associated with higher GLS. After multivariate logistic regression with backward model selection, only male gender (OR: 5.78 [2.27–14.71], p < 0.001) and β-blocker use (OR: 14.00 [1.60, 122.51], p = 0.017) remained significant. In simple logistic regression models, BMI (OR: 1.11 [1.02–1.20], p = 0.015), systolic blood pressure (OR: 1.03 [1.00–1.06], p = 0.027) and β-blocker use (OR: 17.12 [2.15–136.20], p = 0.007) were associated with higher E/SRe - a novel measure of left ventricular filling pressure. After backward elimination, only β-blocker use (OR: 17.22 [2.16, 137.14], p = 0.007) remained significant. Higher GLS and E/SRe are common in ADPKD patients, even in patients with preserved eGFR and normal left ventricular EF. GLS and E/SRe may aid in cardiovascular risk stratification in patients with ADPKD as they represent early markers of cardiac dysfunction.

OBJECTIVES Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation continues to be a morbid complication. In this study, we hypothesized that a less invasive approach to implantation would preserve RV function relative to a conventional sternotomy (CS) approach. METHODS All patients (2013-2017) who underwent LVAD implantation were reviewed. Patients were stratified by surgical approach: less invasive left thoracotomy with hemi-sternotomy (LTHS) and CS. The primary outcome was severe RV failure. RESULTS Eighty-three patients (LTHS: 37, CS: 46) were identified. The median Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score was significantly worse in the LTHS compared to the CS cohort, and there was a trend towards higher RV failure scores and HeartMate II mortality scores. Preoperative RV dysfunction, in pulmonary artery pulsatility index and RV stroke work index were similar between the 2 groups. Though operative time did not significantly differ between the 2 groups, cardiopulmonary bypass time was significantly shorter in the LTHS group (61 vs 95 min, P < 0.001). The incidence of postoperative severe RV failure was significantly reduced in the LTHS group (16% vs 39%, P = 0.030), along with the need for temporary right ventricular assist device (3% vs 26%, P = 0.005). Improvement in RV function, along with a change in pulmonary artery pulsatility index, was significantly greater in the LTHS cohort. There was a trend towards improved Kaplan-Meier 1-year survival in the LTHS cohort (91% vs 56%, P = 0.056). CONCLUSIONS In this cohort, less invasive LVAD implantation appears to be associated with reduced postoperative RV failure, and equivalent or improved survival compared to conventional LVAD implantation.

Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. In human atherosclerotic lesions, CD163(+) macrophages were associated with plaque progression, microvascularity, and a high level of HIF1 alpha and VEGF-A expression. We observed irregular vascular endothelial cadherin in intraplaque microvessels surrounded by CD163(+) macrophages. Within these cells, activation of HIF1 alpha. via inhibition of prolyl hydroxylases promoted VEGF-mediated increases in intraplaque angiogenesis, vascular permeability, and inflammatory cell recruitment. CD163(+) macrophages increased intraplaque endothelial VCAM expression and plaque inflammation. Subjects with homozygous minor alleles of the SNP rs7136716 had elevated microvessel density, increased expression of CD163 in ruptured coronary plaques, and a higher risk of myocardial infarction and coronary heart disease in population cohorts. Thus, our findings highlight a nonlipid-driven mechanism by which alternative macrophages promote plaque angiogenesis, leakiness, inflammation, and progression via the CD163/HIF1 alpha/VEGF-A pathway.