Managing Ischemic Heart Disease in Women: Role of a Women's Heart Center.

PURPOSE OF REVIEW: Heart centers for women (HCW) were developed due to the rising cardiovascular morbidity and mortality in women in the United States in the early 1990s. Our review encompasses the epidemiology, risk factors, diagnostic strategies, treatments, and the role of HCW in managing women with ischemic heart disease (IHD). RECENT FINDINGS: HCW use a multidisciplinary team to manage women with IHD. Due to the paucity of randomized controlled trials investigating various manifestations of IHD, some treatments are not evidence-based such as those for coronary microvascular dysfunction and spontaneous coronary artery dissection. Sex-specific risk factors have been identified and multimodality cardiac imaging is improving in diagnosing IHD in women. Treatments are being studied to help improve symptoms and outcomes in women with IHD. There has been progress in the care of women with IHD. HCW can be instrumental in treating women with IHD, doing research, and being a source of research study participants.

N-Terminal pro-B-type natriuretic peptide and coronary microvascular dysfunction in women with preserved ejection fraction: A report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study.

BACKGROUND: Women with symptoms and signs of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD), often have coronary microvascular dysfunction (CMD), and are at risk of future heart failure with preserved ejection fraction (HFpEF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used to evaluate HF and myocardial ischemia. Relationships between NT-proBNP and CMD are not well defined in this population. METHODS: We evaluated resting NT-proBNP levels in 208 women with symptoms and signs of ischemic heart disease, preserved LVEF and no obstructive CAD undergoing clinically indicated invasive coronary flow reserve (CFR) as a measure of CMD-related ischemia and resting left ventricular end-diastolic pressure (LVEDP). Chi-square testing was used for categorical variables and ANOVA or Kruskal-Wallis tests were used for continuous variables. RESULTS: Overall, 79% had an elevated resting LVEDP, and mean NT-proBNP was 115 ± 158 pg/mL. NT-proBNP levels correlated directly with age (r = 0.28, p = <0.0001), and indirectly with body mass index (r = -0.21, p = 0.0006), but did not independently associate with CFR. When stratified by NT-proBNP thresholds, higher NT-proBNP was initially associated with lower CFR, which did not persist with adjustment for multiple testing (p = 0.01 and 0.36, respectively). CONCLUSION: Among women with symptoms and signs of ischemia, preserved LVEF, no obstructive CAD, and undergoing clinically indicated functional coronary angiography (FCA) for suspected CMD, while a majority had elevated resting LVEDP, we failed to find an independent association between CFR and NT-proBNP, although stratified clinical thresholds may relate to lower CFR. Further work is needed to investigate if these findings support the hypothesis that CMD-related ischemia may be a precursor to HFpEF.

Not typical angina and mortality in women with obstructive coronary artery disease: Results from the Women's Ischemic Syndrome Evaluation study (WISE).

BACKGROUND: Women frequently present with symptoms not typical of angina (NTA) making ischemic heart disease recognition, diagnosis and treatment challenging. We compared mortality in women with obstructive coronary artery disease (CAD) with NTA vs typical angina (TA). METHODS: We studied 326 Women's Ischemia Syndrome Evaluation (WISE) participants undergoing coronary angiography for suspected myocardial ischemia with core-lab measured obstructive CAD. TA was defined as sub-sternal chest pain precipitated by physical exertion or emotional stress and relieved with rest or nitroglycerin; NTA did not meet criteria for TA. The women were followed for non-fatal events and death for a median of 5.9 and 9.6 years respectively. Multivariate cox proportional hazards regression determined relations to events. RESULTS: Overall, 115 (35%) of the women had TA. Baseline demographics, risk factors or additional symptom characteristics were similar between the two angina groups. Non-fatal events did not differ between groups. Women with NTA had a higher mortality compared to TA women (36% vs 26%, respectively, p = 0.047). Despite adjustment for additional major risk variables, NTA was an independent predictor of mortality compared to TA with a hazard ratio of 1.73 (95% Confidence interval: 1.04, 2.89). CONCLUSIONS: Among women with suspected ischemia undergoing coronary angiography with obstructive CAD, NTA was more common than TA, and predicted a higher longer-term mortality. Further investigation is needed to confirm these results, and investigate potential explanations for the higher mortality observed in women with NTA women, including lower recognition or action in the setting of obstructive CAD.

Sex and gender medicine in physician clinical training: results of a large, single-center survey.

BACKGROUND: "Sex and Gender Medicine" is a novel medical discipline that takes into account the effects of sex and gender on the health of women and men. The Institute of Medicine in the USA declared in its 2001 and 2010 statements that being a woman or a man significantly impacts the course of diseases, and therefore, this fact must be considered in diagnosis and therapy. We evaluated the representation of Sex and Gender Medicine in clinical training at Cedars-Sinai Medical Center, a large, tertiary, non-profit, academic medical training center in the Western United States. METHODS: Post-graduate physician trainees (residents and fellows) in all medical and surgical departments (medicine, surgery, OB-GYN, pediatrics, anesthesiology, pathology, urology, electrophysiology, pulmonary critical care, cardiology, women's heart, medical genetics, radiology, neurosurgery, and radiation oncology) were surveyed online; 80 (55 and 45 % female and male residents, respectively) out of 890 physicians (9 % response rate) responded to questions regarding sex and gender-based medicine. RESULTS: Seventy percent of post-graduate physician trainees indicated that gender medicine concepts are never or only sometimes discussed/presented in their training program. Slightly greater than 70 % of the trainees indicated that gender concepts are never or only sometimes incorporated into didactic lectures or clinical teaching. However, more than 65 % felt that gender medicine concepts are important, and 60 % agreed that gender medicine curriculum should be implemented and taught in their clinical program. CONCLUSIONS: Current physician trainees endorse both a current lack of and need for Sex and Gender Medicine clinical training.

Heart failure hospitalization in women with signs and symptoms of ischemia: A report from the women's ischemia syndrome evaluation study.

BACKGROUND: Women with signs and symptoms of ischemia, no obstructive coronary artery disease, and preserved left ventricular ejection fraction enrolled in the National Heart Lung and Blood Institute (NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study have an unexpectedly high rate of subsequent heart failure (HF) hospitalization. We sought to verify and characterize the HF hospitalizations. METHODS: A retrospective chart review was performed on 223 women with signs and symptoms of ischemia, undergoing coronary angiography for suspected coronary artery disease followed for 6±2.6years. Data were collected from a single site in the WISE study. RESULTS: At the time of study enrollment, the women were 57±11years of age, all had preserved left ventricular ejection fraction, and 81 (36%) had obstructive CAD (defined as >50% stenosis in at least one epicardial artery). Among the 223 patients, 25 (11%) reported HF hospitalizations, of which 14/25 (56%) had recurrent HF hospitalizations (>2 hospitalizations). Medical records were available in 13/25 (52%) women. Left ventricular ejection fraction was measured in all verified cases and was found to be preserved in 12/13 (92%). HF hospitalization was not related to obstructive CAD. CONCLUSION: Among women with signs and symptoms of ischemia undergoing coronary angiography for suspected obstructive CAD, HF hospitalization at 6-year follow-up was predominantly characterized by a preserved ejection fraction and not associated with obstructive CAD.

Cardiac magnetic resonance imaging for myocardial perfusion and diastolic function-reference control values for women.

Angina, heart failure with preserved ejection fraction (HFpEF) and coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease (CAD) are more common in women and are associated with adverse cardiovascular prognosis. Cardiac magnetic resonance imaging (CMRI) is established for assessment of left ventricular (LV) morphology and systolic function and is increasingly used to assess myocardial perfusion and diastolic function. Indeed, stress CMRI allows measurement of myocardial perfusion reserve index (MPRI) using semi-quantitative techniques, and quantification of LV volumetric filling patterns provides valuable insight into LV diastolic function. The utility of these two techniques remains limited, because reference control values for MPRI and LV diastolic function in asymptomatic middle-aged, women have not previously been established. To address this limitation, we recruited twenty women, without clinical cardiovascular disease or cardiovascular risk factors, with normal maximal Bruce protocol exercise treadmill testing. Subjects underwent CMRI (1.5 tesla) using a standardized protocol of adenosine stress and rest perfusion and LV cinematic imaging. Commercially available with automated CMRI segmentation was used for calculation of MPRI, LV filling profiles, and ejection fraction. Mean age was 54±9 years and mean body mass index was 25±4 kg/m(3). The exercise treadmill testing results demonstrated a normotensive group with normal functional capacity and hemodynamic response. We report reference control values for semi-quantitative MPRI as well as measures of LV systolic and diastolic function including ejection fraction, stroke volume, peak filling rate (PFR), PFR adjusted for end-diastolic volume (EDV) and stroke volume, time to PFR, and EDV index. The data herein provide reference values for MPRI and diastolic function in a cohort of healthy, middle-aged of women. These reference values may be used for comparison with a variety of patient populations, including women with CMD and HFpEF.

Corneal nerves in health and disease.

Corneal nerves are responsible for the sensations of touch, pain, and temperature and play an important role in the blink reflex, wound healing, and tear production and secretion. Corneal nerve dysfunction is a frequent feature of diseases that cause opacities and result in corneal blindness. Corneal opacities rank as the second most frequent cause of blindness. Technological advances in in vivo corneal nerve imaging, such as optical coherence tomography and confocal scanning, have generated new knowledge regarding the phenomenological events that occur during reinnervation of the cornea following disease, injury, or surgery. The recent availability of transgenic neurofluorescent murine models has stimulated the search for molecular modulators of corneal nerve regeneration. New evidence suggests that neuroregenerative and inflammatory pathways in the cornea are intertwined. Evidence-based treatment of neurotrophic corneal diseases includes using neuroregenerative (blood component-based and neurotrophic factors), neuroprotective, and ensconcing (bandage contact lens and amniotic membrane) strategies and avoiding anti-inflammatory therapies, such as cyclosporine and corticosteroids.