Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.

Increased prescription dose for large vessel intravascular brachytherapy.

BACKGROUND: Most randomized studies testing the effectiveness of IVBT were limited to vessels less than 4 mm diameter. In fact, it is now common to treat vessels larger than 4 mm. Accordingly, the authors instituted a prescription dose increase to 34 Gy at 2 mm from source center for vessels greater than 4.0 mm. The increase in prescription dose to 34 Gy at 2 mm from center is substantial, being 50% higher than the conventional maximum of 23 Gy. AIM: To take a close look at group of patients treated to 34 Gy, and for whom follow-up angiograms are available. METHODS: Ten patients treated for ISR with a prescription dose of 34 Gy and for whom follow-up angiograms were available were studied. Beta-radiation brachytherapy was performed with a Novoste Beta-Cath System using a strontium-90 (beta) source (Best Vascular, Springfield, VA). Source lengths of 40 or 60 mm were used. A dose of 34 Gy was prescribed at 2 mm from the source center. RESULTS: Patients were re-catheterized from 2 to 21 months (median: 16 months) following IVBT, all for symptoms suggested of restenosis. All patients had some degree of ISR of the target vessel, but no IVBT-treated vascular segment showed angiographic signs of degeneration, dissection or aneurysm. CONCLUSION: The authors' clinical impression, along with detailed review of the 10 cases, suggest that using a 34 Gy prescription dose at 2 mm from source center does not result in increased toxicity.

The Role of Echocardiography in the Evaluation of Pulmonary Arterial Hypertension.

The evaluation of pulmonary arterial hypertension (PAH) requires a multimodality approach that combines invasive and noninvasive imaging studies to ensure accurate diagnosis and classification. Given the complexity of the hemodynamic relationships between the left heart, pulmonary circulation, and right heart, the diagnosis of PAH is often a challenging task. Right heart catheterization is the gold standard for diagnosis, providing the hemodynamic information that defines the disease. Nonetheless, echocardiography continues to be a valuable tool in the approach to the patient with suspected PAH. Echocardiographic assessment generates a wealth of information about the response of the right heart to elevated pulmonary pressures and provides essential diagnostic and prognostic data to the clinician. Numerous measurements can be used to identify alterations in right heart morphology, pressure, and function; although each variable in isolation may have little utility, meaningful information is revealed when multiple parameters are considered together. In this article, we will review the echocardiographic measurements employed in assessment of the right heart and seek to clarify the role of echocardiography in the diagnostic workup of PAH.

Extreme coronary radiation doses from intravascular brachytherapy.

PURPOSE: To evaluate coronary artery integrity after very high radiation doses from intravascular brachytherapy (IVBT) in the setting of source asymmetry. METHODS: Ten patients treated for right coronary artery (RCA) in-stent restenosis (ISR) between 2017 and 2021 and for whom follow-up angiograms were available were identified from departmental records. Procedural angiograms, taken to document source position, were used to estimate vascular wall doses. The 2.5 mm proximal source marker was used to estimate the distance from source center to the media and adventitia. Distances were converted to dose (Gy) using the manufacturers' dose fall-off table, measured in water. Follow-up films were scrutinized for any sign of late vascular damage. RESULTS: The average minimal distance from catheter center to the adjacent media and the adventitia was 0.9 mm (±0.2) mm and 1.4 mm (±0.2), respectively. The average maximum media and adventitial doses adjacent to the source were 75 Gy (±26) and 39 Gy (±14), respectively. Follow-up angiograms were available from 0.6 years to 3.9 years following IVBT (median: 1.6 years). No IVBT-treated vascular segment showed signs of degeneration, dissection or aneurysm. CONCLUSION: IVBT vascular wall doses are frequently far higher than prescribed. The lack of complications in this unselected group of patients gives a modicum of reassurance that raising the prescription dose is unlikely to lead to a sudden appearance of complications.

Responses of mental stress-induced myocardial ischemia to escitalopram treatment: background, design, and method for the Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment trial.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is common in patients with clinically stable coronary heart disease (CHD) and is associated with poor outcomes. Depression is a risk factor of MSIMI. The REMIT trial investigates whether selective serotonin reuptake inhibitor (SSRI) treatment can improve MSIMI. The rationale and outline of the study are described. METHOD: In this single-center randomized clinical trial, adult patients with clinically stable CHD are recruited for baseline mental and exercise stress testing assessed by echocardiography. In addition, psychometric questionnaires are administered, and blood samples are collected for platelet activity analysis. Patients who demonstrate MSIMI, defined by new abnormal wall motion, ejection fraction reduction ≥8%, and/or development of ischemic ST change in electrocardiogram during mental stress testing, are randomized at a 1:1 ratio to escitalopram or placebo for 6 weeks. Approximately 120 patients with MSIMI are enrolled in the trial. The stress testing, platelet activity assessment, and psychometric questionnaires are repeated at the end of the 6-week intervention. The hypothesis of the study is that SSRI treatment improves MSIMI via mood regulation and modification of platelet activity. CONCLUSION: The REMIT study examines the effect of SSRI on MSIMI in vulnerable patients with CHD and probes some potential underlying mechanisms.

Spontaneous coronary artery dissection: Principles of management.

Spontaneous coronary artery dissection (SCAD) is an acute noniatrogenic tear in the coronary arterial wall, leading to disruption of coronary blood flow and myocardial infarction. Previously considered rare, it is now recognized as a common cause of acute coronary syndrome, particularly in young women. Despite growing awareness of this disease, there is a paucity of data on acute and long-term therapy. This review summarizes the existing literature on treatment of SCAD and describes a comprehensive management strategy.

Effect of sialylated O-glycans in pro-brain natriuretic peptide stability.

BACKGROUND: Atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP) are important in regulating a variety of cardiovascular and cellular functions. In cells, these peptides are made as proforms that are converted to mature forms. BNP and its related peptides are biomarkers for the diagnosis of heart failure. In this study, we examined glycosylation in pro-ANP, pro-BNP, and pro-CNP, which may alter their biochemical and metabolic properties. METHODS: Human pro-ANP, pro-BNP, and pro-CNP were expressed in HEK 293 cells and murine HL-1 cardiomyocytes and analyzed by immunoprecipitation and Western blotting. We used deglycosylation enzymes to determine the carbohydrate content on these peptides and examined the effects of inhibiting O-glycosylation on cellular expression and stability of the peptides. RESULTS: In HEK 293 and HL-1 cells, pro-BNP, but not pro-ANP and pro-CNP, from the culture medium had a greater molecular mass than that from cell lysate. Digestion with PNGase F, O-glycosidase, and sialidase A indicated that pro-BNP contained O-glycans but not N-glycans. The O-glycans on pro-BNP had sialic acids at their termini, protecting it from O-glycosidase digestion. In contrast, pro-ANP and pro-CNP contained no detectable amounts of N- or O-glycans. Inhibition of O-glycosylation on pro-BNP did not prevent its expression in the cells. However, partially O-glycosylated pro-BNP was much less stable than fully O- glycosylated pro-BNP. CONCLUSIONS: O-glycosylation is not necessary for pro-BNP expression but important for its stability.