Diagnostic Yield and Clinical Utility of Coronary Angiography Versus Coronary Function Testing in Women With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Approximately 50% of women referred for invasive coronary angiography have angina and nonobstructive coronary arteries, which includes coronary microvascular dysfunction, vasospastic angina, and other vasomotor disorders. We sought to determine the real-world diagnostic yield of invasive coronary angiography and coronary function testing in women with angina and nonobstructive coronary arteries. METHODS AND RESULTS: From 2018 to 2023, we enrolled 198 women who underwent either coronary angiography (CA) alone (n=99) or coronary function testing (CFT; n=99). Mean±SD age was 62±10 years (CA alone) compared with 57±10 years (CFT). Coronary angiography was interpreted as nonobstructive coronary artery disease more frequently after CA alone (79% versus 52%). Of the women who underwent CFT, 82% (N=81) were found to have vasomotor disorders, including coronary microvascular dysfunction (27%), vasospastic angina (32%), mixed coronary microvascular dysfunction/vasospastic angina (16%), endothelial dysfunction (10%; without spasm), elevated resting flow (2%), or symptomatic myocardial bridging (4%). Compared with women undergoing CA alone, medications were changed more frequently after CFT at 24 hours (41% versus 65%; P=0.001) and between 24 hours and 30 days (30% versus 44%; P=0.04) with intensification of antianginal therapy (79% versus 92%; P<0.0001) and increased use of calcium channel blockers (36% versus 63%; P<0.0001). CONCLUSIONS: Our findings demonstrate that women presenting with suspected ischemic heart disease undergoing CA alone only received an anatomic diagnosis, whereas >80% of women undergoing CFT received a specific diagnosis of a coronary vasomotor disorder and greater intensification of antianginal therapy.

Evaluating Ischemic Heart Disease in Women: Focus on Angina With Nonobstructive Coronary Arteries (ANOCA).

Ischemic heart disease (IHD) is common in women, and cardiovascular disease is a leading cause of morbidity and mortality. While obstructive coronary artery disease is the most common form of IHD, millions of women suffer from angina with nonobstructive coronary arteries (ANOCA), an umbrella term encompassing multiple nonatherosclerotic disorders of the coronary tree. The underlying pathology leading to ischemia in these syndromes may be challenging to diagnose, leaving many women without a diagnosis despite persistent symptoms that impact quality of life and adversely affect long-term cardiovascular prognosis. In the last decade, there have been significant advances in the recognition and diagnostic evaluation of ANOCA. Despite these advances, the standard approach to evaluating suspected IHD in women continues to focus predominantly on the assessment of atherosclerotic coronary artery disease, leading to missed opportunities to accurately diagnose and treat underlying coronary vasomotor disorders. The goal of this review is to describe advances in diagnostic testing that can be used to evaluate angina in women and present a pragmatic diagnostic algorithm to guide evaluation of ANOCA in symptomatic patients. The proposed approach for the assessment of ANOCA is consistent with prior expert consensus documents and guidelines but is predicated on the medical interview and pretest probability of disease to inform a personalized diagnostic strategy.

Clinical Interpretation of Serum Troponin in the Era of High-Sensitivity Testing.

Cardiac troponin (Tn) plays a central role in the evaluation of patients with angina presenting with acute coronary syndrome. The advent of high-sensitivity assays has improved the analytic sensitivity and precision of serum Tn measurement, but this advancement has come at the cost of poorer specificity. The role of clinical judgment is of heightened importance because, more so than ever, the interpretation of serum Tn elevation hinges on the careful integration of findings from electrocardiographic, echocardiographic, physical exam, interview, and other imaging and laboratory data to formulate a weighted differential diagnosis. A thorough understanding of the epidemiology, mechanisms, and prognostic implications of Tn elevations in each cardiac and non-cardiac etiology allows the clinician to better distinguish between presentations of myocardial ischemia and myocardial injury-an important discernment to make, as the treatment of acute coronary syndrome is vastly different from the workup and management of myocardial injury and should be directed at the underlying cause.

Molecular Genetics Augment Cytopathologic Evaluation and Surgical Planning of Pediatric Thyroid Nodules.

PURPOSE: Molecular genetic testing in conjunction with cytopathology may improve prediction of malignancy in thyroid nodules, particularly those with indeterminate cytology (Bethesda III/IV). Though now commonplace in adults, pediatric data are limited. This study examines molecular genetics of pediatric nodules with correlation to cytologic and histologic classification at time of surgery and the distribution of mutations. METHODS: Retrospective chart review of 164 patients <22 years who underwent surgical resection of a thyroid nodule between 2002 and 2020 with molecular testing on fine-needle aspiration biopsy (FNA) or final histopathology. RESULTS: 85 (52 %) of 164 patients undergoing thyroid resection had available molecular genetic testing. BRAF V600E testing was performed on the FNA samples of 73 (86 %) patients and on 15 (18 %) surgical specimens; 31 (37 %) were positive. Of the remaining 54 patients, 21 had additional mutation/fusion testing. In 17 (81 %) cases, an alternate mutation/fusion was identified including 8 gene fusions, 3 DICER1 mutations, 4 NRAS mutations, one BRAF variant, and one unknown variant. BRAF, DICER1 mutations, and gene fusions predicted malignancy. Greater than 95 % of BRAF mutations were in Bethesda V/VI lesions and associated with classic variant PTC whereas fusions and DICER1 mutations clustered in Bethesda IV nodules. Bethesda III nodules harbored BRAF and NRAS mutations. In Bethesda IV nodules, a gene fusion or DICER mutation altered the surgical decision-making (upfront thyroidectomy rather than lobectomy) in 70 % of nodules submitted for genetic testing. CONCLUSION: Expanded molecular genetic testing on FNA of pediatric thyroid nodules, particularly Bethesda III/IV, may improve prediction of malignancy and augment surgical decision-making. LEVEL OF EVIDENCE: III.

The role of cysteines in the structure and function of OGG1.

8-Oxoguanine glycosylase (OGG1) is a base excision repair enzyme responsible for the recognition and removal of 8-oxoguanine, a commonly occurring oxidized DNA modification. OGG1 prevents the accumulation of mutations and regulates the transcription of various oxidative stress-response genes. In addition to targeting DNA, oxidative stress can affect proteins like OGG1 itself, specifically at cysteine residues. Previous work has shown that the function of OGG1 is sensitive to oxidants, with the cysteine residues of OGG1 being the most likely site of oxidation. Due to the integral role of OGG1 in maintaining cellular homeostasis under oxidative stress, it is important to understand the effect of oxidants on OGG1 and the role of cysteines in its structure and function. In this study, we investigate the role of the cysteine residues in the function of OGG1 by mutating and characterizing each cysteine residue. Our results indicate that the cysteines in OGG1 fall into four functional categories: those that are necessary for (1) glycosylase activity (C146 and C255), (2) lyase activity (C140S, C163, C241, and C253), and (3) structural stability (C253) and (4) those with no known function (C28 and C75). These results suggest that under conditions of oxidative stress, cysteine can be targeted for modifications, thus altering the response of OGG1 and affecting its downstream cellular functions.