Association of cardiac biomarkers with long-term cardiovascular events in a community cohort.

MATERIALS AND METHODS: The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI). RESULTS: A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models. DISCUSSION: Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

In a community cohort, where a wide range of biomarkers were evaluated, Ceramide score provided additive value over traditional cardiac risk factors alone for predicting stroke/MI. NT ProBNP provided additive value in prediction of MACE/death. Other biomarkers failed to improve the discrimination of these models.

Early Effects of the COVID-19 Pandemic on Patients in a Virtual Multicenter Spontaneous Coronary Artery Dissection (SCAD) Registry.

Background: The COVID-19 pandemic effects among patients with a history of spontaneous coronary artery dissection (SCAD), a cause of acute coronary syndrome associated with emotional and physical stress, are unknown. Methods: For this cross-sectional cohort study, participants of the Mayo Clinic "Virtual" Multicenter SCAD Registry were surveyed about the COVID-19 pandemic. Results: Among 1352 participants, 727 (53.8%) completed surveys between June 2, 2021 and September 29, 2021. The majority of respondents (96.7%) were female, with a mean age of 54.9 ± 9.4 years. At the time of completing the survey, which was early in the pandemic, 91 respondents (12.6%) reported having prior COVID-19 symptoms, with < 1% experiencing hospitalization (n = 4) or cardiac complications (n = 6). A total of 14% had ≥ moderate anxiety symptoms, per the General Anxiety Disorder-7 item survey, and 11.8% had ≥ moderate depressive symptoms, per the Patient Health Questionnaire-9 item. Higher stress scores on the Likert scale were correlated with pandemic-related reduction in work hours and/or pay and/or unemployment (P = 0.013), remote work and/or change of job (P < 0.001), and loss of insurance and/or medical coverage (P = 0.025). A higher anxiety level, as measured on the Likert scale, was correlated with pandemic-related remote work and/or change of job (P = 0.007) and loss of insurance and/or medical coverage (P = 0.008). Since the start of the pandemic, 54% of respondents reported having at least monthly chest pain. Chest pain and COVID symptoms were each associated with higher scores on the General Anxiety Disorder-7 item survey and the Patient Health Questionnaire-9 item. Conclusions: Early in the pandemic, COVID-19 symptoms, hospitalization, and cardiac complications were uncommon among SCAD patients. The burden of anxiety and depressive symptoms was minimal to mild, similar to that in prior reports. Likert-scale measures of stress and anxiety were higher among persons with work and/or pay reduction and/or unemployment, remote work and/or change of job, and loss of insurance and/or medical coverage. Over half of respondents reported experiencing chest pain, which was correlated with depressive and anxiety symptoms, highlighting an overarching clinical need.

Contexte: On ne connaît pas les effets de la pandémie de COVID-19 sur les personnes ayant des antécédents de dissection spontanée de l'artère coronaire (DSAC), une cause du syndrome coronarien aigu qui est une source de stress physique et émotionnel. Méthodologie: Pour les besoins de cette étude de cohorte transversale, les participants au registre « virtuel ¼ multicentrique sur la DSAC de la clinique Mayo ont été interrogés dans le cadre d'une enquête sur la pandémie de COVID-19. Résultats: Parmi les 1 352 participants au registre, 727 (53,8 %) ont répondu à l'enquête entre le 2 juin et le 29 septembre 2021. La majorité des répondants (96,7 %) étaient des femmes, et l'âge moyen était de 54,9 ± 9,4 ans. Au moment de l'enquête, réalisée au début de la pandémie, 91 répondants (12,6 %) avaient indiqué avoir déjà présenté des symptômes de COVID-19, et < 1 % avaient été hospitalisés (n = 4) ou avaient présenté des complications cardiaques (n = 6). Au total, 14 % des participants présentaient des symptômes d'anxiété à tout le moins modérés d'après le questionnaire GAD-7 (General Anxiety Disorder-7 item) et 11,8 %, des symptômes dépressifs à tout le moins modérés d'après le questionnaire PHQ-9 (Patient Health Questionnaire-9 item). Une corrélation a été établie entre un score de stress plus élevé sur une échelle de Likert et une réduction des heures de travail et/ou du salaire, une période de chômage (p = 0,013), le télétravail et/ou un changement d'emploi (p < 0,001) et la perte de l'assurance et/ou de la couverture médicale (p = 0,025) en lien avec la pandémie. Une corrélation a également été établie entre un niveau d'anxiété plus élevé mesuré sur une échelle de Likert et le télétravail et/ou un changement d'emploi (p = 0,007) et la perte de l'assurance et/ou de la couverture médicale (p = 0,008) en lien avec la pandémie. Depuis le début de la pandémie, 54 % des répondants ont indiqué ressentir une douleur thoracique au moins une fois par mois. La douleur thoracique et les symptômes de la COVID-19 ont par ailleurs été associés à des scores plus élevés aux questionnaires GAD-7 et PHQ-9. Conclusions: Au début de la pandémie, les symptômes de la COVID-19, les hospitalisations et les complications cardiaques n'étaient pas fréquents chez les patients présentant une DSAC. Le fardeau des symptômes anxieux et dépressifs allait de minime à léger, comme en faisaient état les rapports précédents. L'anxiété et le stress mesurés sur une échelle de Likert ont été plus élevés chez les personnes ayant connu une réduction des heures de travail et/ou du salaire ou une période de chômage, ayant dû recourir au télétravail et/ou changer d'emploi, ou ayant perdu leur assurance et/ou couverture médicale. Plus de la moitié des répondants ont indiqué ressentir une douleur thoracique, laquelle a été mise en corrélation avec les symptômes d'anxiété et de dépression, ce qui souligne l'existence d'un besoin clinique important.

Coronary Artery Tortuosity and Spontaneous Coronary Artery Dissection: Association With Echocardiography and Global Longitudinal Strain, Fibromuscular Dysplasia, and Outcomes.

BACKGROUND: The etiology and significance of coronary artery tortuosity (TCA) among patients with spontaneous coronary artery dissection (SCAD) are unknown. The aim of this prospective imaging cohort study was to report echocardiographic findings and evaluate whether TCA correlates with cardiac anatomy and function among patients with SCAD. Comorbidities including fibromuscular dysplasia (FMD) and outcomes were also assessed. METHODS: TCA was determined on coronary angiography performed during the diagnosis of SCAD, and cardiac structure and function were evaluated using prospective comprehensive echocardiography. RESULTS: Among 116 patients with SCAD, the mean age at echocardiography was 50.8 ± 8.8 years, a median of 10.9 months after SCAD. Sixty-two patients (53.4%) had FMD, 41 (35.3%) had histories of hypertension, and 17 (14.8%) were hypertensive during echocardiography. Most patients (n = 78 [69%]) had normal left ventricular geometry with normal median ejection fraction (61%; interquartile range, 56% to 64%) and normal global longitudinal strain (-22.2%; interquartile range, -24.0% to -19.9%). Fifteen patients (13.4%) had diastolic dysfunction that was associated with hypertension at the time of echocardiography. Patients with TCA (n = 96 [82.8%]) were older (mean age, 52.1 ± 8.0 vs 44.7 ± 9.9 years; P < .001) with a higher prevalence of FMD (59.4% vs 25%, P = .007) but a similar prevalence of hypertension (35% vs 35%, P > .99) compared with patients without TCA. Across the age range (31.5 to 66.9 years), each decade of age was associated with an approximately 0.89-unit increase in coronary tortuosity score (P < .0001). Echocardiographic parameters were not significantly different between the two groups. Median follow-up duration was 4.4 years (95% CI, 3.8 to 5.2 years). The Kaplan-Meier 3-year SCAD recurrence rate was 9.4% (95% CI, 3.7% to 14.8%). There were no deaths. CONCLUSIONS: The majority of patients with SCAD had normal or near normal echocardiographic results, including global longitudinal strain, with no differences according to TCA. However, patients with SCAD with TCA were older, with a higher prevalence of FMD.

Medium-Term Outcomes of the Different Antithrombotic Regimens After Transcatheter Aortic Valve Implantation.

Bioprosthetic valve thrombosis is associated with accelerated bioprosthesis degeneration and valve re-replacement. Whether 3-month warfarin use after transcatheter aortic valve implantation (TAVI) protects against such consequences is unknown. We aimed to investigate if 3-month warfarin treatment after TAVI is associated with better outcomes than dual antiplatelet therapy (DAPT) and single antiplatelet therapy (SAPT) at medium-term follow-up. Adults who underwent TAVI were identified retrospectively (n = 1,501) and classified into warfarin, DAPT, and SAPT groups based on antithrombotic regimen received. Patients with atrial fibrillation were excluded. Outcomes and valve hemodynamics were compared between the groups. Annualized change from baseline in mean gradients and effective orifice area at last follow-up echocardiography was calculated. Overall, 844 patients were included (mean age: 80 ± 9 years, 43% women; 633 receiving warfarin, 164 DAPT, and 47 SAPT). Median time to follow-up was 2.5 (interquartile range 1.2 to 3.9) years. There were no differences in the adjusted outcome end points of ischemic stroke, death, valve re-replacement/intervention, structural valve degeneration, or their composite end point at follow-up. Annualized change in aortic valve area was significantly higher in DAPT (-0.11 [0.19] cm2/year) than warfarin (-0.06 [0.25] cm2/y, p = 0.03), but annualized change in mean gradients was not different (p >0.05). In conclusion, antithrombotic regimen, including warfarin, after TAVI was associated with marginally lower decrease in aortic valve area but no difference in medium-term clinical outcomes compared with DAPT and SAPT.

Assessing the capacity of methylated DNA markers of cervical squamous cell carcinoma to discriminate oropharyngeal squamous cell carcinoma in human papillomavirus mediated disease.

OBJECTIVE: Early identification of human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) is challenging and novel biomarkers are needed. We hypothesized that a panel of methylated DNA markers (MDMs) found in HPV(+) cervical squamous cell carcinoma (CSCC) will have similar discrimination in HPV(+)OPSCC tissues. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissues were obtained from patients with primary HPV(+)OPSCC or HPV(+)CSCC; control tissues included normal oropharynx palatine tonsil (NOP) and cervix (NCS). Using a methylation-specific polymerase chain reaction, 21 previously validated cervical MDMs were evaluated on tissue-extracted DNA. Discrimination between case and control cervical and oropharynx tissue was assessed using area under the curve (AUC). RESULTS: 34 HPV(+)OPSCC, 36 HPV(+)CSCC, 26 NOP, and 24 NCS patients met inclusion criteria. Within HPV(+)CSCC, 18/21 (86%) of MDMs achieved an AUC ≥ 0.9 and all MDMs exhibited better than chance classifications relative to control cervical tissue (all p < 0.001). In contrast, within HPV(+)OPSCC only 5/21 (24%) MDMs achieved an AUC ≥ 0.90 but 19/21 (90%) exhibited better than chance classifications relative to control tonsil tissue (all p < 0.001). Overall, 13/21 MDMs had statistically significant lower AUCs in the oropharyngeal cohort compared to the cervical cohort, and only 1 MDM exhibited a statistically significant increase in AUC. CONCLUSIONS: Previously validated MDMs exhibited robust performance in independent HPV(+)CSCC patients. However, most of these MDMs exhibited higher discrimination for HPV(+)CSCC than for HPV(+)OPSCC. This suggests that each SCC subtype requires a unique set of MDMs for optimal discrimination. Future studies are necessary to establish an MDM panel for HPV(+)OPSCC.