Matrix Gla protein and the long-term incidence and progression of coronary artery and aortic calcification in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Matrix Gla protein (MGP) is an inhibitor of calcification that requires carboxylation by vitamin K for activity. The inactive form of MGP, dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP), has been associated with increased calcification. However, it is not known whether there is a longitudinal relationship between dephosphorylated-uncarboxylated matrix Gla protein levels and coronary and aortic calcification in large population cohorts. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)]. RESULTS: For every one standard deviation (SD, 178 pmol/L) increment in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p < 0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p = 0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p < 0.001) AU/year. The association was stronger for DTAC in those ≥65 years and with diabetes. CONCLUSIONS: We found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature.

Angiographic characteristics of patients with STEMI and COVID-19: Insights from NACMI registry.

BACKGROUND: To date, there has been no independent core lab angiographic analysis of patients with COVID-19 and STEMI. The study characterized the angiographic parameters of patients with COVID-19 and STEMI. METHODS: Angiograms of patients with COVID-19 and STEMI from the North American COVID-19 Myocardial Infarction (NACMI) Registry were sent to a Core Laboratory in Vancouver, Canada. Culprit lesion(s), Thrombolysis In Myocardial Infarction (TIMI) flow, Thrombus Grade Burden (TGB), and percutaneous coronary intervention (PCI) outcome were assessed. RESULTS: From 234 patients, 74% had one culprit lesion, 14% had multiple culprits and 12% had no culprit identified. Multivessel thrombotic disease and multivessel CAD were found in 27% and 53% of patients, respectively. Stent thrombosis accounted for 12% of the presentations and occurred in 55% of patients with previous coronary stents. Of the 182 who underwent PCI, 60 (33%) had unsuccessful PCI due to post-PCI TIMI flow <3 (43/60), residual high thrombus burden (41/60) and/or thrombus related complications (27/60). In-hospital mortality for successful, partially successful, and unsuccessful PCI was 14%, 13%, and 27%, respectively. Unsuccessful PCI was associated with increased risk of in-hospital mortality (risk ratio [RR] 1.96; 95% CI: 1.05-3.66, P = .03); in the adjusted model this estimate was attenuated (RR: 1.24; 95% CI: 0.65-2.34, P = .51). CONCLUSION: In patients with COVID-19 and STEMI, thrombus burden was pervasive with notable rates of multivessel thrombotic disease and stent thrombosis. Post-PCI, persistent thrombus and sub-optimal TIMI 3 flow rates led to one-third of the PCI's being unsuccessful, which decreased over time but remained an important predictor of in-hospital mortality.

Sex differences in the well-being of interventional cardiologists.

Several studies suggest differences in burnout and coping mechanisms between female and male physicians. We conducted an international, online survey exploring sex-based differences in the well-being of interventional cardiologists. Of 1251 participants, 121 (9.7%) were women. Compared with men, women were more likely to be single and under 50 years old, and they asked more often for development opportunities and better communication with administration. Overall burnout was similar between women and men, but women interventional cardiology attendings were more likely to think that they were achieving less than they should. Improved communication with administration and access to career development opportunities may help prevent or mitigate burnout in women interventional cardiologists.

Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis.

BACKGROUND: Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms. OBJECTIVES: The aim of this study was to discover novel biomarkers with potentially causal associations with AS. METHODS: We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n = 11,430; age 60 ± 6 years) and in late-life (V5; n = 4,899; age 76 ± 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless index by echocardiography at V5 and with incident AV-related hospitalization after V3 with the use of multivariable linear and Cox proportional hazard regression. We assessed associations of candidate proteins with changes in AVmax over 6 years and with AV calcification with the use of cardiac computed tomography, replicated analysis in an independent sample, performed Mendelian randomization, and evaluated gene expression in explanted human AV tissue. RESULTS: Fifty-two proteins cross-sectionally were associated with AVmax and dimensionless index at V5 and with risk of incident AV-related hospitalization after V3. Among 3,413 participants in the Cardiovascular Health Study, 6 of those proteins were significantly associated with adjudicated moderate or severe AS, including matrix metalloproteinase 12 (MMP12), complement C1q tumor necrosis factor-related protein 1 (C1QTNF1), and growth differentiation factor-15. MMP12 was also associated with greater increase in AVmax over 6 years, greater degree of AV calcification, and greater expression in calcific compared with normal or fibrotic AV tissue. C1QTNF1 had consistent potential causal effects on both AS and AVmax according to Mendelian randomization analysis. CONCLUSIONS: These findings identify MMP12 as a potential novel circulating biomarker of AS risk and C1QTNF1 as a new putative target to prevent AS progression.

Characteristics and outcomes of socioeconomically disadvantaged pregnant individuals with adult congenital heart disease presenting to a Cardio-Obstetrics Program.

BACKGROUND: Outcomes of individuals with adult congenital heart disease who are socioeconomically disadvantaged and cared for in cardio-obstetrical programs, are lacking. OBJECTIVE: This study aimed to describe the clinical characteristics, maternal pregnancy outcomes, and contraceptive uptake in individuals with adult congenital heart disease in an urban cardio-obstetrical program. STUDY DESIGN: Retrospective data were collected for individuals with adult congenital heart disease seen in the Maternal Fetal Medicine-Cardiology Joint Program at Montefiore Health System between 2015 and 2021 and compared using modified World Health Organization class I, II vs the modified World Health Organization class ≥II/III. RESULTS: Over 90% of individuals with adult congenital heart disease were pregnant at the time of referral. Modified World Health Organization class I, II (n=77, 62.4% Black or Hispanic/Latina) had a total of 94 pregnancies and modified World Health Organization class ≥II/III (n=49, 49.0% Black or Hispanic/Latina) had a total of 56 pregnancies. Over 25% of individuals in each group had a body mass index ≥30 (P=.78), and very low summary socioeconomic scores. Modified World Health Organization class ≥II/III were more likely to be anticoagulated in the first trimester than modified World Health Organization class I, II (10.7% vs 0.0%, P=.002) and throughout pregnancy (14.3% vs 3.2% P=.02). Modified World Health Organization class ≥II/III were more likely to require arterial monitoring during delivery than modified World Health Organization class I, II (14.3% vs 0.0%, P=.001) or delivery under general anesthesia (8.9% vs 1.1%, P=.03) but had a comparable frequency of cesarean delivery (35.8% vs 41.3%, P=.68). There were no in-hospital maternal deaths. There was no difference in the type of contraception recommended by modified World Health Organization class, however, modified World Health Organization class ≥II/III were more likely to receive long-acting types or permanent sterilization (35.6% vs 54.6%, P=.045). CONCLUSION: In a socioeconomically disadvantaged cohort with adult congenital heart disease from a historically marginalized community, those with modified World Health Organization class ≥II/III had more complex antepartum and intrapartum needs but similar maternal and obstetrical outcomes as modified World Health Organization class I, II. The multidisciplinary approach offered by a cardio-obstetrics program may contribute to successful outcomes in this high-risk cohort, and these data are hypothesis-generating.

A Geriatric Approach to Percutaneous Coronary Interventions in Older Adults, Part II: A JACC: Advances Expert Panel.

We review a comprehensive risk assessment approach for percutaneous coronary interventions in older adults and highlight the relevance of geriatric syndromes within that broader perspective to optimize patient-centered outcomes in interventional cardiology practice. Reflecting the influence of geriatric principles in older adults undergoing percutaneous coronary interventions, we propose a "geriatric" heart team to incorporate the expertise of geriatric specialists in addition to the traditional heart team members, facilitate uptake of the geriatric risk assessment into the preprocedural risk assessment, and address ways to mitigate these geriatric risks. We also address goals of care in older adults, highlighting common priorities that can impact shared decision making among older patients, as well as frequently encountered pharmacotherapeutic considerations in the older adult population. Finally, we clarify gaps in current knowledge and describe crucial areas for future investigation.

Assessment and Management of Older Adults Undergoing PCI, Part 1: A JACC: Advances Expert Panel.

As the population ages, older adults represent an increasing proportion of patients referred to the cardiac catheterization laboratory. Older adults are the highest-risk group for morbidity and mortality, particularly after complex, high-risk percutaneous coronary interventions. Structured risk assessment plays a key role in differentiating patients who are likely to derive net benefit vs those who have disproportionate risks for harm. Conventional risk assessment tools from national cardiovascular societies typically rely on 3 pillars: 1) cardiovascular risk; 2) physiologic and hemodynamic risk; and 3) anatomic and procedural risks. We propose adding a fourth pillar: geriatric syndromes, as geriatric domains can supersede all other aspects of risk.

Extracardiac Prothrombotic Effects of COVID-19.

COVID-19 infection triggers a heightened inflammatory response which in turn, increases thrombosis and thromboembolism. Microvascular thrombosis has been detected in various tissue beds which may account for some of the multi-system organ dysfunction associated with COVID-19. Additional research is needed to understand which prophylactic and therapeutic drug regimens are best for the prevention and treatment of thrombotic complications of COVID-19.

Women's Cardiovascular Health: Prioritizing the Majority Minority.

Women make up the majority of the global population, and [...].

Educational Experience of Interventional Cardiology Fellows in the United States and Canada.

BACKGROUND: The COVID-19 pandemic and iodinated contrast shortage may have affected interventional cardiology (IC) fellowship training. OBJECTIVES: The aim of this study was to investigate the educational experience of first-year IC fellows in the United States and Canada. METHODS: A 59-question online survey was conducted among 2021-2022 first-year IC fellows in the United States and Canada. RESULTS: Of the 360 IC fellows invited to participate, 111 (31%) responded; 95% were from the United States, and 79% were men. Participants were mostly from university programs (70%), spent 61 to 70 hours/week in the hospital, and had an annual percutaneous coronary intervention case number of <200 (5%), 200 to 249 (8%), 250 to 349 (33%), 350 to 499 (39%), 500 to 699 (12%), or ≥700 (3%). For femoral access, a micropuncture needle was used regularly by 89% and ultrasound-guided puncture by 81%, and 43% used vascular closure devices in most cases (>80%). Intravascular ultrasound was performed and interpreted very comfortably by 62% and optical coherence tomography (OCT) by 32%, and 20% did not have access to OCT. Approximately one-third felt very comfortable performing various atherectomy techniques. Covered stents, fat embolization, and coil embolization were used very comfortably by 14%, 4%, and 3%, respectively. Embolic protection devices were used very comfortably by 11% to 24% of IC fellows. Almost one-quarter of fellows (24%) were warned about their high radiation exposure. Eighty-four percent considered IC fellowship somewhat or very stressful, and 16% reported inadequate psychological support. CONCLUSIONS: This survey highlights opportunities for improvement with regard to the use of intravascular imaging, atherectomy techniques, complication prevention and management strategies, radiation awareness and mitigation, and psychological support.

Effect of cooling methods and target temperature on outcomes in comatose patients resuscitated from cardiac arrest: Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Targeted temperature management (TTM) has been recommended after cardiac arrest (CA), however the specific temperature targets and cooling methods (intravascular cooling (IVC) versus surface cooling (SC)) remain uncertain. METHODS: PUBMED and EMBASE were searched until October 8, 2022 for randomized clinical trials (RCTs) investigating the efficacy of TTM after CA. The randomized treatment arms were categorized into the following 6 groups: 31..C to 33..C IVC, 31..C to 33..C SC, 34..C to 36..C IVC, 34..C to 36..C SC, strict normothermia or fever prevention (Strict NT or FP), and standard of care without TTM (No-TTM). The primary outcome was neurological recovery. P-score was used to rank the treatments, where a larger value indicates better performance. RESULTS: We identified 15 RCTs, involving 5,218 patients with CA. Compared to No-TTM as the reference, the other therapeutic options significantly improved neurological outcomes (vs No-TTM; 31..C to 33.. C IVC: RR = 0.67, 95% CI 0.54 to 0.83; 31..C to 33..C SC RR = 0.73, 95% CI 0.61 to 0.87; 34..C to 36.. C IVC: RR = 0.66, 95% CI 0.51 to 0.86; 34..C to 36..C SC: RR = 0.73, 0.59 to 0.90; Strict NT or FP: RR = 0.75, 95% CI 0.62 to 0.90). Overall, 31-33..C IVC had the highest probability to be the best therapeutic option to improve outcomes (the ranking P-score of 0.836). As a subgroup analysis, the ranking P-score showed that IVC might be a better cooling method compared to SC (IVC vs SC P-score: 0.960 vs 0.670). CONCLUSIONS: Hypothermia (31..C to 36..C IVC and SC) and active normothermia (Strict-NT and Strict-FP) were associated with better neurological outcomes compared to No-TTM, with IVC having a greater probability of being the better cooling method than SC.

Maternal Cardiovascular Outcomes of Pregnancy in Childhood, Adolescent, and Young Adult Cancer Survivors.

This review focuses on the maternal cardiovascular risk and outcomes of pregnancy in childhood, adolescent, and young adult cancer survivors who are achieving survival to their prime reproductive years. Childhood, adolescent, and young adult cancer survivors are a growing population and have increasing needs for reproductive care over decades of life. Female cancer survivors have an overall higher risk of maternal cardiovascular events compared to those without a history of cancer. In female cancer survivors with normal cardiac function before pregnancy, the incidence of new heart failure during pregnancy is low. In survivors with cardiotoxicity prior to pregnancy, the risk of heart failure during and immediately after pregnancy is much higher. We recommend cardiomyopathy surveillance with echocardiography before pregnancy for all female survivors treated with anthracyclines and chest radiation. Survivors with cardiotoxicity prior to pregnancy should be cared for by an expert multidisciplinary team, including obstetrics, cardiology, anesthesia, and specialized nursing, among others.

Race-Ethnic Differences of ST-Elevation Myocardial Infarction: Findings from a New York Health System Registry.

Background: Race and ethnicity are major considerations in the incidence, management, and long-term outcome of ST-elevation myocardial infarction (STEMI) in the United States, but there is limited existing comparative data. Methods: We assembled a registry in a health system serving Bronx, NY of STEMI patients from 2008-2014 and analyzed differences in presentation, treatment and mortality between Hispanic/Latino (H/L), non-Hispanic Black (NHB) and non-Hispanic White (NHW). Upon discharge post-treatment for STEMI, all patients were followed for a median of 4.4 years (interquartile range 2.5, 6.0). Out of 966 STEMI patients, mean age was 61 years, 46% were H/L and 65% were male. H/Ls and NHBs had a higher prevalence of hypertension and diabetes mellitus than their NHW counterparts, coinciding with a lower socioeconomic status (SES). Results: The number of critically diseased vessels found at cardiac catheterization and mean troponin levels did not vary by race-ethnicity; neither did the adjusted hazard ratios (HR) for death. However, age-sex adjusted rates of general hospital readmission were higher in NHBs vs NHWs (HR 1.30, P=.03). Age-sex adjusted cardiovascular readmissions rates were higher in H/Ls than NHWs (HR 1.42, P=.03). Age-sex adjusted heart failure readmissions were increased for both H/Ls (HR 2.14, P=.01) and NHBs (HR 2.12, P=.02) over NHWs. Conclusions: Among STEMI patients, a higher prevalence of modifiable cardiovascular risk factors and a lower SES was seen among NHBs and H/Ls compared to NHWs. Despite similar coronary disease severity and in-hospital death, NHBs and H/Ls had a greater risk of general, cardiovascular and heart failure readmissions post-STEMI compared to NHWs.

Maternal Outcomes in Women with Peripartum Cardiomyopathy versus Age and Race-Matched Peers in an Urban US Community.

Peripartum cardiomyopathy (PPCM) is idiopathic systolic congestive heart failure around pregnancy. Comparisons with matched controls are lacking. We investigated maternal characteristics and outcomes up to 12 months in a cohort admitted to Montefiore Health System in Bronx, New York 1999−2015 (n = 53 cases and n = 92 age and race-matched controls, >80% Black or Hispanic/Latina). Compared to peers, women with PPCM had more chronic hypertension (24.5% vs. 8.8%, p = 0.001), prior gestational hypertension (20.8% vs. 5.4%, p = 0.001), prior preeclampsia (17.0% vs. 3.3%, p = 0.001), familial dilated cardiomyopathy (5.7% vs. 0.0%, p = 0.04), smoking (15.1% vs. 2.2%, p = 0.001), lower summary socioeconomic scores (−4.12 (IQR −6.81, −2.13) vs. −1.62 (IQR −4.20, −0.74), p < 0.001), public insurance (67.9% vs. 29.3% p = 0.001), and frequent depressive symptoms. Women with PPCM were often admitted antepartum (34.0% vs. 18.5%, p = 0.001) and underwent Cesarean section (65.4% vs. 30.4%, p = 0.001), but had less preterm labor (27.3% vs. 51.1%, p = 0.001). Women were rarely treated with bromocriptine (3.8%), frequently underwent left ventricular assist device placement (9.4% and n = 2 with menorrhagia requiring transfusion and progesterone) or heart transplantation (3.8%), but there were no in-hospital deaths. In sum, women with PPCM had worse socioeconomic disadvantage and baseline health than matched peers. Programs addressing social determinants of health may be important for women at high risk of PPCM.

High-Density Lipoprotein and Long-Term Incidence and Progression of Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Aortic valve calcification (AVC) shares pathological features with atherosclerosis. Lipoprotein components have been detected in aortic valve tissue, including HDL (high-density lipoprotein). HDL measures have inverse associations with cardiovascular disease, but relationships with long-term AVC progression are unclear. We investigated associations of HDL cholesterol, HDL-particle number and size, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC. METHODS: We used linear mixed-effects models to evaluate the associations of baseline HDL indices with AVC. AVC was quantified by Agatston scoring of up to 3 serial computed tomography scans over a median of 8.9 (maximum 11.2) years of follow-up in the Multi-Ethnic Study of Atherosclerosis (n=6784). RESULTS: After adjustment, higher concentrations of HDL-C (high-density lipoprotein cholesterol), HDL-P (HDL particles), large HDL-P, and apoC3-lacking HDL-C were significantly associated with lower incidence/progression of AVC. Neither small or medium HDL-P nor apoC3-containing HDL-C was significantly associated with AVC incidence/progression. When included together, a significant association was observed only for HDL-C, but not for HDL-P. Secondary analyses showed an inverse relationship between CETP mass, but not activity, and AVC incidence/progression. In exploratory assessments, inverse associations for HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL with AVC incidence/progression were more pronounced for older, male, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups. CONCLUSIONS: In a multiethnic population, HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL-C were inversely associated with long-term incidence and progression of AVC. Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.

Extracardiac Prothrombotic Effects of COVID-19.

COVID-19 infection triggers a heightened inflammatory response which in turn, increases thrombosis and thromboembolism. Microvascular thrombosis has been detected in various tissue beds which may account for some of the multi-system organ dysfunction associated with COVID-19. Additional research is needed to understand which prophylactic and therapeutic drug regimens are best for the prevention and treatment of thrombotic complications of COVID-19.

Sex Differences in Clinical Characteristics, Management Strategies, and Outcomes of STEMI With COVID-19: NACMI Registry.

Background: Women with ST-segment elevation myocardial infarction (STEMI) had worse outcomes than men prior to the COVID-19 pandemic. Although concomitant COVID-19 infection increases mortality risk in STEMI patients, no studies have evaluated sex differences in this context. Methods: The North American COVID-19 STEMI registry is a prospective, multicenter registry of hospitalized STEMI patients with COVID-19 infection. We compared sex differences in clinical characteristics, presentation, management strategies, and in-hospital mortality. Results: Among 585 patients with STEMI and COVID-19 infection, 154 (26.3%) were women. Compared to men, women were significantly older, had a higher prevalence of diabetes and stroke/transient ischemic attack, and were more likely to be on statins on presentation. Men more frequently presented with chest pain, whereas women presented with dyspnea. Women more often had STEMI without an identified culprit lesion than men (33% vs 18%, P < .001). The use of percutaneous coronary intervention was significantly higher in men, whereas medical therapy was higher in women. In-hospital mortality was 33% for women and 27% for men (P = .22). Conclusions: In patients presenting with STEMI in the context of COVID-19, the in-hospital mortality rate was 30% and similar for men and women. Lack of an identifiable culprit lesion was common in the setting of COVID-19 for both sexes but more likely in women (1/3 of women vs 1/5 of men). Evaluation of specific underlying etiologies is underway to better define the full impact of COVID-19 on STEMI outcomes and better understand the observed sex differences.

Measures of high-density lipoprotein function in men and women with severe aortic stenosis.

BACKGROUND: Calcification of the aortic valve is a common heart valve disorder, in some cases leading to clinically impactful severe aortic stenosis (AS). Sex-specific differences in aortic valve calcification (ACV) exist, with women having a lower burden of calcification than men as measured by computed tomography; however, the pathophysiological mechanism that leads to these differences remains unclear. METHODS: Using cultured human Tamm-Horsfall protein 1 (THP-1) macrophages and human aortic valve interstitial cells, the effects of high-density lipoprotein (HDL) particles isolated from the plasma of men and women with severe AS were studied for cholesterol efflux capacity (CEC). RESULTS: HDL-CEC was assessed in 46 patients with severe AS, n = 30 men, n = 16 women. ATP-Binding Cassette A1 (ABCA1)-mediated HDL-CEC was measured from human cultured THP-1 macrophages to plasma HDL samples. Women with severe AS had more ABCA1-mediated HDL-CEC, as compared to men (8.50 ± 3.90% cpm vs. 6.80 ± 1.50% cpm, P = 0.04). HDL pre-ß1 and α-particles were higher in woman than in men by spectral density, (pre-ß1 HDL, 20298.29 ± 1076.15 vs. 15,661.74 ± 789.00, P = 0.002, and α-HDL, 63006.35 ± 756.81 vs. 50,447.00 ± 546.52, P = 0.03). Lecithin-cholesterol acyltransferase conversion of free cholesterol into cholesteryl esters was higher in women than men (16.44 ± 9.11%/h vs. 12.00 ± 8.07%/h, P = 0.03). CONCLUSIONS: Sex-specific changes in various parameters of HDL-CEC were found in patients with severe AS. Sex-based modifications in HDL functionality by HDL-CEC might account for the reduced burden of calcification in women vs. men with severe AS. Therefore, future studies should target sex-related pathways in AS to help to improve understanding and treatment of AS. Sex specifc differences in AVC and differences associated with HDL function in men and women with severe AS. When compared to men, women had higher preß-HDL and α-HDL migrating particles, higher cholesterol efflux to HDL, and higher lecithin cholesterol acyl transferase (LCAT) activity, possibly indicating that improved reverse cholesterol transport may be protective against worsened calcification.