Management of spontaneous coronary artery dissection: Trends over time.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome. Guidance regarding the optimal management of patients with SCAD has been published over the past 10 years, but the impact on clinical practice has not been evaluated. The present study aims to examine if approaches to invasive management, medical therapy, and vascular imaging have changed over time. METHODS: This is a retrospective cohort study of 157 patients treated for SCAD between 2005 and 2019 at an academic health system in Philadelphia, Pennsylvania. We aimed to examine change in management over time, including rates of coronary revascularization, discharge medications, and vascular imaging. RESULTS: Conservative management of SCAD increased over time from 35% before 2013 to 89% in 2019, p < 0.001. Revascularization was associated with younger age, pregnancy-associated SCAD, and lesions of the left main artery, left anterior descending artery, and multiple vessels, p < 0.05 for all. Partial imaging for extracoronary vascular abnormalities ranged from 33% before 2013 to 71% in 2018, p = 0.146. The rate of comprehensive vascular imaging (cross-sectional head to pelvis imaging) remained low in all time categories (10-18%) and did not change over time. Patients who underwent comprehensive imaging were more likely to be diagnosed with fibromuscular dysplasia (FMD) compared to those with partial imaging (63% vs 15%, p < 0.001). CONCLUSION: Management of spontaneous coronary artery dissection has changed over time. More patients are being managed conservatively and undergo screening for extracoronary vascular abnormalities such as FMD. Future efforts should focus on improving rates of comprehensive vascular screening.

Characteristics of Clinical Trial Sites for Novel Transcatheter Mitral and Tricuspid Valvular Therapies.

Importance: Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials. Objective: To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies. Design, Setting, and Participants: This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022. Exposures: Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals. Main Outcome and Measures: The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies. Results: A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code-based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, -2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials. Conclusions and Relevance: In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.

Plasma biomarkers associated with adverse outcomes in patients with calcific aortic stenosis.

AIMS: Enhanced risk stratification of patients with aortic stenosis (AS) is necessary to identify patients at high risk for adverse outcomes, and may allow for better management of patient subgroups at high risk of myocardial damage. The objective of this study was to identify plasma biomarkers and multimarker profiles associated with adverse outcomes in AS. METHODS AND RESULTS: We studied 708 patients with calcific AS and measured 49 biomarkers using a Luminex platform. We studied the correlation between biomarkers and the risk of (i) death and (ii) death or heart failure-related hospital admission (DHFA). We also utilized machine-learning methods (a tree-based pipeline optimizer platform) to develop multimarker models associated with the risk of death and DHFA. In this cohort with a median follow-up of 2.8 years, multiple biomarkers were significantly predictive of death in analyses adjusted for clinical confounders, including tumour necrosis factor (TNF)-α [hazard ratio (HR) 1.28, P < 0.0001], TNF receptor 1 (TNFRSF1A; HR 1.38, P < 0.0001), fibroblast growth factor (FGF)-23 (HR 1.22, P < 0.0001), N-terminal pro B-type natriuretic peptide (NT-proBNP) (HR 1.58, P < 0.0001), matrix metalloproteinase-7 (HR 1.24, P = 0.0002), syndecan-1 (HR 1.27, P = 0.0002), suppression of tumorigenicity-2 (ST2) (IL1RL1; HR 1.22, P = 0.0002), interleukin (IL)-8 (CXCL8; HR 1.22, P = 0.0005), pentraxin (PTX)-3 (HR 1.17, P = 0.001), neutrophil gelatinase-associated lipocalin (LCN2; HR 1.18, P < 0.0001), osteoprotegerin (OPG) (TNFRSF11B; HR 1.26, P = 0.0002), and endostatin (COL18A1; HR 1.28, P = 0.0012). Several biomarkers were also significantly predictive of DHFA in adjusted analyses including FGF-23 (HR 1.36, P < 0.0001), TNF-α (HR 1.26, P < 0.0001), TNFR1 (HR 1.34, P < 0.0001), angiopoietin-2 (HR 1.26, P < 0.0001), syndecan-1 (HR 1.23, P = 0.0006), ST2 (HR 1.27, P < 0.0001), IL-8 (HR 1.18, P = 0.0009), PTX-3 (HR 1.18, P = 0.0002), OPG (HR 1.20, P = 0.0013), and NT-proBNP (HR 1.63, P < 0.0001). Machine-learning multimarker models were strongly associated with adverse outcomes (mean 1-year probability of death of 0%, 2%, and 60%; mean 1-year probability of DHFA of 0%, 4%, 97%; P < 0.0001). In these models, IL-6 (a biomarker of inflammation) and FGF-23 (a biomarker of calcification) emerged as the biomarkers of highest importance. CONCLUSIONS: Plasma biomarkers are strongly associated with the risk of adverse outcomes in patients with AS. Biomarkers of inflammation and calcification were most strongly related to prognosis.

Snare-Assisted Valve Positioning of Self-Expanding Valves for Transcatheter Aortic Valve Replacement.

We describe 4 cases in which technical challenges were anticipated in delivering a self-expanding TAVR valve due to challenging aortic anatomy or a previous placed surgical aortic valve. An upfront snare strategy is described which facilitates valve centralization and atraumatic valve delivery. (Level of Difficulty: Advanced.).

Transcatheter mitral valve replacement: latest advances and future directions.

Mitral regurgitation remains the most common form of valve disease worldwide and given an aging population with a significant proportion of secondary mitral regurgitation, a transcatheter approach to mitral valve replacement has become a major goal of the transcatheter therapeutics field. Mitral regurgitation can be caused by disease of the leaflets (primary) or by diseases of the left atrium or left ventricle (LV) (secondary or functional), and may involve overlap of the two (mixed disease). The location of the mitral valve (and large size), the approach to anchoring a valve replacement, and concerns about left ventricular outflow tract (LVOT) obstruction are all issues that have made the transcatheter delivery of a valve replacement challenging. Despite these challenges, both transapical and transseptal devices are currently being developed, with several in early feasibility trials and several entering pivotal trials. As the field of transcatheter mitral valve replacement (TMVR) improves and develops, a critical part of evaluating patients with mitral valve disease will be utilizing the heart team approach to identify and individualize the most appropriate treatment for each patient.

Mid-term outcomes with the use of extracorporeal membrane oxygenation for cardiopulmonary failure secondary to massive pulmonary embolism.

OBJECTIVES: There has been increasing interest in using extracorporeal membrane oxygenation (ECMO) to rescue patients with pulmonary embolism (PE) in the advanced stages of respiratory or haemodynamic decompensation. We examined mid-term outcomes and risk factors for in-hospital mortality. METHODS: We conducted a retrospective study of 36 patients who required ECMO placement (32 veno-arterial ECMO, 4 veno-venous) following acute PE. Survival curves were estimated using the Kaplan-Meier method. Risk factors for in-hospital mortality were assessed by logistic regression analysis. Functional status and quality of life were assessed by phone questionnaire. RESULTS: Overall survival to hospital discharge was 44.4% (16/36). Two-year survival conditional to discharge was 94% (15/16). Two-year survival after veno-arterial ECMO was 39% (13/32). In patients supported with veno-venous ECMO, survival to discharge was 50%, and both patients were alive at follow-up. In univariable analysis, a history of recent surgery (P = 0.064), low left ventricular ejection fraction (P = 0.029), right ventricular dysfunction ≥ moderate at weaning (P = 0.083), on-going cardiopulmonary resuscitation at ECMO placement (P = 0.053) and elevated lactate at weaning (P = 0.002) were risk factors for in-hospital mortality. In multivariable analysis, recent surgery (P = 0.018) and low left ventricular ejection fraction at weaning (P = 0.013) were independent factors associated with in-hospital mortality. At a median follow-up of 23 months, 10 patients responded to our phone survey; all had acceptable functional status and quality of life. CONCLUSIONS: Massive acute PE requiring ECMO support is associated with high early mortality, but patients surviving to hospital discharge have excellent mid-term outcomes with acceptable functional status and quality of life. ECMO can provide a stable platform to administer other intervention with the potential to improve outcomes. Risk factors for in-hospital mortality after PE and veno-arterial ECMO support were identified.

Transcatheter Mitral Valve Replacement: Rationale and Current Status.

Mitral regurgitation (MR) is the most prevalent form of moderate or severe valve disease in the developed world. MR can result from impairment of any part of the mitral valve apparatus and is classified as primary (disease of the leaflets) or secondary (functional). The presence of at least moderate MR is associated with increased morbidity and mortality. With the goal of avoiding the risks of traditional surgery, transcatheter mitral valve therapies have been developed. The current transcatheter repair techniques are limited by therapeutic target and incomplete MR reduction, and thus transcatheter mitral valve replacement (TMVR) has been pursued. Several devices (both transapical and transseptal) are under development, with both early feasibility and pivotal trials under way. As this field develops, the decision to treat with TMVR will require a heart team approach that takes patient-, disease-, and device-specific factors into account.

Strategies for radiation exposure-sparing in fluoroscopically guided invasive cardiovascular procedures.

BACKGROUND: Minimizing radiation exposure during x-ray fluoroscopically guided procedures is critical to patients and to medical personnel. Tableside adjustment of x-ray image acquisition parameters can vary the fluoroscopic radiation exposure rate. OBJECTIVES: To determine the impact of adjusting four tableside controllable image acquisition parameters on x-ray fluoroscopic radiation exposure rate. METHODS: We made fluoroscopic exposures of a standard radiologic phantom to measure radiation exposure rates as kerma•area product per second of exposure and milligray per x-ray pulse under all possible combinations of detector zoom mode, collimated image field size, fluoroscopy dose mode, and fluoroscopy pulse frequency. RESULTS: Kerma•area product per second was linearly proportional to pulse frequency. Selecting larger detector zoom modes, smaller collimated image field sizes and low dose fluoroscopy mode each decreased exposure rate. We found a > 20-fold variation in dose rates over the range of acquisition parameter combinations. CONCLUSIONS: Selecting the most appropriate fluoroscopy acquisition parameters enables physician operators to adjust radiation exposure rates over a large range. Judicious selection of acquisition parameters can reduce patient and medical personnel radiation exposure by as much as 95% compared to "standard" fluoroscopy protocol settings.

Catheterization Laboratory: Structural Heart Disease, Devices, and Transcatheter Aortic Valve Replacement.

The cardiac catheterization laboratory is advancing medicine by performing procedures on patients who would usually require sternotomy and cardiopulmonary bypass. These procedures are done percutaneously, allowing them to be performed on patients considered inoperable. Patients have compromised cardiovascular function or advanced age. An anesthesiologist is essential for these procedures in case of hemodynamic compromise. Interventionalists are becoming more familiar with transcatheter aortic valve replacement and the device has become smaller, both contributing to less complications. Left atrial occlusion and the endovascular edge-to-edge mitral valve repair devices were approved. Although these devices require general anesthesia, an invasive surgery and cardiopulmonary bypass machine are not necessary for deployment.

Low-Flow Severe Aortic Stenosis: Evolving Role of Transcatheter Aortic Valve Replacement.

The definition of severe aortic stenosis has classically and retrospectively been based on the natural history of patients with medically managed aortic stenosis and preserved left ventricular function in an era where surgical aortic valve replacement was the sole therapy. We now recognize that this disease is more heterogeneous and includes important subsets of patients with low stroke volume index (low flow) and low-gradient with reduced (classical) or preserved (paradoxical) ejection fraction. These patients pose diagnostic and treatment dilemmas, requiring a comprehensive assessment with integration of multimodality imaging, testing, and clinical assessment. Surgery in these patients has been associated with higher operative mortality and lower long-term survival. Transcatheter aortic valve replacement (TAVR), because of its less-invasive nature, avoidance of the detrimental effects of cardiopulmonary bypass, and larger effective orifice area, offers several potential advantages. Studies of TAVR in low-flow severe aortic stenosis patients have demonstrated that TAVR has a significant mortality benefit compared with medical therapy and a similar benefit compared with surgery. Both low flow and low ejection fraction have emerged as important factors in predicting mortality post-TAVR, with particularly poor survival when flow or ejection fraction fail to improve. The recognition, diagnosis, and treatment of patients with low-flow severe aortic stenosis remains challenging. It is likely that TAVR will play an increasingly important role in the management of these patients.

Relation between the Framingham Risk Score, coronary calcium, and incident coronary heart disease among low-risk men.

The Prospective Army Coronary Calcium Project is evaluating the predictive value of coronary artery calcium (CAC) in unselected, healthy, lower-risk, 40- to 50-year-old men. Although this study has found that coronary calcium is predictive of future coronary heart disease (CHD), criteria are needed to narrow the screening population to those in whom CAC measurement is most efficient (vs unselected screening of low-risk men). In 1,634 unselected volunteer men (mean age 42 years, mean 10-year CHD Framingham risk score [FRS] 4.6%, CAC prevalence 22.4%), we evaluated the independent relation between CAC and incident CHD over 5.6 years including hard events (hospitalized unstable angina, myocardial infarction, and CHD death) and coronary revascularization. The cohort was analyzed in tertiles of FRS for the relation between CAC and CHD outcomes. FRS tertile cutpoints were 0% to 3% (n = 547), >3% to 5% (n = 547), and >5% (n = 540) 10-year CHD risk. Over a mean follow-up of 5.6 +/- 1.5 years (range 1.0 to 8.3), there were 22 total CHD events, including 14 hard events and 8 revascularizations. Most events occurred in the highest FRS tertile (n = 14) versus the middle (n = 6) and lowest (n = 2) risk tertiles (p = 0.005). CAC and CHD events increased across FRS tertiles. Only in the highest FRS tertile was there a significant relation between CAC and CHD outcomes (hazard ratio 9.3). In conclusion, CAC screening could be of benefit in refining risk assessment of low-risk men, but only when the FRS exceeds approximately 5%.

Integrins mediate adhesion of medulloblastoma cells to tenascin and activate pathways associated with survival and proliferation.

Medulloblastoma spreads by leptomeningeal dissemination rather than by infiltration that characterizes other CNS tumors, eg, gliomas. This study represents an initial attempt to identify both the molecules that mediate medulloblastoma adhesion to leptomeninges and the pathways that are key to survival and proliferation of tumor following adhesion. As a first step in molecule identification, we produced adhesion of D283 medulloblastoma cells to the extracellular matrix (ECM) of H4 glioma cells in vitro. Within this context, D283 cells preferentially expressed the alpha9 and beta1 integrin subunits; antibody and disintegrin blockade of alpha9 and beta1 binding eliminated the adhesion. The H4 ECM was enriched in tenascin, a binding partner for the alpha9beta1 integrin heterodimer. Purified tenascin-C supported D283 cell adhesion. The adhesion was blocked by antibodies to alpha9 and beta1 integrin. In vivo data were similar; immunohistochemistry of primary human medulloblastomas with leptomeningeal extension demonstrated increased expression of alpha9 and beta1 integrins as well as tenascin at the interface of brain and leptomeningeal tumor. These data suggest that tumor-cell expressions of alpha9 and beta1 integrins in combination with extracellular tenascin are necessary for medulloblastoma adhesion to the leptomeninges. As a first step in the identification of pathways that mediate survival and proliferation of tumor following adhesion, we demonstrated that adhesion to H4 ECM was associated with survival and proliferation of D283 cells as well as activation of the MAPK pathway in a growth factor deficient environment. Antibody blockade of alpha9 and beta1 integrin binding that eliminated adhesion also eliminated the in vitro survival benefit. These data suggest that adhesion of medulloblastoma to the meninges is necessary for the survival and proliferation of these tumor cells at the secondary site.