Intervention for critical aortic stenosis in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.3 years (30%). With this longer lifespan, calcific aortic stenosis (AS) was identified as an emerging critical risk factor for cardiac death in older patients. Intervention to relieve critical AS has the potential for immediate improvement in healthspan and lifespan. However, HGPS patient-device size mismatch, pervasive peripheral arterial disease, skin and bone abnormalities, and lifelong failure to thrive present unique challenges to intervention. An international group of experts in HGPS, pediatric and adult cardiology, cardiac surgery, and pediatric critical care convened to identify strategies for successful treatment. Candidate procedures were evaluated by in-depth examination of 4 cases that typify HGPS clinical pathology. Modified transcatheter aortic valve replacement (TAVR) and left ventricular Apico-Aortic Conduit (AAC) placement were deemed high risk but viable options. Two cases received TAVR and 2 received AAC post-summit. Three were successful and 1 patient died perioperatively due to cardiovascular disease severity, highlighting the importance of intervention timing and comparative risk stratification. These breakthrough interventions for treating critical aortic stenosis in HGPS patients could rewrite the current clinical perspective on disease course by greatly improving late-stage quality of life and increasing lifespan. Expanding worldwide medical and surgical competency for this ultra-rare disease through expert information-sharing could have high impact on treatment success.

Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Lower-extremity pressure, staging, and grading thresholds to identify chronic limb-threatening ischemia.

INTRODUCTION: The Society for Vascular Surgery Threatened Limb Classification System ('WIfI') is used to predict risk of limb loss and identify peripheral artery disease in patients with foot ulcers or gangrene. We estimated the diagnostic sensitivity of multiple clinical and noninvasive arterial parameters to identify chronic limb-threatening ischemia (CLTI). METHODS: We performed a single-center review of 100 consecutive patients who underwent angiography for foot gangrene or ulcers. WIfI stages and grades were determined for each patient. Toe, ankle, and brachial pressure measurements were performed by registered vascular technologists. CLTI severity was characterized using Global Limb Anatomic Staging System (GLASS stages) and angiosomes. Medial artery calcification in the foot was quantified on foot radiographs. RESULTS: GLASS NA (not applicable), I, II, and III angiographic findings were seen in 21, 21, 23, and 35 patients, respectively. A toe-brachial index < 0.7 and minimum ipsilateral ankle-brachial index < 0.9 performed well in identifying GLASS II and III angiographic findings, with sensitivity rates 97.8% and 91.5%, respectively. The diagnostic accuracy rates of noninvasive measures peaked at 74.7% and 89.3% for identifying GLASS II/III and GLASS I+ angiographic findings, respectively. The presence of medial artery calcification significantly diminished the sensitivity of most noninvasive parameters. CONCLUSIONS: The use of alternative noninvasive arterial testing parameters improves sensitivity for detecting PAD. Abnormal noninvasive results should suggest the need for diagnostic angiography to further characterize arterial anatomy of the affected limb. Testing strategies with better accuracy are needed.

Severe triple vessel disease secondary to IgG4-related coronary periarteritis.

BACKGROUND: Immunoglobulin G4-related disease is a rare systemic inflammatory disease that can lead to vascular manifestations such as periarteritis. CASE PRESENTATION: A 41-year-old man with stress angina was referred for coronary bypass surgery due to triple vessel coronary disease. CONCLUSIONS: Operative findings revealed significant adhesions and dense peri-coronary and periaortic thickening, also involving the left internal mammary artery. The IgG4-associated disease was confirmed by aortic pathology. The stress angina subsequently improved with the initiation of treatment with prednisone and rituximab.

Transcatheter Aortic Valve Replacement in a Young Patient With Mandibuloacral Dysplasia.

A young woman with mandibuloacral dysplasia, a syndrome on the progeria spectrum with accelerated vascular calcification and calcific valve stenosis, presented with symptomatic severe aortic stenosis. She underwent transcatheter aortic valve replacement with a balloon-expandable valve, and her exertional symptoms improved significantly. (Level of Difficulty: Intermediate.).

Management of Central Retinal Artery Occlusion: A Scientific Statement From the American Heart Association.

PURPOSE: Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke that causes severe visual loss and is a harbinger of further cerebrovascular and cardiovascular events. There is a paucity of scientific information on the appropriate management of CRAO, with most strategies based on observational literature and expert opinion. In this scientific statement, we critically appraise the literature on CRAO and provide a framework within which to consider acute treatment and secondary prevention. METHODS: We performed a literature review of randomized controlled clinical trials, prospective and retrospective cohort studies, case-control studies, case reports, clinical guidelines, review articles, basic science articles, and editorials concerning the management of CRAO. We assembled a panel comprising experts in the fields of vascular neurology, neuro-ophthalmology, vitreo-retinal surgery, immunology, endovascular neurosurgery, and cardiology, and document sections were divided among the writing group members. Each member received an assignment to perform a literature review, synthesize the data, and offer considerations for practice. Multiple drafts were circulated among the group until consensus was achieved. RESULTS: Acute CRAO is a medical emergency. Systems of care should evolve to prioritize early recognition and triage of CRAO to emergency medical attention. There is considerable variability in management patterns among practitioners, institutions, and subspecialty groups. The current literature suggests that treatment with intravenous tissue plasminogen activator may be effective. Patients should undergo urgent screening and treatment of vascular risk factors. There is a need for high-quality, randomized clinical trials in this field.

Venous thrombosis, thromboembolism, biomarkers of inflammation, and coagulation in coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with abnormal inflammatory and coagulation markers, potentially mediating thrombotic events. Our objective was to investigate the incidence, time course, laboratory features, and in-hospital outcomes of COVID-19 patients with suspected venous thromboembolism (VTE). METHODS: A retrospective observational cohort study was conducted of patients hospitalized with COVID-19 who had undergone ultrasound imaging for suspected VTE from March 13 to May 18, 2020. The medical records of the included patients were reviewed for D-dimer, fibrinogen, prothrombin time, partial thromboplastin time, platelet count, C-reactive protein (CRP), and high-sensitivity troponin T at admission and at up to seven time points before and after ultrasound examination. The clinical outcomes included superficial venous thrombosis, deep vein thrombosis, pulmonary embolism, intubation, and death. Mixed effects logistic, linear, and Cox proportional hazards methods were used to evaluate the relationships between the laboratory markers and VTE and other in-hospital outcomes. RESULTS: Of 138 patients who had undergone imaging studies, 44 (31.9%) had evidence of VTE. On univariable analysis, an elevated admission CRP (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.09; P = .02; per 10-U increase in CRP), platelet count (OR, 1.48; 95% CI, 1.04-2.12; P = .03; per 1000-U increase in platelet count), and male sex (OR, 2.64; 95% CI, 1.19-5.84; P = .02), were associated with VTE. However only male sex remained significant on multivariable analysis (OR, 2.37; 95% CI, 1.01-5.56; P = .048). The independent predictors of death included older age (hazard ratio [HR], 1.04; 95% CI, 1.00-1.07; P = .04), active malignancy (HR, 4.39; 95% CI, 1.39-13.91; P = .01), elevated admission D-dimer (HR, 1.016; 95% CI, 1.003-1.029; P = .02), and evidence of disseminated intravascular coagulation (HR, 4.81; 95% CI, 1.76-13.10; P = .002). CONCLUSIONS: Male sex, elevated CRP, and elevated platelet count at admission were associated with VTE on univariable analysis. However, only male sex remained significant on multivariable analysis. Older age, active malignancy, disseminated intravascular coagulation, and elevated D-dimer at admission were independently associated with death for patients hospitalized with COVID-19.

Clinically isolated aortitis: imaging features and clinical outcomes: comparison with giant cell arteritis and giant cell aortitis.

(1) describe imaging features of CIA, (2) compare dilation rate and wall thickening of aortic aneurysms in patients with CIA versus those with giant cell arteritis/aortitis (GCA), (3) present clinical outcomes of CIA patients. Retrospective search of electronic records from 2004 to 2018 yielded 71 patients, 52 of whom were female, with a mean age of 67.5 ± 9.0 years old, with a new clinical diagnosis of cranial or extracranial GCA (GCA group), and giant cell aortitis revealed by the aortic biopsy (CIA group). Comparisons between groups were conducted using the Wilcoxon rank-sum and Fisher's exact tests. Survival from the date of initial diagnosis to the end of data collection was compared between the two groups through a log-rank test. CIA patients (n = 23; 32%) presented with cardiovascular symptoms, and none had systemic inflammatory symptoms. Inflammatory markers were significantly higher among GCA patients than among CIA patients (p < 0.0001). The CIA group demonstrated thoracic aortic aneurysms without wall thickening. None of the GCA patients (n = 48; 68%) had aneurysmal dilation in the aorta at the time of diagnosis. None of the four CIA patients had FDG uptake in the aorta, while nine out of 13 GCA patients had FDG uptake in the vessels. There was no statistically significant difference in the survival between the two groups (p = 0.12). CIA patients presented with cardiovascular symptoms and was characterized by aneurysm of the aorta without the involvement of the infrarenal aortic segment. The role of FDG-PET/CT in CIA is less certain, though none of the patients in this cohort had FDG uptake in the vessels.

Peripheral Artery Disease: Past, Present, and Future.

Peripheral artery disease is a prevalent but underdiagnosed manifestation of atherosclerosis. There is insufficient awareness of its clinical manifestations, including intermittent claudication and critical limb ischemia and of its risk of adverse cardiovascular and limb outcomes. In addition, our inadequate knowledge of its pathophysiology has also limited the development of effective treatments, particularly in the presence of critical limb ischemia. This review aims to highlight essential elements of the epidemiology and pathophysiology of peripheral artery disease, bring attention to the often-atypical manifestations of occlusive arterial disease of the lower extremity, increase awareness of critical limb ischemia, briefly describe the diagnostic role of the ankle brachial index, and go over the contemporary management of peripheral artery disease. An emphasis is placed on evidence-based medical treatments to improve symptoms and quality of life and to reduce the risk of cardiovascular and limb events in these patients, including supervised exercise training, smoking cessation, antagonism of the renin-angiotensin system, lipid-lowering, antiplatelet, and antithrombotic therapies.

Bridging Experience With Eptifibatide After Stent Implantation.

BACKGROUND: Patients who have undergone intracoronary stent implantation often require surgery within the first year after the procedure. Planned or emergent surgical intervention requires interruption of antiplatelet therapy and is associated with an increased risk of stent thrombosis. Eptifibatide, an intravenous glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa), can be considered for antiplatelet bridging of high-risk patients in the periprocedural period. OBJECTIVES: The aim of this report is to describe the management of antiplatelet therapy and outcomes of patients who were bridged with eptifibatide perioperatively within 1 year of intracoronary stent implantation. METHODS: We performed a retrospective analysis of patients identified through the hospital's computer system consecutively from January 1, 2011 to December 31, 2014. We included 18 patients who were bridged from an oral P2Y12-receptor antagonist with eptifibatide before surgery. Outcome measures were the incidence of thromboembolic events or stent thrombosis within 30 days of surgery and death within 90 days of hospital discharge. Safety measures were the incidence of thrombolysis in myocardial infarction major, minor, or minimal bleeding. RESULTS: Of the 18 patients assessed, no patients experienced thromboembolic events or stent thrombosis. There was one major bleeding event and one minimal bleeding event postoperatively. Antiplatelet therapy management was highly variable in the perioperative period with 72.2% receiving the recommended GPIIb/IIIa loading dose, 50% of patients not continuing aspirin throughout the surgery, 27.8% of patients stopping antiplatelet therapy less than 5 days before surgery, and 50% not receiving a loading dose of an oral P2Y12-receptor antagonist postoperatively. CONCLUSIONS: Within a limited sample size, bridging with an intravenous GPIIb/IIIa inhibitor appeared feasible. Further study is needed on the optimal strategy to manage patients with recent stenting who need surgical procedures.

Normal ventricular diameter ratio on CT provides adequate assessment for critical right ventricular strain among patients with acute pulmonary embolism.

There is variability in guideline recommendations for assessment of the right ventricle (RV) with imaging as prognostic information after acute pulmonary embolism (PE). The objective of this study is to identify a clinical scenario for which normal CT-derived right-to-left ventricular (RV/LV) ratio is sufficient to exclude RV strain or PE-related short-term death. This retrospective cohort study included 579 consecutive subjects (08/2003-03/2010) diagnosed with acute PE with normal CT-RV/LV ratio (<0.9), 236 of whom received subsequent echocardiography. To identify a clinical scenario for which CT-RV/LV ratio was considered sufficient to exclude RV strain or PE-related short-term death, a multivariable logistic model was created to detect factors related to subjects for whom subsequent echocardiography detected RV strain or those who did not receive echocardiography and died of PE within 14 days (n = 55). The final model included five variables (c-statistic = 0.758, over-fitting bias = 2.52 %): congestive heart failure (adjusted odds ratio, OR 4.32, 95 % confidence interval, CI 1.88-9.92), RV diameter on CT >45 mm (OR 3.07, 95 % CI 1.56-6.03), age >60 years (OR 2.59, 95 % CI 1.41-4.77), central embolus (OR 1.96, 95 % CI 1.01-3.79), and stage-IV cancer (OR 1.94, 95 % CI 0.99-3.78). If these five factors were all absent (37.1 % of the population), the probability that "CT-RV/LV ratio is sufficient to exclude RV strain/PE-related short-term death" was 0.97 (95 % CI = 0.95-0.99). Normal CT-RV/LV ratio plus readily obtained five clinical predictors were adequate to exclude RV strain or PE-related short-term mortality.

Comparative Effectiveness of Carotid Artery Stenting Versus Carotid Endarterectomy Among Medicare Beneficiaries.

BACKGROUND: Effectiveness of carotid artery stenting (CAS) relative to carotid endarterectomy (CEA) among Medicare patients has not been established. We compared effectiveness of CAS versus CEA among Medicare beneficiaries. METHODS AND RESULTS: We linked Medicare data (2000-2009) to the Society for Vascular Surgery's Vascular Registry (2005-2008) and the National Cardiovascular Data Registry's (NCDR) Carotid Artery Revascularization and Endarterectomy Registry (2006-2008/2009). Medicare patients were followed up from procedure date until death, stroke/transient ischemic attack, periprocedural myocardial infarction, or a composite end point for these outcomes. We derived high-dimensional propensity scores using registry and Medicare data to control for patient factors and adjusted for provider factors in a Cox regression model comparing CAS with CEA. Among 5254 Society for Vascular Surgery's Vascular Registry (1999 CAS; 3255 CEA) and 4055 Carotid Artery Revascularization and Endarterectomy Registry (2824 CAS; 1231 CEA) Medicare patients, CAS patients had a higher comorbidity burden and were more likely to be at high surgical risk (Society for Vascular Surgery's Vascular Registry: 96.7% versus 44.5%; Carotid Artery Revascularization and Endarterectomy Registry: 71.3% versus 44.7%). Unadjusted outcome risks were higher for CAS. Mortality risks remained elevated for CAS after adjusting for patient-level factors (hazard ratio, 1.24; 95% confidence interval, 1.06-1.46). After further adjustment for provider factors, differences between CAS and CEA were attenuated or no longer present (hazard ratio for mortality, 1.13; 95% confidence interval, 0.94-1.37). Performance was comparable across subgroups defined by sex and degree of carotid stenosis, but there was a nonsignificant trend suggesting a higher risk of adverse outcomes in older (>80) and symptomatic patients undergoing CAS. CONCLUSIONS: Outcomes after CAS and CEA among Medicare beneficiaries were comparable after adjusting for both patient- and provider-level factors.