Developmental or Procedural Vena Cava Interruption and Venous Thromboembolism: A Review.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.

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.

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.

Interpretation of peripheral arterial and venous Doppler waveforms: A consensus statement from the Society for Vascular Medicine and Society for Vascular Ultrasound.

This expert consensus statement on the interpretation of peripheral arterial and venous spectral Doppler waveforms was jointly commissioned by the Society for Vascular Medicine (SVM) and the Society for Vascular Ultrasound (SVU). The consensus statement proposes a standardized nomenclature for arterial and venous spectral Doppler waveforms using a framework of key major descriptors and additional modifier terms. These key major descriptors and additional modifier terms are presented alongside representative Doppler waveforms, and nomenclature tables provide context by listing previous alternate terms to be replaced by the new major descriptors and modifiers. Finally, the document reviews Doppler waveform alterations with physiologic changes and disease states, provides optimization techniques for waveform acquisition and display, and provides practical guidance for incorporating the proposed nomenclature into the final interpretation report.

Comparison of different exercise ankle pressure indices in the diagnosis of peripheral artery disease.

Although the resting ankle-brachial index (ABI) is commonly used as a tool to diagnose peripheral artery disease (PAD), several additional indices measured after exercise may have increased sensitivity for identifying PAD. The aim of this study was to determine the utility of resting ABI and three post-exercise physiological parameters for diagnosing PAD confirmed by arterial imaging studies. For each qualifying study, we assessed the performance measures for identifying PAD for resting ABI < 0.90, exercise ABI < 0.90, a decrease in ABI > 20% with exercise, and a decrease in ankle pressure > 30 mmHg with exercise. Of the 199 exams that met our inclusion criteria, imaging showed a > 75% stenotic lesion in at least one limb in 138 (69%) of patients. For stenoses > 75%, resting ABI < 0.90 had a sensitivity of 64% (95% CI: 56-72%) and exercise ABI < 0.90 had a sensitivity of 88% (95% CI: 82-93%). The sensitivity for a post-exercise ABI decrease > 20% was 67% (95% CI: 59-75%) and the sensitivity for a decrease in ankle pressure > 30 mmHg was 4% (95% CI: 2-9%). For individuals with a normal resting ABI but stenotic lesions > 75% confirmed by imaging (n=49), the addition of exercise ABI testing correctly identified an additional 25% of this population. Overall, exercise ABI < 0.90 exhibits a greater sensitivity for detecting PAD compared to resting ABI. Furthermore, exercise ABI < 0.90 had added clinical utility in patients with normal resting ABIs and was superior to other commonly used exercise indices.

Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.

BACKGROUND: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation. METHODS: Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial. RESULTS: No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial. CONCLUSIONS: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.

Surgeon case volume and 30-day mortality after carotid endarterectomy among contemporary medicare beneficiaries: before and after national coverage determination for carotid artery stenting.

BACKGROUND AND PURPOSE: After the 2005 National Coverage Determination to reimburse carotid artery stenting (CAS) for Medicare beneficiaries, the number of CAS procedures increased and carotid endarterectomy (CEA) decreased. We evaluated trends in surgeons' past-year CEA case-volume and 30-day mortality after CEA, and their association before and after the National Coverage Determination. METHODS: In a retrospective cohort study of patients undergoing CEA (2001-2008) and CAS (2005-2008) using Medicare data, we described yearly trends of CEA and CAS rates, patient characteristics, and 30-day mortality after CEA. We used logistic regression adjusting for patient- and surgeon-level factors to assess the effect of surgeon case volume on 30-day mortality after CEA. RESULTS: We identified 454 717 CEA and 27 943 CAS patients. Patients undergoing CEA in recent years were older and had more comorbidities than earlier years. CEA rates per 10 000 beneficiaries declined from 18.1 in 2002 to 12.7 in 2008, whereas median surgeon past-year case-volume declined from 27 to 21. The CAS rates peaked at 2.3 per 10 000 beneficiaries in 2006 but declined to 1.8 in 2008, resulting in declining overall revascularization procedure rates during 2005 to 2008. Thirty day post-CEA mortality was 1.40% (95% confidence interval, 1.34-1.47) in 2001 to 2002 and 1.17% (1.10-1.24) in 2007 to 2008. Surgeon's past-year case-volume of <10 was associated with higher 30-day mortality consistently during 2001 to 2008. CONCLUSIONS: The rate of CEA procedures decreased substantially during 2001 to 2008, as did surgeon past-year case-volume. The postprocedural mortality in Medicare beneficiaries was high compared with trial patients but somewhat improved over time. Those operated by lower past-year case-volume surgeons had increased mortality.

Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.

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.