Migraine headache in patients with spontaneous coronary artery dissection: A report of the iSCAD Registry.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified. METHODS: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine. RESULTS: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were more likely to be women (96.9% vs 90.3%, p = 0.0003). The presence of underlying carotid fibromuscular dysplasia was associated with migraine (35% vs 27%, p = 0.0175). There was not a significant association with carotid artery dissection and migraine. Current migraine frequency was less than monthly (58%), monthly (24%), weekly (16%), and daily (3%). Triptan use was reported in 32.5% of patients, and 17.5% used daily migraine prophylactic medications. Using the MIDAS to quantify disability related to migraine, 60.2% reported little or no disability, 14.4% mild, 12.7% moderate, and 12.7% severe. The mean MIDAS score was 9.9 (mild to moderate disability). Patients with SCAD had higher rates of depression and anxiety (28.2% vs 17.7% [p = 0.0004] and 35.3% vs 26.7% [p = 0.0099], respectively). CONCLUSIONS: Migraines are common, frequent, and a source of disability in patients with SCAD. The association between female sex, anxiety, and depression may provide some insight for potential treatment modalities.

ACR Appropriateness Criteria® Pulmonary Arteriovenous Malformation (PAVM): 2023 Update.

Pulmonary arteriovenous malformations (PAVMs) occur in 30% to 50% of patients with hereditary hemorrhagic telangiectasia. Clinical presentations vary from asymptomatic disease to complications resulting from the right to left shunting of blood through the PAVM such as paradoxical stroke, brain abscesses, hypoxemia, and cardiac failure. Radiology plays an important role both in the diagnosis and treatment of PAVM. Based on different clinical scenarios, the appropriate imaging study has been reviewed and is presented in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Posttraumatic Stress Disorder After Spontaneous Coronary Artery Dissection: A Report of the International Spontaneous Coronary Artery Dissection Registry.

BACKGROUND: Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry-based cohort, we documented prevalence of lifetime and past-month SCAD-induced PTSD, as well as related treatment seeking, and examined a range of health-relevant correlates of SCAD-induced PTSD. METHODS AND RESULTS: Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD-induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD-induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD-induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past-month PTSD. Of 811 patients ever reporting any SCAD-induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD-induced PTSD diagnoses reported never receiving trauma-related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past-month PTSD symptom severity in multivariable regression models. Greater past-month SCAD-induced PTSD symptoms were associated with greater past-week sleep disturbance and worse past-month disease-specific health status when adjusting for various risk factors. CONCLUSIONS: Given the high prevalence of SCAD-induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496687.

Aortic Dimensions Are Larger in Patients With Fibromuscular Dysplasia.

Background Fibromuscular dysplasia (FMD) is a disease of unknown etiology that causes stenosis, aneurysmal dilatation, and dissection of vascular beds. Known to affect medium-sized arteries, FMD is not typically considered to affect the aorta. We tested the hypothesis that aortic size in FMD is abnormal compared with age- and sex-matched controls. Methods and Results Medical records and computed tomography angiography images were reviewed in female patients with a diagnosis of FMD who were seen in the vascular medicine clinic at Emory Healthcare. Aortic dimensions were measured at 6 different landmarks. Using 2 sample t tests, the aortic measurements and height-indexed measurements were compared with published normal values in healthy women of a similar age. A total of 94 female patients were included in the study. The median age was 57 (interquartile range, 50-65). FMD involvement was present most commonly in the extracranial carotid (77.7%) and renal (43.6%) arteries. All 6 aortic segments were found to be larger in both absolute measures and height-indexed measures in the FMD population (P<0.001). The largest differences were observed within the absolute measures of the sinotubular junction with mean±SD (mm) (29.9±4.1) versus (27±2.5), ascending aorta (32.7±4.4) versus (30.0±3.5), and descending aorta (24.7±3.0) versus (22.0±2.0) (P<0.001). Conclusions Aortic diameters in female patients with FMD are larger when compared with published age- and sex-matched normal values. These findings suggest that FMD may also affect the large-sized arteries.

Measuring the quality of sentinel lymph node biopsy in breast cancer using newly developed quality indicators: a feasibility study.

BACKGROUND: Measurement of the quality of sentinel lymph node biopsy (SLNB) has not been reported beyond the false-negative rate and sentinel lymph node identification rate. This study's purpose is to determine the feasibility of measuring 11 quality indicators (QIs) that were recently developed using a modified Delphi process. METHODS: All patients who underwent SLNB for breast cancer at a tertiary health-care center from January 1st 2005 to December 31st 2007 were identified using a SLNB registry. Patient charts were reviewed retrospectively and the QIs were abstracted. RESULTS: Nine of the 11 QIs were measurable: 7 required chart-level abstraction, 2 were confirmed at an institutional level, and 2 were immeasurable due to registry limitations. Of the 497 identified patients, 13 patients had failed SLNB, resulting in 484 SLNBs. The axillary positivity rate was 19%. The method of SLN identification was reported in 97% of cases, and in 388 (80%) more than one SLN was removed. All SLNs were serially sectioned according to protocol, though only 102 (21%) of pathology reports explicitly stated the cancer stage. Nearly all SLNBs were performed alongside the primary breast surgery. Among SLN-positive patients: 78 (87%) underwent axillary lymph node dissection, 10 patients refused, and chart data were missing in 2 others. No "ineligible" patients had SLNB. CONCLUSION: Measurement of newly developed QIs for SLNB is feasible for abstraction from inpatient charts at a single institution. These QIs can provide baseline measures for ongoing quality assessment of SLNB using hospital chart review.

Premature atherosclerotic peripheral artery disease: An underrecognized and undertreated disorder with a rising global prevalence.

Premature atherosclerotic peripheral artery disease (PAD) of the lower extremities is characterized by disease diagnosis before the age of 50 years. The global prevalence of premature PAD has increased, and the disease is often underdiagnosed given heterogenous patient symptoms. Traditional cardiovascular risk factors like smoking, diabetes, hypertension, and hyperlipidemia as well as non-traditional risk factors like elevated lipoprotein(a), family history of PAD, hypercoagulability, and systemic inflammation are associated with premature PAD. Patients with premature PAD tend to have an aggressive vascular disease process, a high burden of cardiovascular risk factors, and other concomitant atherosclerotic vascular diseases like coronary artery disease. Prevention of cardiovascular events, improvement of symptoms and functional status, and prevention of adverse limb events are the main goals of patient management. In this review, we discuss the epidemiology, risk factors, clinical evaluation, and management of patients with premature PAD.

Association of Fibromuscular Dysplasia and Pulsatile Tinnitus: A Report of the US Registry for Fibromuscular Dysplasia.

Background Fibromuscular dysplasia (FMD) is a nonatherosclerotic arterial disease that has a variable presentation including pulsatile tinnitus (PT). The frequency and characteristics of PT in FMD are not well understood. The objective of this study was to evaluate the frequency of PT in FMD and compare characteristics between patients with and without PT. Methods and Results Data were queried from the US Registry for FMD from 2009 to 2020. The primary outcomes were frequency of PT among the FMD population and prevalence of baseline characteristics, signs/symptoms, and vascular bed involvement in patients with and without PT. Of 2613 patients with FMD who were included in the analysis, 972 (37.2%) reported PT. Univariable analysis and multivariable logistic regression were performed to explore factors associated with PT. Compared with those without PT, patients with PT were more likely to have involvement of the extracranial carotid artery (90.0% versus 78.6%; odds ratio, 1.49; P=0.005) and to have higher prevalence of other neurovascular signs/symptoms including headache (82.5% versus 62.7%; odds ratio, 1.82; P<0.001), dizziness (44.9% versus 22.9%; odds ratio, 2.01; P<0.001), and cervical bruit (37.5% versus 15.8%; odds ratio, 2.73; P<0.001) compared with those without PT. Conclusions PT is common among patients with FMD. Patients with FMD who present with PT have higher rates of neurovascular signs/symptoms, cervical bruit, and involvement of the extracranial carotid arteries. The coexistence of the 2 conditions should be recognized, and providers who evaluate patients with PT should be aware of FMD as a potential cause.

Beyond the false negative rate: development of quality indicators for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SNLB) has been adopted as the standard method of axillary staging for women with clinically node-negative early-stage breast cancer. The false negative rate as a quality indicator is impractical given the need for a completion axillary dissection to calculate. The objective of this study was to develop practical quality indicators for SLNB using an expert consensus method and to determine if they were feasible to measure. MATERIALS AND METHODS: We used a modified Delphi consensus process to develop quality indicators for SLNB. A multidisciplinary expert panel reviewed potential indicators extracted from the medical literature to select quality indicators that were relevant and measurable. Feasibility was determined by abstracting the quality indicator variables from a retrospective chart review. RESULTS: The expert panel prioritized 11 quality indicators as benchmarks for assessing the quality of surgical care in SNLB. Nine of the indicators were measurable at the chart or institutional level. CONCLUSIONS: A systematic evidence- and consensus-based approach was used to develop measurable quality indicators that could be used by practicing surgeons and administrators to evaluate performance of SLNB in breast cancer.

High-density lipoprotein therapy: is there hope?

OPINION STATEMENT: The treatment of lipid abnormalities generally has focused on low-density lipoprotein cholesterol (LDL-C) reduction based on extensive clinical trials and the National Cholesterol Education Program Adult Treatment Panel III guidelines. Unfortunately, it has become increasingly clear that a significant percentage of patients continue to have cardiovascular events despite being on LDL-C-lowering medications and having LDL-C levels below 100 mg/dL. Numerous epidemiologic studies have associated low high-density lipoprotein cholesterol (HDL-C) levels with increased risk of cardiovascular disease (CVD). Furthermore, recent data show that up to 55% of patients hospitalized for CVD have low HDL-C levels (<40 mg/dL) on admission, suggesting a possible target for further reducing CVD. Low HDL-C also is part of the atherogenic phenotype associated with obesity, glucose intolerance, and hypertension, termed the metabolic syndrome, and often is seen in patients with insulin resistance states. In general, the first line of therapy for increasing HDL-C in patients with levels below 40 mg/dL is lifestyle modification with smoking cessation, exercise, weight loss, and diet modifications. The pharmacologic treatment of isolated low HDL-C in patients without coronary disease is controversial but should be considered in those with a strong family history of CVD. In patients with coronary artery disease and isolated low HDL-C, statins remain the first-line therapy and should be instituted after lifestyle modifications, with the goal of increasing HDL-C above 40 mg/dL. If concomitant hypertriglyceridemia is present, a fibrate or niacin should be considered. Although statins do offer some HDL-C-raising properties, they tend to have modest effects. If treatment goals have not been achieved with either lifestyle changes or statin therapy, then the next agent of choice is niacin. Among the various HDL-C-raising therapies, niacin continues to be the most potent therapeutic option available. There are several novel HDL-C therapies in the research pipeline; however, only one class of medications is relatively close to clinical use, the cholesteryl ester transferase protein (CETP) inhibitors. Although one of the CETP inhibitors, torcetrapib, has received much negative attention from a large randomized trial showing increased mortality associated with its use, the overall class of therapeutic agents may still hold some benefit. Currently, two new CETP inhibitors without the off-target effects of torcetrapib are undergoing clinical research. Overall, the use of HDL-C-modifying agents likely will increase over the next decade.

New-Onset Uncontrolled Hypertension and Renal Failure in a Young Woman.

This report describes the case of a previously healthy 30-year-old woman who presented with uncontrolled hypertension and renal failure. This case emphasizes the importance of considering renal artery disease. The differential diagnosis for renal artery stenosis is discussed, and the diagnosis and management of Takayasu's arteritis in this patient are highlighted. (Level of Difficulty: Beginner.).

Long-term outcomes following salvage surgery for locally recurrent rectal cancer: A 15-year follow-up study.

BACKGROUND: Locally recurrent rectal cancer (LRRC) is a complex problem requiring multidisciplinary consultation and specialized surgical care. Given the paucity of published longer-term survival data, skepticism persists regarding the benefit of major extirpative surgery. We investigated ultra-long-term (~15 years) outcomes following radical resection of LRRC and sought relevant clinicopathologic prognostic variables. METHODS: A cohort of 52 consecutive patients who underwent resection of LRRC at our institution between 1997 and 2005 were followed with serial exams and imaging up to the point of death, or 30/06/2019. RESULTS: Median follow-up time was 16.5 years (9.9-18.3) for patients who were alive at last follow-up; only one patient was lost to follow-up, at 9.9 years. For the entire cohort of 52 patients, disease-specific survival (DSS) at 5, 10, and 15 years following salvage surgery was 41%, 33%, and 31%, respectively. All patients who had distant metastatic disease at the time of LRRC resection (n = 6) subsequently died of cancer, at a median of 21 months (4-46). In those without distant metastases at time of salvage surgery (n = 46), DSS at 5, 10, and 15 years was 47%, 38%, and 35%, respectively, median 60 months. Negative resection margin (R0) was independently predictive of superior outcomes. In patients with M0 disease who had R0 resection (n = 37), DSS at 5, 10 and 15 years was 58%, 47%, and 44%, respectively, median 73 months. No patient developed re-recurrence after 5.5 years. CONCLUSIONS: This study demonstrates exceptionally durable long-term cancer-free survival following salvage surgery for LRRC, indicating that cure is possible.

Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study.

BACKGROUND: Lower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promising results in experimental models and phase I/IIA clinical trials. The GPAD-3 trial will study the effect of two successive administrations of GM-CSF at 3-month interval for improving claudication among patients with lower extremity PAD. METHODS: We plan to recruit 176 patients in this ongoing randomized, double-blind, placebo-controlled Phase IIB trial. After screening for inclusion and exclusion criteria, eligible subjects undergo a 4-week screening phase where they perform subcutaneous placebo injections thrice weekly and walk at least three times a day until they develop claudication. After the screening phase, eligible subjects undergo baseline testing and are randomized 2:1 to receive 500 µg/day of GM-CSF subcutaneously thrice weekly for three weeks or placebo injections. After 3 months, follow-up endpoint testing is performed and subjects in the GM-CSF group receive the second administration of the drug for three weeks while subjects in placebo group receive matching placebo injections. All participants undergo endpoint testing at six-month and nine-month follow-up. The primary endpoint is change in 6-min walk distance between baseline and 6-month follow-up. CONCLUSION: GPAD-3 explores a novel approach to address the need for alternative therapies that can alleviate symptoms among patients with lower extremity PAD. If successful, this study will pave the way for a pivotal Phase III trial.

Live/real time three-dimensional transthoracic echocardiographic assessment of pulmonary regurgitation.

There is no gold standard for the measurement of pulmonary regurgitation (PR) severity. Two-dimensional (2D) transthoracic echocardiography is most commonly used to quantify PR severity using color Doppler criteria for aortic regurgitation. However, this method is limited by visualization of only one or two dimensions of the proximal PR jet or vena contracta (VC) precluding accurate assessment of its shape or size. This limitation would be expected to be obviated by three-dimensional (3D) transthoracic echocardiography, which could provide a more accurate quantitative assessment of PR severity. This study evaluated 82 adult patients with PR using 2D and 3D. PR VC area by 3D was obtained by planimetry by positioning the cropping plane exactly parallel to the VC, which was viewed en face by cropping of the 3D data set. Regurgitant volumes were calculated by 2D (assuming a circular VC) and by 3D as a product of the VC and velocity time integral obtained by color Doppler-guided conventional Doppler interrogation of the PR jet.The 3D VC area correlated with 2D jet width (JW)/right ventricular outflow tract (RVOT) width (r = 0.71) and 2D VC area (r = 0.79). 3D JW/RVOT width correlated with 2D JW/RVOT (r = 0.87). 3D regurgitant volumes also correlated with 2D regurgitant volumes (r = 0.76). The 3D VC values of <0.20, 0.20-0.45, 0.46-1.15, and >1.15 cm(2) and regurgitant volumes of <15 ml, 15-50 ml, 51-115 ml, and >115 ml were effective as cutoffs for grades 1, 2, 3, and 4 PR, respectively. In conclusion, quantification of 3D VC area and regurgitant volumes correlate reasonably well with the current 2D methods for measurement of PR. Since 3D visualizes PR VC in three dimensions, it would be expected to provide a more accurate and more quantitative assessment of PR severity as compared to 2D.