Association of sex and cardiovascular risk factors with atherosclerosis distribution pattern in lower extremity peripheral artery disease.

Objective: Atherosclerosis expression varies across not only coronary, cerebrovascular, and peripheral arteries but also within the peripheral vascular tree. The underlying pathomechanisms of distinct atherosclerosis phenotypes in lower extremity peripheral artery disease (PAD) is poorly understood. We investigated the association of cardiovascular risk factors (CVRFs) and atherosclerosis distribution in a targeted approach analyzing symptomatic patients with isolated anatomic phenotypes of PAD. Methods: In a cross-sectional analysis of consecutive patients undergoing first-time endovascular recanalization for symptomatic PAD, data of patients with isolated anatomic phenotypes of either proximal (iliac) or distal (infrageniculate) atherosclerosis segregation were extracted. We performed a multivariable logistic regression model with backward elimination to investigate the association of proximal and distal PAD with CVRFs. Results: Of the 637 patients (29% females) with endovascular recanalization, 351 (55%) had proximal and 286 (45%) had distal atherosclerosis. Female sex [odds ratio (OR) 0.33, 95% confidence interval (CI) 0.20-0.54, p = 0.01], active smoking (OR 0.16, 95% CI 0.09-0.28, p < 0.001), and former smoking (OR 0.33, 95% CI 0.20-0.57, p < 0.001) were associated with proximal disease. Diabetes mellitus (DM) (OR 3.25, 95% CI 1.93-5.46, p < 0.001), chronic kidney disease (CKD) (OR 1.18, 95% CI 1.08-1.28, p < 0.001), and older age (OR 1.31, 95% CI 1.06-1.61, p = 0.01) were associated with distal disease. Conclusion: Female sex, particularly in the context of smoking, is associated with clinically relevant, proximal atherosclerosis expression. Our additional findings that distal atherosclerosis expression is associated with DM, CKD, and older age suggest that PAD has at least two distinct atherosclerotic phenotypes with sex-specific and individual susceptibility to atherogenic risk factors.

Clinical presentation of simple and combined or syndromic arteriovenous malformations.

OBJECTIVE: Arteriovenous malformations of the lower extremities (AVMLE) can present as simple or complex combined or syndromic forms (eg, Parkes Weber Syndrome). We aimed to characterize the differences in clinical presentation and natural history of these potentially life- and limb-threatening congenital vascular malformations. METHODS: We conducted a retrospective analysis of a consecutive series of patients with AVMLE who presented to a tertiary referral center in Switzerland between 2008 and 2018. Clinical baseline characteristics, D-dimer level, and course were summarized and differences between simple, non-syndromic and combined or syndromic AVMLE determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: Overall, 506 patients were prospectively enrolled in the Bernese Congenital Vascular Malformation Registry, 31 (6%) with AVMLE. There were 16 women and 15 men, with a mean age of 18 years at first diagnosis (range, 1 month to 72 years). Simple AVMLE was present in 22 (71%) and combined or syndromic AVMLE with limb overgrowth in 9 patients (29%), respectively. Common symptoms and signs were pain (n = 25; 81%), swelling (n = 21; 68%), and soft tissue hypertrophy (n = 13; 42%). Among combined or syndromic patients, three patients died from wound infection with sepsis or disseminated intravascular coagulation with bleeding complications (intracranial hemorrhage and bleeding from extensive leg ulcers). Combined or syndromic patients presented more often with bleeding (67% vs 5%; P < .001), malformation-related infection (44% vs 5%; P = .017) and leg length difference (56% vs 14%; P = .049). D-dimer levels were elevated (mean, 17,256 µg/L; range, 1557-80,000 µg/L) and angiographic appearance showed complex, mixed type of AVMs, including interstitial type IV, in all patients with combined or syndromic AVMLE. CONCLUSIONS: Patients with congenital simple AVMLE most often present with benign clinical features and rarely with complications related to hemodynamic changes. Patients with combined or syndromic AVMLE often face serious outcomes dominated by complications other than direct high-flow-related heart failure.

A systematic review of the safety and efficacy of currently used treatment modalities in the treatment of patients with PIK3CA-related overgrowth spectrum.

BACKGROUND: PIK3CA (activating mutations of the p110α subunit of phosphatidylinositol 3-kinases)-related overgrowth spectrums (PROS) include a variety of clinical presentations that are associated with hypertrophy of different parts of the body. We performed a systematic literature review to assess the current treatment options and their efficacy and safety for PROS. METHODS: A literature search was performed in Embase, MEDLINE (Ovid), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar to retrieve studies on the treatment of hypertrophy in PROS. Randomized controlled trials, cohort studies, and case series with ≥10 patients were included in the present review. The titles, abstracts, and full text were assessed by two reviewers independently. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: We included 16 studies of the treatment of hypertrophy in PROS patients, 13 (81.3%) from clinical retrospective studies and 3 (13.7%) from prospective cohort studies. The risk of bias grade was low for 2, medium for 12, and high for 2 studies. Of the 16 studies, 13 reported on surgical treatment and 3 reported pharmacologic treatment using phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway inhibitors in PROS patients. In 3 studies, PROS was defined by a mutation in the PIK3CA gene, and 13 studies relied on a clinical definition of PROS. Surgical therapy was beneficial for a specific subgroup of PROS (macrodactyly). However, little has been reported concerning surgery and the potential benefits for other PROS entities. The reported side effects after surgical therapy were mostly prolonged wound healing or scarring. PI3K/mTOR pathway inhibition was beneficial in patients with PROS by reducing hypertrophy and systemic symptoms. The adverse effects reported included infection, changes in blood count, liver enzymes, and metabolic measures. CONCLUSIONS: Surgery is a locally limited treatment option for specific types of PROS. A promising treatment option for PROS is pharmacologic PIK3CA inhibition. However, the level of evidence on the treatment of overgrowth in PROS patients is limited.

Capillary-venule malformation is a microfistulous variant of arteriovenous malformation.

OBJECTIVE: To describe typical clinical presentation of patients with microfistular, capillary-venule (CV) malformation as a variant form of arteriovenous malformations (AVM). METHODS: A retrospective clinical analysis of 15 patients with CV-AVM confirmed by a computational flow model enrolled in a prospective database of patients with congenital vascular malformation between January 2008 and May 2018. RESULTS: The mean age of the patients at first time of presentation was 30 years with balanced sex ratio. Presentation was dominated by soft tissue hypertrophy (n = 12 [80.0%]) and atypical varicose veins (n = 11 [73.3%]). The anatomic location of enlarged varicose veins gave no uniform pattern and did not correspond with the typical picture of primary varicose vein disease. Most often, symptomatic CV-AVM was found at the lower extremities in this series of unselected patients. The most frequent compartment affected was the subcutis (n = 14 [93.3%]), involvement of muscle was recorded in one-third and cutis in one-fourth of patients. CONCLUSIONS: A high grade of clinical suspicion is needed to recognize CV-AVM and to prevent inadequate therapy owing to missed diagnosis.