High Frequency of Microvascular Dysfunction in US Outpatient Clinics: A Sign of High Residual Risk? Data from 7,105 Patients

Previous studies have linked peripheral microvascular dysfunction measured by arterial tonometry to high residual risk in on-statin patients. Digital thermal monitoring (DTM) of microvascular function is a new and simplified technique based on fingertip temperature measurements that has been correlated with the burden of atherosclerosis and its risk factors. Here, we report analyses of DTM data from two large US registries: Registry-I (6,084 cases) and Registry-II (1,021 cases) across 49 US outpatient clinics. DTM tests were performed using a VENDYS device during a 5-minute arm-cuff reactive hyperemia. Fingertip temperature falls during cuff inflation and rebounds after deflation. Adjusted maximum temperature rebound was reported as vascular reactivity index (VRI). VRI distributions were similar in both registries, with mean ± SD of 1.58 ± 0.53 in Registry-I and 1.52 ± 0.43 in Registry-II. In the combined dataset, only 18% had optimal VRI (≥2.0) and 82% were either poor (<1.0) or intermediate (1.0-2.0). Women had slightly higher VRI than men ( 1.62 ± 0.56 vs. 1.54 ± 0.47 , p < 0.001 ). VRI was inversely but mildly correlated with age ( r = − 0.19 , p < 0.001 ). Suboptimal VRI was found in 72% of patients <50 years, 82% of 50-70 years, and 86% of ≥70 years. Blood pressure was not correlated with VRI. In this largest registry of peripheral microvascular function measurements, suboptimal scores were highly frequent among on-treatment patients, possibly suggesting a significant residual risk. Prospective studies are warranted to validate microvascular dysfunction as an indicator of residual risk.

Healthcare Practitioners’ Knowledge of Lymphedema

Objectives. Lymphedema is neglected in medical education, and a review on healthcare practitioners’ (HCPs) knowledge is necessary to shed light on gaps and to provide evidence for establishing educational programs on lymphedema. Methods. This systematic review was performed based on the PRISMA guideline in PubMed, Scopus, Web of Science, and Google Scholar databases. There was no limitation on the type of lymphedema or HCPs. The quality assessment was performed based on QATSDD. Data regarding study characteristics, questionnaire context, and findings of the study were summarized from each article. Results. After the screening, 16 articles were included that 12 were cross-sectional, two were qualitative, and two were interventional pilot studies. Breast cancer and other cancer-related lymphedema, lymphatic filariasis, and podoconiosis were included, and the majority of articles were focused on primary HCPs. The overall knowledge was low and average in five and 11 articles, respectively, and prior education was a significant factor related to higher knowledge of lymphedema in two studies. Conclusion. Structured education of lymphedema is needed to increase the knowledge of HCPs and to enhance their collaboration in multidisciplinary care teams. Improvement of HCPs’ knowledge may lead to better outcomes of lymphedema patients’ management which are neglected.

A Review of Risk Factors and Predictors for Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

Acute ischemic strokes (AIS) and hemorrhagic strokes lead to disabling neuropsychiatric and cognitive deficits. A serious and fatal complication of AIS is the occurrence of hemorrhagic transformation (HT). HT is cerebral bleeding that occurs after an ischemic event in the infarcted areas. This review summarises how specific risk factors such as demographic factors like age, gender, and race/ethnicity, comorbidities including essential hypertension, atrial fibrillation, diabetes mellitus, congestive heart failure, and ischemic heart disease along with predictors like higher NIHSS score, larger infarction size, cardioembolic strokes, systolic blood pressure/pulse pressure variability, higher plasma glucose levels, and higher body temperature during ischemic event, lower low-density lipoprotein and total cholesterol, early ischemic changes on imaging modalities, and some rare causes make an individual more susceptible to developing HT. We also discuss few other risk factors such as the role of blood-brain barrier, increased arterial stiffness, and globulin levels in patients postreperfusion using thrombolysis and mechanical thrombectomy. In addition, we discuss the implications of dual antiplatelet therapy and the length of treatment in reference to the incidence of developing HT. Current research into inflammatory mediators and biomarkers such as Cyclooxygenase-2, matrix metalloproteinases, and soluble ST2 and their potential role as treatment options for HT is also briefly discussed. Finally, this review calls for more research into use of dual antiplatelet and the timing of antiplatelet and anticoagulant use in reference to hemorrhagic transformation.

Segmental Arterial Mediolysis: A Multiguised Vasospastic Arteriopathy with Collateral Mesangial Cell Hyperplasia and Cardiac Toxicity Generated by Norepinephrine and Hyperdense Adrenoceptors Alone or by Crosstalk with Other Pressor Agents

Segmental arterial mediolysis (SAM), an uncommon vasospastic arteriopathy occurring in the muscular arteries innervated by the peripheral sympathetic nervous system, usually presents with catastrophic abdominal and retroperitoneal hemorrhages in elderly patients. SAM is initiated by the coupling of norepinephrine to plastically derived hyperdense foci of alpha-1 adrenergic receptors on the sarcolemma of arterial muscle. This ligand is created by stimuli signaled by iatrogenic sympathomimetic agonists, some beta-2 agonists, or an excessive release of adrenal catecholamines. Coupling of this ligand with cytoplasmic heterotrimeric Gq protein excessively signals a cascade of biochemical events generating two principal lesions of injurious-phase SAM—the shearing of the outer media from the adventitia and an overload of cytoplasmic calcium ions toxic to mitochondria causing mediolysis and/or apoptosis. The massive hemorrhages are caused by ruptured gap aneurysms created by the transmedial loss of the medial muscle. A norepinephrine-directed reparative response rapidly develops either resolving angiographic injurious lesions or creating a body of vascular disorders, the new guises of SAM with ischemic clinical profiles. These present in the epicardial, vertebral, intestinal, and retroperitoneal arteries, often in younger females as fibromuscular dysplasia, dissecting hematomas, and persistent aneurysms. Norepinephrine can crosstalk with other pressor agents to create SAM lesions—serotonin with idiopathic pulmonary hypertension and persistent pulmonary hypertension in the newborn, histamine in spontaneous coronary artery dissections with eosinophilia, and endothelin-1 in a field effect generated by SAM that creates venous fibromuscular dysplasia. Norepinephrine also participates in the collateral development of mesangial hyperplasia with focal segmental glomerulosclerosis and myocardial mediolysis and apoptosis in subjects with markedly elevated heart rates. Conclusion. Norepinephrine coupling with plastically elevated alpha-1 adrenoceptor or other pressor agents generates SAM, a histologically recognizable vasospastic arteriopathy, that with repair is transformed into several different standardized arterial diseases that alter SAM’s clinical profile from a hemorrhagic to an ischemic disorder.

Use of the AFX Stent Graft in Patients with Extremely Narrow Aortic Bifurcation: A Multicenter Retrospective Study

Introduction. This study analyzed the patient outcomes following endovascular aortic aneurysm repair (EVAR) for infrarenal aortic pathologies with very narrow aortic bifurcations using the AFX stent graft. Methods. The data was retrieved from the archived medical records of 35 patients treated for abdominal aortic aneurysm (AAA) (48.6%) or penetrating aortic ulcer (PAU) (51.4%) with very narrow aortic bifurcation between January 2013 and May 2020. Patient survival, freedom from endoleak (EL), and limb occlusion were estimated applying the Kaplan–Meier method. Results. The mean follow-up time was 20.4 ± 22.8 months. The mean aortic bifurcation diameter was 15.8 ± 2.2 mm . Technical success was 100%, and no procedure-related deaths occurred. Two type II ELs occurred within 30-day follow-up. We observed one common iliac artery stenosis at four months and one type III EL at 54 months in the same patient, both of which required re-intervention. Overall patient survival was 95 ± 5 % (AAA: 100%; PAU: 89 ± 10 % ), freedom from limb occlusion was 94 ± 5 % (AAA: 91 ± 9 % ; PAU: 100%), freedom from type II EL was 94 ± 4 % (AAA: 88 ± 8 % ; PAU: 100%), and freedom from EL type III was 83 ± 15 % (AAA: 80 ± 18 % ; PAU: 100%) at the end of the follow-up period. Conclusions. Very narrow aortic bifurcations may predispose patients to procedure-related complications following EVAR. Our results suggest a safe use of the AFX stent graft in such scenarios. The overall short- and long-term procedure-related patient outcomes are satisfying albeit they may seem superior for PAU when compared to AAA.

Retrograde Popliteal Access for Challenging Superficial Femoral Artery Occlusion

Retrograde popliteal access has long been established as an alternative to the antegrade approach to occlusive lesions in the superficial femoral artery (SFA). However, early reports with high complication rates (dissection, hematomas, aneurysms, and arteriovenous shunts at the puncture site) reduced enthusiasm for this technique. In recent years, with the development of thinner sheaths and low profile angioplasty devices, retrograde popliteal access has resurfaced as a viable technique, mostly in combination with or after failure of the more classical antegrade approach. In this retrospective study, we will report the safety and efficacy of the retrograde popliteal approach in the treatment of superficial femoral artery chronic total occlusions, in 13 consecutive patients between January 2017 and January 2021. The results showed 100% successful puncture of the popliteal artery and 100% successful recanalization and stenting of the superficial femoral artery with a total of 2 complications related to the puncture site and zero periprocedural mortality. In conclusion, the retrograde popliteal approach appears to be an effective and safe alternative to the common SFA complete total occlusion (CTO) treatment approach.

Adherence to the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline on the Use of Oral Anticoagulant Agents in Middle Eastern Patients with Atrial Fibrillation: The Jordan Atrial Fibrillation (JoFib) Study

Background. There is a scarcity of studies that evaluate adherence to the utilization of guideline-recommended oral anticoagulant agents (OACs) in patients with atrial fibrillation (AF) in the Middle East. The Jordan Atrial Fibrillation (JoFib) Study evaluated baseline clinical profiles and the utilization of OACs, including vitamin K antagonists (VKAs) and direct OACs (DOACs), in patients with valvular AF (VAF) and nonvalvular AF (NVAF) according to the 2019 focused update of the 2014 AHA/ACC/HRS guidelines. Methods. Consecutive patients with AF were enrolled in 29 hospitals and outpatient clinics. The use of OACs was evaluated in patients with VAF and NVAF according to the prespecified guideline. Results. Of 2000 patients, 177 (8.9%) had VAF and 1823 (91.1%) had NVAF. A VKA was prescribed for 88.1% of the VAF group. In the NVAF group, 1468 (80.5%) of patients had a high CHA2DS2-VASc score, i.e., a score of ≥3 in women and ≥2 in men; 202 (11.1%) patients had an intermediate CHA2DS2-VASc score, i.e., a score of 2 in women and 1 in men; and 153 (8.4%) patients had a low CHA2DS2-VASc score, i.e., a score of 1 in women and 0 in men. Of patients with a high CHA2DS2-VASc score, 1204 (82.0%) received OACs, including DOACs for 784 (53.4%) and VKA for 420 (28.6%) patients. Among patients with an intermediate score, OACs were prescribed for 148 (73.3%) patients, including 107 (53.0%) who received DOACs and 41 (20.3%) patients who received VKA. In patients with a low score, OACs were omitted in 94 (61.4%) patients and prescribed for 59 (38.6%) patients. Multivariate analysis showed that age between 50 and 70 years, CHA2DS2-VASc score of ≥2, a diagnosis of stroke or systemic embolization, and nonparoxysmal AF were significantly associated with increased odds of OAC prescription. Conclusions. The current status of the utilization of OACs in Middle Eastern AF patients appears to be promising and is consistent with the 2019 focused update of the 2014 AHA/ACC/HRS guideline. This trial is registered with NCT03917992.

Thermal Disparity among Fingers and Its Amelioration by CO2-Water Bathing in Connective Tissue Disease Patients

Objective. Correlation between a low finger temperature and thermal disparity among fingers was studied in connective tissue disease (CTD) patients. Whether the thermal disparity may be ameliorated by hand immersion in a warm carbon dioxide- (CO2-) water bath was analyzed. Methods. CTD patients with suspected peripheral circulation disorder underwent a thermography test. From before to 30 min after hand immersion in CO2-water (CO2 bathing; 1000 ppm CO2, 42°C, 10 min), the nailfold temperatures were measured. The mean temperature (m-Temp) and the coefficient of variation of the temperature ( CV = SD / m ‐ Temp of one hand; the mean of CVs of both hands was adopted as the indicator of thermal disparity) were monitored. The correlation between m-Temp and CV was also analyzed. Results. Forty-seven (45 females and 2 males) patients were included, 32 of whom had Raynaud’s phenomenon. The m-Temp was 30.8 ± 3.0 ° C at the baseline, increased to 35.3 ± 1.0 ° C immediately after CO2 bathing, and remained significantly higher than that at the baseline until 30 min after ( 32.1 ± 1.9 ° C ). The CV was 0.0291 ± 0.0247 at the baseline, decreased to 0.0135 ± 0.0039 immediately after CO2 bathing, and remained significantly lower than the baseline until 30 min after ( 0.0163 ± 0.0143 ). Between m-Temp and CV, a negative correlation was observed throughout the measurements. Conclusion. Thermal disparity was observed at baseline measurement in CTD patients. Warm CO2 bathing markedly ameliorated the disparity, and this amelioration remained until after 30 min. Throughout the observation, the lower the m-Temp, the more severe the thermal disparity among fingers.

The Role of Angiotensin Antagonism in Coronary Plaque Regression: Insights from the Glagovian Model

The benefit of antagonizing the effect of the renin angiotensin aldosterone system (RAAS), notably by the use of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II type 1 receptor blocker (ARB) for coronary artery disease (CAD), has been demonstrated in multiple studies, which may be attributed to their ability to inhibit the deleterious effect of RAAS to the cardiovascular system. It is well known that angiotensin II (Ang II) plays a vital role in atheromatous plaque formation and progression through multiple pathways, including inflammatory and arterial remodeling aspects. Significant coronary atheromatous plaque regression has been previously demonstrated in various studies using statin agents. Similar results have been reported in different studies using angiotensin inhibitor agents, notably ARB agents. Analysis from various trials utilizing ARB showed a significant plaque regression using olmesartan and telmisartan as evaluated by IVUS studies. In contrary, the use of ACEi did not demonstrated significant plaque regression, which may be attributed to the heavy plaque calcification in respective studies. On this review, we aim to present the basic mechanism on the role of RAAS in plaque modulation and its arterial remodeling aspect, which is then integrated with the clinical evidence based on the available intravascular ultrasonography (IVUS) studies on coronary arteries.

Renal Vascular Response to Angiotensin II Administration in Two Kidneys-One Clip Hypertensive Rats Treated with High Dose of Estradiol: The Role of Mas Receptor

Backgrounds. High blood pressure is one of the most important causes of death around the world. The renin-angiotensin system (RAS) and estradiol are two important items that regulate arterial blood pressure in women. However, hypertension, RAS, and sex hormone estradiol may influence renal vascular responses. This study was designed to determine the role of Mas receptor (MasR) on renal vascular response to angiotensin II (Ang II) administration in two kidneys-one clip (2K1C) hypertensive rats treated with estradiol. Method. The ovariectomized rats were subjected to 2K1C or non-2K1C and simultaneously treated with estradiol (500 μg/kg/weekly) or placebo for a period of 4 weeks. Subsequently, under anesthesia, renal vascular responses to graded doses of Ang II administration with MasR blockade (A779) or its vehicle were determined. Results. A779 or its vehicle did not alter mean arterial pressure (MAP), renal perfusion pressure (RPP), and renal blood flow (RBF). However, in non-2K1C rats, Ang II infusion decreased RBF and increased renal vascular resistance (RVR) responses in a dose-related manner ( P treat < 0.0001 ). The greatest responses were found in ovariectomized estradiol-treated rats that received A779 ( P group < 0.05 ) in non-2K1C rats. Such findings were not detected in 2K1C hypertensive rats. For example, in estradiol-treated rats that received A779, at 1000 ng/kg/min of Ang II infusion, RBF reduced from 1.6 ± 0.2 to 0.89 ± 0.19 ml/min in non-2K1C rats, and it reduced from 1.6 ± 0.2 to 1.2 ± 0.2 ml/min in 2K1C rats. Conclusion. Hypertension induced by 2K1C may attenuate the role of A779 and estradiol in renal vascular responses to Ang II infusion. Perhaps, this response can be explained by the reduction of Ang II type 1 receptor (AT1R) expression in the 2K1C hypertensive rats.