Quantitative assessment of angioplasty-induced vascular inflammation with 19F cardiovascular magnetic resonance imaging.

BACKGROUND: Macrophages play a pivotal role in vascular inflammation and predict cardiovascular complications. Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorocarbon allows a background-free direct quantification of macrophage abundance in experimental vascular disease models in mice. Recently, perfluorooctyl bromide-nanoemulsion (PFOB-NE) was applied to effectively image macrophage infiltration in a pig model of myocardial infarction using clinical MRI scanners. In the present proof-of-concept approach, we aimed to non-invasively image monocyte/macrophage infiltration in response to carotid artery angioplasty in pigs using 19F MRI to assess early inflammatory response to mechanical injury. METHODS: In eight minipigs, two different types of vascular injury were conducted: a mild injury employing balloon oversize angioplasty only (BA, n = 4) and a severe injury provoked by BA in combination with endothelial denudation (BA + ECDN, n = 4). PFOB-NE was administered intravenously three days after injury followed by 1H and 19F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using X-ray angiography, intravascular ultrasound and immunohistology in at least 10 segments per carotid artery. RESULTS: Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and concomitant infiltration of monocytes/macrophages. No severe adverse reactions were observed following PFOB-NE administration. In vivo 19F signals were only detected in the four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8. Ex vivo analysis revealed a linear correlation of 19F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was estimated at approximately 410 cells/mm2. CONCLUSIONS: In this proof-of-concept study, 19F MRI enabled quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This may provide the opportunity to non-invasively monitor vascular inflammation with MRI in patients after angioplasty or even in atherosclerotic plaques.

A patient with chest pain and a high-risk ECG pattern: The Wellens' syndrome.

This case highlights the ECG interpretation in acute coronary syndrome absence from ST - elevation myocardial infarction. A patient with acute chest pain and biphasic T - waves or deep inverted T- waves in V2-V3 is at risk for myocardial infarction. Timely cardiological assessment and coronary angiography is required.

Endovascular snare retrieval of an Angio-Seal causing acute limb ischemia.

Vascular complications (VCs) remain an important source of morbidity and mortality following percutaneous arterial catheterization. Vascular closure devices are popular and frequently used, but sometimes cause vessel occlusions that may require vascular surgery or complex endovascular procedures. In this case report, we describe the endovascular retrieval of an embolized Angio-Seal device causing acute limb ischemia in a severely diseased 75-year-old female patient. This case highlights the endovascular technique using a snare catheter and adds another example to the growing evidence of an endovascular approach to manage vascular access site complications in comorbid patients at risk.

Impact of high on-treatment platelet reactivity after angioplasty in patients with critical limb ischemia.

OBJECTIVES: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard of care in patients with peripheral artery disease (PAD) after percutaneous transluminal angioplasty (PTA). However, high on treatment platelet reactivity (HTPR) to DAPT is frequent and associated with major adverse limb events (MALE) in PAD patients. Nevertheless, association of MALE and HTPR in patients with critical limb ischemia (CLI) is not known. Moreover, comorbidities might confound response to antiplatelet medication further. Hence, in this trial we analyzed pharmacodynamic responses to DAPT and clinical events in CLI patients post PTA. METHODS: In this prospective single center pilot analysis, we included 71 CLI patients. Patients received DAPT after PTA. Antiplatelet effect were measured by light transmission aggregometry (LTA) and vasodilator-stimulated protein phosphorylation assay (VASP). MALE, major adverse cardiac and cerebrovascular events (MACCE) and BARC bleeding within 12 months follow-up were assessed. RESULTS: Mean age of patients was 73.37 ± 7.36 years and 47 (66.2%) were male. Overall HTPR appeared in 46 patients (64.8%). MALE and MACCE showed no differences between patients with and patients without HTPR. However, bleeding was higher in patients with sufficient pharmacodynamic response to DAPT (Bleeding - HTPR: 13.4% vs. no HTPR: 36.0%; log-rank HR: 0.32; 95% CI 0.1079 to 0.9396 p = 0.0217). This finding remained robust in multivariate analysis. CONCLUSION: HTPR to DAPT is frequent in CLI patients. However, bleeding was higher in patients with sufficient response to DAPT. Ischemic events did not differ. Hence, CLI patients might benefit from an alternative antithrombotic approach.

Angioplasty of Flow-Limiting Stenosis Reduces Aortic and Brachial Blood Pressure in Patients With Peripheral Artery Disease.

Background Arterial hypertension affects cardiovascular outcome in patients with peripheral artery disease (PAD). We hypothesized that angioplasty of peripheral arterial stenoses decreases aortic (aBP) and brachial blood pressure (bBP). Methods and Results In an index cohort (n=30), we simultaneously measured aBP, bBP, augmentation index (AIx), and aortic pulse wave velocity (PWV) before and after angioplasty of the iliac and femoropopliteal arteries; diagnostic angiography served as a control. In an all-comer registry cohort (n=381), we prospectively measured bBP in patients scheduled for angioplasty of the iliac, femoral, and crural arteries or diagnostic angiography. Systolic aBP decreased after iliac (Δ-25 mmHg; 95% CI, -30 to -20; P<0.0001) and femoropopliteal angioplasty (Δ-12 mmHg; 95% CI, -17 to -5; P<0.0001) as compared with diagnostic angiography. Diastolic aBP decreased after iliac (Δ-9 mmHg; 95% CI, -13 to -1; P=0.01) but not femoropopliteal angioplasty. In parallel, AIx significantly dropped, whereas PWV remained stable. In the registry cohort, systolic bBP decreased after angioplasty of the iliac (Δ-17 mmHg; 95% CI, -31 to -8; P=0.0005) and femoropopliteal arteries (Δ-10 mmHg; 95% CI, -23 to -1; P=0.04) but not the crural arteries, as compared with diagnostic angiography. Diastolic bBP decreased after iliac (Δ-10 mmHg; 95% CI, -17 to -2; P=0.01) and femoropopliteal angioplasty (Δ-9 mmHg; 95% CI, -15 to -1; P=0.04). Multivariate analysis identified baseline systolic bBP and site of lesion as determinants of systolic bBP drop after endovascular treatment. Conclusions Angioplasty of flow-limiting stenoses in patients with peripheral artery disease lowers aortic and brachial blood pressure with more pronounced effects at more proximal lesion sites and elevated baseline systolic blood pressure. These data indicate a role of endovascular treatment to acutely optimize blood pressure in patients with peripheral artery disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02728479.

Impact of high on-treatment platelet reactivity after angioplasty in patients with peripheral arterial disease.

Objective: High on-treatment platelet reactivity (HTPR) to dual antiplatelet therapy (DAPT) predicts adverse events in coronary artery disease patients. In peripheral artery disease (PAD) patients, data concerning the clinical impact of HTPR are limited. Therefore, we evaluated the incidence of (i) HTPR to DAPT and (ii) its impact on 6 months outcome after angioplasty.Methods and results: In this prospective single center analysis, we investigated 102 consecutive patients with PAD from 2016 to 2017. All patients underwent peripheral endovascular treatment due to intermittent claudication (Fontaine IIb). Clopidogrel effects were measured using vasodilator-stimulated protein phosphorylation (VASP) assay, aspirin effects by light-transmission aggregometry (LTA). Major adverse limb events (MALE), major adverse cardiac and cerebrovascular events (MACCE) and BARC bleeding (bleeding academic research consortium classification) within 6 months were assessed. HTPR to clopidogrel (n = 37, 36%), to aspirin (n = 11, 11%) and to both (n = 11, 11%) were frequent. Compared to sufficient platelet inhibition by aspirin and clopidogrel (n = 43, 42%), patients with dual HTPR showed a higher risk of MALE at 6 months (27% vs. 7%; hazard ratio [HR]: 4.45; 95% confidence interval [CI]: 1.1 to 67.8; p = .03). This was independent of diabetes, creatinine, body mass index, and age as well as of procedural details in a multivariate logistic regression analysis. MACCE (n = 2) and BARC bleeding rates (n = 2) were low.Conclusion: In this small exploratory study, HTPR was frequent in PAD patients. Furthermore, the results are suggestive that MALE might be associated with dual HTPR. This leads to the hypothesis that optimized antithrombotic regimens post percutaneous transluminal angioplasty should be tested in clinical trials.

Lipid lowering therapy in cardiovascular disease: From myth to molecular reality.

Lipid-lowering therapy is one major cornerstone of medical treatment of cardiovascular disease in order to modulate atherosclerosis. Statins, ezetimibe and novel PCSK9-inhibitors are already recommended in current guidelines and were shown to improve lipid profiles and have positive effects on the rate of ischemic events and cardiovascular mortality. Recent studies suggest that the concept of "The lower the better" might be valid at least regarding low density lipoproteins. In addition, lowering lipoprotein (a) still displays a major challenge in lipid therapy. Furthermore, also lowering triglycerides seems to improve cardiovascular outcome. Regarding triglycerides, icosapent ethyl, a polyunsaturated fatty acid recently attracted attention showing cardiovascular risk reduction due to triglyceride lowering. Therefore, new therapeutic strategies and drug classes are eagerly awaited. Targeting LDL, bempedoic acid and the siRNA inclisiran provide promising results. Moreover, regarding TG a monoclonal antibody called evinacumab and an antisense-oligonucleotide against ANGPTL3 showed effective TG-lowering. At least, using antisense-oligonucleotides against ApoC-III and Lp(a) resulted in promising outcomes. In this review, current and future options for lipid management are presented depending on different drug classes.

Endovascular Occlusion of a Renal Arteriovenous Fistula with Renal Vein Aneurysm Formation for Rupture Prevention.

PURPOSE: To report the effectiveness of left renal artery (LRA) occlusion using Amplatzer Vascular Plug (AVP) II as treatment for a high-flow renal arteriovenous fistula (RAVF) with multiple renal vein aneurysms (RVA) to prevent aneurysm rupture and cardiac decompensation. CASE REPORT: A 59-year-old female suffering from a post-traumatic RAVF presented with tachycardia and increased cardiac output (CO). Doppler ultrasonography and computed tomography (CT) scan revealed a high-flow RAVF with multiple RVAs and unilateral critically reduced kidney function. Appreciating recent interventional therapeutic advances, the patient was treated with endovascular placement of AVP II into the left renal artery (LRA) resulting in complete occlusion of the RAVF to effectively reduce the risk of RVA rupture and cardiac decompensation. No anti-platelet medication was administrated after the occlusion of the LRA. The patient's physical capacity improved since right heart volume strain was normalized, and CO was reduced. CONCLUSION: Transbrachial AVP II occlusion of the LRA is effective to occlude high-flow RAVFs to prevent risk of life-threatening RVA rupture. Additional follow-up is warranted to verify long-term effectiveness of this approach.

[Update ESC-Guideline 2017: Focus on PAD]. / Update ESC-Leitlinie 2017: Periphere arterielle Verschlusserkrankung.

The updated ESC guidelines on PAD were developed, for the first time, as a collaboration between cardiologists and vascular surgeons and unveiled at the European Society of Cardiology (ESC) 2017 congress. Although awareness has improved, PAD is still associated with significant morbidity, mortality, and quality of life impairment. Primarily, the guidelines emphasize the need for a multidisciplinary management of these patients and propose "a vascular team". A new chapter on antithrombotic therapies is provided. In patients with symptomatic peripheral artery disease, clopidogrel can be considered over aspirin therapy (class IIb). Antiplatelet therapy is no longer recommended in asymptomatic peripheral artery disease patients (class III). After peripheral arterial intervention, dual antiplatelet therapy is recommended as a consensus. Moreover, all patients with lower extremity artery disease should be treated with statins to improve walking distance (class I) as well as supervised exercise therapy, even after revascularization. In claudicants, cardiovascular prevention and exercise training remain the cornerstones of management. The WIFI classification (risk stratification based on wound ischemia and foot infection) is proposed to primarily describe wound lesions. Regarding surgical or interventional therapies, the new guidelines propose an endovascular approach for short lesions (< 5 cm) in the aortoiliac or aortobifemoral region. Patients with infrapopliteal lesions should be treated with bypass surgery or endovascular therapy. Patients with coronary artery disease or heart failure should be considered for lower extremity peripheral artery disease screening (class IIb).

Stent fractures after common femoral artery bail-out stenting due to suture device failure in TAVR.

BACKGROUND: Vascular access site-related complications are frequent in the context of transfemoral transcatheter aortic valve replacement (TAVR). The implantation of a covered stent graft is an effective treatment option for bleeding control. However, the external iliac and common femoral arteries are exposed to flexion of the hip joint. Therefore, stent compression and stent/strut fractures may occur, facilitating stent occlusion. PATIENTS AND METHODS: In all 389 patients who received transfemoral TAVR from 2013-2015 at the Düsseldorf Heart Centre, we monitored the management of vascular access site-related complications. Our analyses focused on immediate technical success and bleeding control, primary patency, and the occurrence of stent/strut fractures after six to 12 months of follow-up. RESULTS: Vascular access site-related complications occurred in 13 % (n = 51), whereof in 10 patients, the bleeding was successfully managed by prolonged compression. In 40 out of 51 patients, a covered stent graft was implanted in the common femoral artery, leading to 100 % immediate bleeding control. After a mean follow-up of 334 ± 188 days, 28 stents out of 29 patients with completed follow-up (excluding e. g. death) were without flow-limiting stenosis (primary patency 97 %) or relevant stent compression (diameter pre/post 8.6/8.1 mm, p = 0.048, late lumen loss 1.1 ± 0.2 mm, mean flow velocity 92 ± 34 cm/s). In four asymptomatic patients, stent/strut fractures were detected (14 %) without flow-limiting stenosis. CONCLUSIONS: The implantation of a covered stent graft is highly effective and safe to control vascular access site-related complications after TAVR. Stent/strut fractures in the flexible segment of the common femoral artery may occur, as consequently verified by X-ray visualization, but show no impairment on flow or clinical parameters after six to 12 months.

Evaluation of a structured training program for arterial femoral sheath removal after percutaneous arterial catheter procedures by assistant personnel.

After cardiac catheterization procedures, arterial closure can be achieved by manual compression (MC), using external mechanical compression devices, or by applying vascular closure devices (VCDs) with comparable vascular access site-related complication rates. The aim of the present study was to assess vascular access site-related complications during the implementation of structured sheath removal and MC by paramedics after catheterization procedures. After an observational phase of 3 months to assess the baseline complication rate, a structured 4-level training program was implemented to train assistant personnel, in this case paramedics, in the management of sheath removal by MC. Access site-related complication rates after sheath removal were assessed prospectively and MC by paramedics compared with MC by physicians and application of VCDs. To account for imbalances in procedure- and patient-related risk factors of access-site complications, propensity score-based matching analysis was performed (ClinicalTrials.gov identifier NCT00825331). All consecutive percutaneous transfemoral arterial cardiac catheterization procedures were prospectively assessed over a period of 8 months (n = 3,503). MC was performed in 2,315 cases, of which 180 were performed by paramedics and 2,135 by physicians; VCDs were applied in 1,188 procedures. Rates of access site-related complications were significantly lower for paramedics compared with physicians (p = 0.03) and similar between paramedics and VCDs (p = 0.77). In conclusion a structured program for paramedics to be trained in sheath removal after percutaneous cardiac catheterization procedures can be readily implemented during clinical routine with low in-hospital complication rates.