Cholesterol Crystal Dissolution Rate of Serum Predicts Outcomes in Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Aortic stenosis has pathophysiological similarities with atherosclerosis, including the deposition of cholesterol-containing lipoproteins. The resulting cholesterol crystals activate the NLRP3 (NOD-like receptor protein 3) inflammasome, leading to inflammation and cardiovascular diseases. We aimed to investigate the cholesterol crystal dissolution rate (CCDR) of serum in patients with aortic stenosis and to assess the prognostic value of this biomarker. METHODS AND RESULTS: The study included 348 patients with aortic stenosis undergoing transcatheter aortic valve replacement. The CCDR was measured using flow cytometry to enumerate cholesterol crystals that were added to a serum solution, at baseline and after 2 hours of incubation. Based on the median CCDR, the cohort was stratified into high and low cholesterol crystal dissolvers. The incidence of the primary end point, a composite of 1-year all-cause mortality and major vascular complication, was significantly lower in the high CCDR group (7.3 per 100 person-years) compared with the low CCDR group (17.0 per 100 person-years, P=0.01). This was mainly driven by a lower 1-year mortality rate in patients with a high CCDR (7.3 versus 15.1 per 100 person-years, P=0.04). Unplanned endovascular interventions were significantly less frequent in high cholesterol crystal dissolvers (12.8 versus 22.6 per 100 person-years, P=0.04). Although low-density lipoprotein cholesterol levels were comparable in both groups (101.8±37.3 mg/dL versus 97.9±37.6 mg/dL, P=0.35), only patients with a low CCDR showed a benefit from statin treatment. In multivariate analysis, low CCDR (hazard ratio, 2.21 [95% CI, 0.99-4.92], P=0.04) was significantly associated with 1-year mortality. CONCLUSIONS: The CCDR is a novel biomarker associated with outcome in patients with aortic stenosis undergoing transcatheter aortic valve replacement. It may provide new insights into patients' anti-inflammatory capacity and additional prognostic information beyond classic risk assessment.

Pulmonary affection of patients with Pseudoxanthoma elasticum: Long-term development and genotype-phenotype-correlation.

Pseudoxanthoma elasticum (PXE) is a rare, heritable disease caused by various, mainly recessively transmitted mutations in the ABCC6 gene. Due to calcification of soft connective tissue phenotypic hallmarks are progressive loss of vision, alternation of the skin and early onset atherosclerosis. Beside these main features patients also suffer from impaired alveolar diffusion. The present study focused on impaired lung functioning based on a large cohort of patients with PXE, its long-term development, and genotype-phenotype correlation. Retrospectively, 98 patients and 45 controls were enrolled. All patients underwent body plethysmography and carbon monoxide diffusion testing. Of 35 patients three or more body plethysmographic records were available for long-term analysis. For genotype-phenotype analysis ABCC6 genotypes were grouped as two missense, mixed, or two nonsense mutations. Patients with PXE showed significantly reduced vital capacity (p < 0.05), diffusion capacity (p < 0.01), and diffusion transfer coefficient (p < 0.05). Over a mean period of 38 months diffusion capacity (p < 0.05) and diffusion transfer coefficient (p < 0.01) dropped significantly whereas lung volumes remained unchanged. Genotype-phenotype correlation revealed no connection between gene variants and lung functioning. In conclusion, PXE is accompanied by progressive reduction of alveolar diffusion indicating progressive alterations of lung tissue. Genotype-phenotype correlation with genotypes sorted as missense and nonsense mutations do not explain impaired lung functioning.

Long-term clinical outcome and mortality risks after paclitaxel-coated balloon angioplasty in patients with peripheral artery disease: An observational clinical study.

BACKGROUND AND AIMS: Drug-eluting devices (DEDs) are usually used as a standard therapy for revascularization in femoropopliteal artery disease. Randomized controlled trails have found that DEDs with paclitaxel result in superior patency rates and decreased target lesion revascularization. A meta-analysis by Katsanos et al indicated an increased long-term mortality in patients treated with paclitaxel-coated devices. The aim of this observational clinical study was to assess the long-term clinical outcomes and mortality risk after paclitaxel-coated balloon angioplasty in patients with symptomatic peripheral artery disease. METHODS: We retrospectively evaluated 287 patients with peripheral interventions, including 173 drug-coated balloon (DCB) angioplasties and 114 plain old balloon angioplasties (POBA), performed at our center between 2015 and 2018. RESULTS: There were no significant differences in mortality rates between patients who received DCB angioplasty and those who received POBA. In the first year, the hazard ratio (HR) for DCB angioplasty was 0.59 (95% confidence interval [CI] 0.31 to 1.12, P = .104). After 2 years, this HR was 0.64 (95% CI 0.36-1.17, P = .145), while the 3-year and 4-year HR increased to 0.71 and 1.30 (3-year: 95% CI 0.37-1.33, P = ,283; 4-year: 95% CI 0.55-3.08, P = .546). No paclitaxel dose-response relationship with mortality rate was identified when adjusted for key predictors of mortality. CONCLUSIONS: Analyses of patient level data identified no significant mortality differences between DCB angioplasty and POBA after 4 years of follow-up. Furthermore, there was no dose-response relationship between paclitaxel and mortality. These findings demonstrate that paclitaxel DCB is safe. Further long-term multicenter studies are needed to determine the risk of late mortality.

Endovascular management of femoral access-site and access-related vascular complications following percutaneous coronary interventions (PCI).

BACKGROUND: Major vascular complications (VCs) of ilio-femoral arterial access after percutaneous coronary interventions are infrequent, but are associated with increased mortality and morbidity. Routine endovascular repair of VCs is becoming the treatment of choice, especially for patients who cannot tolerate vascular surgery due to advanced cardiovascular disease or are in a bailout situation. Here, we review the different types of vascular access site complications associated with percutaneous coronary interventions (PCIs) and assess the safety and efficacy of endovascular treatment. METHODS: Data were retrospectively analysed from patients who experienced VCs after transfemoral PCIs, from December 2014 to May 2018. During this period, out of 2833 patients who underwent femoral coronary interventions, 53 (1.9%) experienced major VCs. RESULTS: In total, 40/53 (75.5%) cases with major VCs led to unplanned endovascular repair and 13/53 (24.5%) cases required surgical repair. VCs included 17 (32.1%) retroperitoneal bleeding events (BARC-2, 3a,b), 20 (37.7%) intimal dissections, and 16 (30.2%) femoral pseudoaneurysms. Overall, 32 (60.4%) patients received a covered stent, two (3.8%) received a nitinol stent, five (9.4%) patients with dissections were treated with prolonged balloon angioplasty alone, and one patient with femoral pseudoaneurysm underwent thrombin injection with simultaneous balloon occlusion. The mean hospital stay for patients after endovascular treatment was 11.06 ± 5.2 days, while for patients after surgical repair it was 17 ± 8.2 days. Endovascularly treated patients were transfused with red blood cells (13/40 32.5% vs. 2/13 15.4%) significantly more often than patients treated surgically, although surgically treated patients received more red blood cell concentrates per unit than endovascularly treated patients (1 ± 0.47 vs. 2 ± 0.93). During the one-year follow-up, no intermittent claudication was reported, and no patient required secondary endovascular or surgical repair. CONCLUSIONS: For patients who cannot tolerate vascular surgery due to advanced cardiovascular disease or are in a bailout situation, endovascular management of VCs following PCIs seems to be a feasible and safe treatment option, and represents an alternative to surgical repair in life-threatening situations. Endovascular treatment was associated with significantly fewer red blood cell concentrates per patient and fewer days in hospital than surgical treatment.

Pseudoxanthoma elasticum - also a microvascular disease.

Background: Pseudoxanthoma elasticum (PXE) is a heritable recessive disease characterized by calcification and fragmentation of soft connective tissue. Besides progressive loss of vision, alternations of the skin, and early-onset atherosclerosis different reports have suggested a microvascular manifestation of PXE and restrictive lung disease. Aim of this study was to elaborate a specific pattern of capillary alterations in PXE as well as to contemplate a possible connection to restrictive lung disease. Patients and methods: 53 consecutive patients with PXE and 26 controls were studied. All patients underwent nailfold capillaroscopy, body plethysmography, capillary blood gas analysis, and venous puncture to assess titer of autoantibodies. Results: PXE was associated with highly pathological alterations of capillaries compared to control. Atypical capillaries, such as ramifications and bushy forms, as well as dilatations varied at highest significance (p < .001). This effect was mirrored by perivascular edema, density and tortuous capillaries. Titer of anti-nuclear autoantibodies were not elevated in patients with PXE. Further analysis revealed negative correlation between vital capacity and presence of atypical capillaries. Conclusions: This study firstly describes the pattern of nailfold capillaries in PXE. Capillaries are highly pathological and consist of ramifications and bushy forms as well as dilatations. Frequently, tortuous capillaries, pericapillary edema and reduced denseness of capillary loops occur. Frequency of atypical capillaries is negatively correlated with vital capacity which can be interpreted as further lead on restrictive lung disease.

Comparative study of pressure (ankle-brachial pressure index) and flow (strain gauge plethysmography and reactive hyperaemia) measurements in diagnosis of peripheral arterial disease in patients with severe aortic stenosis.

BACKGROUND: The measurement of the ankle-brachial pressure index is a straightforward method for the detection of peripheral disease in the lower limbs. Only a few old studies with small numbers of patients have been conducted comparing the gold standard, ankle-brachial pressure index measurement, with strain gauge plethysmography and reactive hyperaemia for detecting peripheral arterial disease. The purpose of this study was to evaluate the feasibility and accuracy of strain gauge plethysmography values compared with the Doppler ultrasound method, ankle-brachial pressure index, in the assessment of peripheral arterial disease, especially in patients with severe aortic stenosis. METHODS: 221 ankle-brachial pressure index measurements and strain gauge plethysmography measurements of patients with suspected peripheral arterial disease, diagnosed peripheral arterial disease with or without aortic stenosis were compared. RESULTS: Irrespective of aortic stenosis in patients with and without peripheral arterial disease, the resting arterial blood flow was within the normal range. In patients with aortic stenosis, the time-to-peak flow couldn't detect peripheral arterial disease and was found to be a false negative. In patients without aortic stenosis, time-to-peak flow correlated well with the ankle-brachial pressure index for detecting peripheral arterial disease. Peak flow at 5 seconds was the one of the flow values that correlated with ankle-brachial pressure index and detected peripheral arterial disease in patients with and without aortic stenosis. CONCLUSION: Peak flow at 5 seconds is one of flow value that correlated well with ankle-brachial pressure index in detecting peripheral arterial disease in patients with and without aortic stenosis. Detection of peripheral arterial disease in patients with severe aortic stenosis seems to be less sensitive with flow measurements than with ankle-brachial pressure index.