The impact of percutaneous peripheral interventions on endothelial function.

Background: Treatment of symptomatic peripheral artery disease (PAD) through endovascular interventions is the primary revascularization strategy. Interventions restore perfusion but may cause severe injury to the vascular endothelium, which regulates vascular tone. Endothelial dysfunction is involved in the progression of cardiovascular disease, with higher incidences of vascular events. We aimed to determine the impact of percutaneous interventions on change in endothelial function. Patients and methods: Endothelial function was determined using flow-mediated dilation (FMD) before, the day after lower limb intervention with paclitaxel-coated balloons or stent guided interventions and after a six-month follow-up in the target limb, control limb and the systemic circulation in 42 PAD patients aged 70.2±9 years and 66% men. Additionally, macro- and microvascular function were assessed. Results: In PAD patients aged 70.2±9 years and 66% men, we observed an immediate enhancement of macro-, microvascular and endothelial function after endovascular treatment (FMD of superficial femoral artery (SFA) 3.7±0.2% to 4.1±0.1%, n=42, p=0.02), a sustained long-term improvement after 6-months (FMD SFA 3.7±0.2% to 4.2±0.1%, n=42, p=0.01), and moreover an improved systemic endothelial function (FMD brachial artery 4.3±0.1% to 4.7±0.2, n=42, p=0.01) following peripheral interventions. Subgroup analysis however revealed that following paclitaxel-based percutaneous intervention, the paclitaxel dosage applied was inversely related to the chronic improvement in local endothelial function (r=-0.6, n=22, p=0.005) without evidence for systemic effects (r=-0.25, p=0.27). Conclusions: We demonstrate an improved local and systemic endothelial function after treatment of atherosclerotic peripheral disease with a distinguished response after endovascular intervention with higher dosage of applied paclitaxel restraining the benefits. Further studies have to determine the optimal interventional strategy with respect to different treatment modalities to maintain vessel functions.

Therapy limitation in octogenarians in German intensive care units is associated with a longer length of stay and increased 30 days mortality: A prospective multicenter study.

PURPOSE: The approach to limit therapy in very old intensive care unit patients (VIPs) significantly differs between regions. The focus of this multicenter analysis is to illuminate, whether the Clinical Frailty Scale (CFS) is a suitable tool for risk stratification in VIPs admitted to intensive care units (ICUs) in Germany. Furthermore, this investigation elucidates the impact of therapeutic limitation on the length of stay and mortality in this setting. METHODS: German cohorts' data from two multinational studies (VIP-1, VIP-2) were combined. Univariate and multivariate logistic regression were used to evaluate associations with mortality. RESULTS: 415 acute VIPs were included. Frail VIPs (CFS > 4) were older (85 [IQR 82-88] vs. 83 [IQR 81-86] years p < .001) and suffered from an increased 30-day-mortality (43.4% versus 23.9%, p < .0001). CFS was an independent predictor of 30-day-mortality in a multivariate logistic regression model (aOR 1.23 95%CI 1.04-1.46 p = .02). Patients with any limitation of life-sustaining therapy had a significantly increased 30-day mortality (86% versus 16%, p < .001) and length of stay (144 [IQR 72-293] versus 96 [IQR 47.25-231.5] hours, p = .026). CONCLUSION: In German ICUs, any limitation of life-sustaining therapy in VIPs is associated with a significantly increased ICU length of stay and mortality. CFS reliably predicts the outcome.

Impact of previous left atrial ablation procedures on the mechanism of left atrial flutter: A single-centre experience.

INTRODUCTION: Left atrial flutter predominantly occurs after surgical or ablation procedures but this entity has also been recently reported in individuals without previous interventions. The use of high-density electroanatomical mapping-systems (HDM) has improved the understanding of underlying mechanisms beyond entrainment maneuvers and substrate analyses. We aimed to evaluate the mechanism of left atrial (LA) flutters in preablated vs ablation-naïve individuals and sought to assess the efficacy of empiric ablations sets in these groups. METHODS AND RESULTS: We included 55 patients admitted for ablation of LA flutter between July 2017 and August 2019. On the basis of HDM analyses the arrhythmia mechanism was determined with consecutive ablation targeting the suspected critical isthmus. Mean age was 69.8 ± 10.7 years, with 26 of 55 (47.3%) male patients. Thirty-nine (71%) patients had previously undergone LA ablation. Arrhythmia mechanisms differed between preablated and ablation-naïve patients as anatomical structure-related LA flutters (perimitral, roof-dependent, within-pulmonary veins) were more frequent in the preablated cohort compared to ablation-naïve individuals (74.4% vs 43.8%; P = .03). In ablation-naïve patients, most flutters (9 of 16, 56.3%) were related to low-voltage areas at the anterior/posterior wall. Acute termination rates were high (>90%) in both groups. Empirical mitral isthmus or roof lines showed a potential higher success rate in preablated patients. CONCLUSION: We identified different mechanisms of LA flutters in preablated vs ablation-naïve patients. In ablation-naïve patients, most tachycardias involved low-voltage areas rather than anatomical structures. Using HDM, acute success rates were high. Hypothetical linear ablations were less successful in ablation-naïve individuals, further highlighting the need to identify the specific individual tachycardia mechanism in these patients.

Impact of Cancer in Patients Undergoing Transcatheter Aortic Valve Replacement: A Single-Center Study.

BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) in cancer survivors and patients with active cancer (AC) in cancer survivors and patients with active cancer (AC) is expanding, suggesting a need to adjust the indications and risk assessment pre-TAVR. OBJECTIVES: The purpose of this study was to determine the impact of cancer on peri-procedural complications and survival in a long-term, single-center cohort of patients treated with TAVR. METHODS: Patients treated with TAVR between January 2006 and December 2018 were grouped as follows: controls (patients without cancer), stable cancer (SC), and AC. The primary endpoints were peri-procedural complications and 30-day survival. A secondary endpoint was 10-year survival. RESULTS: A total of 1,088 patients (age 81 ± 5 years, 46.6% men) treated with transfemoral TAVR were selected: 839 controls, 196 SC, and 53 AC. Predominant malignancies were breast, gastrointestinal, and prostate cancer. No differences were observed between patients with cancer and controls regarding peri-procedural complications. Patients with AC had similar 30-day survival compared with controls and SC (94.3% vs. 93.3% vs. 96.9%, p = 0.161), but as expected, reduced 10-year survival. AC was associated with a 1.47 (95% CI 1.16 to 1.87) fold increased risk of all-cause 10-year mortality in multivariable adjusted models. CONCLUSIONS: TAVR should be performed in patients with cancer when indicated, considering that patients with cancer have similar periprocedural complications and short-term survival compared with control patients. However, patients with AC have worse 10-year survival. Future studies are needed to define cancer-specific determinants of worse long-term survival.

True Lumen Stabilization to Overcome Malperfusion in Acute Type I Aortic Dissection.

Acute type I aortic dissection (AD) complicated by true lumen (TL) collapse and malperfusion downstream is associated with devastating prognosis. The study reports an institutional mid-term experience with TL stabilization by uncovered stents to restore perfusion as a supplement to proximal thoracic aortic surgery. Between January 2007 and May 2017, 181 out of 270 acute type A AD patients were operated on type I AD. Eighteen uncovered stents (10%) were used to expand the aortic TL in presence of visceral and/or peripheral malperfusion. The procedures took place in a hybrid operating room and were combined with proximal aortic surgery. During follow-up (mean ± standard deviation 3.44 ± 2.1 years), the fate of AD was evaluated by computed tomography. Indication for TL stenting included visceral (44%) or peripheral malperfusion (11%) or both (45%). Stenting of aortic branches followed in 33%. All patients underwent proximal repair and were combined with frozen elephant trunk (67%) or retrograde descending aorta stent grafting (11%). Thirty-day mortality was 16.7%. Two-year survival was 71.8%. The false lumen around the uncovered stents remained patent in 89% and the aortic diameter increased 0.1 cm/y. No intimal rupture or occlusion of arteries occurred. In 1 patient, the stented aortic lumen was visualized after 6.3 years and neointima ingrowth covering the nitinol frame was found. In acute type I AD, combined endovascular-surgical procedures in a hybrid operation room setting can be used safely to resolve distal malperfusion. Encapsulation of uncovered stents within the intimal wall provides a stable fundament for endovascular techniques to close entry tears and false lumen.

Clinical Frailty Scale (CFS) reliably stratifies octogenarians in German ICUs: a multicentre prospective cohort study.

BACKGROUND: In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs. METHODS: This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality. RESULTS: Patients had a median age of 84 [IQR 82-87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival. CONCLUSIONS: The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany. TRIAL REGISTRATION: The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807 ) on May 1, 2017.

Intestinal T lymphocyte homing is associated with gastric emptying and epithelial barrier function in critically ill: a prospective observational study.

BACKGROUND: Impaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little is known about gut-directed immune activation, intestinal barrier function and its association with impaired gastric emptying in critically ill patients at ICU admission. METHODS: We conducted a prospective observational study at two tertiary care medical ICUs. Fifty consecutive patients needing invasive mechanical ventilation were recruited within 24 h of ICU admission, prior to any nutritional support. The acute physiology and chronic health evaluation (APACHE) II score, the sequential organ failure assessment (SOFA) score and the multiple organ dysfunction score (MODS) were used to assess illness severity and multiple organ dysfunction. Gastric emptying was assessed by paracetamol absorption test. Peripheral blood mononuclear cells were freshly isolated and cultured for 24 h, and TNF-α, IL-1ß and IL-10 measured in cell culture supernatants and in serum by ELISA. The intestinal epithelial barrier was assessed, quantifying serum concentrations of intestinal fatty acid binding protein (I-FABP), ileal bile-acid binding protein (I-BABP) and zonulin-1 by ELISA. Small bowel homing T lymphocytes (CD4+ α4ß7 + CCR9+) were analyzed by flow cytometry. The Mann-Whitney test and Spearman correlation were used in statistical evaluation. RESULTS: CD4 + α4ß7 + CCR9+ T lymphocytes were inversely correlated with gastric emptying. Patients with delayed gastric emptying at ICU admission (n = 35) had significantly higher serum and PBMC-induced TNF-α and IL-1ß and increased intestinal barrier disruption reflected by higher I-FABP, I-BABP and zonulin-1. Patients who died in the ICU had significantly impaired gastric empting at admission compared to ICU survivors. No differences were observed in APACHE II, SOFA or MODS in patients with delayed gastric emptying compared to patients with normal gastric emptying. CONCLUSIONS: Exaggerated CD4 + α4ß7 + CCR9+ T lymphocyte homing with increased pro-inflammatory cytokine release and intestinal epithelial barrier disruption are associated with delayed gastric emptying. This is not simply due to differences in overall severity of illness at ICU admission and may represent a pathophysiological mechanism of gut-directed immune activation leading to impaired barrier function in the critically ill.

Silent cerebral ischemia after thoracic endovascular aortic repair: a neuroimaging study.

BACKGROUND: The risk of clinically apparent, periprocedural stroke after thoracic endovascular aortic repair (TEVAR) due to dislodgement and embolization of aortic debris from intravascular manipulation of guidewires, catheters, and large-bore delivery systems ranges between 2% and 6% and has been associated with increased postoperative mortality. The rate of clinically silent cerebral ischemia is yet unknown, but may be even higher. METHODS: Nineteen patients (13 male, 6 female) who underwent TEVAR were included into this descriptive study. Periprocedural apparent and silent cerebral ischemia was assessed by daily clinical neurologic assessment and serial cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) at baseline and 5 days (median, interquartile range: 3.5) after the procedure. RESULTS: The TEVAR was successful in all patients without immediate clinically apparent neurologic deficits. Postinterventional cerebral DW-MRI detected a total of 29 new foci of restricted diffusion in 12 of 19 TEVAR patients (63%). Lesions were usually multiple (1 to 6 lesions per patient) and ranged in size between 15 mm3 and 300 mm3; 16 lesions were found in the left hemisphere, 13 lesions in the right hemisphere. Overstenting of the left subclavian artery was performed in 8 cases, but was not associated with lateralization of lesions. There were no additional apparent neurologic events during the in-hospital period. CONCLUSIONS: Thoracic endovascular aortic repair resulted in a high incidence of new foci of restricted diffusion on cerebral DW-MRI in a pattern suggestive of periprocedural embolization. Although multiple lesions per patients were found, these lesions were not associated with apparent neurologic deficits during the in-hospital period. Further developments in TEVAR should be directed toward reducing the risk of periprocedural cerebral embolization.

Recurrent lymphocytic myocarditis in a young male with ulcerative colitis.

Awareness of myocarditis in association with inflammatory bowel diseases is crucial as it bears a rare but serious risk for mortality. This report describes the case of a young Caucasian male, whose heart biopsy was tested negative for giant cells and bacterial or viral genomes or proteins. He was experiencing severe lymphocytic myocarditis (other than mesalamine-induced) along with cardiogenic shock during ulcerative colitis exacerbation. This is an extremely rare, if not unique, clinical constellation. We chose to study the epidemiologic grounds and all major aspects of differential pathogenesis and treatment of this serious health problem.

Recurrent infective endocarditis with uncommon Gram-negative Pasteurella multocida and Pseudomonas aeruginosa: a case report.

Infective endocarditis (IE) due to Gram-negative bacteria is a rare occurrence, with a relative frequency of less than 10% compared to that caused by Gram-positive bacteria. Herein is presented the fatal case of a 66-year-old man who had undergone mechanical aortic valve replacement 10 years previously, and developed aortic valve IE after sepsis with Pasteurella multocida caused by a cat bite at the left medial ankle. In addition, the patient suffered five months later from mitral and aortic valve endocarditis caused by Pseudomonas aeruginosa. Recurrent surgical therapy was mandatory. This unique case of recurrent Gram-negative IE shows that the condition must still be regarded as complex and often fatal, despite adequate medical and surgical treatment.

Large mobile thrombus in non-atherosclerotic thoracic aorta as the source of peripheral arterial embolism.

The presence of thrombi in the atherosclerotic and/or aneurysmatic aorta with peripheral arterial embolism is a common scenario. Thrombus formation in a morphologically normal aorta, however, is a rare event. A 50 years old woman was admitted to the mergency department for pain, coldness, and anesthesia in the the left foot. She had a 25 years history of cigarette smoking, a history of postmenopausal hormone replacement therapy (HRT), hypercholesterolemia and hyperfibrinogenemia. An extensive serologic survey for hypercoagulability, including antiphospholipid antibodies, and vasculitis disorders was negative. Transesophageal echocardiography revealed a large, pedunculated and hypermobile thrombus attached to the aortic wall 5 cm distal of the left subclavian artery. The patient was admitted to the surgery department, where a 15 cm long fresh, parietal thrombus could be removed from the aorta showing no macroscopic wall lesions or any other morphologic abnormalities. This case report demonstrates the possibility of evolving a large, pedunculated thrombus in a morphologically intact aorta in a postmenopausal woman with thrombogenic conditions such as hyperfibrinogenemia, hypercholesterolemia, smoking and HRT. For these patients, profiling the individual risk and weighing the benefits against the potential risks is warranted before prescribing HRT.