An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

From varicose veins to venous thromboembolic events.

Varicose veins (VVs) mostly represent benign disease. However, in some cases, they can lead to serious complications including deep venous thrombosis (DVT) and pulmonary embolism (PE). Besides deteriorated blood flow caused by VVs inflammation is most probably a common denominator of VVs and DVT, which promotes a procoagulant state and thrombus formation also in deep veins. Patients with VVs have increased levels of interleukins, the most specific inflammatory markers of vascular wall inflammation that promote coagulation. The studies showed that VVs may increase the risk for DVT. However, the evidence of the risk and incidence of DVT in patients with VVs and without additional risk factors is poor. The increased risk is associated with previous venous thromboembolism (VTE), malignancy, estrogen use, pregnancy and postpartum, hospitalization in the last 6 months, age, and obesity. Varicose veins represent also an increased risk for VTE during long-term immobilization and long air travel or road trip. Further, superficial venous thrombosis is related to an increased risk for DVT, particularly if the thrombus in the superficial vein extends close to the saphenofemoral or femoropopliteal junction. Increased risk for DVT is increased during and after invasive treatment of VVs. Thromboprophylaxis after invasive procedures is recommended in subjects older than 60 years and those with another thrombophilic state.

Delayed versus primary sternal closure for left ventricular assist device implantation: Impact on mechanical circulatory support infections.

BACKGROUND: Delayed sternal closure may be required after left ventricular assist device (LVAD) implantation due to coagulopathy or hemodynamic instability. There is conflicting data regarding infection risk. METHODS: We performed a single-center, retrospective analysis of patients who received their first LVAD between May 2012 and January 2021. Patients were divided into delayed sternal closure (DSC) and primary sternal closure (PSC) groups. We used chi-squared or Fisher Exact tests, as appropriate, to compare the incidence of postoperative LVAD-related infections (mediastinal/sternal wound) and LVAD-specific infections (driveline and pump pocket) after definitive chest closure between these two groups. RESULTS: A total of 327 patients met eligibility criteria, including 127 (39%) patients that underwent DSC and 200 (61%) patients that had a PSC. Demographic and clinical characteristics were similar except for an overrepresentation of men (87% vs. 75%, p = .016), Interagency Registry of Mechanically Assisted Circulatory Support class I-II patients (89% vs 66%, p < .001), patients with a previous sternotomy (43% vs 13%, p < .001), and patients with chronic kidney disease (55% vs 43%, p = .030) in the DSC group. The median DSC time was 24 (IQR: 24-48) hours. The incidence of LVAD-related mediastinal/sternal wound infection was similar between the DSC and PSC groups (4.7% vs 3.0%, p = .419). There was no difference between DSC and PSC groups in the incidence of driveline infection (6.3% vs 9%, p = .411) and pump pocket infection (1.6% vs 1.5%, p =.901), respectively. CONCLUSIONS: DSC does not seem to increase the incidence of LVAD-related or LVAD-specific infection rates in heart failure patients undergoing device implantation surgery.

Why do guidelines recommend screening for abdominal aortic aneurysms, but not for asymptomatic carotid stenosis? A plea for a randomized controlled trial.

BACKGROUND: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. METHODS: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. RESULTS: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. CONCLUSIONS: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

Concomitant tricuspid valve repair in left ventricular assist device implantation may increase the risk for temporary right ventricular support but does not impact overall outcomes.

OBJECTIVES: Tricuspid valve repair in left ventricular assist device implantation continues to pose a challenge and may impact the occurrence of early and late right heart failure. We investigated the effects of concomitant tricuspid repair on clinical outcomes. METHODS: A retrospective, multicentre study enrolled adult patients who received continuous-flow left ventricular assist devices between 2005 and 2017 and compared those who received concomitant tricuspid valve repair to those who did not. Primary outcomes were early right heart failure necessitating temporary ventricular assist devices and right heart failure-related rehospitalizations requiring inotropic or diuretic treatment. RESULTS: Out of 526 patients who underwent left ventricular assist device implantation, 110 (21%) received a concomitant tricuspid valve repair. Those patients were sicker, and most had moderate or severe tricuspid regurgitation. A significantly higher incidence of temporary right ventricular assist devices was observed in the group with concomitant tricupid valve repair (18% vs. 11%, P = 0.049), with a significantly elevated risk for temporary right heart assist device (sHR 1.68, 95% CI 1.04-2.72; P = 0.037). After adjusting for confounders, no significant differences were found in the incidence of and risk for most clinical outcomes, including right heart failure-related rehospitalizations (P = 0.891) and death (P = 0.563). CONCLUSIONS: Concomitant tricuspid valve repair, when deemed necessary in left ventricular assist device implantation, may increase the risk of early right heart failure requiring a temporary right ventricular assist device but does not impact the incidence or risk of death or rehospitalizations due to late right heart failure.

Clinicopathological correlations in heart transplantation recipients complicated by death or re-transplantation.

Purpose: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation. Methodology and study design: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were grouped according to the presence of AMI and compared. Results: We identified 47 patients with truncated outcomes after the first OHT. The median age was 59 years, 36 patients (76%) were male, 25 patients (53%) had a prior history of cardiac operation, and 21 patients (45%) were supported with a durable assist device before OHT. Of those, AMI was identified in 22 (47%) patients (AMI group), and 25 patients had no AMI (non-AMI group). Groups were comparable in baseline and perioperative data. Histopathological observations in AMI group included a non-significant higher incidence of antibody-mediated rejection Grade 1 or higher (pAMR ≥ 1) (32% vs. 12%, P = 0.154), and non-significant lower incidence of severe acute cellular rejection (ACR ≥ 2R) (32% vs. 40%, P = 0.762). Clinical observations in the AMI group found a significantly higher occurrence of severe primary graft dysfunction (68% vs. 20%, P = 0.001) and a highly significant shorter duration from transplantation to death or re-transplantation (42 days [IQR 26, 120] vs. 1,133 days [711-1,664], P < 0.0001). Those patients had a significantly higher occurrence of cardiac-related deaths (64% vs. 24%, P = 0.020). No difference was observed in other outcomes. Conclusion: In heart transplant recipients with a truncated postoperative course leading to either death or re-transplantation, AMI in endomyocardial biopsies was a common pathological phenomenon, which correlated with the clinical occurrence of severe primary graft dysfunction. Those patients had significantly shorter survival times and higher cardiac-related deaths. The presence of AMI suggests a truncated course after OHT.

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

Management of patients with asymptomatic carotid stenosis may need to be individualized: a multidisciplinary call for action. Republication of J Stroke 2021;23:202-212.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery Guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g. silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Time Course of Inflammatory and Procoagulant Markers in the Early Period After Total Hip Replacement.

Our study aimed to investigate the levels and time-course of systemic inflammatory and hemostasis markers in the early postoperative period in patients undergoing total hip replacement (THR). The study included 70 patients of both sexes, average age 68.4 ± 10.9 years. Levels of inflammatory and hemostasis markers were measured before surgery (POD 0), a day after the surgery (POD 1) and 5 days after surgery (POD 5). In the postoperative period inflammatory markers increased. The operation provoked a significant increase of CRP on POD 1 in comparison to POD 0 (68.5 ± 5.4 vs 6.8 ± 2.2 µg/mL, p < 0.001) and the additional increase was registered on POD 5 (87.5 ± 8.1 vs 68.5 ± 5.4 µg/mL, p < 0.001). Interleukin-6 significantly increased on POD 1 (251.5 ± 21.6 vs 14.6 ± 7.1 µg/mL, p < 0.001) and after that (POD 5) decreased. After surgery leukocyte count, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly higher compared to POD 0. Activation of coagulation in the postoperative period was shown by increased peak thrombin on POD 5 in comparison to POD 0 (185 ± 27 vs. 124 ± 31 nM, p < 0.001). D-dimer was increased on POD 1 and an additional rise was observed on POD 5. vWF also progressively increased in the observed period. Results of our study showed that after THR systemic inflammatory markers increased and coagulation function was enhanced. Determination of inflammatory and procoagulant markers could help identify patients at risk for cardiovascular thromboembolic events.

Use of Transthoracic Echocardiogram to Detect Left Ventricular Thrombi.

BACKGROUND: The presence of a left ventricular thrombus (LVT) poses a risk of thromboembolic complications and excludes patients from undergoing left ventricular assist device (LVAD) implantation without the aid of cardiopulmonary bypass (CPB). Transthoracic echocardiography (TTE) and transesophageal echocardiography are used to detect LVT in patients with heart disease; however, the detection validity of these imaging studies has not been definitively elucidated. METHODS: A retrospective analysis of patients with end-stage heart failure who underwent LVAD implantation from May 2012 to August 2018 in a single center was completed. To be included, patients' medical records had to have presurgical TTE and transesophageal echocardiographic images, as well as intraoperative digital and visual exploration observations. A total of 301 patients underwent LVAD implantation; 239 of these patients had an LVAD implanted with the use of CPB. A total of 230 patients had complete data sets and were included in the analysis. RESULTS: Preoperative TTE identified LVT in 23 of the 230 patients (10%); 15 patients (6.5%) had LVT confirmed by surgical intraventricular visualization. Of the patients with visual LVT confirmation, preoperative TTE identified an LVT in all but 1 case (93%; 14 of 15). Preoperative TTE of LVT had a high sensitivity (94%) and specificity (96%), as well as high negative predictive value (99%). CONCLUSIONS: The results of this study show that preoperative TTE is highly accurate for LVT detection. The high negative predictive value could have significant implications for the choice of surgical procedure because with TTE, surgeons can reasonably determine whether LVAD placement procedure can be attempted without CPB support.

Inflammation of carotid plaques and risk of cerebrovascular events.

Carotid atherosclerotic plaques represent a risk for ischemic stroke. The data indicate that the risk for distal embolization from atherosclerotic lesions in internal carotid arteries is not related only to the degree of stenosis but also to the composition of plaques. The stability of atherosclerotic plaque depends on the thickness of the fibrous cap and plaque hemorrhage. Recent research indicated that the inflammatory activity of atherosclerotic lesions is pivotal in the progression of atherosclerotic plaques. It also promotes the development of unstable atherosclerotic lesions and is related to thromboembolic cerebrovascular complications. Inflammation destabilizes atherosclerotic plaques through the degradation of their fibrotic structure. Inflammation of atherosclerotic plaques was confirmed by histopathologic findings and levels of circulating inflammatory markers which were correlated to the intensity of the inflammation in atherosclerotic lesions. Recently, new techniques like fluorodeoxyglucose positron emission tomography (18-FDG PET) were developed for the identification of inflammation of atherosclerotic lesions in the vessel wall in vivo. Systemic inflammatory markers, particularly interleukins, tumor necrosis factor-alpha and metalloproteinases were shown to be related to the intensity of the inflammatory process in atherosclerotic lesions and the cerebrovascular events. Identification of inflamed atherosclerotic plaques may help to identify unstable atherosclerotic lesions and subjects at high risk for cerebrovascular incidents who need intensive preventive measures including anti-inflammatory medication.

Short-Term Experience with Off-Pump Versus On-Pump Implantation of the HeartWare Left Ventricular Assist Device.

Implantation of left ventricular assist devices while avoiding cardiopulmonary bypass (CPB) may decrease bleeding and improve postoperative recovery. To understand the effectiveness of this approach, we reviewed the charts of 26 patients who underwent HeartWare left ventricular assist device (HVAD) implantation without use of CPB (off-CPB group) and 22 patients who had HVAD implanted with CPB (CPB group) with an emphasis on the 30 day postoperative period. Preoperatively, both groups had similar demographic, functional, and hemodynamic characteristics. Off-CPB patients had significantly shorter surgery times than CPB patients, 188.5 (161.5-213.3) min versus 265.0 (247.5-299.5) min, respectively; p < 0.001. Blood transfusion requirements during surgery and within the postoperative 48 hour period were significantly lower in the off-CPB group than in the CPB group (odds ratio: 5.9; 95% confidence interval: 1.1-31.1, p = 0.042). Compared with the CPB group, the off-CPB group patients had a shorter intubation time, 21 (17.4-48.5) hours versus 41 (20.6-258.4) hours; p = 0.042. Intensive care unit stay was 7.0 (4.75-13.5) days for off-CPB versus 10.0 (6.0-19.0) days for CPB (p = 0.256). The off-CPB approach allows HVAD to be implanted quickly with significantly less perioperative bleeding and transfusion requirements and facilitates postoperative rehabilitation.

Comparison of different methods investigating functional and morphological markers of early atherogenesis in obese women with polycystic ovary syndrome.

BACKGROUND: The prognostic importance of preclinical markers of atherosclerosis and their interrelationship are inconclusive. In this study interrelationship between different methods investigating endothelial function and intima media thickness (IMT) was investigated in patients with polycystic ovary syndrome (PCOS). METHODS: Endothelial function was assessed by endothelium-dependent flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), low-flow-mediated constriction (L-FMC) and peripheral arterial tonometry (PAT). Arterial stiffness was determined by pulse wave velocity (PWV) and the Augmentation Index (AI). The IMT of carotid arteries was measured. RESULTS: Twenty-eight obese women were recruited with the diagnosis of PCOS, mean age 27±7.2 years and Body Mass Index 38.8±6.3 kg/m2. A relationship between FMD and NMD (r=0.44, P=0.02) was shown. FMD as well as NMD of the brachial artery were not correlated with L-FMC or PAT. The AI and PWV, indicators of arterial stiffness were not interrelated with FMD, and there was no significant interrelationship between IMT and FMD or NMD. The AI was related only to IMT (r=0.45, P=0.30). CONCLUSIONS: The relationship between available methods for evaluation of endothelial function/dysfunction is weak in PCOS. This indicates that different methods investigate different mechanisms and various sections of the circulatory system.