Surgical Revascularization Research Articles

Systematic Review of the Efficacy of Orbital Atherectomy in Improving the Outcome of Percutaneous Corornary Intervention in People With Diabetes.

The optimal approach to deal with severe coronary artery calcification (CAC) in people with diabetes remains ill-defined. People with diabetes have a significant risk of developing severe vessel calcification and coronary artery disease (CAD). CADis the leading cause of death in people with diabetes. Individuals with diabetes mainly present with severe multivessel stenosis, diffuse coronary calcification, and severe atherosclerosis, which are poor prognostic factors of revascularization procedures. Studies have shown that the revascularization of arteries in people with diabetes often results in worse outcomes than in people without diabetes. Coronary artery bypass grafting (CABG) has been recommended as the standard of care for people with DM and complex anatomic diseases, including left main CAD. However, percutaneous coronary intervention (PCI)is more acceptable to patients in clinical practice because of decreased trauma and rapid recovery. Severe CAC has traditionally been challenging for PCI and a frequent indication for surgical revascularization. This study aims to determine the effectiveness of orbital atherectomy (OA) in improving PCIoutcomes in patients with diabetes and identify possible adverse effects that preclude its use. The study is reported according to PRISMA and analyzed according to Cochrane guidelines on synthesis without meta-analysis. A comprehensive literature search of EMBASE, Scopus, Web of Science, Cochrane Library, CINAHL, and MEDLINE was conducted for studies that utilized OA before PCI in people with diabetes. A reference list of the eligible articles was also screened. A narrative synthesis was done by representing the data on the effect direction plot, followed by vote counting. Eighteen studies were included in the analysis. Success rate/successful stent delivery was >90%, while freedom from angiographic complication and major adverse cardiovascular and cerebrovascular events (MACCE) were both >80% on the effect direction plot for people with diabetes and those without diabetes. People with diabetes had low event rates similar to those without diabetes. OA appears to be a viable treatment approach for people with diabetes. However, RCTs with a longer duration of follow-up are required to establish the appropriate treatment strategy for severe CAC in people with diabetes.

Perioperative Kidney Function of Cardiac Surgery Patients with Impaired Glucose Metabolism

Aimto study influence of impaired glucose metabolism on perioperative kidney function of cardiac surgery patients with coronary artery disease (CAD). Material and methodsretrospective analysis of 354 high-risk randomly selected patients with CAD who were discharged after cardiac surgery. For all patients performed laboratory tests, ECG, ECHO, coronary angiography and surgical myocardial revascularization in 194 cases, for 160 patients except CABG we performed correction of postinfarction aneurysm of left ventricle or valves pathology. Resultsimpaired glucose metabolism was found in 251 (70.9%) patients, between which type 2 diabetes mellitus (DM) had 90 (25.4%) pts, impaired glucose tolerance (IGT) – 161 (45.4%). Glomerular filtration rate (GFR) was lower in patients with impaired glucose metabolism (see table 1).Blood parameters and GFR in the perioperative period of patients depending on glucose metabolism, n=354Acute kidney injury (AKI) in postoperative period occurred in 10 (2.8%) patients, between which 6 (60%) had type 2 DM, 2 (20%) – IGT, 2 (20%) – with normal glucose metabolism. None of the patients required renal replacement therapy due to timely correction of drug therapy. Conclusionscardiac surgery patients with coronary artery disease in 70.9% cases had impaired glucose metabolism. Analyses of laboratory parameters in perioperative period had shown decrease of kidney function especially in patients with type 2 DM. AKI occurred in 10 patients, between which 80% had impaired glucose metabolism.

Transcranial Doppler in Childhood Moyamoya: An Underutilized Tool?

BackgroundChildren with moyamoya are at high risk for incident and recurrent stroke. Transcranial Doppler (TCD) ultrasound is an attractive option to screen high-risk populations for moyamoya and to provide stroke risk stratification information due to its safety and cost-effectiveness. We used TCD to evaluate cerebral blood flow velocities in children with presurgical moyamoya and to determine if velocities differ between children with stable and unstable disease. MethodsFourteen participants aged ≤21 years with a radiographic diagnosis of moyamoya or moyamoya-like arteriopathy underwent a research TCD at a median age of 7.2 years. TCDs were performed outside of the setting of acute stroke and before surgical revascularization. Arteriopathy was classified as unstable if the participant had a stroke or transient ischemic attack within three months preceding the TCD. ResultsMiddle cerebral artery and internal carotid artery (ICA) blood flow velocities were elevated. The median M1 velocity was 138 cm/s (interquartile range [IQR] 106 to 168). Individual M1 flow velocities were a median of 5.0 S.D.s above age-based normative values. The median distal ICA velocity was 146 cm/s (IQR 124 to 163). Individual ICA flow velocities were a median of 5.9 S.D.s above normative values. Participants with unstable arteriopathy had higher M1 velocities compared with those with stable arteriopathy (170 vs 119 cm/s, P = 0.0003). We did not identify velocity differences based on comorbid conditions or age. ConclusionsThese preliminary data suggest that TCD is a promising tool for screening for cerebral arteriopathies in high-risk pediatric populations and assessment for unstable disease.

Outcomes of atherectomy in patients undergoing lower extremity revascularisation.

There is a paucity of real-world data on the in-hospital (IH) and post-discharge outcomes in patients undergoing lower extremity peripheral vascular intervention (PVI) with adjunctive atherectomy. In this retrospective, registry-based study, we evaluated IH and post-discharge outcomes among patients undergoing PVI, treated with or without atherectomy, in the National Cardiovascular Data Registry PVI Registry. The IH composite endpoint included procedural complications, bleeding or thrombosis. The primary out-of-hospital endpoint was major amputation at 1 year. Secondary endpoints included repeat endovascular or surgical revascularisation and death. Multivariable regression was used to identify predictors of atherectomy use and its association with clinical endpoints. A total of 30,847 patients underwent PVI from 2014 to 2019, including 10,971 (35.6%) treated with atherectomy. The unadjusted rate of the IH endpoint occurred in 524 (4.8%) of the procedures involving atherectomy and 1,041 (5.3%) of non-atherectomy procedures (p=0.07). After adjustment, the use of atherectomy was not associated with an increased risk of the combined IH endpoint (p=0.68). In the 6,889 (22.4%) patients with out-of-hospital data, atherectomy was associated with a reduced risk of amputation (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI]: 0.51-0.85; p<0.01) and surgical revascularisation (aHR 0.63, 95% CI: 0.44-0.89; p=0.017), no difference in death rates (p=0.10), but an increased risk of endovascular revascularisation (aHR 1.21, 95% CI: 1.06-1.39; p<0.01) at 1 year. The use of atherectomy during PVI is common and is not associated with an increase in IH adverse events. Longitudinally, patients treated with atherectomy undergo repeat endovascular reintervention more frequently but experience a reduced risk of amputation and surgical revascularisation.

Risk Factors for Cerebral Hyperperfusion Syndrome After Combined Revascularization in Adult Patients with Moyamoya Disease.

Cerebral hyperperfusion syndrome (CHS) is known as a complication after bypass surgery for Moyamoya disease (MMD). However, the incidence of CHS has not been accurately reported, and there is no consensus on the risk factors associated with it. The aim of this study was to determine the risk factors associated with postoperative CHS after surgical combined revascularization used to treat adult patients with MMD. To assess the frequency and characteristics of CHS in patients with MMD after revascularization operations. Patients who received combined revascularization from Jan 2021 to Nov 2022 were retrospectively reviewed. Preoperative clinical characteristics and radiographic features were recorded. Postoperative CHS after surgery were examined. Multivariate logistic regression analyses were performed to identify the risk factors for CHS. A total of 133 patients (141 hemispheres) were included in this study. Postoperative CHS were observed in 28 hemispheres (19.8%), including focal cerebral hyperperfusion syndrome (FCHS) in 20 hemispheres (14.2%), hemorrhage in 4 (2.8%) hemispheres, seizures in 4 (2.8%) hemispheres. The results of multivariate logistic regression analysis indicated that preoperative hypertension (OR 4.705, 95% CI 1.323 ~ 12.554, p = 0.014), cerebral hemorrhage onset (OR 5.390, 95% CI 1.408 ~ 20.642, p = 0.014) and higher Hct level (OR 1.171, 95% CI 1.051 ~ 1.305, p = 0.004) were significantly associated with CHS after combined revascularization. Preoperative hypertension, cerebral hemorrhage onset, and higher Hct level were independent risk factors for CHS after combined revascularization.

Cell Therapy in the Treatment of Coronary Heart Disease

Heart failure is a leading cause of death in patients who have suffered a myocardial infarction. Despite the timely use of modern reperfusion therapies such as thrombolysis, surgical revascularization and balloon angioplasty, they are sometimes unable to prevent the development of significant areas of myocardial damage and subsequent heart failure. Research efforts have focused on developing strategies to improve the functional status of myocardial injury areas. Consequently, the restoration of cardiac function using cell therapy is an exciting prospect. This review describes the characteristics of various cell types relevant to cellular cardiomyoplasty and presents findings from experimental and clinical studies investigating cell therapy for coronary heart disease. Cell delivery methods, optimal dosage and potential treatment mechanisms are discussed.

Outcomes After Open Surgical, Hybrid, and Endovascular Revascularization for Acute Limb Ischemia.

To report the performance of surgical treatment (ST), hybrid treatment (HT), and endovascular treatment (ET) for patients with acute limb ischemia (ALI). This is a retrospective, comparative study of all consecutive patients with ALI treated in 2 tertiary centers between April 2010 and April 2020. Amputation and/or death (amputation-free survival; AFS) was the primary composite endpoint. Mortality, major amputation, and reintervention during follow-up were additionally analyzed. Proportional hazards modeling was used to identify confounders, results are presented as hazard ratio (HR) and 95% confidence intervals (CIs). In total, 395 patients (mean age=71.1±13.6 years; 51.1% female) were treated during the study period. Surgical treatment was preferred in 150 patients (38%), while 98 were treated by HT (24.8%) and 147 by ET (37.2%). Rutherford class IIa was the most common clinical presentation in the ET group (50.3%), whereas Rutherford IIb was most common in the ST (54%) and HT (48%) groups (p<0.001). Significantly, more patients presented with a de novo lesion in the ST and HT groups (79.3% and 64.3%, respectively) compared with ET (53.7%; p<0.001). Median follow-up was 20 months (range=0-111 months). In the multivariate analysis, ET showed significantly better AFS during follow-up compared with ST (HR=1.89, 95% CI=1.2-2.9, p<0.001) and HT (HR=1.73, 95% CI=1.1-3.1, p<0.001). Mortality during follow-up was also significantly lower after ET compared with ST (HR=2.21, 95% CI=1.31-3.74, p=0.003) and HT (HR=2.04, 95% CI=1.17-3.56, p=0.012). Endovascular treatment was associated with lower amputation rate compared with ST (HR=2.27, 95% CI=1.19-4.35, p=0.013) but was comparable with HT (HR=2.00, 95% CI=0.98-4.06, p=0.055). Reintervention rates did not differ significantly between the groups (ET vs ST: HR=1.52, 95% CI=0.99-2.31, p=0.053; ET vs HT: HR=1.3, 95% CI=0.81-2.07, p=0.27). Endovascular treatment for ALI was associated with improved AFS and comparable reintervention rates compared with open surgical and hybrid therapy. Treatment of acute lower limb ischemia remains a challenge for clinicians with high morbidity and mortality rates. Endovascular revascularization is considered first line treatment for many and hybrid treatments are becoming more common, however data is limited to either old trials, small series or with short follow-up. We present herein our 10-year experience with all available devices and techniques for open surgical, endovascular and hybrid acute limb ischemia treatments and compare their outcomes.

Outcomes after surgical revascularization for adult Moyamoya disease: A Southeast Asian tertiary centre experience

There are numerous studies on the natural history and outcomes of adult Moyamoya disease (MMD) in the literature, but limited data from Southeast Asian cohorts. Hence, we aimed to retrospectively review the clinical characteristics and outcomes after surgical revascularization for adult MMD in our Southeast Asian cohort. Patients were included if they were above 18 years old at the first surgical revascularization for MMD, and underwent surgery between 2012 and 2022 at the National University Hospital, Singapore. The outcomes were transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, and all-cause mortality during the postoperative follow-up period. In total, 26 patients who underwent 27 revascularization procedures were included. Most patients were of Chinese ethnicity, and the mean (SD) age at the time of surgery was 47.7 (12.6) years. The commonest clinical presentation was intracerebral hemorrhage, followed by TIA and ischemic stroke. Direct revascularization with superficial temporal artery-middle cerebral artery (STA-MCA) bypass was the most common procedure (24/27 surgeries, 88.9 %). The mean (SD) follow-up duration was 4.2 (2.5) years, during which the overall incidence of postoperative TIA/stroke was 25.9 % (7/27 surgeries), with most cases occurring within 7 days postoperatively. There were no mortalities during the postoperative follow-up period. Risk factors for 30-day postoperative TIA/stroke included a higher number of TIAs/strokes preoperatively (p = 0.044) and indirect revascularization (p = 0.028). Diabetes mellitus demonstrated a trend towards an increased risk of 30-day postoperative TIA/stroke, but this was not statistically significant (p = 0.056). These high-risk patients may benefit from more aggressive perioperative antithrombotic and hydration regimens.

Effect of health literacy and socioeconomic deprivation on outcomes after lower limb surgical revascularisation for chronic limb-threatening ischaemia: the HeaLTHI study

Introduction: Research has suggested a relationship between health literacy, socioeconomic status and health-related outcomes. The aim of the study was to study the association between health literacy, socioeconomic status and outcomes following infra-inguinal bypass surgery for chronic limb-threatening ischaemia (CLTI). Methods: Patients with CLTI undergoing lower limb surgical bypass graft operations between January 2016 and December 2018 were included in a cross-sectional observational study. The HLS19-Q12 questionnaire categorised participant’s health literacy as inadequate, problematic, sufficient or excellent. Socioeconomic status was assessed using the Index of Multiple Deprivation (IMD). Primary outcomes were major lower limb amputation (MLLA) and adverse cardiovascular events. Secondary outcomes included length of hospital stay, and early postoperative complications including pneumonia, surgical site and graft infection. Kaplan– Meier survival curves were used to compare health literacy and amputation, and Cox proportional regression analysis was conducted to identify differences in limb loss risk against health literacy and social deprivation levels. Results: The study consisted of 50 patients with an average age of 70±8.7 years. The participants' levels of health literacy were classified as inadequate (28%), problematic (38%), sufficient (24%) or excellent (10%). Approximately 40% of the patients lived in the most deprived areas. While all health literacy groups had similar postoperative outcomes, low health literacy was connected with lower socioeconomic status (r=0.308, p=0.029). IMD (p=0.017, HR 0.502 (95% CI 0.285 to 0.883)) and haemoglobin (p=0.001, HR 0.919 (95% CI 0.872 to 0.968)) were significant predictors of MLLA. Conclusion: Patients with lower health literacy are more likely to face higher levels of social deprivation, which may predict amputation following bypass surgery. Enhancing health literacy could play a role in reducing health disparities caused by social deprivation, thereby potentially addressing a vascular James Lind Alliance priority.

Relative anemia and perioperative stroke in children with moyamoya

ObjectivesSurgical revascularization for moyamoya arteriopathy decreases long-term stroke risk but carries a risk of perioperative ischemic complications. We aimed to evaluate modifiable stroke risk factors in children undergoing surgical revascularization for moyamoya. Materials and MethodsIn this exploratory, single-center, retrospective cohort study, medical records of pediatric patients undergoing surgical revascularization for moyamoya arteriopathy at our center between 2003 and 2021 were reviewed. Candidate modifiable risk factors were analyzed for association with perioperative stroke, defined as ischemic stroke ≤7 days after surgery. ResultsWe analyzed 53 surgeries, consisting of 39 individual patients undergoing indirect surgical revascularization of 74 hemispheres. Perioperative ischemic stroke occurred following five surgeries (9.4%). There were no instances of hemorrhagic stroke. Larger pre-to-postoperative decreases in hemoglobin (OR 3.90, p=0.017), hematocrit (OR 1.69, p=0.012) and blood urea nitrogen (OR 1.83, p=0.010) were associated with increased risk of perioperative ischemic stroke. Weight-adjusted intraoperative blood loss was not associated with risk of perioperative ischemic stroke (OR 0.94, p=0.796). Among children with sickle cell disease, all of whom underwent exchange transfusion within one week prior to surgery, none experienced perioperative stroke. ConclusionsDecreases in hemoglobin, hematocrit, and blood urea nitrogen between the preoperative and postoperative periods are associated with increased risk of perioperative stroke. These novel findings suggest that dilutional anemia, possibly due to standardly administered hyperhydration, may increase the risk of perioperative stroke in some children with moyamoya. Further work optimizing both mean arterial pressure and oxygen-carrying capacity in these patients, including consideration of alternative blood transfusion thresholds, is necessary.

Treatment of ischemic heart disease in end-stage kidney disease patients on renal replacement therapy

This review paper aims to analyze the problem of diagnosis and treatment of coronary heart disease (CHD), also called ischemic heart disease (IHD), in patients with end-stage renal disease (ESRD). The analysis is based on current literature data. The issues of CHD risk stratification before patient listing for kidney transplantation (KT) and possible difficulties of diagnosing CHD using non-invasive examination methods in ESRD patients are considered. The effectiveness of myocardial revascularization and drug therapy, endovascular and surgical myocardial revascularization, is compared. The paper also discusses the peculiarities of drug therapy, particularly antiplatelet and antihyperlipidemic therapy in the treatment of CHD in dialysis-dependent patients and kidney recipients.

Surgical Strategy for Sternal Closure in Patients with Surgical Myocardial Revascularization Using Mammary Arteries.

Coronary artery bypass grafting has evolved from all venous grafts to bilateral mammary artery (BIMA) grafting. This was possible due to the long-term patency of the left and right internal mammary demonstrated in angiography studies compared to venous grafts. However, despite higher survival rates when using bilateral mammary arteries, multiple studies report a higher rate of surgical site infections, most notably deep sternal wound infections, a so-called "never event". We designed a prospective study between 1 January 2022 and 31 December 2022 and included all patients proposed for total arterial myocardial revascularization in order to investigate the rate of surgical site infections (SSI). Chest closure in all patients was performed using a three-step protocol. The first step refers to sternal closure. If the patient's BMI is below 35 kg/m2, sternal closure is achieved using the "butterfly" technique with standard steel wires. If the patient's BMI exceeds 35 kg/m2, we use nitinol clips or hybrid wire cable ties according to the surgeon's preference for sternal closure. The main advantages of these systems are a larger implant-to-bone contact with a reduced risk of bone fracture. The second step refers to presternal fat closure with two resorbable monofilament sutures in a way that the edges of the skin perfectly align at the end. The third step is skin closure combined with negative pressure wound therapy. This system was applied to 217 patients. A total of 197 patients had bilateral mammary artery grafts. We report only 13 (5.9%) superficial SSI and only one (0.46%) deep SSI. The preoperative risk of major wound infection was 3.9 +/- 2.7. Bilateral mammary artery grafting was not associated with surgical site infection in a univariate analysis. We believe this strategy of sternal wound closure can reduce the incidence of deep surgical site infection when two mammary arteries are used in coronary artery bypass surgery.

Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial

BackgroundIn the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous coronary intervention (PCI) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization and a conservative (CON) strategy of initial medical therapy. ObjectivesThe authors analyzed separately the outcomes of INV patients treated with PCI or CABG. MethodsPatients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) was used. ResultsAmong INV-CABG patients, primary outcome events occurred in 84 of 512 (16.4%) at a median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs. Among INV-PCI patients, primary outcome events occurred in 147 of 1,500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) occurred within 30 days after PCI, including 24 procedural MIs. In comparison, 352 of 2,591 CON patients (13.6%) had primary outcome events at a median follow-up of 3.2 years, 22 of which (6.3%) occurred within 30 days of randomization. The adjusted primary outcome risks were higher after both CABG and PCI within 30 days (HR: 16.25 [95% CI: 11.44-23.07] and HR: 2.99 [95% CI: 1.97-4.53]) and lower thereafter (0.63 [95% CI: 0.44-0.89] and 0.66 [95% CI: 0.53-0.82]). ConclusionsIn ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, owing to protocol-defined procedural MIs.

The everolimus eluting Synergy MegatronTM drug-eluting stent platform: Early outcomes from the European Synergy MegatronTM Implanters' Registry.

The Synergy MegatronTM is an everolimus-drug eluting stent that may offer advantages in the treatment of aorto-ostial disease and large proximal vessels. To report the short- to medium-term clinical outcomes from the European Synergy MegatronTM Implanters' Registry. This registry was an investigator-initiated study conducted at 14 European centers. The primary outcome was target lesion failure (TLF), defined as the composite of cardiovascular death, target vessel myocardial infarction (MI), and target lesion revascularisation. Five hundred seventy-five patients underwent PCI with MegatronTM between 2019 and 2021. Patients were 69 ± 12 years old, 26% had diabetes mellitus, 24% had moderate-severe left ventricular impairment and 59% presented with an acute coronary syndrome. 15% were deemed prohibitively high risk for surgical revascularisation. The target vessel involved the left main stem in 55%, the ostium of the RCA in 13% and was a true bifurcation (Medina 1,1,1) in 50%. At 1 year, TLF was observed in 40 patients, with 26 (65%) occurring within the first 30 days. The cumulative incidence of TLF was 4.5% at 30 days and 8.6% (95% CI 6.3-11.7) at 1 year. The incidence of stent thrombosis was 0.5% with no late stent thromboses. By multivariate analysis, the strongest independent predictors of TLF were severe left ventricular impairment (HR 3.43, 95% CI: 1.67-6.76, p < 0.001) and a target vessel involving the left main (HR 4.00 95% CI 1.81-10.15 p = 0.001). Use of the Synergy MegatronTM everolimus eluting stent in a 'real-world' setting shows favorable outcomes at 30 days and 1 year.

Can machine learning improve risk prediction and individualise decision making between percutaneous and surgical revascularisation?

Abstract Background/Introduction In patients with three-vessel coronary artery disease (CAD) and/or left main (LM) CAD, individual risk prediction plays a key role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Purpose The aim of this study was to assess whether these individualised revascularization decisions can be improved by applying machine learning (ML) algorithms and integrating clinical, biological, and anatomical factors. Methods The present study consisted of patients enrolled in the SYNTAX study, which is a randomized trial comparing PCI and CABG in patients with complex coronary artery disease. ML algorithms were used to develop a prognostic index for 5-year death, which was combined, in the second stage, with assigned treatment (PCI or CABG), and pre-specified effect-modifiers: disease type (3-vessel or LMCAD) and anatomical SYNTAX score. The model’s discriminative ability to predict the risk of 5-year death and treatment benefit between PCI and CABG was cross-validated in the SYNTAX trial (n=1800 patients) and externally validated in the CREDO-KYOTO registry (n=7362), and then compared to the original SYNTAX score II 2020 (SS2020). Results The gradient boosting ML model identified the top 10 prognostic factors at the time of decision making as: age, creatinine clearance, left ventricular ejection fraction, peripheral vascular disease, C-reactive protein, hemoglobin, HbA1c, glucose, systolic and diastolic pressure. The ML model performed best for predicting 5-year all-cause death with C-indexes of 0.78 (95% CI 0.75-0.81) in cross-validation and 0.77 (95% CI 0.76-0.79) in external validation. The ML model discriminated 5-year mortality better than the SS2020 in the external validation cohort (vs C-index 0.72 for SS2020, p &amp;lt;0.001) and identified heterogeneity in the treatment benefit of CABG versus PCI (Figure). Conclusions An ML-based approach for identifying individuals who benefit from CABG or PCI is feasible and effective. Implementation of this model in health care systems—trained to collect large numbers of parameters—may harmonize decision making.Figure

Impact of repeat revascularization within 5 years on 10-year mortality after percutaneous or surgical revascularization

Abstract Background The SYNTAX trial demonstrated negative impact of repeat revascularization (RR) on 5-year outcomes following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with three-vessel (3VD) and/or left main coronary artery disease (LMCAD). We aimed to investigate the impact of RR within 5 years, on 10-year mortality in patients with 3VD and/or LMCAD after PCI or CABG. Methods The SYNTAXES study evaluated the vital status out to 10 years of patients with 3VD and/or LMCAD. Patients were stratified by RR within 5 years and randomized treatment. The association between RR within 5 years and 10-year mortality was assessed. Results A total of 330 (220 RR after initial PCI and 110 RR after initial CABG) out of 1800 patients (18.3%) underwent RR within 5 years from initial revascularization. RR occurred more frequently after initial PCI than after initial CABG (25.9% vs 13.7%, p&amp;lt;0.001). Overall, 10-year mortality was comparable between patients undergoing RR and those not (28.2% vs 26.1%, adjusted HR: 1.17, 95% CI: 0.93-1.48, p=0.187). Among patients requiring RR, those who underwent PCI as initial revascularization had a higher risk of 10-year mortality compared to initial CABG (33.5% vs 17.6%, adjusted HR: 2.09, 95% CI: 1.21-3.61, p=0.008). Conclusions In the SYNTAXES study, RR within 5 years had no impact on 10-year all-cause death in the population overall. Among patients requiring any repeat procedures, 10-year mortality was higher after initial treatment with PCI than after CABG. These exploratory findings should be investigated with larger populations in future studies.Graphic Abstract

Interim prediction of two-year all-cause mortality in patients with de novo multivessel coronary artery disease undergoing intended multivessel PCI

Abstract Background/Introduction coronary revascularization in patients with de novo three-vessel coronary artery disease (3VD) without Left Main disease can be performed by either PCI or CABG after objective Heart Team consensus. In the ongoing Multivessel TALENT trial (NCT04390672)1, the intended multivessel PCI is performed using DES with ultrathin struts and biodegradable polymers under the guidance of quantitative flow ratio (QFR) and intracoronary imaging with IVUS or OCT. Purpose The Logistic Clinical SYNTAX score (logSYNTAX) to predict 2-year all-cause mortality after PCI was developed in 15,883 patients treated in the GLOBAL LEADERS trial and externally validated in 10,100 patients. This study aims to predict 2-year all-cause mortality after intended multivessel PCI in the currently enrolled trial population to identify patients who should be considered high risk. Methods and results We performed an interim analysis in the first consecutive 781 patients of the ongoing Multivessel TALENT Trial aimed to enrol 1550 patients. Thirteen clinical predictors are used in the logSYNTAX score: SYNTAX I-score, presence of 3VD and/or LM disease, age, creatinine clearance in mL/min, LVEF, BMI, serum hemoglobin level(g/dL), the White Blood Cell Count (WBC, in 109 cells/L) and the presence of COPD, PVD, diabetes mellitus, current smoking and/or a history of stroke. LVEF and BMI have additional squared terms to adjust for non-linear associations with all-cause mortality. The predicted mortality was estimated using the survival function developed in the GLOBAL LEADERS trial. We considered patients high-risk if the estimated risk was above the 3rd quartile. In 563 patients, all thirteen predictors necessary for 2-year mortality prediction were available. Median 2-year all-cause mortality of 1.9% (1.09-3.82; IQR2.73). 142 patients (25%) with an increased estimated 2-year mortality risk (&amp;gt;3.8%) due to higher prevalence of the aforementioned predictors; higher median age [75 (9.0) vs. 67 (12.0), p &amp;lt;0.001], a lower median LVEF [55% (20) vs. 94% (35.5), p &amp;lt;0.001] and a higher median SYNTAX score [26.0 (13.5) vs. 20.0(11.0), p &amp;lt;0.001]. A complete overview of predictors can be found in table 1. High age, an impaired LVEF, and an increased anatomical SYNTAX-I score were the main contributors to high mortality in this study cohort (see figure 1). Conclusion(s) In 563 patients, the median predicted 2-year all-cause mortality was 1.9%. Nevertheless, a non-neglectable amount of patients were estimated to be at increased risk for all-cause 2-year mortality. Accurate prediction by knowledge of aforementioned predictors is pivotal for appropriate mortality risk prediction to segregate high-risk patients with 3VD for individual decision-making on coronary revascularization, even if surgical revascularization is no option, and guide optimal treatment with use of intravascular imaging to achieve an optimal PCI result.Table 1Figure 1

Histone Mono-methylation by SETD7 Orchestrates Angiogenic Response in Diabetic Limb Ischemia

Abstract Background Peripheral artery disease (PAD) is highly prevalent in patients with diabetes (DM) and associates with a high rate of limb amputation and poor prognosis. Surgical and catheter-based revascularization have failed to improve outcome in DM patients with PAD. Hence, a need exists to develop new treatment strategies able to promote blood vessel growth in this setting. Mono-methylation of histone 3 at lysine 4 (H3K4me1) - a specific epigenetic signature induced by the histone methyltransferase SETD7 - favours an open chromatin thus enabling gene transcription. Purpose: To investigate whether SETD7-dependent epigenetic changes modulate angiogenic response in diabetes. Methodology: Primary human aortic endothelial cells (HAECs) were exposed to normal glucose (NG, 5 mM) or high glucose (HG, 25 mM) concentrations for 48 hours. Unbiased gene expression profiling was performed by RNA sequencing (RNA-seq) followed by Ingenuity Pathway Analysis (IPA). In vitro assays, namely cell migration and tube formation were employed to study angiogenic properties in HAECs. SETD7 and H3K4me1 levels were investigated by Western blot and Chromatin immunoprecipitation (ChIP). Pharmacological blockade of SETD7 was achieved by using the highly selective inhibitor (R)-PFI-2. Mice with streptozotocin-induced diabetes were orally treated with (R)-PFI-2 or vehicle and underwent hindlimb ischemia by femoral artery ligation for 14 days. Blood flow recovery was analysed at 30 minutes, 7 and 14 days by laser Doppler imaging. Our experimental findings were also translated in gastrocnemius muscle samples from patients with and without diabetes. Results RNA-seq in HG-treated HAECs revealed a profound upregulation of the methyltransferase SETD7, an enzyme involved in mono-methylation of lysine 4 at histone 3 (H3K4me1). SETD7 upregulation in HG-treated HAECs was associated with increased H3K4me1 levels as well as with impaired endothelial cell migration and tube formation. Both SETD7 gene silencing and pharmacological inhibition by (R)PFI-2 rescued hyperglycemia-induced impairment of HAECs migration and tube formation, while SETD7 overexpression blunted the angiogenic response. RNA-seq and ChIP assays showed that SETD7-dependent H3K4me1 regulates the transcription of the angiogenesis inhibitor semaphorin-3G (SEMA-3G, (Figure 1). Moreover, SEMA-3G overexpression blunted migration and tube formation in SETD7-depleted HAECs. In diabetic mice with hindlimb ischemia, treatment with (R)-PFI-2 improved limb vascularization and perfusion as compared to vehicle (Figure 2). Finally, SETD7/SEMA3G axis was upregulated in muscle specimens from T2D patients as compared to controls (Figure 2) Conclusion: Targeting SETD7 represents a novel epigenetic-based therapy to boost neovascularization in diabetic patients with PAD.

Long-term follow-up of patients with complex coronary artery disease treated with minimally invasive direct coronary artery bypass.

Patients with complex coronary artery disease (CAD) may benefit from surgical myocardial revascularization but weighing the risk of peri-operative complications against the expected merit is difficult. Minimally invasive direct artery bypass (MIDCAB) procedures are less invasive, provide the prognostic advantage of operative revascularization of the left anterior descending artery and may be integrated in hybrid strategies. Herein, the outcomes between patients with coronary 1-vessel disease (1-VD) and patients with 2-VD and 3-VD after MIDCAB procedures were compared in this single-center study. Between 1998 and 2018, 1363 patients underwent MIDCAB at the documented institution. 628 (46.1%) patients had 1-VD, 434 (31.9%) patients 2-VD and 300 (22.0%) patients suffered from 3-VD. Data of patients with 2-VD, and 3-VD were pooled as multi-VD (MVD). Patients with MVD were older (66.2 ± 10.9 vs. 62.9 ± 11.2 years; p < 0.001) and presented with a higher EuroScore II (2.10 [0.4; 34.2] vs. 1.2 [0.4; 12.1]; p < 0.001). Procedure time was longer in MVD patients (131.1 ± 50.3 min vs. 122.2 ± 34.5 min; p < 0.001). Post-operatively, MVD patients had a higher stroke rate (17 [2.3%] vs. 4 [0.6%]; p = 0.014). No difference in 30-day mortality was observed (12 [1.6%] vs. 4 [0.6%]; p = 0.128). Survival after 15 years was significantly lower in MVD patients (p < 0.01). Hybrid procedures were planned in 295 (40.2%) patients with MVD and realized in 183 (61.2%) cases. MVD patients with incomplete hybrid procedures had a significantly decreased long-term survival compared to cases with complete revascularization (p < 0.01). Minimally invasive direct coronary artery bypass procedures are low-risk surgical procedures. If hybrid procedures have been planned, completion of revascularization should be a major goal.

Impact of visceral adipose tissue on mortality in patients undergoing transcatheter aortic valve implantation

Abstract Background Computed tomography (CT) is a recognized method to assess body composition. The analysis of CT-scans at third lumbar vertebra level (L3-CT) allows to detect sarcopenia, which plays a negative prognostic role in patients undergoing Transcatheter Aortic Valve Implantation (TAVI). Conversely, the effect of visceral adipose tissue (VAT), a pro-inflammatory and metabolically active organ associated with unfavorable cardiovascular outcomes, is still poorly explored. Purpose We investigated the association between preoperative VAT and 30-days and 1-year mortality in patients undergoing TAVI. Methods Anamnestic, laboratory and clinical data of patients who underwent TAVI in 2010-2020 were collected. Preoperative CT were analyzed to measure VAT area (cm2), normalized for stature obtaining VAT index (VATi, cm2/m2). The sample was classified according to VATi values into two groups: low VATi [1st quartile] vs. high VATi [2nd to 4th quartiles]. The two groups were compared by T-test for continuous variables (expressed as mean ± SD) and Chi-square test for categorical variables (expressed as%). Mortality analyses were performed through Kaplan-Meier curves with log rank test. To address for potential confounding factors a propensity score (1:1 matching)based on STS mortality score and Euroscore II values was calculated in order to create two comparable groups. Results We enrolled 168 patients (45.8%males), 150 of whom had CT images available. Mean value of VATi was 58.6±37.2cm2/m2(range1.7-172.3). Patients with higher VATi presented higher levels of glycemia (124±40vs111±23mg/dl,p=0.021), HbA1c (6±0.8vs.5.6± 0.5%,p=0.001) and neutrophils (5.4±2.7vs4.5±1.8x103/µl,p=0.028). No differences were found between the two groups in terms of age, CKD (GFR&amp;lt;30ml/min), previous stroke/myocardial infarction/ surgical or percutaneous revascularization, intra-hospital complications and presence of comorbidities such as cancer, atrial fibrillation, diabetes, and COPD. Overall, 1-year and 30-days mortality were 16.1%and5.4%, respectively. High VATi group [range25.9-172.3cm2/m2] presented higher 1-year mortality (19.5%vs5.4%,OR= 4.2, p=0.046) as compared with low VATi group [range 1.7-25.7cm2/m2], while no significant differences were found in 30-days mortality (6.2%vs2.7%,p=0.421); survival curves are shown in Fig.1A and 1B. After propensity score creation, 37 pairs of patients were successfully matched; in the matched population, high VATi was significantly associated with a higher 1-year mortality (21.6%vs5.5%, p=0.041,Fig.2). Conclusions High levels of VATi are independently associated with a four-fold increased risk of 1-year mortality in patients treated by TAVI, possibly mediated by enhanced inflammatory status and augmented incidence of metabolic complications related with abundant abdominal VAT. Adding VAT evaluation to the scores currently used in clinical practice could help to optimize pre-operative risk stratification in patients undergoing TAVI.