Cardiac Thrombosis Research Articles

Right Atrial Thrombosis and Pulmonary Embolism: A Narrative Review.

Prompt diagnosis of pulmonary embolism (PE) remains challenging, which often results in a delayed or inappropriate treatment of this life-threatening condition. Mobile thrombus in the right cardiac chambers is a neglected cause of PE. It poses an immediate risk to life and is associated with an unfavorable outcome and high mortality. Thrombus residing in the right atrial appendage (RAA) is an underestimated cause of PE, especially in patients with atrial fibrillation. This article reviews achievements and challenges of detection and management of the right atrial thrombus with emphasis on RAA thrombus. The capabilities of transthoracic and transesophageal echocardiography and advantages of three-dimensional and two-dimensional echocardiography are reviewed. Strengths of cardiac magnetic resonance imaging (CMR), computed tomography, and cardiac ventriculography are summarized. We suggest that a targeted search for RAA thrombus is necessary in high-risk patients with PE and atrial fibrillation using transesophageal echocardiography and/or CMR when available independently on the duration of the disease. High-risk patients may also benefit from transthoracic echocardiography with right parasternal approach. The examination of high-risk patients should involve compression ultrasonography of lower extremity veins along with the above-mentioned technologies. Algorithms for RAA thrombus risk assessment and protocols aimed at identification of patients with RAA thrombosis, who will potentially benefit from treatment, are warranted. The development of treatment protocols specific for the diverse populations of patients with right cardiac thrombosis is important.

Impact of SYNTAX score 2 on 7-year clinical outcomes in patients treated with cobalt-chromium everolimus-eluting stent

Abstract Background Impact of SYNTAX score II (SSII) on long-term clinical outcomes after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation remains unclear. Methods Between February 2010 and May 2011, 1064 consecutive patients with 1440 lesions were treated only with CoCr-EES implantation. Of these, the SSII was calculated in 1013 patients with 1345 lesions. Patients were divided into the tertile group: Tertiles for SSII (low SSII [12–28.9], n=334; intermediate SSII [29–39.1], n=339; and high SSII [39.2–80.8], n=340). We assessed the cumulative 7-year incidences of major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, definite stent thrombosis, and clinically driven target lesion revascularization (CDTLR) based on SSII groupings. Results Cumulative 7-year incidence of MACE was significantly higher in the high SSII group than in the other groups (34.1% vs. 18.6% vs. 17.2%, p<0.001). The cumulative incidence of cardiac death, myocardial infarction and stent thrombosis were significantly higher in the high SSII group than in the other groups (22.1% vs. 2.0% vs. 5.3%, p<0.001; 6.6% vs. 4.9% vs. 1.7%, p=0.01; 2.9% vs. 1.7% vs. 0.3%, p=0.03, respectively). The cumulative incidence of CDTLR was similar between the groups (15.2% vs. 12.8% vs. 15.7%, p=0.57). High SSII group (hazard ratio [HR] 2.18 [vs. low SS], 95% confidence intervals [CI]: 1.56–3.06, p<0.001) and diabetes mellitus (HR 1.37, 95% CI: 1.04–1.81, p=0.03) were predictors of 7-year MACE. Conclusions SSII has significantly impact on 7 years clinical outcomes after CoCr-EES implantation. Cumulative incidence of MACE Funding Acknowledgement Type of funding source: None

Side branch long lesion with main vessel vulnerable plaques by optical coherence tomography predict target-vessel myocardial infarction after provisional stenting in patients with coronary bifurcation

Abstract Background Provisional side branch (SB) stenting is correlated with target-vessel myocardial infarction (TVMI) in patients with coronary bifurcation lesions. However, the underlying mechanisms remain unknown. Objectives We aimed to determine the correlation of SB lesion length with vulnerable plaques using optical coherence tomography (OCT) and TVMI in patients with coronary bifurcation lesions treated by a provisional approach. Methods A total of 405 patients with 405 bifurcation lesions who underwent pre-PCI OCT imaging of both main vessel (MV) and SB was prospectively enrolled. Patients were defined as Long-SB lesion (SB lesion length ≥10 mm) and Short-SB lesion (SB lesion length <10 mm) groups according to quantitative coronary analysis and were also stratified by the presence of vulnerable plaques based on OCT findings. The primary endpoint was the occurrence of TVMI after provisional stenting at one-year follow-up. Results 178 (43.9%) patients had long SB lesions. Vulnerable plaques predominantly localized in the main vessel (MV) and more frequently in the Long-SB lesion group (42.7%) compared to 24.2% in the Short-SB lesion group (p<0.001). At one-year follow-up after provisional stenting, there were 31 (8.1%) TVMIs, with 11.8% in the Long-SB lesion group and 4.4% in the Short-SB lesion group (p=0.009), leading to significant difference in target lesion failure between two groups (15.2% vs. 6.6%, p=0.007). The rate of cardiac death, revascularization, and stent thrombosis was comparable between study groups. By multivariate regression analysis, long SB lesion length (p=0.011), presence of vulnerable plaques in the polygon of confluence (p=0.001), and true coronary bifurcation lesions (p=0.004) were three independent factors of TVMI. Conclusions Long-SB lesion length with MV vulnerable plaques predict increased TVMI after provisional stenting in patients with true coronary bifurcation lesions. Further study is warranted to identify the better stenting techniques for coronary bifurcation lesions with long lesion in the SB Kaplan-Meier survival curve Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): NSFC

Onyx ONE: outcomes in patients with acute coronary syndrome

Abstract Background/Introduction The Onyx ONE Global Study (Onyx ONE), a randomized, single-blind, international trial, demonstrated non-inferiority of a zotarolimus-eluting stent (ZES) to a polymer-free drug-coated stent (DCS) in high-bleeding risk patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT). More than half of the Onyx ONE patients presented with an acute coronary syndrome (ACS). The safety and effectiveness of ZES and DCS in ACS patients treated with SAPT after 30 days remains unknown. Purpose To evaluate the safety and effectiveness outcomes for ZES and DCS in Onyx ONE patients presenting with ACS. Methods The primary outcome of the trial was a composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year. To align with the time that DAPT is interrupted, we also evaluated the primary endpoint between the 2 stent groups in a landmark analysis between 30 days and 1 year. All analyses were performed in ACS patients (includes unstable angina, non ST-elevation myocardial infarction and ST-elevation myocardial infarction). Results Among the 1996 patients randomized in Onyx ONE, 982/1902 (51.6%) presented with ACS, of which 511/982 (52.0%) and 471/982 (48.0%) were treated with ZES and DCS respectively. In a pre-defined subgroup analysis in ACS patients, the event rates between the two stent groups regarding the primary outcome at one year were similar (18.5% ZES; 20.8% DCS; HR: 0.91; 95% CI [0.68, 1.22]; p=0.523). In the landmark analysis beyond day 30, the primary outcome rate tended to be lower among those treated with the ZES (8.4%) compared with the DCS (12.1%) [HR: 0.66 (95% CI: 0.43, 1.01), p=0.055] (Figure). This was primarily driven by lower rates of myocardial infarction with ZES (6.5% ZES; 10.2% DCS; [HR: 0.58 (95% CI: 0.36, 0.93); p=0.025], while other components were similar: cardiac death, 2.6% ZES vs. 2.8% DCS [HR: 1.00 (95% CI: 0.44, 2.27); p>0.99) and stent thrombosis, 1.4% ZES vs. 1.4% DCS [HR: 0.93 (95% CI: 0.27, 3.21); p=0.91]. Conclusions In Onyx ONE, high-bleeding risk patients presenting with ACS had similar safety and efficacy at 1 year in both the ZES and DCS stent groups. However, a trend was present for greater safety with the ZES with SAPT treatment beyond 30 days driven by lower myocardial infarction rates in that time period thus warranting additional confirmatory studies. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Medtronic sponsored the Onyx ONE Global Study

Medical and Invasive Management of Cardiac Thrombosis in Children with Congenital and Acquired Heart Disease

In this manuscript, we review the diagnosis, causes, and management of cardiac thrombosis in children with congenital and acquired heart disease. Indications for invasive management and surgery are discussed. The differential diagnostic considerations and management of cardiac thromboses will be reviewed, including those that occur as a consequence of repair and palliation of congenital heart disease. The definition of venous thromboembolism has recently been expanded to include thromboses within both the right and left heart chambers. Direct thrombin inhibitors (DTIs) and direct oral anticoagulants (DOACs) are emerging as treatment alternatives to the heparins and vitamin K antagonists for the management of thrombosis in pediatric heart disease. Thrombosis within the heart occurs as a consequence of abnormalities and alterations in blood flow resulting in stasis and turbulence. Children with acquired and congenital heart disease carry a number of risk factors in Virchow’s triad. Thrombosis can occur throughout any part of the cardiovascular system in congenital heart disease and after surgery for repair or palliation of defects.

Comparative influence of bleeding and ischemic risk factors on diabetic patients undergoing percutaneous coronary intervention with everolimus-eluting stents.

To investigate the impact of ischemic and bleeding risk factors on long-term clinical outcomes of patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) with everolimus-eluting stents. Second-generation drug-eluting stents have substantially improved outcomes after PCI in the general population; however, DM patients continue to experience high rates of ischemic and bleeding complications. DM patients from the pooled XIENCE V registry were divided into high or low bleeding and ischemic risk groups (HBR, LBR, HIR, and LIR) based on established bleeding (age ≥ 75 years; chronic kidney disease; anemia; prior stroke; oral anticoagulation; thrombocytopenia; prior major bleeding) and ischemic (acute coronary syndrome; prior myocardial infarction [MI]; ≥3 stents implanted; ≥3 vessels treated; ≥3 lesions treated; stent length > 60 mm; bifurcation treated with ≥2 stents; chronic total occlusion) risk factors. The primary outcomes were major adverse cardiac events (MACE; cardiac death, MI, or stent thrombosis) and major bleeding at 4-year follow-up. A total of 3,704 DM patients were divided into four groups (21.5% LBR/LIR; 39.0% LBR/HIR; 15.6% HBR/LIR; 23.9% HBR/HIR). Compared with LBR/LIR patients, those at HBR/HIR and HBR/LIR had a significantly higher risk of MACE (HR (95% CI) 2.7 (1.9-3.9) and 2.2 (1.5-3.2), respectively) and major bleeding (2.7 (1.6-4.8) and 2.6 (1.4-4.7), respectively), while LBR/HIR patients did not. Among DM patients undergoing PCI, presence of bleeding risk factors was associated with a higher risk of both ischemic and bleeding events, whereas commonly used features of ischemic risk did not impact long-term clinical outcomes.

Covid-19 Pandemic and Possible Links with Mthfr Mutations, Homocysteinemia, and Metabolic Disturbances: Short Review

Coronovirus-19 (COVID-19) is an associate degree infection caused by the SARS-CoV-2 virus inflicting a worldwide pandemic and chiefly characterized by respiratory symptoms, many times accompanied by a cytokine storm. It causes migration of the neutrophils, macrophages and inflammatory cytokines resulting in the destruction of the alveolar-capillary walls. Coagulopathy in patients with COVID-19 may be a common complication that jeopardizes the clinical course and is related to poorer outcomes and probable death. The methylenetetrahydrofolate enzyme (MTHFR) is coded by the gene with the image MTHFR on chromosome one location p36.3 in humans, and there are desoxyribonucleic acid sequence variants (genetic polymorphisms) related to this gene. However, the 2 commonest ones are C677T and A1298C. Deficiencies within the production of this accelerator are related to raise risk of cardiac muscle infarctions, stroke, thrombosis, and several conditions. Homocysteine (Hcy) is a chemical in the blood formed when the amino acid methionine, a building block of the proteins, is naturally metabolized to be excreted in the urine; throughout this breakdown method, our body will recycle homocysteine to be reused to make different proteins. For this utilization, we need vitamins B12, B6, and folate. Also, for utilization to be the foremost economical, the accelerator MTHFR is needed. Transmissible mutations within the factor that create the MTHFR accelerator will result in an associate degree accelerator that’s not optimally active and should result in elevated homocysteine levels. Several medical conditions, like vascular disorders, obesity, diabetic disorder, peripheral neuropathy, and thrombophilia’s inside others, are associated with high Hcy levels and MTHFR mutations. Few reports link the high risk and poor prognosis with COVID-19 with MTHFR mutation and metabolic disorders like obesity and Diabetes mellitus. In this this review, we provide recommendations to prevent complications in patients with COVID, MTHFR mutations, Diabetes, and Obesity.

Clinical Approach to Renal Artery Thromboembolism

Objective: We aimed to reveal the clinical, laboratory, radiological findings of infarction in the renal artery and its branches due to thrombosis, its effects on renal functions and the measures to be taken. Materials and Methods: The study sample included 8 patients who were admitted to the emergency department of Kutahya University of Health Sciences Evliya Celebi Training and Research Hospital between 2018-2020, and who were hospitalized with the diagnosis of acute renal infarction. Patients were retrospectively analyzed with clinical findings, CT angiography-abdomen, clinical observations, prognosis and complications. Results: Of the patients, 5 were male and 3 were female. The mean age was 55.13 (29-69) years. One patient presented with bilateral renal infarction, while 7 had unilateral renal infarction. The etiology of the patients was idiopathic in 2, atrial fibrilation (AF) in 3 patients, and atherosclerosis in 3 patient. The mean serum creatinine of 1.24 (0.7-3.2) mg/dl and the mean blood leukocyte level of 16925 (11000-26000) mcL were determined. The mean length of hospital stay was 4.6 (3-7) days. Anticoagulant therapy was initiated in all patients for risk of recurrent renal infarction and thromboembolism. Conclusion: We revealed that renal infarction, rarely seen in urology practice, has nonspecific clinical findings; therefore, it should be kept in mind in differential diagnosis for patients presenting with sudden-onset oblique or abdominal pain, and that diagnosis can be made using contrast-enhanced CT. We determined that AF and valvular heart diseases which cause atherosclerosis and cardiac thrombosis play an important role in the etiology.

Drug-coated stents versus bare metal stents in Academic Research Consortium-defined high bleeding risk patients.

More effective and progressively safer generations of drug-elut-ing stents (DES) have replaced bare metal stents (BMS) in rou-tine clinical practice. However, patients considered to be at high bleeding risk (HBR) have traditionally been underrepresented in pivotal DES trials. The aim of this study was to model the safety and effectiveness of drug-coated stents (DCS) versus BMS in HBR patients according to the Academic Research Consortium (ARC) criteria. Participants from the LEADERS FREE (LF) and LEADERS FREE II (LFII) studies were pooled into one data set. Participants were treated with 30 days of DAPT. The primary safety (composite of cardiac death, myocardial infarction, or stent thrombosis) and effectiveness (target lesion revascularisation) endpoints were compared between DCS and BMS in the subgroup of patients satisfying the ARC-HBR definition using propensity-score modelling. From the 3,635 participants included in the combined LF and LFII data set, 2,898 (79.7%) satisfied the ARC-HBR criteria (DCS: 1,923; BMS: 975). The primary safety endpoint occurred in 184 (9.8%) and in 132 (13.8%) participants in the DCS and BMS groups, respectively (adjusted HR 0.72, 95% CI: 0.57-0.91; p=0.006). The risk of the primary effectiveness endpoint was also significantly lower with DCS (6.2%) versus BMS (8.8%) (adjusted HR 0.70, 95% CI: 0.52-0.94; p=0.016). The safety and effectiveness of DCS versus BMS were consistent according to ARC-HBR status (p for interaction=0.206 and 0.260, respectively). DCS are safer and more effective than BMS in an ARC-defined HBR population.

Related factors and the long-term outcome after percutaneous coronary intervention of premature acute myocardial infarction

Objective: To explore the related factors of premature acute myocardial infarction(AMI), and to compare the the long-term outcomes in patients with and without premature AMI after percutaneous coronary intervention (PCI). Methods: This study was a prospective cohort study.From January 2013 to December 2013, 10 724 consecutive patients with coronary heart disease undergoing PCI in Fuwai Hospital were enrolled. Among them 1 920 patients with the diagnosis of AMI were divided into two groups: premature AMI (man≤50 years old, woman≤60 years old) and non-premature AMI. The baseline characteristics were collected, and multivariate logistic regression was uesed to analysis the related factors of premature AMI. The clinical outcomes, including the major adverse cardiovascular and cerebrovascular events(MACCE) which was the composite of cardiac death, myocardial infarction, revascularization, stroke and stent thrombosis, as well as bleeding events, during hospitalization, at 2 years and 5 years follow-up were analyzed. Results: A total of 1 920 AMI patiens were included(age was (56.5±11.3) years old)，with 1 612(84.0%) males. There were statistically significant differences between the two groups in gender, body mass index, blood lipid, complications, inflammatory markers, etc (all P<0.05). Multivariate logistic regression analysis showed body mass index(OR=1.06, 95%CI 1.01-1.10, P<0.01), triglyceride(OR=1.47, 95%CI 1.14-1.90, P<0.01), serum uric acid level(OR=1.02, 95%CI 1.01-1.04, P<0.01), high density lipoprotein cholesterol level(OR=0.33, 95%CI 0.14-0.78, P=0.01) and history of hypertension(OR=0.72, 95%CI 0.56-0.93, P=0.01) were independent related factors of premature AMI. The incidence of all-cause death and cardiac death were lower during hospitalization, at 2 years and 5 years follow-up in the premature AMI group than in non-premature AMI group(all P<0.05). In the premature AMI group, the incidence of MACCE and stroke was lower, with more bleeding events in 5 years follow-up(all P<0.05). Conclusions: Metabolic abnormalities, including high BMI, high triglyceride level and high serum uric acid, low high-density lipoprotein cholesterol level are the related factor of premature AMI. The incidence of ischemic events in patients with premature AMI is lower, while the incidence of bleeding events is higher than non-premature AMI patients.

Cytocompatibility Evaluation of a Novel Series of PEG-Functionalized Lactide-Caprolactone Copolymer Biomaterials for Cardiovascular Applications.

Although the use of bioresorbable materials in stent production is thought to improve long-term safety compared to their durable counterparts, a recent FDA report on the 2-year follow-up of the first FDA-approved bioresorbable vascular stent showed an increased occurrence of major adverse cardiac events and thrombosis in comparison to the metallic control. In order to overcome the issues of first generation bioresorbable polymers, a series of polyethylene glycol-functionalized poly-L-lactide-co-ε-caprolactone copolymers with varying lactide-to-caprolactone content is developed using a novel one-step PEG-functionalization and copolymerization strategy. This approach represents a new facile way toward surface enhancement for cellular interaction, which is shown by screening these materials regarding their cyto- and hemocompatibility in terms of cytotoxicity, hemolysis, platelet adhesion, leucocyte activation and endothelial cell adhesion. By varying the lactide-to-caprolactone polymer composition, it is possible to gradually affect endothelial and platelet adhesion which allows fine-tuning of the biological response based on polymer chemistry. All polymers developed were non-cytotoxic, had acceptable leucocyte activation levels and presented non-hemolytic (<2% hemolysis rate) behavior except for PLCL-PEG 55:45 which presented hemolysis rate of 2.5% ± 0.5. Water contact angles were reduced in the polymers containing PEG functionalization (PLLA-PEG: 69.8° ± 2.3, PCL-PEG: 61.2° ± 7.5) versus those without (PLLA: 79.5° ± 3.2, PCL: 76.4° ± 10.2) while the materials PCL-PEG550, PLCL-PEG550 90:10 and PLCL-PEG550 70:30 demonstrated best endothelial cell adhesion. PLLA-PEG550 and PLCL-PEG550 70:30 presented as best candidates for cardiovascular implant use from a cytocompatibility perspective across the spectrum of testing completed. Altogether, these polymers are excellent innovative materials suited for an application in stent manufacture due to the ease in translation of this one-step synthesis strategy to device production and their excellent in vitro cyto- and hemocompatibility.

Cardiovascular activity of Micrurus lemniscatus lemniscatus (South American coralsnake) venom

Envenomation by coralsnakes (Micrurus spp.) is characterized by blockade of peripheral neurotransmission mediated by the presence of α- and β-neurotoxins. However, little is known about their cardiovascular activity. Micrurus lemniscatus lemniscatus is a coralsnake found in the Amazon basin and occasionally causes envenomation in humans. In this study, we examined the hemodynamic, vascular and atrial responses to M. l. lemniscatus venom. Anesthetized rats were used for hemodynamic and electrocardiogram (ECG) recordings; in vitro experiments were carried out in rat isolated thoracic aorta and atria preparations. In vivo, venom (0.1 and 0.3 mg/kg) caused immediate and persistent hypotension that was maximal within the first minute with both doses being lethal after ~40 and ~20 min, respectively. ECG, heart and respiratory rates were not altered during the transient hypotension phase induced by venom but all altered prior to death. There was no evidence of myonecrosis in cardiac muscle tissue, pulmonary hemorrhage nor thrombosis in anesthetized rats exposed to venom. In vitro, venom (10 μg/ml) did not contract aortic strips nor affected the maximal responses to pre-contraction with phenylephrine (PE, 0.0001–30 μM) in strips with and without endothelium. However, venom (10 μg/ml) relaxed aortic strips with endothelium pre-contracted with PE. In aortic strips pre-contracted with PE, venom prevented acetylcholine (0.0001–30 μM)-induced relaxation in strips with endothelium without affecting relaxation induced by sodium nitroprusside (0.1–100 nM) in strips without endothelium. Venom (30 μg/ml) produced a transient increase of atrial contractile force without affecting atrial rate. Taken together these findings indicate a predominantly vascular action of the venom, most likely involving toxins interacting with muscarinic receptors.

Outcomes of stent optimisation in intravascular ultrasound-guided interventions for long lesions or chronic total occlusions.

We sought to investigate the incidence, predictors, and clinical outcomes of stent optimisation with intravascular ultrasound (IVUS) in long coronary lesions treated with new-generation drug-eluting stents (DESs). From four randomised trials comparing IVUS and angiography guidance in long (≥26 mm) or chronic total occlusion coronary lesions, a total of 1,396 patients who underwent IVUS-guided intervention were classified into two groups (stent optimisation and non-optimisation) according to optimisation criteria (minimal stent area [MSA] ≥5.5 mm2 or 80% of mean reference lumen area [MLA]). Major adverse cardiac event (MACE) occurrence, defined as a composite of cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularisation, was compared. Stent optimisation was not met in 578 (41%) patients. Predictors of non-optimisation were older age, longer lesion length, and smaller stent diameter. The MACE rate was significantly higher in the non-optimisation versus the stent optimisation group (4.8% vs 1.9%, log-rank p=0.002; adjusted hazard ratio 2.95, 95% CI: 1.43-6.06). Among possible combinations of absolute and relative expansion criteria, the one best predicting MACE was at least one of MSA ≥5.4 mm2 and/or ≥80% of MLA (Youden index=0.264). Achieving stent optimisation using IVUS evaluation was associated with favourable outcomes in IVUS-guided, new-generation DES implantation for long coronary lesions including CTOs.

Clinical outcomes following polymer-free sirolimus-eluting stent implantations in unselected patients: A descriptive subgroup analysis in patients with renal impairment.

Patients with chronic kidney disease (CKD are frequently excluded from coronary artery disease trials. The aim of this assessment was to study the clinical outcomes of polymer-free sirolimus-eluting stent implantations in patients with impaired renal function.Large-scale, international, single-armed, multicenter, ‘all comers’ observational studies (ClinicalTrials.gov Identifier: NCT02629575 and NCT02905214) were used for this post-hoc subgroup analysis to compare the clinical outcomes in patients with normal renal function (NRF) to those with renal insufficiency (CKD, dialysis dependence). The accumulated target lesion revascularization rate was the primary endpoint at 9 to 12 months whereas the accumulated major adverse cardiac event, stent thrombosis (ST) and procedural success rates were part of the secondary endpoints.There were 6791 patients with NRF, whereas 369 patients had CKD and 83 patients were dialysis dependent. The target lesion revascularization rate at 9 to 12 months was significantly higher in dialysis patients (2.1% vs 3.3% vs 6.7%, P = .011). The accumulated major adverse cardiac events rates in the dialysis and in the CKD group were significantly higher as compared to patients with NRF (13.3% vs 4.0%, P < .001; 6.5% vs 4.0%, P = .024). Finally, ST rates (NRF: 0.7%, CKD: 0.6%, dialysis: 1.3%) were not statistically different between subgroups (P = .768). All-cause cumulative mortality rates were 3.3% (CKD) and 4.0% (dialysis) respectively.Percutaneous coronary interventions with polymer-free, ultra-thin strut sirolimus-eluting stents have comparable revascularization rates in CKD and dialysis dependent patients as compared to percutaneous coronary interventions with other 2nd generation drug-eluting stents. ST and all-cause mortality rates were low as compared to available literature references.

Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series.

BackgroundThere is increasing recognition of a prothrombotic state in COVID-19. Post-mortem examination can provide important mechanistic insights.MethodsWe present a COVID-19 autopsy series including findings in lungs, heart, kidneys, liver, and bone, from a New York academic medical center.FindingsIn seven patients (four female), regardless of anticoagulation status, all autopsies demonstrated platelet-rich thrombi in the pulmonary, hepatic, renal, and cardiac microvasculature. Megakaryocytes were seen in higher than usual numbers in the lungs and heart. Two cases had thrombi in the large pulmonary arteries, where casts conformed to the anatomic location. Thrombi in the IVC were not found, but the deep leg veins were not dissected. Two cases had cardiac venous thrombosis with one case exhibiting septal myocardial infarction associated with intramyocardial venous thrombosis, without atherosclerosis. One case had focal acute lymphocyte-predominant inflammation in the myocardium with no virions found in cardiomyocytes. Otherwise, cardiac histopathological changes were limited to minimal epicardial inflammation (n = 1), early ischemic injury (n = 3), and mural fibrin thrombi (n = 2). Platelet-rich peri‑tubular fibrin microthrombi were a prominent renal feature. Acute tubular necrosis, and red blood cell and granular casts were seen in multiple cases. Significant glomerular pathology was notably absent. Numerous platelet-fibrin microthrombi were identified in hepatic sinusoids. All lungs exhibited diffuse alveolar damage (DAD) with a spectrum of exudative and proliferative phases including hyaline membranes, and pneumocyte hyperplasia, with viral inclusions in epithelial cells and macrophages. Three cases had superimposed acute bronchopneumonia, focally necrotizing.InterpretationIn this series of seven COVID-19 autopsies, thrombosis was a prominent feature in multiple organs, in some cases despite full anticoagulation and regardless of timing of the disease course, suggesting that thrombosis plays a role very early in the disease process. The finding of megakaryocytes and platelet-rich thrombi in the lungs, heart and kidneys suggests a role in thrombosis.FundingNone.

Efficacy and Safety of Ticagrelor Compared to Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis.

The Platelet Inhibition and Patient Outcomes (PLATO) study found that ticagrelor plus aspirin (TA) was more effective than clopidogrel plus aspirin (CA), without an increase in the risk of massive bleeding in patients undergoing percutaneous coronary intervention (PCI). Data from other studies indicate that the conclusion is controversial with the results obtained by PLATO. To investigate the efficacy and safety of TA, compared with CA, in patients with acute coronary syndrome (ACS) after PCI. A systematic literature search was performed in the MEDLINE, EMBASE, and Cochrane databases to compare the efficacy and safety of CA and TA treatment in patients with ACS after PCI. The endpoints were major adverse cardiac events (MACEs), death, stroke, myocardial infarction (MI), stent thrombosis, and bleeding events. The data analysis was performed using RevMan 5.3 software, and the odds ratios (ORs) and their 95% confidence intervals (CI) were calculated. The standards of reporting were in accordance with the PRISMA guidelines. 13 studies with a total of 58,062 patients were included in this study with a subgroup analysis of the European/American and Asian populations. In terms of effectiveness for MACEs, the European, American and Asian populations benefitted more from the TA treatment than the CA treatment (European and American populations, OR = 0.82, P = 0.0002; Asian, OR = 0.66, P < 0.0001; total, OR = 0.78, P < 0.0001). In terms of specific effectiveness indicators, such as stroke, MI, and stent thrombosis, the results of TA and CA groups in the European, American, and Asian populations were not consistent. In terms of safety, there was no statistical difference in total bleeding events between TA and CA treatments (OR = 1.19, P = 0.21). However, in the Asian population, the incidence of total bleeding events (OR = 1.52, P = 0.0004) in the TA group was higher than that in the CA group. The TA treatment in the European and American populations is more beneficial and safer than CA treatment. However, although the Asian population has this benefit, the risk of bleeding is significantly increased as well, and antiplatelet drugs should be chosen carefully.

Clinical Outcomes Following Coronary Bifurcation PCI Techniques: A Systematic Review and Network Meta-Analysis Comprising 5,711 Patients

ObjectivesThe aim of this study was to compare clinical outcomes of different bifurcation percutaneous coronary intervention (PCI) techniques. BackgroundDespite several randomized trials, the optimal PCI technique for bifurcation lesions remains a matter of debate. Provisional stenting has been recommended as the default technique for most bifurcation lesions. Emerging data support double-kissing crush (DK-crush) as a 2-stent technique. MethodsPubMed and Scopus were searched for randomized controlled trials comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE). Secondary outcomes of interest were cardiac death, myocardial infarction, target vessel or lesion revascularization, and stent thrombosis. Summary odds ratios (ORs) were estimated using Bayesian network meta-analysis. ResultsTwenty-one randomized controlled trials including 5,711 patients treated using 5 bifurcation PCI techniques were included. Investigated techniques were provisional stenting, T stenting/T and protrusion, crush, culotte, and DK-crush. Median follow-up duration was 12 months (interquartile range: 9 to 36 months). When all techniques were considered, patients treated using the DK-crush technique had less occurrence of MACE (OR: 0.39; 95% credible interval: 0.26 to 0.55) compared with those treated using provisional stenting, driven by a reduction in target lesion revascularization (OR: 0.36; 95% credible interval: 0.22 to 0.57). No differences were found in cardiac death, myocardial infarction, or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed among provisional stenting, culotte, T stenting/T and protrusion, and crush. In non–left main bifurcations, DK-crush reduced MACE (OR: 0.42; 95% credible interval: 0.24 to 0.66). ConclusionsIn this network meta-analysis, DK-crush was associated with fewer MACE, driven by lower rates of repeat revascularization, whereas no significant differences among techniques were observed for cardiac death, myocardial infarction, and stent thrombosis. A clinical benefit of 2-stent techniques was observed over provisional stenting in bifurcation with side branch lesion length ≥10 mm.

Polymer-free drug-coated vs. bare-metal coronary stents in patients undergoing non-cardiac surgery: a subgroup analysis of the LEADERS FREE trial.

To compare the outcomes of patients undergoing non-cardiac surgery (NCS) after PCI with either a drug-coated stent (DCS) or a bare-metal stent (BMS), followed by 1-month dual antiplatelet therapy and to explore the impact of the timing of NCS. This is a subgroup analysis of the LEADERS FREE trial. The primary safety end point was a composite of cardiac death, myocardial infarction, or stent thrombosis, and the primary efficacy end point was clinically driven target lesion revascularization (TLR). Out of 2432 patients included in the LEADERS FREE trial, 278 (11.4%) underwent NCS within 1 year after PCI. Among NCS patients, the 1-year safety end point was numerically lower with DCS; however, this difference was not significant as compared to BMS (4.7% vs. 10.1%, HR: 0.459 [0.178-1.183], p = 0.099), clinically driven TLR was significantly lower after DCS (2.4% vs. 8.3%, HR: 0.281 [0.079-0.996], p = 0.036), and BARC 3-5 bleeding was similarwith DCS vs. BMS (10.2% vs. 7.5%, p = 0.438). In patients treated with BMS, NCS within 3 months after PCI was associated with higher incidence of the safety end point than NCSs performed later: 14.9% vs. 4.4%, HR: 3.586 [1.012-12.709], p = 0.034. The timing of surgery had no impact on patients treated with DCS (4.7% vs. 4.7%, p = 0.947). Among patients undergoing NCS after PCI, DCS-treated patients had a lower probability of clinically driven TLR compared with BMS. However, there was no significant difference in the occurrence of the primary composite safety end point or bleeding complications. Early NCS after BMS-PCI was associated with impaired safety, while the timing of NCS had no such influence after DCS implantation.

Sex-Based Outcomes in Patients With a High Bleeding Risk After Percutaneous Coronary Intervention and 1-Month Dual Antiplatelet Therapy

Female sex has been identified as a risk factor for bleeding after percutaneous coronary intervention (PCI) and may have contributed to the underuse of drug-eluting stents in women. This risk may be further enhanced among patients with a high bleeding risk. To assess the 2-year outcomes by sex in patients with a high bleeding risk who were enrolled in the LEADERS FREE trial. This cohort study is a prespecified, sex-based secondary analysis of the LEADERS FREE double-blind, randomized clinical trial that was conducted at 68 sites in 20 countries from December 2012 to May 2014. Patients with a high bleeding risk who underwent PCI and met the trial eligibility criteria were enrolled at the participating sites and followed up for up to 2 years. Patients were randomized 1:1 to either a bare-metal stent or a polymer-free, biolimus A9-eluting drug-coated stent with 1-month of dual antiplatelet therapy. The primary safety end point was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target lesion revascularization. Bleeding was assessed using the Bleeding Academic Research Consortium (BARC) scale, and the source of bleeding was recorded. A total of 2432 patients with a high bleeding risk were included in the study. Of these patients, the mean (SD) age was 75 (9) years, and 1694 (69.7%) were men and 738 (30.3%) were women. Women and men had similar incidence of the 2-year primary safety (14.7% vs 13.6%; P = .37) and efficacy (9.2% vs 9.5%; P = .70) end points. The drug-coated stent was found to be superior to the bare-metal stent in both sexes, with lower target lesion revascularization (women: 6.3% vs 12.1%; men: 7.0% vs 12.0%; P for interaction = .70) and similar rates of the primary safety end point (women: 12.4% vs 17.0%; men: 12.6% vs 14.5%; P for interaction = .40). Overall, 2-year BARC types 3 to 5 major bleeding (10.2% vs 8.6%; P = .14) was not statistically different between the sexes, but women experienced greater BARC types 3 to 5 major bleeding within the first 30 days (5.1% vs 2.4%; P = .007) and greater vascular access site major bleeding than men (2.2% vs 0.5%; P < .001). In both sexes, vascular (women: hazard ratio [HR], 3.45 [95% CI, 1.51-7.87]; men: HR, 4.14 [95% CI, 1.33-12.95]) and nonvascular major bleeding (women: HR, 3.76 [95% CI, 2.17- 6.53]; men: HR, 4.62 [95% CI, 3.23-6.61]) were associated with greater 2-year mortality. This study found no sex differences in the ischemic outcomes of patients with a high bleeding risk after PCI, but women appeared to demonstrate greater early bleeding and major bleeding from the vascular access site. Both women and men with major bleeding seemed to experience worse 2-year mortality, suggesting that bleeding avoidance strategies should be uniformly adopted for all patients, with close attention dedicated to women to avoid denying them the benefits of PCI. ClinicalTrials.gov Identifier: NCT02843633.

Clinical and Angiographic Outcomes With Drug-Coated Balloons for De Novo Coronary Lesions: A Meta-Analysis of Randomized Clinical Trials.

BackgroundThe role of drug‐coated balloons (DCBs) in the treatment of de novo coronary lesions is not well established.Methods and ResultsElectronic databases and major conference proceedings were searched for randomized controlled trials that compared DCBs with stents or angioplasty for de novo coronary lesions. The primary outcome was target lesion revascularization. Summary estimates were conducted using random‐effects analysis complemented by several subgroup and sensitivity analyses. A total of 14 randomized controlled trials with 2483 patients were included. At a mean follow up of 12 months, DCBs were associated with no difference in the incidence of target lesion revascularization as compared with alternative strategies (risk ratio [RR], 0.79; 95% CI, 0.35–1.76). There was no difference in treatment effect based on the indication (ie, small‐vessel disease, myocardial infarction, bifurcation, or high bleeding risk) (P interaction=0.22). DCBs were associated with lower target lesion revascularization compared with bare metal stents and similar target lesion revascularization compared with drug‐eluting stents (P interaction=0.03). There was no difference between DCBs and control in terms of major adverse cardiac events, vessel thrombosis, or cardiovascular mortality. However, DCBs were associated with a lower incidence of myocardial infarction (RR, 0.48; 95% CI, 0.25–0.90) and all‐cause mortality (RR, 0.45; 95% CI, 0.22–0.94).ConclusionsIn patients with de novo coronary lesions, use of DCBs was associated with comparable clinical outcomes irrespective of the indication or comparator device. DCBs had a similar rate of target lesion revascularization compared with drug‐eluting stents. A randomized trial powered for clinical outcomes and evaluating the role of DCBs for all‐comers is warranted.