Role of Occlusion Position in Coronary Artery Fistulas with Terminal Aneurysms: A Hemodynamic Perspective.

PURPOSE: Thrombosis within an occluded coronary arterial fistula (CAF) may cause angina and myocardial infarction. This study aims to estimate how the occlusion position of CAFs with terminal aneurysm affects the risk stratification of thrombosis in the fistula in terms of hemodynamics. METHODS: Twelve CAF models were reconstructed based on patient-specific computed tomography angiogram (CTA) images. They were classified into three groups: preserved group (untreated fistula), aneurysm-reserved group (occluded at the fistula terminal: distal occlusion) and aneurysm-removed group (occluded before the aneurysm: proximal occlusion). Hemodynamics results were analyzed and compared with the clinical follow-up results. RESULTS: The results showed that: (1) Hemodynamic patterns within the fistula before and after treatment were significantly different among patients. (2) Aneurysm-removed occlusions showed better improvements with respect to the CAF blood-stealing phenomena. (3) Irrespective of whether aneurysms were removed or not, a disturbed flow pattern was observed. Areas having high OSI and low TAWSS were present in the post-occluded CAFs. The removal of the aneurysm, however, would alleviate the flow disturbance, and decrease the proportion of the area of OSI > 0.3. (4) The thrombosis region spotted in the follow-up patient CTAs was consistent with the computed high OSI area. CONCLUSIONS: A proximal occlusion, namely, removing the aneurysm of the CAF, may help in reducing the risk of thrombosis after surgery. However, follow-up studies with a larger cohort should be carried out to test and verify this speculation in the future.

Challenges associated with treatment of left internal mammary artery graft thrombosis.

Acute occlusion of the left internal mammary artery (LIMA) graft late after coronary artery bypass grafting surgery is a rare and potentially life-threatening complication. We describe a case of acute myocardial infarction 19 years after coronary artery bypass graft surgery due to acute occlusion of the distal anastomosis of a LIMA graft to the left anterior descending artery. Aspiration thrombectomy failed to remove the thrombus. Laser thrombectomy caused perforation. After drug-eluting and covered stent implantation, antegrade TIMI 3 flow was restored with an uneventful postprocedural course.

Imaging the injured beating heart intravitally and the vasculoprotection afforded by haematopoietic stem cells.

AIMS: Adequate microcirculatory perfusion, and not just opening of occluded arteries, is critical to salvage heart tissue following myocardial infarction. However, the degree of microvascular perfusion taking place is not known, limited primarily by an inability to directly image coronary microcirculation in a beating heart in vivo. Haematopoietic stem/progenitor cells (HSPCs) offer a potential therapy but little is known about their homing dynamics at a cellular level and whether they protect coronary microvessels. This study used intravital microscopy to image the anaesthetized mouse beating heart microcirculation following stabilization. METHODS AND RESULTS: A 3D-printed stabilizer was attached to the ischaemia-reperfusion injured (IRI) beating heart. The kinetics of neutrophil, platelet and HSPC recruitment, as well as functional capillary density (FCD), was imaged post-reperfusion. Laser speckle contrast imaging (LSCI) was used for the first time to monitor ventricular blood flow in beating hearts. Sustained hyperaemic responses were measured throughout reperfusion, initially indicating adequate flow resumption. Intravital microscopy confirmed large vessel perfusion but demonstrated poor transmission of flow to downstream coronary microvessels. Significant neutrophil adhesion and microthrombus formation occurred within capillaries with the latter occluding them, resulting in patchy perfusion and reduced FCD. Interestingly, 'patrolling' neutrophils were also observed in capillaries. Haematopoietic stem/progenitor cells readily trafficked through the heart but local retention was poor. Despite this, remarkable anti-thromboinflammatory effects were observed, consequently improving microvascular perfusion. CONCLUSION: We present a novel approach for imaging multiple microcirculatory perturbations in the beating heart with LSCI assessment of blood flow. Despite deceptive hyperaemic responses, increased microcirculatory flow heterogeneity was seen, with non-perfused areas interspersed with perfused areas. Microthrombi, rather than neutrophils, appeared to be the major causative factor. We further applied this technique to demonstrate local stem cell presence is not a pre-requisite to confer vasculoprotection. This is the first detailed in vivo characterization of coronary microcirculatory responses post-reperfusion injury.

Transient sinus arrest due to sinus node artery thrombus after revascularisation of the left circumflex artery.

We present a case of sinus arrest and junctional escape rhythm from sinus node artery (SNA) thrombus in a 55-year-old man after revascularisation of right coronary and proximal circumflex arteries for infero-posterior wall ST-segement elevation myocardial infarction (STEMI). Sinus arrest from occlusion of the SNA is uncommon. The ensuing bradycardia may have haemodynamic consequences requiring temporary pacing but is almost always self-limited.

rLj-RGD3, a novel recombinant toxin protein from Lampetra japonica, prevents coronary thrombosis-induced acute myocardial infarction by inhibiting platelet functions in rats.

Recombinant Lampetra japonica RGD-peptide (rLj-RGD3), a soluble protein containing three RGD sequences, was acquired from the oral salivary glands of Lampetra japonica using recombinant DNA technology. The aim of this study was to investigate the protective effects of rLj-RGD3 against acute myocardial infarction (AMI) induced by coronary artery thrombosis, as well as the underlying mechanisms. A rat model of AMI caused by ferric chloride-induced thrombosis on the surface of the left anterior descending (LAD) coronary artery was successfully established. Rats were given various doses of rLj-RGD3 (12 µg/kg, 24 µg/kg and 48 µg/kg) via sublingual intravenous delivery 10 min before AMI. ST segment elevation was recorded by electrocardiogram (ECG) until the end of the model. Left ventricular Evans blue content and histopathological changes were examined. Blood samples were collected to determine 5-hydroxytryptamine (5-HT), ß-thromboglobulin (ß-TG), platelet factor 4 (PF4) and cAMP levels. The effects of rLj-RGD3 on platelet aggregation, adhesion and intracellular calcium concentrations were also measured. rLj-RGD3 significantly reduced ST segment elevation, prevented thrombus formation in the coronary artery and decreased Evans blue content in the left ventricular myocardium. Meanwhile, rLj-RGD3 exerted an inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation and blocked platelet adhesion to collagen. Treatment with rLj-RGD3 prevented 5-HT, ß-TG and PF4 release and significantly elevated intracellular cAMP levels in a dose-dependent manner but decreased the level of cytosolic-free Ca2+, an aggregation-inducing molecule. These results show that rLj-RGD3 can effectively reduce coronary thrombosis in AMI rats by strongly inhibiting platelet function, indicating that the recombinant RGD toxin protein rLj-RGD3 may serve as a potent clinical therapeutic agent for AMI.

A Swine Model of Percutaneous Intracoronary Ethanol Induced Acute Myocardial Infarction and Ischemic Mitral Regurgitation.

Ischemic mitral regurgitation (IMR) is a frequent complication after a myocardial infarction (MI), which doubles mortality. Transcatheter mitral repairs are emerging as alternative treatment options to open heart surgery for IMR, but animal models to test them are lacking. We report a percutaneous swine model of IMR. Seventeen swine were randomized to (group 1, n = 12) MI causing IMR, and (group 2, n = 5) controls. In group 1, MI was induced via percutaneous ethanol injection into the obtuse marginal branches of the left circumflex artery, resulting in ST elevating myocardial infarction. Nine animals were survived to 8-10 weeks with weekly echocardiograms and three swine were survived to 16-20 weeks with MRI at termination. In group 1 animals, average IMR fraction at termination was 26.6 ± 2.3% in the echo group, and 24.51 ± 0.41% in the MRI group. None of the animals in group 2 had IMR. Left ventricular dysfunction and significant dilatation were evident in group 1 animals, compared to the controls. In conclusion, a reproducible model of IMR is reported for use in pre-clinical testing of new mitral technologies.

Atypical presentation of paroxysmal nocturnal hemoglobinuria treated by eculizumab: A case report.

RATIONALE: Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant acquired hematopoietic stem cell disease, which can be revealed by hemolytic anemia, thromboembolism, or bonemarrow failure. Thrombosis can occur at any site, but coronary thrombosis is extremely rare. Controlled trials have demonstrated that eculizimab, an inhibitor of the terminal complement cascade, was able to reduce both hemolysis and thrombosis, but its efficacy in cases of PNH with coronary thrombosis is unknown. PATIENT CONCERNS AND DIAGNOSES: We report herein the unusual case of a 73-year-old patient presenting with recurrent coronary syndromes without associated stenosis, fever, marked inflammatory syndrome, and anemia, leading to a delayed diagnosis of PNH. INTERVENTION AND OUTCOMES: Eculizumab allowed the resolution of fever and inflammation, and prevented further thromboembolism. LESSONS: This case emphasizes the importance of performing aflow cytometry test for PNH in front of unusual or unexplained recurrent thromboses. Thromboses, as observed in our case, may be associated with fever and marked inflammation. This case also provides useful information on eculizumab ability to prevent further thromboembolism in PNH patients with a medical history of arterial thrombosis.

Catastrophic Left Ventricular Thrombosis Complicating Extra-corporeal Membrane Oxygenation: A Case Report.

A massive left ventricular thrombosis represents a rare however, catastrophic complication of a central veno-arterial extra-corporeal membrane oxygenation. We report a case of such complication in a patient with severe left ventricular dysfunction after cardiac surgery. Its management and preventive measures are described and discussed.

[Aftermaths of lesions of coronary arteries in Kawasaki disease].

Kawasaki disease, also known as cutaneous-mucous-glandular mucocutaneous glandular syndrome, is acute systemic vasculitis of small-to-medium calibre arteries, frequently involving coronary arteries, affect almost exceptionally children, with reports concerning cases of Kawasaki syndrome in 20-to-30-year-old adults being extremely rare. The most serious manifestation of Kawasaki disease is coronaritis and formation of coronary artery aneurysms. The dynamics of the formed coronary aneurysms and, consequently, the fate of patients may be different. Thrombosis of an aneurysm in the early period of the disease and stenosing of the affected coronary artery later on present possible complications of Kawasaki disease and potential causes of myocardial infection in young adults. Increased risk of coronary artery thromboses in Kawasaki disease is conditioned by a decrease in velocity of blood flow and its turbulent pattern in the aneurysms, endothelial dysfunction due to currently existing or endured coronaritis and thrombocytosis typical of this pathology. Predisposing factors of coronary artery stenosing are unfavourable haemodynamic conditions appearing at the sites of the "entry" and "exit" of the aneurysm. Described herein are two case reports of myocardial infarction, one of which being a complication of an acute case of Kawasaki disease in a 29-year-old patient, with the second one being a consequence of coronary artery stenosing in a 25-year-old patient who had endured Kawasaki disease in his childhood.

Distal coronary embolization following acute myocardial infarction increases early infarct size and late left ventricular wall thinning in a porcine model.

BACKGROUND: Distal coronary embolization (DCE) of thrombotic material occurs frequently during percutaneous interventions for acute myocardial infarction and can alter coronary flow grades. The significance of DCE on infarct size and myocardial function remains unsettled. The aims of this study were to evaluate the effects of DCE sufficient to cause no-reflow on infarct size, cardiac function and ventricular remodeling in a porcine acute myocardial infarction model. METHODS AND RESULTS: Female Yorkshire pigs underwent 60 min balloon occlusion of the left anterior descending coronary artery followed by reperfusion and injection of either microthrombi (prepared from autologous porcine blood) sufficient to cause no-reflow (DCE), or saline (control). Animals were sacrificed at 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI. Cardiovascular magnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) and survival kinase (Akt) activities were assessed. At 3d, DCE increased infarct size (CMR: 18.8% vs. 14.5%, p = 0.04; serum troponin-I: 13.3 vs. 6.9 ng/uL, p < 0.05) and MMP-2 activity levels (0.81 vs. 0.49, p = 0.002), with reduced activation of Akt (0.06 versus 0.26, p = 0.02). At 6 weeks, there were no differences in infarct size, ventricular volume or ejection fraction between the two groups, although infarct transmurality (70% vs. 57%, p< 0.04) and ventricular thinning (percent change in mid anteroseptal wall thickness:-25.6% vs. 0.7%, p = 0.03) were significantly increased in the DCE group. CONCLUSIONS: DCE increased early infarct size, but without affecting later infarct size, cardiac function or ventricular volumes. The significance of the later remodelling changes (ventricular thinning and transmurality) following DCE, possibly due to changes in MMP-2 activity and Akt activation, merits further study.

Desfechos clínicos tardios de pacientes diabéticos tratados com stents farmacológicos eluidores de sirolimus ou everolimus: uma análise do registro DESIRE / Late clinical outcomes of diabetic patients treated with sirolimus or everolimus drug-eluting stents: an analysis of the DESIRE registry

Stents farmacológicos (SF) de segunda geração demonstraram melhor desempenho clínico que os de primeira geração, sobretudo pela redução nas taxas de trombose, mas ainda não está claro se esse benefício se estende a diabéticos da prática diária. Objetivamos comparar o desempenho de pacientes diabéticos não selecionados tratados com SF eluidores de sirolimus (SES; primeira geração) vs. SF eluidoresde everolimus (SEE; segunda geração).Métodos: Entre 2007 e 2014, 798 diabéticos foram tratados com SES (n = 414) ou SEE (n = 384) e incluídosnesta análise. Seguimento clínico tardio foi obtido em 99,4% da população e os grupos foram comparados quanto à ocorrência de eventos cardíacos adversos maiores (ECAM) e trombose de stent. Resultados: A idade da população foi semelhante, com predomínio do sexo masculino. Em ambas as coortes, a apresentação clínica mais frequente foi a doença coronária estável. Número de vasos tratados (1,50 ± 0,62 vs. 1,52 ± 0,72; p = 0,88) e extensão total de stents (36,1 ± 20,4 mm vs. 37,7 ± 22,2 mm; p = 0,32) foram semelhantes. Os pacientes tratados com SEE apresentaram menores taxas de ECAM (15% vs. 6,8%; p < 0,001), sobretudo à custa de menor mortalidade cardíaca (5,3% vs. 1,3%; p < 0,001). Observou-se também menor ocorrência de trombose de stent definitiva/provável com SF de segunda geração (3,4% vs. 0,5%; p = 0,004).Conclusões: Nesta experiência unicêntrica, o uso de SEE em diabéticos mostrou-se com menor mortalidadecardíaca e trombose da endoprótese. Esse benefício se fez mais evidente no seguimento mais tardio...

Despite the better clinical performance of second-generation drug-eluting stents (DES)when compared to first-generation DES in controlled trials, mainly due to reduction in thrombosis rate, it remains unclear whether this benefit extends to diabetic patients treated in the daily practice. We sought to compare the clinical outcomes of unselected diabetic patients treated with either sirolimus eluting stents - SES (first-generation DES) or everolimus-eluting stents - EES (second-generation DES). Methods: Between January 2007 and October 2014 a total of 798 diabetic patients were treated with SES(n = 414) and EES (n = 384). Long-term clinical follow-up was achieved in 99,4% of the population andthe groups were compared regarding the occurrence of major adverse cardiac events (MACE) and stent thrombosis. Results: In both cohorts age was similar, and most patients were male. Stable coronary disease was the most frequent clinical presentation. The number of treated vessels (1.50 ± 0.62 vs. 1.52 ± 0.72; p = 0.88)and the total stent length (36.1 ± 20.4 vs. 37.7 ± 22.2 mm; p = 0.32) were similar between groups. Patients treated with EES showed lower rates of MACE (15% vs. 6.8%, p < 0.001), mainly due to a lower cardiac death(5.3% vs. 1.3%, p < 0.001). There was also less definitive/ probable thrombosis with the second generation DES (3.4% vs. 0.5%, p = 0.004)...

Biomarkers of plaque instability.

Atherosclerosis is the proximate cause of arterial thrombosis, leading to acute occlusive cardiovascular syndromes. Thrombosis in atherosclerosis usually results from rupture of the fibrous cap of atherosclerotic plaques with a smaller proportion resulting from superficial endothelial erosion. Ruptured plaques are often associated with intimal and adventitial inflammation, increased size of lipid-rich necrotic core with thinned out collagen-depleted fibrous cap, outward remodeling, increased plaque neovascularity, intraplaque hemorrhage, and microcalcification. By inference, non-ruptured plaques with similar compositional features are considered to be at risk for rupture and hence are labeled vulnerable plaques or high-risk plaques. Identification of vulnerable plaques may help in predicting the risk of acute occlusive syndromes and may also allow targeting for aggressive systemic and possibly local therapies. Plaque rupture is believed to result from extracellular matrix (which comprises the protective fibrous cap) dysregulation due to excessive proteolysis in the context of diminished matrix synthesis. Inflammation is believed to play a key role by providing matrix-degrading metalloproteinases and also by inducing death of matrix-synthesizing smooth muscle cells. Systemic markers of inflammation are thus the most logical forms of potential biomarkers which may predict the presence of vulnerable or high-risk plaques. Several studies have suggested the potential prognostic value of a variety of systemic markers, but regrettably, their overall clinical predictive value is modestly incremental at best, especially for individual subjects compared to groups of patients. Nevertheless, continued investigation of reliable, cost-effective biomarkers that predict the presence of a high-risk plaque and future athero-thrombotic cardiovascular events with greater sensitivity and specificity is warranted.

Correlates and outcomes of late and very late drug-eluting stent thrombosis: results from DESERT (International Drug-Eluting Stent Event Registry of Thrombosis).

OBJECTIVES: The aim of this study was to identify clinical, procedural, and angiographic correlates of late/very late drug-eluting stent (DES) thrombosis as well as to determine the clinical outcomes of these events. BACKGROUND: Late/very late DES thromboses are a poorly studied phenomenon, partly due to the relative infrequency of these events, even in large cohort studies. METHODS: In the DESERT (International Drug-Eluting Stent Event Registry of Thrombosis), a retrospective, case-control registry, 492 cases of late/very late definite DES thrombosis from 21 international sites were matched in a 1:1 fashion with controls without stent thrombosis (ST). Controls were matched according to 2 criteria: same enrolling institution and date of initial DES implantation. Baseline and procedural variables were collected, and clinical follow-up was obtained for patients with ST as long as 1 year after the event. Offline quantitative coronary angiography was performed for a subset of 378 case-control pairs. RESULTS: The majority of ST events occurred after 1 year (75%) and continued to occur for as long as 7.3 years. The clinical presentation of late/very late ST events was mainly myocardial infarction (66.7% ST-segment elevation myocardial infarction and 22.0% non-ST-segment elevation myocardial infarction); in-hospital mortality was 3.8%. A minority of patients (30%) with ST were receiving dual-antiplatelet therapy at the time of the event. Independent clinical correlates of late/very late ST were younger age, African-American race, current smoking, multivessel disease, longer stented length, overlapping stents, and percutaneous coronary intervention of vein graft lesions. Independent angiographic correlates for late/very late ST were lesions within the left anterior descending artery or a bypass graft, thrombus, and a larger residual diameter stenosis after the initial DES implantation. Despite the large sample of ST cases, all identified correlates of late/very late ST had weak associations with subsequent ST (all odds ratios <2.5). CONCLUSIONS: Despite a large sample of ST cases and use of limited matching to maximize the identification of predictive factors associated with late/very late ST, the variables associated with the development of late/very late ST were only weakly predictive of subsequent events. Additionally, a relatively low observed mortality rate of ST in this series may reflect a different pathophysiology of these late/very late events compared with acute/subacute ST. (Drug Eluting Stent Registry of Thrombosis [DESERT]; NCT00812552).

The involvement of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the regulation of inflammation following coronary microembolization.

BACKGROUND/AIMS: Growing evidence shows that phosphatase and tensin homolog deleted on chromosome ten (PTEN) is involved in regulating inflammation in different pathological conditions. Therefore, we hypothesized that the upregulation of PTEN correlates with the impairment of cardiac function in swine following coronary microembolization (CME). METHODS: To possibly disclose an anti-inflammatory effect of PTEN, we induced swine CME by injecting inertia plastic microspheres (42 µm in diameter) into the left anterior descending coronary artery and analyzed the myocardial tissue by immunochemistry, qRT-PCR and western blot analyses. In addition, we downregulated PTEN using siRNA. RESULTS: Following CME, PTEN mRNA and protein levels were elevated as early as 3 h, peaked at 12 h, and then continuously decreased at 24 h and 48 h but remained elevated. Through linear correlation analysis, the PTEN protein level positively correlated with cTnI and TNF-α but was negatively correlated with LVEF. Furthermore, PTEN siRNA reduced the microinfarct volume, improved cardiac function (LVEF), reduced the release of cTnI, and suppressed PTEN and TNF-α protein expression. CONCLUSION: This study demonstrated, for the first time, that PTEN is involved in CME-induced inflammatory injury. The data generated from this study provide a rationale for the development of PTEN-based anti-inflammatory strategies.