Case Report: Role of numerical simulations in the management of acute aortic syndromes.

Penetrating aortic ulcer (PAU) represents a subset of acute aortic syndromes characterized by high rupture risk and management challenges, particularly in elderly patients with significant comorbidities. This case report showcases a 75-year-old patient with a history of coronary artery bypass graft (CABG) and with multiple PAUs involving the aortic arch, deemed unfit for conventional open surgery. A branched aortic endograft with a pre-cannulated side component for the left subclavian artery (LSA) was employed to preserve the patency of the previous CABG. Two computational fluid dynamics (CFD) simulations and a morphological analysis were performed on the pre- and post-intervention aortic configurations to evaluate changes in flow rate and pressure drop at LSA level and differences in the lumen size. The results revealed a decrease in the flow rate equal to 2.38% after the intervention and an increase in pressure drop of 4.48 mmHg, while the maximum differences in LSA cross-sectional areas and diameters were 1.49 cm2 and 0.64 cm, respectively. Minimal alteration in LSA blood flow due to the chosen intervention approach confirmed the effectiveness of the selected unibody design endograft with LSA preservation, ensuring myocardial perfusion. Therefore, CFD simulations demonstrate to be a powerful tool to evaluate the hemodynamic consequences of interventions by accurately estimating the main fluid dynamic parameters.

Preliminary Outcomes of Zone 2 Thoracic Endovascular Aortic Repair Using Castor Single-Branched Stent Grafts: A Single-Center Experience.

In the context of thoracic endovascular aortic repair (TEVAR), the reconstruction of the left subclavian artery (LSA) has emerged as a crucial component in establishing a sufficient proximal landing zone. However, the technical difficulty of these procedures raises the possibility of endoleaks and neurological consequences. Single-branched stent grafts offer good anchoring and LSA flow for these patients. This study evaluates the feasibility of utilizing novel single-branched stent grafts in the treatment of distal aortic arch disease, identifying good results in the short and medium term. From September 2019 to March 2023, TEVAR and revascularized LSA were performed on ten patients at the Ospedale del Cuore-FTGM in Massa, Italy, using Castor single-branched thoracic aortic stent grafts (Microport Medical, Shanghai, China). The authors' first findings demonstrated that, after an average follow-up of one year, the Castor branching aortic stent graft system was safe and achieving an appropriate proximal landing zone and maintaining sufficient LSA perfusion was possible. With regard to the endovascular treatment of distal aortic arch diseases, this product offers a compelling substitute for surgery. For the purpose of assessing the long-term effectiveness of this approach, the follow-up period should be extended.

Total Endovascular Treatment of Ascending Aorta Pseudoaneurysm After Bentall Procedure.

Ascending aorta pseudoaneurysms represent uncommon but life-threatening complications that can be observed even after a long time in patients who have undergone aortic surgery. We describe an interesting case of a patient with ascending aorta pseudoaneurysm after the Bentall procedure treated with endovascular coil embolization from the right coronary artery. (Level of Difficulty: Intermediate.).

Endovascular Intervention for Aortic Dissection Is "Ascending".

Ascending aorta diseases represent an important cause of mortality worldwide. Notably, acute and chronic thoracic aorta pathologies have increased during the last years, but medical therapy does not seem to influence their natural history. Currently, although open surgery is the first choice of treatment, many patients are still rejected or have poor outcomes. In this scenario, endovascular treatment is raised as a valuable option. In this review we describe the limitations of conventional surgery and the state-of-art of endovascular ascending aorta repair.

Life-threatening paradoxical thromboembolism in a patient with patent foramen ovale.

BACKGROUND: Venous thromboembolism represents the third most frequent acute cardiovascular syndrome worldwide. Its clinical manifestations are deep vein thrombosis and/or pulmonary embolism. Despite a considerable mortality, diagnosis is often missed.  CASE PRESENTATION: We report the management of a female patient with high-risk pulmonary thromboembolism treated initially with thromboaspiration, complicated by embolus jailing in a patent foramen ovale. In this situation, left cardiac chambers and systemic circulation were jeopardized by this floating embolus. CONCLUSIONS: High-risk pulmonary embolism requires reperfusion strategy but sometimes mechanical thromboaspiration may be not fully successful; transesophageal echocardiography led to a prompt diagnosis of this unexpected finding; in this very particular case, open surgery represented a bail-out procedure to avoid cerebral and systemic embolism.

Etiology, clinical presentation, and management of left main coronary artery aneurysms.

BACKGROUND AND AIM OF THE STUDY: The widespread use of noninvasive/invasive coronary imaging increased the probability of recognition of coronary aneurysms. Left main coronary aneurysms (LMCA), though rare, are potentially life-threatening but in the absence of controlled studies, guidelines do not provide any specific recommendation for their management. We, therefore, aimed to investigate the epidemiology, clinical presentation, therapeutic strategies, and prognostic implication of LMCA. METHODS: A systematic review of the literature was performed to retrieve all the reported cases of LMCA as of December 2021, which were summarized and classified according to their etiology, clinical presentation, and therapeutic management. RESULTS: Out of 1997 works retrieved, 180 studies were analyzed, describing 209 LMCA cases (aged 51 ± 19 years, 68% males). Atherosclerosis was the most common etiology (40%), followed by inflammatory (12%), congenital (9%), or degenerative (6%) conditions. Stable angina (43%) and acute coronary syndromes (32%) were more often the first clinical manifestations, while 29 (14%) LMCA were incidental findings. Most cases were treated surgically (53%), while percutaneous intervention was rarely adopted (7%). Data about antithrombotic therapies were scarce and heterogeneous. Finally, when longitudinal data were reported (n = 81), LMCA resulted associated with a severe prognosis, with a 15% mortality over an 8-month median follow-up. CONCLUSIONS: LMCA are most frequently, but not exclusively, caused by advanced atherosclerosis. Irrespective of their etiology and clinical presentation, LMCA may be associated with high short-term mortality. In absence of controlled studies, a careful evaluation of each case is warranted to optimize therapeutic strategies.

Penetrating Aortic Ulceration Treated with Castor Branched Aortic Stent Graft-A Case Series.

Penetrating aortic ulceration (PAU) is an acute aortic syndrome similar to aortic dissection and intramural hematoma. It is the result of a tunica intima ulceration due to atherosclerotic disease. This clinical condition can lead to serious complications and a poor short-term prognosis, especially in high-surgical-risk patients. We report three cases of patients referred to "Ospedale del Cuore" of Massa (Italy) with PAU at the aortic arch-proximal descending aorta level who could not undergo surgical intervention. For the first time in Italy, we successfully treated these patients with a full percutaneous implantation of a Castor branched aortic stent graft. Our case series shows that this type of endovascular graft is an effective, safe, and feasible treatment for PAU involving a distal aortic arch and avoiding surgery and related complications.

Transcatheter Treatment of "Complex" Aortic Coarctation Guided by Printed 3D Model.

The transcatheter approach is nowadays considered a cost-effective alternative to surgery in adults with "complex" aortic coarctation. The printed 3D model was crucial in planning transcatheter treatment of a complex case of postsurgical aortic re-coarctation, due to coexistence of transverse aortic arch stenosis and pseudoaneurysm as well as aneurysm of the descending aorta. (Level of Difficulty: Advanced.).

Hybrid Approach in Acute and Chronic Aortic Disease.

The management of patients with aortic disease that involves the ascending aorta, the aortic arch, and the descending aorta represent a surgical challenge. Open surgical repair remains the gold standard for aortic arch pathologies. However, this operation requires a cardiopulmonary bypass and a period of profound hypothermia and circulatory arrest, which carries a substantial rate of mortality and morbidity. For these reasons, hybrid arch repair that involves a combination of open surgery with endovascular aortic stent graft placement has been introduced as a therapeutic alternative for those patients deemed unfit for open surgical procedures. Hybrid repair requires varying degrees of invasiveness and can be performed as a single-stage procedure or as a two-stage procedure. The choice of the technique is multifactorial, depending on the characteristics of the diseased arch with regard to position of the stent graft proximal landing zone, patient fitness and comorbid status, as well as surgical expertise and hospital facilities. Among the evolving hybrid procedures is the so-called "frozen" or stented elephant trunk technique. Adapted from the classical elephant trunk technique, this approach facilitates the repair of a concomitant aortic arch and proximal descending aortic aneurysms in a single stage under circulatory arrest. This technique is increasingly being used to treat extensive thoracic aortic disease and has shown promising results.

Custom-made endograft with left subclavian artery branch in a patient with Takayasu aortitis complicated by type-B dissection and inflammatory involvement of the epiaortic vessels.

Type-B aortic dissection in a patient affected by Takayasu disease is a rarely described condition and its management can be challenging. A 47-year-old woman with Takayasu aortitis and previous aortic valve and ascending aorta replacement was admitted to hospital for type-B aortic dissection. The recent instabilization of aortic disease, the persistence of episodes of transient chest pain and the largest size of the aneurismatic tract of thoracic descending aorta rendered an invasive approach mandatory. Since the patient presented a complete bilateral occlusion of the subclavian artery just after the origin of the vertebral artery and a subcritical, smooth, bilateral stenosis of the common carotid artery, a custom-made endograft with left subclavian artery branch was successfully positioned, thus allowing the preservation of antegrade left vertebral circulation. This is the first case reporting an entirely endovascular exclusion of type-B dissection in a patient affected by Takayasu aortitis using a custom-made endograft with a subclavian branch allowing the preservation of the antegrade flow to left vertebral artery.

Hybrid treatment of a huge complex aortic pseudo-aneurysm subsequent to a coarctation.

Endovascular treatment of pseudo-aneurysms subsequent to a pre-existing aortic coarctation is becoming a well-accepted technical solution especially in patients presenting anatomical challenges involving the aortic arch. We report the case of a 65-year-old woman with a huge pseudo-aneurysm of the descending thoracic aorta. Diagnostic imaging assessment documented also the presence of an aneurysmatic aberrant right subclavian artery. Due to patient's anatomical arterial condition, we decided to treat the aneurysm applying a hybrid approach.

Endovascular treatment of acute thoracic aortic syndromes with a proximal landing zone extension strategy: procedural and follow-up results.

PURPOSE: To report the procedural and long-term follow-up data (mean, 43 ± 29 months; range, 12-90 months) of endovascular stent grafting (ESG) of acute thoracic aortic syndromes (ATAS) with a proximal landing zone extension strategy. METHODS: From November 1999 to May 2008, 26 patients (25 males, 1 female; mean age, 57.9 ± 17 years) with ATAS underwent ESG at our institution. Underlying pathologies were: penetrating aortic ulcer (n=7); rupture of a descending aorta aneurysm (n=5), post-traumatic false aneurysm (n=5); acute type B dissection (n=6) and traumatic descending aorta transection (n=3). RESULTS: ESG was performed successfully in all patients. In 5 patients (19%), an extra-anatomic revascularization of the supra-aortic vessels was performed. In 19 patients (73%), overstenting of the left subclavian artery, without preliminary revascularization, was performed. The mean proximal landing zone length was 57 ± 19 mm. No intraprocedural deaths occurred; 3 patients died postoperatively (1 from an unrelated cause, 1 from a myocardial infarction and 1 for the sequelae of an ischemic stroke). One patient underwent cardiac surgery for post-procedural retrograde type-A dissection. Follow up involved a computed tomography (CT) scan at 1, 3, 6 and 12 months, then yearly thereafter. At follow up, no deaths or major complications occurred. The CT scans revealed 1 small type-IB endoleak at 1 year. CONCLUSION: In ATAS patients treated with ESG, the extension of the proximal landing zone, despite the need of subclavian coverage or hybrid procedures, is associated with an immediate procedural outcome and low morbidity at follow-up.

Drug-eluting stents versus bare-metal stents in acute ST-segment elevation myocardial infarction. a single-center experience with long-term follow up.

OBJECTIVES: To compare the efficacy and safety of drugeluting stents (DES) vs. bare-metal stents (BMS) in patients with acute ST-segment-elevation myocardial infarction (STEMI). BACKGROUND: DES effectively reduce restenosis in elective percutaneous coronary intervention. Limited data are available about the use of DES in patients with STEMI. METHODS: 453 consecutive patients who presented with STEMI between July 2003 and May 2006 were studied. The procedural characteristics, 30-day, 12-, 18- and 26-month outcomes of 277 patients treated with DES were compared with 176 patients treated with BMS. RESULTS: At 26-month follow up, DES therapy was associated with a significant decrease in major adverse cardiac events (MACE) (relative risk [RR] -35%; p = 0.01) and target lesion revascularization [TLR], RR -64%; p = 0.009). The DES group included more diabetic patients (20% vs. 9%; p < 0.001), and the stents were longer (22 +/- 0.28 mm vs. 19.4 +/- 0.36 mm; p < 0.001) and smaller (diameter: 2.9 +/- 0.02 mm vs. 3.1 +/- 0.02 mm; p < 0.001). The rate of stent thrombosis was similar and the prolonged combined antiplatelet therapy was an independent factor predicting a protective effect on MACE. CONCLUSIONS: DES reduce the incidence of TLR and MACE in patients with STEMI without evidence of additional risks at 2-year follow up. DES therapy was associated with more complex interventional techniques, which yielded similar procedural results and clinical outcomes that may be influenced by prolonged combined antiplatelet therapy.

Relationships between optical aggregometry (type born) and flow cytometry in evaluating ADP-induced platelet activation.

BACKGROUND: Platelet response to activating agents is used to monitor the efficacy of anti-aggregation therapies. The aim of our study has been to demonstrate the existence of relationships between early events of ADP-induced platelet activation, measured by flow cytometry and platelet-rich plasma aggregation, quantified by optical aggregometry. METHODS: We evaluated peripheral blood of 12 donors. The following parameters were quantified by cytometry after stimulation with adenosine diphosphate (ADP) (0.5, 1, 2, 5, 10, 20 muM): CD62P (P-selectin) and PAC-1 expression, and cytosolic Ca(2+) mobilization. Aggregation was measured by optical aggregometry. We also studied 13 patients, undergoing coronary stenting, treated with aspirin (before procedure) or with aspirin plus clopidogrel (after procedure). We evaluated CD62P and PAC-1 expression, aggregation, and vasodilator-stimulated phopshoprotein phosphorylation (platelet reactivity index, PRI). RESULTS: Flow procedures were more sensitive than aggregometry, with a lowest interindividual variability. Linear relationships existed in donors between CD62P expression and Ca(2+) mobilization (P < 0.0001), and between aggregation and Ca(2+) mobilization (P < 0.0001). Linear relationships existed between aggregation and CD62P expression, as percentage (P < 0.0001), or relative fluorescence intensity (RFI) (P < 0.0001). Exponential equations related aggregation and PAC-1 expression, as percentage (P < 0.0001), or RFI (P < 0.0001). Linear relationships between aggregation and CD62P expression (as percentage) existed in the patients before (P = 0.0022) and after procedure (P = 0.0020). Exponential relationships between aggregation and PAC-1 expression (as percentage) existed before (P = 0.0012) and after procedure (P = 0.0024). Linear correlations related aggregation response predicted on CD62P expression, and measured aggregation inhibition after clopidogrel (P = 0.0013) as well as predicted aggregation and PRI inhibition (P = 0.0031). CONCLUSIONS: Tight relationships between aggregation and cytometric quantification of platelet markers in whole blood, in particular CD62P, allow to predict aggregation response to ADP from flow data in patients treated with aspirin alone or with aspirin plus clopidogrel.

Predictive value of less than moderate residual mitral regurgitation as assessed by transesophageal echocardiography for the short-term outcomes of patients with mitral regurgitation treated with mitral valve repair.

BACKGROUND: Traditionally, in patients with mitral regurgitation (MR) a successful mitral valve repair is considered when residual MR by post-pump transesophageal echocardiography (TEE) is less than moderate or absent. Little is known about the prognostic value of less than moderate (mild or mild-to-moderate) residual MR for the early outcome of patients treated with mitral valve repair. METHODS: Eligible for this study were patients undergoing isolated mitral valve repair. Patients with moderate or severe residual MR after valve repair were excluded. The primary endpoint of the study was the composite of death or need of reintervention. RESULTS: A total of 98 patients (54 with no residual MR-Group 1, and 44 with less than moderate residual MR-Group 2) were analyzed. Of these, 72% presented with New York Heart Association (NYHA) 3/4, and 38% were women. The primary endpoint of the study occurred in 3 (5.5%) patients in Group 1 and 6 (13.6%) patients in Group 2 MR (P = 0.31). There was a trend toward a higher incidence of use of inotropic drugs post-interventional (P = 0.12), and a longer hospital stay among patients with less than moderate residual MR (P = 0.18). CONCLUSION: In our study population, patients with less than moderate residual MR had a trend toward a higher risk of early adverse outcomes as compared with patients with no residual MR by post-pump TEE. Studies with a larger patient population and longer follow-up data may be useful to better define the clinical significance of residual mild MR after mitral vale repair.

GSTM1, GSTT1 and CYP1A1 detoxification gene polymorphisms and susceptibility to smoking-related coronary artery disease: a case-only study.

Cigarette smoking is a powerful risk factor for coronary artery disease (CAD), leading to the formation of DNA alterations within blood vessels and heart. However, the degree of smoking-related atherosclerosis varies from individual to individual. Genetic polymorphisms of relevant xenobiotic metabolising enzymes may determine the susceptibility of an individual response to environmental toxicants. The purpose of this study was to test the hypothesis that the inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1 MspI) and glutathione S-transferases (GSTM1(null) and GSTT1(null)) may be causally associated with the presence and severity of smoking-induced CAD. In a case-only design, 222 (179 male, 57.8+/-10.3 years) consecutive smoker patients who had undergone elective and diagnostic coronary angiography were recruited. We found a group (n=169) of smoker patients with significant CAD, defined as>50% reduction in diameter of at least one major vessel, and a group without obstructive CAD (n=53). No significant differences were observed in CYP1A1 genotypes frequencies between CAD and non-CAD smokers (p=0.1). Homozygous deletion of GSTM1 had a frequency of 58.6% among patients with CAD and 45.3% among those without CAD (p=0.08). The frequency of the GSTT1(null) genotype was 43.8% among the patients with CAD and 24.5% among CAD-free subjects (p=0.01). After adjustment for traditional risk factors, the presence of combined GSTM1(null)GSTT1(null) genotypes was significantly associated with an increased risk of CAD (OR=3.9; 95% CI: 1.3-11.4, p=0.01). Moreover, smokers with combined GSTM1(null)GSTT1(null) genotypes had significantly higher number of stenosed vessels than those with the positive genotype (2.3+/-0.9 versus 1.7+/-0.8, p=0.03). Our findings showed that smokers carrying GST deleted genotypes have an increased susceptibility to the smoking related coronary artery disease. Exploring gene-smoking effect provides an excellent model in order to understand gene-environment toxicants interaction and its implications to cardiovascular disease.

Coronary artery bypass grafting surgery is associated with a marked reduction in serum homocysteine and folate levels in the early postoperative period.

OBJECTIVE: It has been suggested that cardiac surgery-related ischemia-reperfusion injury to the myocardium is caused by the oxidative stress, derived from the formation of reactive oxygen species in the early phases of the reperfusion. The availability of cysteine, mostly deriving from homocysteine (Hcy) via the trans-sulfuration pathway, is determinant for the synthesis of glutathione (GSH), which in turn acts as a first line of defence against oxidative stress. Indeed, an increased consumption of Hcy in response to oxidative stress has been described. Previous research has shown that Hcy levels increase during the first weeks or months after coronary artery bypass grafting (CABG). This study was designed to evaluate the Hcy metabolism in CABG patients during the early postoperative period. METHODS: Serum Hcy and folate were measured by an automatic immunometric system on blood samples obtained from 48 (mean age 67+/-10 years) consecutive patients undergoing CABG, preoperatively and at 0, 12, 48, and 120 h after surgery. A subgroup of 22 of these patients was also studied 6 months postoperatively. RESULTS: A significant decrement of Hcy and folate was observed throughout the study (P<0.0001) from 17.3+/-9.3 to 8.5+/-5.6 micromol/l at 12 h postoperatively for Hcy, and from 5.1+/-2.8 to 2.5+/-1.5 ng/ml at 48 h for folate. The reduction of Hcy and folate levels remained significant after correction for haemodilution (as assessed by measurement of plasma proteins). Furthermore, the use of cardiopulmonary bypass significantly interacted with the time of sampling in affecting the Hcy levels. Hcy levels returned to near-baseline values 48 h postoperatively, and were similar to base-line at follow-up. CONCLUSION: Our study indicates that serum Hcy and folate levels are markedly reduced during the early postoperative period after CABG. This reduction is at least in part independent of haemodilution, and may be caused by an altered Hcy turnover, due to an increased consumption of GSH during and soon after CABG.

C677T polymorphism of the methylenetetrahydrofolate reductase gene is a risk factor of adverse events after coronary revascularization.

BACKGROUND: A common point mutation (C677T) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with hyperhomocysteinemia, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD). The aim of this study was to investigate whether C677T polymorphism can be a predictor of major adverse cardiac events after myocardial revascularization. METHODS: We determined MTHFR genotype in 159 patients with CAD undergoing myocardial revascularization [72 percutaneous transluminal coronary angioplasty (PTCA) and 87 coronary artery bypass graft (CABG)]. Recurrent angina, nonfatal myocardial infarction (MI), target vessel revascularization, heart failure and cardiac death were considered major adverse cardiac events that occurred after discharge from index hospitalization. RESULTS: During the follow-up (6.9+/-0.3 months, mean+/-S.E.M.), the composite endpoint accounted for 25.9%, 11.4% and 4.3% for TT, CT and CC genotype (log-rank statistic 5.2, p=0.02), respectively. Subjects with mutant TT genotype had a threefold increase of any cardiac event (hazard ratio [HR]=3.0; 95% [CI], 1.1-8.1). In multiple-variable regression Cox, predictors of events were TT genotype (HR=2.8; 95% CI, 1.01-7.62, p=0.047), low-ejection fraction<40% (HR=4.5; 95% CI, 1.62-12.6, p=0.004) and revascularization procedure (HR=6.1; 95% CI, 1.86-20.34, p=0.003). CONCLUSIONS: These data indicate that the TT genotype seems to be significantly associated with major adverse cardiac events after myocardial revascularization in CAD patients, suggesting a potential pathological influence of homocysteine in the clinical outcome.

Interactive effect of the glutathione S-transferase genes and cigarette smoking on occurrence and severity of coronary artery risk.

Cardiovascular diseases and cancer are the main causes of death in developed countries. Mortality trends for these diseases suggest that they share common pathogenetic mechanisms. Glutathione S-transferase (GST) is a family of enzymes that detoxify reactive electrophiles, particularly present in tobacco smoke. Glutathione S-transferase null M1 and T1 (GSTM1 and GSTT1) genotypes have often been associated with increased risk of developing cancer. Our hypothesis was that the polymorphic GSTM1 and GSTT1 genes modulate the risk of smoking-coronary artery disease (CAD). We evaluated the distribution of GST genotypes in 430 angiographically defined patients (308 CAD and 122 non-CAD). The frequencies of GST null genotypes did not differ significantly between patients with CAD and without CAD. However, smokers with GSTM1 and GSTT1 null genotypes had a significantly higher risk of CAD than never-smokers with these genotypes present (OR 2.2 and 3.4 for smokers with null GSTM1 and GSTT1 genes, respectively). There was also evidence of multiple interaction between GSTM1 and GSTT1 deleted genotypes and smoking. In nonsmokers carrying both null genotypes the risk of CAD was 0.66. In smokers with both present genotypes the OR was 1.5 and was significantly increased in smokers with concurrent lack for GSTM1 and GSTT1 genes (OR=4.0). Moreover, smokers lacking GST genes had both more stenosed vessels and a higher Duke score than smokers expressing the genes. We also examined the levels of DNA damage in 66 men patients using the micronucleus test, a sensitive assay for evaluating chromosome damage. Micronucleus levels were higher in smokers with null genes than in smokers with present genes. These observations suggest that GST-null genotypes strengthen the effect of smoking on CAD risk by modulating the detoxification of genotoxic atherogens.