Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients.

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression. Methods and Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences. Conclusions: Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies.

Systematic bilateral internal mammary artery grafting: lessons learned from the CATHolic University EXtensive BIMA Grafting Study.

OBJECTIVES: Despite claims of feasibility, to date no study has examined the effect of systematic bilateral internal mammary artery (BIMA) use in a large cohort of real-world unselected patients. The CATHolic University EXtensive BIMA Grafting Study (CATHEXIS) registry was designed to assess the feasibility and safety of systematic BIMA grafting. METHODS: The CATHEXIS was a single-centre, prospective, observational, propensity-matched study. The study was supposed to include 2 arms of 500 patients each: a prospective arm and a retrospective arm. The prospective arm included almost all patients referred for coronary artery bypass grafting (CABG) at our institution after the start of the CATHEXIS with very few exceptions. BIMA would have been used in all these patients. The retrospective arm included patients submitted to CABG before the start of the CATHEXIS and propensity matched to the prospective group (average BIMA use 50%; the radial artery was extensively used). Safety analyses were scheduled after enrolment of 200, 300 and 400 BIMA patients. RESULTS: After the first 226 patients, the BIMA use percentage was 88.5% (200 of 226). In 178 (89%) patients, mammary arteries were used as Y graft. Postoperative mortality was 2%, and incidence of perioperative myocardial infarction, graft failure and sternal complications were 3.5%, 3% and 5.5%, respectively. No perioperative stroke occurred. The incidence of major adverse cardiac events (particularly graft failure and sternal complications) in the BIMA arm were significantly higher than those in the propensity-matched cohort; the study was stopped for safety. CONCLUSIONS: In a real world setting the systematic use of BIMA was associated with a higher incidence of perioperative adverse events (particularly sternal complications). Individualization of the revascularization strategy and use of alternative arterial conduits are probably preferable to systematic use of BIMA.

Prosthetic valve endocarditis: predictors of early outcome of surgical therapy. A multicentric study.

OBJECTIVES: Prosthetic valve endocarditis (PVE) is an uncommon yet dreadful complication in patients with prosthetic valves that requires a distinct analysis from native valve endocarditis. The present study aims to investigate independent risk factors for early surgical outcomes in patients with PVE. METHODS: A retrospective cohort study was conducted in 8 Italian Cardiac Surgery Units from January 2000 to December 2013 by enrolling all PVE patients undergoing surgical treatment. RESULTS: A total of 209 consecutive patients were included in the study. During the study period, the global rate of surgical procedures for PVE among all operations for isolated or associated valvular disease was 0.45%. Despite its rarity this percentage increased significantly during the second time frame (2007-2013) in comparison with the previous one (2000-2006): 0.58% vs 0.31% (P < 0.001). Intraoperative and in-hospital mortality rates were 4.3% and 21.5%, respectively. Logistic regression analysis identified the following factors associated with in-hospital mortality: female gender [odds ratio (OR) = 4.62; P < 0.001], shock status (OR = 3.29; P = 0.02), previous surgical procedures within 3 months from the treatment (OR = 3.57; P = 0.009), multivalvular involvement (OR = 8.04; P = 0.003), abscess (OR = 2.48; P = 0.03) and urgent surgery (OR = 6.63; P < 0.001). CONCLUSIONS: Despite its rarity, PVE showed a significant increase over time. Up to now, in-hospital mortality after surgical treatment still remains high (>20%). Critical clinical presentation and extension of anatomical lesions are strong preoperative predictors for poor early outcome.

Epicardial adipose tissue microbial colonization and inflammasome activation in acute coronary syndrome.

BACKGROUND: Epicardial adipose tissue (EAT) has a close functional and anatomic relationship with epicardial coronary arteries. Accumulating evidence suggests that host microbiome alterations may play a role in several inflammatory/immune disorders, triggering a robust proinflammatory response also involving interleukin-1ß (IL-1ß) and the NALP3 inflammasome. In the current study, we explore the hypothesis that in patients with non-ST elevation acute coronary syndrome (ACS), EAT contains potentially pro-atherosclerotic bacteria that might elicit inflammasome activation. METHODS: EAT samples were obtained during coronary artery bypass grafting from ACS (n=18) and effort stable angina (SA; n=16) patients, and as controls, from patients with angiographically normal coronary arteries undergoing surgery for mitral insufficiency (MVD; n=13). In all patients, NALP3 and proIL-1ß mRNA expressions were evaluated with qRT-PCR. In 3 patients from each group, EAT microbiota composition was determined using next-generation sequencing technologies. RESULTS: In EAT, mRNA expression of both NALP3 and pro-IL1ß was significantly higher in ACS than in SA and MVD (P=0.028 and P=0.005, respectively). A broad range of bacterial species (n=76) was identified in both ACS and SA, with different predominant species. In contrast, microbial DNA was barely observed in MVD. CONCLUSIONS: Our study demonstrated the presence of bacterial DNA directly into EAT, surrounding diseased coronary arteries, of patients with ACS. Furthermore, ACS is associated with NALP3/inflammasome pathway activation in EAT. Our data suggest that the EAT environment is susceptible to microbial colonization that might stimulate a proinflammatory response. These findings add new elements to the pathogenesis of ACS and suggest novel therapeutic targets.

Presentación clínica aguda de seudoaneurisma y fístula aortopulmonar como complicación tardía de la reparación quirúrgica de la coartación de aorta / Acute clinical presentation of pseudoaneurysm and aortopulmonary fistula as a very late complication of aortic coarctation patch repair

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Radial Artery as a Coronary Artery Bypass Conduit: 20-Year Results.

BACKGROUND: There is a lack of evidence for the choice of the second conduit in coronary surgery. The radial artery (RA) is a possible option, but few data on very-long-term outcomes exist. OBJECTIVES: This study describes 20-year results of RA grafts used for coronary artery bypass grafting and the effects of RA removal on forearm circulation. METHODS: We report the results of the prospective 20-year follow-up of the first 100 consecutive patients who received the RA as a coronary bypass conduit at our institution. RESULTS: Follow-up was 100% complete. There were 64 deaths, 23 (35.9%) from cardiovascular causes. Kaplan-Meier 20-year survival was 31%. Of the 36 survivors, 33 (91.6%) underwent RA graft control at a mean of 19.0 ± 2.5 years after surgery. The RA was found to be patent in 24 cases (84.8% patency). In the overall population, probability of graft failure at 20 years was 19.0 ± 0.2% for the left internal thoracic artery (ITA), 25.0 ± 0.2% for the RA, and 55.0 ± 0.2% for the saphenous vein (p = 0.002 for RA vs. saphenous vein, 0.11 for RA vs. ITA, and p < 0.001 for ITA vs. saphenous vein). Target vessel stenosis >90%, but not location of distal anastomosis, significantly influenced long-term RA graft patency. No patients reported hand or forearm symptoms. The ulnar artery diameter was increased in the operated arm (2.44 ± 0.43 mm vs. 2.01 ± 0.47 mm; p < 0.05) and correlated with the peak systolic velocity of the second palmar digital artery (Pearson coefficient: 0.621; p < 0.05). CONCLUSIONS: The 20-year patency rate of RA grafts is good, and not inferior to the ITA, especially when the conduit is used to graft a vessel with >90% stenosis. RA harvesting does not lead to hand or forearm symptoms, even at a very-long-term follow-up.

Late reoperations after acute aortic dissection repair: Single-center experience.

BACKGROUND: After repair of acute type A aortic dissection, aortic complications can develop, and reoperations might be necessary. In our retrospective study, we wanted to assess early and late outcomes in this cohort of patients. METHODS: From September 2005 to July 2012, 21 consecutive patients previously operated on for acute type A aortic dissection underwent 27 redo aortic surgical procedures. Indications for redo procedures were: enlargement of the false lumen in the residual aorta (18 events), severe aortic regurgitation with or without aortic root dilatation (8 events), suture dehiscence and pseudoaneurysm at the proximal or distal aortic graft anastomosis (5 events) or at the coronary button anastomosis in patients who previously underwent a Bentall procedure (1 patient). In all cases, total or partial cardiopulmonary bypass was used. Hypothermic cardiocirculatory arrest was needed in 22 (81%) procedures. RESULTS: Hospital mortality was 3.7% (1/27), reexploration for bleeding and paraplegia rates were 7.4% and 7.4%, respectively. Marfan patients received 3.2 procedures per patient vs. 1.5 in non-Marfan patients (p < 0.01). At a mean follow-up of 6.5 years, 2 aortic events occurred: 1 aortic death, and 1 additional aortic redo surgery. CONCLUSIONS: When procedures are carried out on elective basis, redo aortic surgery can be performed in all segments of the aorta with good early and late outcomes. Close lifelong clinical and radiological follow-up is mandatory. After repair of acute type A aortic dissection, Marfan patients are more prone to develop late complications, with a more rapid evolution.

Predictors of postoperative atrial fibrillation in patients with coronary artery disease undergoing cardiopulmonary bypass: a possible role for myocardial ischemia and atrial inflammation.

OBJECTIVE: To evaluate the preoperative presence of C-reactive protein (CRP) and troponin T(hs-TnT) in patients with coronary artery disease (CAD) undergoing cardiopulmonary bypass (CPB) in order to better clarify the role of atrial inflammation and/or myocardial ischemia in the development of postoperative atrial fibrillation (POAF). DESIGN: Prospective, nonrandomized study. SETTING: University hospital. PARTICIPANTS: Thirty-eight consecutive ischemic patients admitted to the authors' hospital for CAD undergoing elective on-pump coronary artery bypass grafting (CABG). INTERVENTION: Elective on-pump CABG. MEASUREMENTS AND MAIN RESULTS: Peripheral blood samples were collected from all patients before and 24 hours after CABG to assess high sensitive (hs)-CRP and troponin T (hs-TnT) levels. The patients' heart rhythm was monitored by continuous ECG telemetry. Biopsies from the right atrial appendage were obtained at the beginning of the CABG procedure in order to perform immunohistochemistry for CRP and reverse transcription polymerase chain reaction for CRP mRNA expression. Fourteen patients out of 38 (36%) developed POAF. Atrial CRP was found in 31 patients (82%), 10 with POAF and 21 with sinus rhythm (71% v 87% respectively, p = ns). None of the atrial samples was positive for CRP mRNA. Atrial CRP did not correlate with serum hs-CRP levels and with occurrence of POAF, but with the incidence of diabetes (p = 0.010). Postoperative hs-TnT levels, but not hs-CRP levels, were identified as the only predictor of POAF occurrence (p = 0.016). CONCLUSIONS: In patients undergoing CABG, neither peripheral nor tissue preoperative CRP levels, but only postoperative hs-TnT levels, correlated with POAF, suggesting the primary role of an ischemic trigger of atrial fibrillation.

Femoral cannulation with long arterial cannula in aortic dissection.

The optimal cannulation site in repair of DeBakey type I aortic dissection is controversial, and malperfusion during cardiopulmonary bypass is facilitated by retrograde flow. We propose the use of a long arterial cannula through the femoral artery to achieve a proximal antegrade perfusion. The tip of the cannula is placed in the true lumen of the distal aortic arch through the common femoral artery (Seldinger technique and transesophageal echography guidance). In 9 patients, there was one case of operative mortality (cardiac death), and no cases of perioperative stroke, bowel ischemia, severe renal failure, or local complications. Proximal perfusion can achieved rapidly and through an easily accessible site.

Asymptomatic carotid artery disease in valvular heart surgery: impact of systematic screening on surgical strategy and neurological outcome.

We evaluated the prevalence of asymptomatic carotid artery disease in patients scheduled for valvular cardiac surgery. Preoperative screening of the carotid arteries was performed. Among 1012 patients scheduled for valvular cardiac surgery, 267 (26.4%) had carotid stenosis graded >50%; 37 had carotid stenosis >70% and underwent combined valvular surgery and carotid endarterectomy (CEA); and 230 (86%) had carotid stenosis >50% to ≤ 69% and received valvular cardiac surgery under hypothermic cardiopulmonary bypass. Operative mortality and the rate of perioperative adverse neurological events were comparable among the groups. During 6.8 years of follow-up, patients with carotid stenosis not exceeding 69% at the time of surgery had CEA more frequently (P < .05) and stroke/transient ischemic attack ([TIA] P < .05) versus patients treated with combined surgery. The prevalence of asymptomatic carotid stenosis is not negligible in patients undergoing isolated valvular surgery. Combined valvular and carotid surgery is safe and reduces the incidence of CEA and stroke/TIA during follow-up.

Results of reoperation on the aortic root and the ascending aorta.

BACKGROUND: Reoperations on the aortic root and the ascending aorta after previous aortic valve and proximal aortic surgery are increasingly frequent and highly demanding. The scarce comparability of the published series and the heterogeneity of clinical pictures contribute to the challenges of this subgroup. METHODS: Forty-one patients (2004 to 2010) who were reoperated on the aortic root and the ascending aorta for aneurysmal, pseudoaneurysmal, or infectious disease were retrospectively analyzed from a prospectively filled-in database. RESULTS: Mean logistic European system for cardiac operative risk evaluation was 29.8%. At index reoperation, procedures were classic Bentall (51%), prosthesis-sparing operation (17%), supracoronary ascending aortic replacement plus aortic valve replacement-repair (22%), and root replacement using valved homografts (9.7%). Distally, the operation involved the arch in 51% of cases (17 hemiarch replacement, 4 total transverse arch, 3 elephant trunk). Operative mortality was 12% and rate of major operative morbidity was 17%. At a mean 26-months follow-up, the patients surviving the operation had a good survival and functional class. The rate of adverse events during the follow-up was acceptable. CONCLUSIONS: Reoperations on the aortic root-ascending aorta in the elective patients have respectable operative mortality-morbidity despite the high-risk profile, and are justified by the excellent follow-up survival. The mortality can be diminished by integrated surgical strategies and optimal myocardial protection. Our findings encourage complete resection of borderline dilated ascending aortic-root tissue at primary and redo operation.

Aortic expansion rate in patients with dilated post-stenotic ascending aorta submitted only to aortic valve replacement long-term follow-up.

OBJECTIVES: This study was conceived to describe the evolution of aortic dimensions in patients with moderate post-stenotic ascending aorta dilation (50 to 59 mm) submitted to aortic valve replacement (AVR) alone. BACKGROUND: The appropriate treatment of post-stenotic ascending aorta dilation has been poorly investigated. METHODS: Ninety-three patients affected by severe isolated calcific aortic valve stenosis in the tricuspid aortic valve accompanied by moderate dilation of the ascending aorta (50 to 59 mm) were submitted to AVR only. All patients were followed for a mean of 14.7 ± 4.8 years by means of periodic clinical evaluations and echocardiography and tomography scans of the thorax. RESULTS: Operative mortality was 1.0% (1 patient). During the follow-up, 16 patients died and 2 had to be reoperated for valve dysfunction. No patients experienced acute aortic events (rupture, dissection, pseudoaneurysm), and no patient had to be reoperated on the aorta. There was not a substantial increase in aortic dimensions: mean aortic diameter was 57 ± 11 mm at the end of the follow-up versus 56 ± 02 mm pre-operatively (p = NS). The mean ascending aorta expansion rate was 0.3 ± 0.2 mm/year. CONCLUSION: In the absence of connective tissue disorders, AVR alone is sufficient to prevent further aortic expansion in patients with moderate post-stenotic dilation of the ascending aorta. Aortic replacement can probably be reserved for patients with a long life expectancy.

Case series of resection of pelvic leiomyoma extending into the right heart: surgical safeguards and clinical follow-up.

OBJECTIVE: To analyze the clinical features, surgical management and oncologic results of a series of six patients undergoing seven operations for resection of uterine leiomyoma extending into the right cardiac chambers. METHODS: A retrospective review of patients operated on for surgical resection of a pelvic leiomyomatous mass originating from the uterus and extending into the right cardiac chambers was performed. The most common symptoms at presentation were syncope and dyspnea; two patients were asymptomatic. Four patients had been misdiagnosed as having intracardiac thrombus or primary cardiac tumor. The intracardiac and upper intracaval portion was removed under circulatory arrest in moderate hypothermia; the remaining portion was removed by caval incision. In one patient with cardiogenic shock, the sole intracardiac portion of the mass was removed at primary surgery. A mean of 2.8 +/- 1.5 years of follow-up was available, consisting of clinical and radiological tests (computed tomography scan, echocardiography). RESULTS: There were no cases of operative mortality in the present series. No recurrence was observed at the end of the follow-up in all cases of complete resection of the mass from its intracardiac to its pelvic end. Conversely, in the only case in which partial resection was performed due to the patient's clinical condition, recurrence of the intracardiac involvement was observed 6 months after primary surgery. CONCLUSION: Radical resection is curative for uterine leiomyomatosis extending into the right cardiac chambers. Surgery can be afforded with acceptable risks. A high level of suspicion for intracardiac extension of pelvic leiomyomatosis should be retained in the presence of a floating mass within the right cardiac chambers. Such a finding should prompt radiographic evaluation of the abdomen and the pelvis.

Diagnostic and surgical issues in emergency presentation of a pelvic leiomyoma in the right heart.

A computed tomography scan in a 43-year-old woman with a nonsignificant previous medical history demonstrated an inferior caval mass prolapsing through the right atrium and the tricuspid valve. The mass was misdiagnosed as a thrombus-in-transit, and heparin was started. The clinical picture suddenly evolved into cardiogenic shock, and the patient underwent an emergency resection of the intracardiac portion of the mass. Macroscopic and microscopic features were consistent with leiomyoma. In the presence of an inferior caval mass, historical elements and computed tomography imaging that do not corroborate the hypothesis of caval thrombosis should raise the suspicion of intracaval tumor originating from an abdominal or pelvic organ. The preferred treatment strategy is an elective combined thoracic and abdominal resection.

Assessment of the position of retrograde cardioplegia catheter: comparison of hemodynamic versus manual evaluation in a prospective randomized trial.

OBJECTIVE: To evaluate a hemodynamic method for the assessment of the position of the retrograde cardioplegia catheter (RCC) versus conventional Manual Assessment. METHODS: We randomized 200 patients undergoing aortic valve surgery to Manual (n = 101) or Hemodynamic Assessment (n = 99). In the Hemodynamic group a 25% pressure increase at the tip of the RCC when a fistula with the ascending aorta was created via a luer-lock was considered indicative of correct RCC placement. Transesophageal echocardiography was used as a comparison evaluation method. RESULTS: The Hemodynamic and Manual Assessment considered the RCC positioning successful in 89.9% versus 85.1% of cases. Echocardiography confirmed these results in Hemodynamic group but revealed 23 cases of misrecognized incorrect placement in the Manual group (p < 0.0001). Manual maneuvers resulted in 18 cases of secondary displacement and 19 cases of hemodynamic instability (p < 0.0001). CONCLUSIONS: The Hemodynamic Method is quantitative, reproducible, highly reliable, and safer than palpation in the posterior atrioventricular groove.

Myocardial apoptosis predicts postoperative course after aortic valve replacement in patients with severe left ventricular hypertrophy.

BACKGROUND AND AIM OF THE STUDY: Myocardial apoptosis has been implicated in heart failure and post-infarct remodeling. In some patients with severe aortic stenosis, delayed valvular replacement is associated with a poor in-hospital outcome. The study aim was to evaluate the impact of cardiomyocyte apoptosis on the postoperative course after aortic valve replacement (AVR) for severe aortic stenosis. METHODS: During elective AVR, myocardial biopsies were obtained from the left ventricle of 11 patients with severe left ventricular hypertrophy (LVH), and the samples analyzed for apoptosis. RESULTS: The mean apoptotic rate was 10.4 +/- 3.7 per thousand. (range: 5-16 per thousand). The apoptotic rate correlated directly with preoperative NYHA functional class, duration of intensive care unit (ICU) stay, number of days of postoperative acute renal insufficiency, and serum level of troponin T at 24 h; the apoptotic rate correlated inversely with cardiac index at 24 h postoperatively. At multivariate analysis, the apoptotic rate and left ventricular mass index were independent predictors of prolonged ICU stay. The apoptotic rate and duration of cardiopulmonary bypass were predictive of the duration of postoperative acute renal insufficiency. CONCLUSION: The study results showed an association between myocardial apoptosis and postoperative outcome in patients with severe LVH submitted for AVR. Non-invasive correlates of apoptosis may be introduced as a means of identifying patients at a higher operative risk, and may help in the evaluation of asymptomatic patients with severe aortic stenosis. Anti-apoptotic strategies before and during surgery would possibly ameliorate the surgical results.