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.

Fungal Endocarditis Due to Aspergillus oryzae: The First Case Reported in the Literature.

Infective endocarditis (IE) is a severe disease with high mortality and morbidity. Prosthetic valve endocarditis is a life-threatening complication which can occur in less than 10% of patients with valve prosthesis. A fungal etiology of IE is rare and accounts for only 2-4% of all case of endocarditis, but is associated with a higher mortality and morbidity. Herein is reported the first case of fungal endocarditis of aortic valve prosthesis due to Aspergillus oryzae in a 67-year-old caucasian man who nine years previously underwent mitral and aortic valve replacement with mechanical prostheses, and tricuspid annuloplasty for acute IE due to Enterococcus spp. Seven months previously, the patient also underwent a redo cardiac procedure to replace a mitral valve prosthesis with a new mechanical device due to a leakage. Aspergillus oryzae showed impressive growth with strong and unexpected virulence in both local and systemic settings.

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.

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.

Growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery.

BACKGROUND: The efficacy of bypass surgery in patients with ischemic cardiomyopathy is not easily predictable; preoperative clinical conditions may be similar, but the outcome may differ significantly. We hypothesized that the growth reserve of cardiac stem cells (CSCs) and circulating cytokines promoting CSC activation are critical determinants of ventricular remodeling in this patient population. METHODS AND RESULTS: To document the growth kinetics of CSCs, population-doubling time, telomere length, telomerase activity, and insulin-like growth factor-1 receptor expression were measured in CSCs isolated from 38 patients undergoing bypass surgery. Additionally, the blood levels of insulin-like growth factor-1, hepatocyte growth factor, and vascular endothelial growth factor were evaluated. The variables of CSC growth were expressed as a function of the changes in wall thickness, chamber diameter and volume, ventricular mass-to-chamber volume ratio, and ejection fraction, before and 12 months after surgery. A high correlation was found between indices of CSC function and cardiac anatomy. Negative ventricular remodeling was not observed if CSCs retained a significant growth reserve. The high concentration of insulin-like growth factor-1 systemically pointed to the insulin-like growth factor-1-insulin-like growth factor-1 receptor system as a major player in the adaptive response of the myocardium. hepatocyte growth factor, a mediator of CSC migration, was also high in these patients preoperatively, as was vascular endothelial growth factor, possibly reflecting the vascular growth needed before bypass surgery. Conversely, a decline in CSC growth was coupled with wall thinning, chamber dilation, and depressed ejection fraction. CONCLUSIONS: The telomere-telomerase axis, population-doubling time, and insulin-like growth factor-1 receptor expression in CSCs, together with a high circulating level of insulin-like growth factor-1, represent a novel biomarker able to predict the evolution of ischemic cardiomyopathy following revascularization.

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.

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.

Different clinical pictures of penetrating ulcer of the aorta, an underrated aortic disease.

Penetrating ulcer of the aorta has been recognized as a distinct aortic disorder, defined by the ulceration of an atherosclerotic plaque. The lesion has the potential to evolve acutely into aortic rupture, but chronic pictures are possible. Late evolution into rupture, frank aortic dissection and progressive aortic enlargement have been documented. We discuss different modalities of presentation on the basis of recent clinical cases. As the optimal treatment, either surgical (open or endovascular) or medical, is based on a correct diagnosis, we highlight the importance of including aortic ulcers in the differential diagnosis of chest pain. Although endovascular treatment can be advisable in cases with favorable anatomic condition and in patients with multiple comorbidities, the open surgical option should be available given the heterogeneous location and clinical scenarios of these lesions.

Cardiac myxoma presenting with sensory neuropathy.

A 51-year-old man was admitted for burning dysesthesias over the soles. Neurologic examination showed a pansensory loss over both feet associated with weakness of toes dorsiflexion. Motor conduction study of the sural nerve showed a significant reduction of nerve conduction velocity (21.4 m/s) suggesting a demyelinating neuropathy. In the following days he was referred to the cardiologist because of the sudden onset of a rapid atrial tachycardia, which was terminated by adenosine. Echocardiography showed a left atrial mass arising from the atrial septum consistent with the diagnosis of cardiac myxoma. The patient underwent cardiac surgery to remove the tumor, which was confirmed a myxoma by pathology. In the days following cardiac mass removal, neurological symptoms progressively disappeared in the absence of anti-inflammatory and steroid therapy and control motor conduction study showed complete normalization of nerve conduction velocity (54.5 m/s). Peripheral demyelinating neuropathy represented the first clinical presentation of cardiac myxoma in our patient and should be included among the possible paraneoplastic manifestations of this cardiac tumor.

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.

Extracorporeal circulation by peripheral cannulation before redo sternotomy: indications and results.

OBJECTIVES: Cardiac reoperations are challenging and time-consuming, and have a high risk for reentry injuries. We discuss the indications, advantages, and technologic features of cardiopulmonary bypass by peripheral cannulation before resternotomy. METHODS: Of 610 redo cardiac interventions from 2000 to 2006, 158 (25.9%) were performed with peripheral cannulation and ongoing cardiopulmonary bypass before resternotomy. This was indicated in the following: close adhesions between the sternum and the anterior cardiac surface; ascending aorta or bypass grafts (computed tomography scan); and patients with functional tricuspid regurgitation, hemodynamic/electric instability, previous mediastinitis, or depressed ejection fraction. Intraoperative transesophageal echocardiography was always performed. RESULTS: Venous drainage was obtained by cannulation of the common femoral vein (Seldinger technique) and right internal jugular vein (percutaneously). Arterial nonocclusive cannula was placed in the femoral artery (Seldinger technique). Cardiopulmonary bypass time before cardiotomy was 35 +/- 14.7 minutes. There were 5 perioperative deaths, none due to reentry injury. Damage to mediastinal structures at resternotomy occurred in 4 cases. In all cases, peripheral cardiopulmonary bypass allowed adequate and comfortable repair. The operative time was 296 +/- 60 minutes. The average total postoperative bleeding was 264 +/- 38 mL/m(2). No patient experienced complications related to femoral cannulation. The Seldinger method allowed little vascular trauma and intraoperative patency of femoral vessels. CONCLUSION: In selected patients, cardiopulmonary bypass before resternotomy is a valid and reproducible option to render cardiac reoperations safer and more expeditious in the reentry phase. The absence of cannulae in the operating field makes the procedure more comfortable. The liberal use of this strategy is recommended in redo cases.