Giovanni Ruvolo

Aim: The aim of the present study was to analyze retrospectively the results of patients who underwent early-staged, i.e., within 24–48 h, carotid artery stenting (e-s CAS) before coronary artery bypass grafting (CABG). Methods: Between December 2014 and December 2022, 1046 consecutive patients underwent CABG; 31 of these patients (3%) were subjected to e-s CAS prior to CABG (e-s CAS + CABG group). Preoperative and intraoperative variables and early and mid-term results of the e-s CAS + CABG group were compared with those of patients who underwent isolated CABG (CABG group). Results: As compared with the CABG group, the e-s CAS + CABG group showed a worse clinical risk profile due to higher Euroscore-2 values and incidence of obstructive pulmonary disease and bilateral carotid artery and peripheral artery diseases (p < 0.05, for all comparisons). The combined end point of operative mortality, periprocedural myocardial infarction, and stroke was 3.2% (0%/0%/3.2%) in the e-s CAS + CABG group vs. 5.9% (2.2%/2.8%/0.9%) in the CABG group (p > 0.5, for all measurements). At 5 years, actuarial survival was 74% ± 16% in the e-s CAS + CABG group vs. 93% ± 4.0% in the CABG group, freedom from cardiac death was 100% vs. 98% ± 1.0% (p = 0.6), and freedom from MACCEs was 85% ± 15% vs. 97% ± 2.5% (p > 0.1, for all comparisons). Independent predictors of all-causes death were advanced age at the operation (p < 0.0001), a lower value for left ventricular ejection fraction (p = 0.05), and a high Euroscore-2 (p = 0.04). Conclusions: CABG preceded by e-s CAS appears to be associated with satisfactory early outcomes while limiting the risk of myocardial infarction to a very short time interval between the two procedures. Freedom from late all-causes death, cardiac death, and MACCEs were comparable and equally satisfactory, underscoring the positive protective effects of CAS and CABG on the carotid and coronary territories over time.

(1) Objective: Twenty years’ experience of Bentall–De Bono operations by one surgeon. (2) Methods: From January 2003 to September 2023, four-hundred-and-two patients aged 65.9 ± 15 years underwent a Bentall operation. The EuroScore-2 was 5.0% ± 3.8%. Associated procedures were performed on 113 patients (28.1%). Results: Operative mortality was 1.2% (n = 5), in particular 0.69% (n = 2/289) for isolated Bentall operation, 2.65% (n = 3/113) for combined procedures (p < 0.05). Postoperative acute heart failure occurred in 38 patients (9.45%). Preoperative pulmonary hypertension (44 ± 14 vs. 33 ± 7 mmHg), cardiopulmonary bypass time (169 ± 61 min. vs. 124 ± 42 min.) and aortic cross-clamp time (133 ± 45 min. vs. 107 ± 34 min.) have been recognized as independent predictors of mortality and cardiac complications (p < 0.05). Conclusions: In our experience, the Bentall operation was associated with low operative mortality and low rate of complications. For this reason, in agreement with the patients, we have modified surgical indication for ascending aortic aneurysms and now we think that it is time to change surgical guidelines.

Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 gene mutations leading to TGF-β signaling hyperactivation, vascular wall weakness, and thoracic aortic aneurysms (TAAs). The pathogenetic mechanisms are not completely understood and patients undergo early vascular surgery to prevent TAA ruptures. We previously reported miR-632 upregulation in MFS TAA tissues compared with non-genetic TAA tissues. DNAJB6 is a gene target of miR-632 in cancer and plays a critical role in blocking epithelial-to-mesenchymal transition by inhibiting the Wnt/β catenin pathway. TGF-β signaling also activates Wnt/β catenin signaling and induces endothelial-to-mesenchymal transition (End-Mt) and fibrosis. We documented that miR-632 upregulation correlated with DNAJB6 expression in both the endothelium and the tunica media of MFS TAA (p < 0.01). Wnt/β catenin signaling, End-Mt, and fibrosis markers were also upregulated in MFS TAA tissues (p < 0.05, p < 0.01 and p < 0.001). Moreover, miR-632 overexpression inhibited DNAJB6, inducing Wnt/β catenin signaling, as well as End-Mt and fibrosis exacerbation (p < 0.05 and p < 0.01). TGF-β1 treatment also determined miR-632 upregulation (p < 0.01 and p < 0.001), with the consequent activation of the aforementioned processes. Our study provides new insights about the pathogenetic mechanisms in MFS aortopathy. Moreover, the high disease specificity of miR-632 and DNAJB6 suggests new potential prognostic factors and/or therapeutic targets in the progression of MFS aortopathy.

Aim: To analyze early and mid-term outcomes of the Bentall operation. Methods: Two hundred and seventeen patients (mean age 65.6 ± 15.9 years, males/females 172/45) underwent Bentall operation in a 7-year period (January 2015–December 2021), on average, 30 Bentall operations occurred per year, using biological (n = 104) or mechanical (n = 113) valved conduits for the treatment of ascending aorta–aortic root aneurysms. Associate procedures were performed in 58 patients (26.7%); coronary artery bypass grafting (CABG) in 35 (16%). Mean follow-up was 55.2 ± 24 (median 60.2) months. Cox model analysis was used to assess risk factors, Kaplan–Meier and log-rank tests were used to assess different survival rates. Results: Operative mortality was 1.38%. At 7 years, survival, freedom from cardiac death, and event-free survival were 93% ± 2%, 99% ± 1%, and 81% ± 5%. NYHA class (p < 0.0001), trans-aortic valve mean (p < 0.0001) and maximum (p < 0.000) gradients, left ventricular hypertrophy (p < 0.05), and pulmonary arterial pressure (p = 0.002) significantly improved vs. preoperative values. Concomitant CABG during Bentall operation independently affected late outcomes (HR 1.9–2.3; p-values < 0.05). Late survival was affected by concomitant CABG (84% ± 8% vs. 95% ± 2%, p = 0.04), preoperative myocardial infarction (91% ± 9% vs. 97% ± 2%, p = 0.02), and biological vs. mechanical prostheses valved conduits (91% ± 9% vs. 95% ± 3%, p = 0.02). Event-free survival also was affected by concomitant CABG (62% ± 14% vs. 85% ± 5%, p = 0.005) and biological prostheses (78% ± 8% vs. 84% ± 6%, p = 0.06). Freedom from endocarditis–redo operation was 83% ± 9% for biological prostheses vs. 89% ± 6% for mechanical prostheses (p = 0.49). Conclusions: Low rates of operative mortality and late complications make Bentall operation the gold standard for the treatment of ascending aorta–aortic root aneurysms. Coronary ischemic disease affects late outcomes. Biological prostheses should be preferred for the elderly.

Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery in conventional extracorporeal circulation (CECC), with an incidence of 15–50%. The POAF pathophysiology is not known, and no blood biomarkers exist. However, an association between increased ferritin levels and increased AF risk, has been demonstrated. Based on such evidence, here, we evaluated the effectiveness of ferritin and other haematological parameters as POAF risk biomarkers in patients subjected to cardiac surgery. We enrolled 105 patients (mean age = 70.1 ± 7.1 years; 70 men and 35 females) with diverse heart pathologies and who were subjected to cardiothoracic surgery. Their blood samples were collected and used to determine hematological parameters. Electrocardiographic and echocardiographic parameters were also evaluated. The data obtained demonstrated significantly higher levels of serum ferritin, red cell distribution width (RDW), and platelets (PLTs) in POAF patients. However, the serum ferritin resulted to be the independent factor associated with the onset POAF risk. Thus, we detected the ferritin cut-off value, which, when ≥148.5 ng/mL, identifies the subjects at the highest POAF risk, and with abnormal ECG atrial parameters, such as PW indices, and altered structural heart disease variables. Serum ferritin, RDW, and PTLs represent predictive biomarkers of POAF after cardiothoracic surgery in CECC; particularly, serum ferritin combined with anormal PW indices and structural heart disease variables can represent an optimal tool for predicting not only POAF, but also the eventual stroke onset.

Background: Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery in conventional extracorporeal circulation (CECC), with an incidence of 15-50%. The POAF pathophysiology is not known, and no blood biomarkers exist. However, an association between increased ferritin levels and increased AF risk, has been demonstrated. Based on such evidence, here, we evaluated the effectiveness of ferritin and other haemato-chemical parameters as a POAF onset biomarker in subjected to cardiac surgery. Materials and Methods: We enrolled 90 patients (mean age= 66.9±2.8 years; 40 men and 20 females) with diverse heart pathologies and subjected to cardiothoracic surgery. Their blood samples were collected and used to determine haemato-chemical parameters. The tree test approach was used to detect the best data-driven ferritin cuff-off value (=141 ng/ml) to predict POAF risk. Results: The data obtained demonstrated significant higher concentrations, absolute values, and percentages, of ferritin, RDW, PLTs, in POAF patients. However, the ferritin resulted to be the independent factor associated with the onset POAF risk. Thus, we detected the ferritin cut-off value, which, when ≥ 141 ng/ml identifies the subjects at the highest POAF risk. Conclusions: Ferritin values≥ 141 ng/ml might be used as predictive POAF biomarker.

The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood and only partially characterized. AAA are also complicated in case of bicuspid aorta valve (BAV) anatomy. There is emerging evidence about the crucial role of endothelium-related pathways, which show in AAA an altered expression and function. Here, we examined the involvement of ERG-related pathways in the differential progression of disease in aortic tissues from patients having a BAV or tricuspid aorta valve (TAV) with or without AAA. Our findings identified ERG as a novel endothelial-specific regulator of TGF-β-SMAD, Notch, and NO pathways, by modulating a differential fibrotic or calcified AAA progression in BAV and TAV aortas. We provided evidence that calcification is correlated to different ERG expression (as gene and protein), which appears to be under control of Notch signaling. The latter, when increased, associated with an early calcification in aortas with BAV valve and aneurysmatic, was demonstrated to favor the progression versus severe complications, i.e., dissection or rupture. In TAV aneurysmatic aortas, ERG appeared to modulate fibrosis. Therefore, we proposed that ERG may represent a sensitive tissue biomarker to monitor AAA progression and a target to develop therapeutic strategies and influence surgical procedures.

The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood and only partially characterized. AAA are also complicated in case of bicuspid aorta valve (BAV) anatomy. There is emerging evidence about the crucial role of endothelium-related pathways, which show in AAA an altered expression and function. Here, we examined the involvement of ERG-related pathways in the differential progression of disease in aortic tissues from patients having a BAV or tricuspid aorta valve (TAV) with or without AAA. Our findings identified ERG as a novel endothelial-specific regulator of TGF-β-SMAD, Notch, and NO pathways, by modulating a differential fibrotic or calcified AAA progression in BAV and TAV aortas. We provided evidence that calcification is correlated to different ERG expression (as gene and protein), which appears to be under control of Notch signaling. The latter, when increased, associated with an early calcification in aortas with BAV valve and aneurysmatic, was demonstrated to favor the progression versus severe complications, i.e., dissection or rupture. In TAV aneurysmatic aortas, ERG appeared to modulate fibrosis. Therefore, we proposed that ERG may represent a sensitive tissue biomarker to monitor AAA progression and a target to develop therapeutic strategies and influence surgical procedures.

(1) Background: We sought to analyze and compare the outcomes in terms of early and late mortality and freedom from a redo operation in patients undergoing surgical treatment for a type A acute aortic dissection in relation to the initial surgical treatment strategy, i.e., proximal or distal extension of the aortic segment resection, compared with isolated resection of the supracoronary ascending aorta. (2) Methods: This is a retrospective study in which we included 269 patients who underwent operations for a type A acute aortic dissection in the Department of Cardiac Surgery of Tor Vergata University from May 2006 to May 2016. The patients were grouped according to the extent of the performed surgical treatment: isolated replacement of the supracoronary ascending aorta (NE, no extension), replacement of the aortic root (PE, proximal extension), replacement of the aortic arch (DE, distal extension), and both (BE, bilateral extension). The analyzed variables were in-hospital mortality, postoperative complications (incidence of neurological damage, renal failure and need for prolonged intubation), late mortality and need for a redo operation. (3) Results: Unilateral cerebral perfusion was performed in 49.3% of the patients, and bilateral perfusion—in 50.6%. The overall in-hospital mortality was 31.97%. In the multivariate analysis, advanced age, cardiopulmonary bypass time and preoperative orotracheal intubation were independent predictors of in-hospital mortality. In the population of patients who survived the surgery, the probability of survival at 92 months was 70 ± 5%, the probability of freedom from a redo operation was 71.5 ± 5%, the probability of freedom from the combined end-point death and a redo operation was 50 ± 5%. The re-intervention rate in the general population was 16.9%. The overall probability of freedom from re-intervention was higher in patients undergoing aortic root replacement, although not reaching a level of statistical significance. Patients who underwent aortic arch treatment showed reduced survival. (4) Conclusions: In the treatment of type A acute aortic dissection, all the surgical strategies adopted were associated with satisfactory long-term survival. In the group of patients in which the aortic root had not been replaced, we observed reduced event-free survival.

Study objective: To evaluate the long-term outcomes of clampless off-pump coronary artery bypass grafting (C-OPCAB) compared with conventional on-pump double clamping coronary artery bypass grafting (C-CABG). Methods: From October 2006 to December 2011, 366 patients underwent isolated coronary artery bypass grafting. After propensity score matching of preoperative variables, 143 pairs were selected who received C-OPCAB with the use of device-assisted PAS-Port proximal venous graft anastomoses or C-CABG, performed by the same surgeon experienced in both techniques. Data of the two groups of patients were retrospectively analyzed up to 14 years of follow-up. Results: As compared with C-OPCAB, in the C-CABG patients, the performed number of grafts per patient was higher (2.9 ± 0.5 vs. 2.6 ± 0.6, p-value 0.0001). At 14 years, overall survival, including in-hospital death, was 64 ± 4.7% for the C-OPCAB vs. 55 ± 5.5% for the C-CABG, freedom from overall MACCEs 51 ± 6.2% vs. 41 ± 7.7%, and from late cardiac death 94 ± 2.4% vs. 96 ± 2.2% (p-value not significant, for all comparisons). No significant statistical differences were observed in the actual rates of adverse events during follow-up. Independent predictors of survival were advanced age at operation (p-value 0.001) and a lower mean value of preoperative left ventricular ejection fraction (p-value 0.015). Conclusions: Our single-center study analysis suggests that clampless OPCAB using device-assisted proximal anastomoses proved to be not inferior to double-clamping CABG in the long-term follow-up, provided that involved surgeons are familiar with both techniques. These conclusions are supported by a large and long-term follow-up period, eliminating potential bias, i.e., by means of the propensity score matching and analyzing single-surgeon experience.