Controversy. On pump or off pump: what will I do when I grow up? A narrative systematic review.

The transition from the second to the third millennium happened to be a turning point in the history of myocardial revascularization on a beating heart, which moved from technical development to critical evaluation. This article describes how the initial acceptance and spread of off-pump coronary artery bypass grafting (OPCABG) was followed by the general perception that the technique could not fulfill the expectations placed in it and provides some insight on what should we do with the know-how of OPCABG in the present and the future of coronary surgical revascularization.

Interrupted inferior vena cava draining into the coronary sinus associated with circumflex artery to coronary sinus fistula.

In an adult patient, coronary artery fistula involving the circumflex artery (CX) connected to the coronary sinus caused aneurysm of the left main and CX associated with ectasia of the intermediate branch. The patient had posterolateral infarction with severe ischemic mitral regurgitation and moderate tricuspid regurgitation. A rare venous return anomaly was also present. The inferior vena cava, which was interrupted at the level of the liver, continued with the hemiazygos to drain into a persistent left superior vena cava, which in turn drained into the coronary sinus. Surgery included CX closure and mitral and tricuspid repair. The strategy had to be adapted to the anatomy. The fistula was dissected and snared for cardioplegia delivery, and venous return was achieved by cannulation of the superior vena cava and femoral vein. The procedure was uneventful, and 4 years later the patient is asymptomatic.

Correlations between the alpha-Gal antigen, antibody response and calcification of cardiac valve bioprostheses: experimental evidence obtained using an alpha-Gal knockout mouse animal model.

Introduction: Preformed antibodies against αGal in the human and the presence of αGal antigens on the tissue constituting the commercial bioprosthetic heart valves (BHVs, mainly bovine or porcine pericardium), lead to opsonization of the implanted BHV, leading to deterioration and calcification. Murine subcutaneous implantation of BHVs leaflets has been widely used for testing the efficacy of anti-calcification treatments. Unfortunately, commercial BHVs leaflets implanted into a murine model will not be able to elicit an αGal immune response because such antigen is expressed in the recipient and therefore immunologically tolerated. Methods: This study evaluates the calcium deposition on commercial BHV using a new humanized murine αGal knockout (KO) animal model. Furtherly, the anti-calcification efficacy of a polyphenol-based treatment was deeply investigated. By using CRISPR/Cas9 approach an αGal KO mouse was created and adopted for the evaluation of the calcific propensity of original and polyphenols treated BHV by subcutaneous implantation. The calcium quantification was carried out by plasma analysis; the immune response evaluation was performed by histology and immunological assays. Anti-αGal antibodies level in KO mice increases at least double after 2 months of implantation of original commercial BHV compared to WT mice, conversely, the polyphenols-based treatment seems to effectively mask the antigen to the KO mice's immune system. Results: Commercial leaflets explanted after 1 month from KO mice showed a four-time increased calcium deposition than what was observed on that explanted from WT. Polyphenol treatment prevents calcium deposition by over 99% in both KO and WT animals. The implantation of commercial BHV leaflets significantly stimulates the KO mouse immune system resulting in massive production of anti-Gal antibodies and the exacerbation of the αGal-related calcific effect if compared with the WT mouse. Discussion: The polyphenol-based treatment applied in this investigation showed an unexpected ability to inhibit the recognition of BHV xenoantigens by circulating antibodies almost completely preventing calcific depositions compared to the untreated counterpart.

Evidence of an anti-inflammatory effect of PCSK9 inhibitors within the human atherosclerotic plaque.

BACKGROUND AND AIMS: Preclinical evidence suggests that proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors hold anti-inflammatory properties independently of their ability to lower LDL-cholesterol (C). However, whether PCSK9 inhibitors exert anti-inflammatory effects within the atherosclerotic plaque in humans is unknown. We explored the impact of PCSK9 inhibitors, used as monotherapy, compared with other lipid-lowering drugs (oLLD) on the expression of inflammatory markers within the plaque, assessing also the subsequent incidence of cardiovascular events. METHODS: In an observational study, we recruited 645 patients on stable therapy for at least six months and undergoing carotid endarterectomy, categorizing patients according to the use of PCSK9 inhibitors only (n = 159) or oLLD (n = 486). We evaluated the expression of NLRP3, caspase-1, IL-1ß, TNFα, NF-kB, PCSK9, SIRT3, CD68, MMP-9, and collagen within the plaques in the two groups through immunohistochemistry, ELISA, or immunoblot. A composite outcome including non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality was assessed during a 678 ± 120 days follow-up after the procedure. RESULTS: Patients treated with PCSK9 inhibitors had a lower expression of pro-inflammatory proteins and a higher abundance of SIRT3 and collagen within the plaque, a result obtained despite comparable levels of circulating hs-CRP and observed also in LDL-C-matched subgroups with LDL-C levels <100 mg/dL. Patients treated with PCSK9 inhibitors showed a decreased risk of developing the outcome compared with patients on oLLD, also after adjustment for multiple variables including LDL-C (adjusted hazard ratio 0.262; 95% CI 0.131-0.524; p < 0.001). The expression of PCSK9 correlated positively with that of pro-inflammatory proteins, which burden was associated with a higher risk of developing the outcome, independently of the therapeutic regimen. CONCLUSIONS: The use of PCSK9 inhibitors is accompanied by a beneficial remodelling of the inflammatory burden within the human atheroma, an effect possibly or partly independent of their LDL-C lowering ability. This phenomenon might provide an additional cardiovascular benefit.

Constrictive Pericarditis With Massive Calcification in Systemic Sclerosis Treated With Pericardiectomy: A Case Report.

Calcific constrictive pericarditis is a very rare complication of systemic sclerosis. This is the first report of surgically treated calcific constrictive pericarditis in systemic sclerosis. A 53 years-old woman, affected by limited systemic sclerosis, had a diagnosis of calcific constrictive pericarditis. She had a medical history of congestive heart failure since 2022. The patient was treated with pericardiectomy. Via a median sternotomy, the pericardium was dissected and removed from the midline to the left phrenic nerve, thus freeing the heart. Three months after the pericardiectomy, there was a significant clinical improvement. The calcific evolution of chronic pericarditis is a rare complication of systemic sclerosis. This case represents, at best of our knowledge, the first report of calcific constrictive pericarditis, in systemic sclerosis, treated with pericardiectomy.

Cutting the second order chords during mitral valve repair.

The chordae tendinae connect the papillary muscles (PMs) to the mitral valve. While the first-order chordae serve to secure the leaflets to maintain valve closure and prevent mitral valve prolapse, the second-order chordae are believed to play a role in maintaining normal left ventricle size and geometry. The PMs, from where the chordae tendinae originate, function as shock absorbers that compensate for the geometric changes of the left ventricular wall. The second-order chordae connect the PMs to both trigons under tension. The tension distributed towards the second-order chordae has been demonstrate to be more than threefold that in their first-order counterpart. Cutting the second-order chordae puts all the tension on the first-order chordae, which are then closer to their rupture point. However, it has been experimentally demonstrated that the tension at which the first-order chordae break is 6.8 newtons (N), by far higher than the maximal tension reached, that is 0.4 N. Even if the clinical reports have been favorable, the importance of cutting the second-order chordae to recover curvature of the anterior leaflet and increase the coaptation length between the mitral valve leaflets has been slowly absorbed by the surgical world. Nevertheless, there are progressive demonstrations that chordal tethering affects the anterior leaflet not only in secondary, but also in primary mitral regurgitation, having a not negligible role in the long-term outcome of mitral repair.

Polyphenols could be Effective in Exerting a Disinfectant-Like Action on Bioprosthetic Heart Valves, Counteracting Bacterial Adhesiveness.

Background: The incidence of infective endocarditis in patients with bioprosthetic heart valves is over 100 times that of the general population with S. aureus recognized as the causative organism in approximately 1/3 of cases. In this study, (1) the microbicidal and virucidal effect of a polyphenolic solution was carefully evaluated. The same solution was then adopted for the treatment of a commercial bioprosthetic heart valve model for (2) the assessment of inhibition of S. aureus adhesiveness. Methods: (1) the viability of 9 microorganisms strains (colony-forming units) and the infectivity degree of 3 viral strains (cellular infection capacity) were evaluated after suspension in the polyphenolic solution. (2) Leaflets from a treated and untreated commercial surgical valve model were incubated with a known concentration of S. aureus. After incubation, the leaflets were homogenized and placed in specific culture media to quantify the bacterial load. Results: (1) The polyphenolic solution proved to be effective in eliminating microorganisms strains guaranteeing the killing of at least 99.9%. The effectiveness is particularly relevant against M. chelonae (99.999%). (2) The polyphenol-based treatment resulted in the inhibition of the S. aureus adhesiveness by 96% concerning untreated samples. Conclusions: The data suggest an interesting protective effect against infections and bacterial adhesiveness by a polyphenolic-based solution. Further studies will plan to extend the panel of microorganisms for the evaluation of the anti-adhesive effect; however, the use of optimized polyphenolic blends could lead to the development of new treatments capable to make transcatheter-valve substitutes more resistant to infection.

Outcome of permanent pacemaker implantation in transcatheter or surgical aortic valve replacement: A still unsolved problem.

Despite advances in technologies and clinical experience, conduction disorders, after transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR), represent the weak point of these procedures, requiring permanent pacemaker implantation (PPI) till 37.7% of patients in TAVR recipients. The role of PPI in TAVR and SAVR remains controversial in mid- and long-term outcomes. Indeed, many studies have been published with contradictory results, leaving doubts rather than certainties.

Perioperative incidence of ECMO and IABP on 5901 mitral valve surgery procedures.

BACKGROUND: Report the incidence and results of peri-operative extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP) of patients undergoing mitral valve surgery (MVS) through right mini-thoracotomy (RT) and conventional full sternotomy (FS) for a period of 6 years from eleven tertiary Cardiac Surgery Institutes of GVM Care & Research Italia. METHODS: From January 2016 to November 2021, a total of 5901 consecutive patients underwent MVS through RT and FS. The primary outcome of the study was the mortality and incidence of low cardiac output syndrome (LCOS) treated with intra-aortic balloon pump (IABP) with or without inotropic support and the incidence of Postcardiotomy Cardiogenic Shock (PCS) treated with Veno-arterial (VA) Extracorporeal Membrane Oxygenation (ECMO) on patients undergoing mitral valve surgery (MVS) through right mini-thoracotomy (RT) versus conventional full sternotomy (FS). RESULTS: The mean age was 66 ± 15 years, 3389 patients underwent in RT approach 2512 in FS, 3081 (52%) patients were male and 2.3% had previous cardiac operations. Cardiopulmonary bypass time was 93 min for RT and 81 min for FS and cross clamp time 75 min for RT and 63 min for FS for mitral valve repair. Incidence of perioperative IABP for the treatment of low cardiac output was reported on 99 patients (1.6%), 51 for RT (1.5%), 35% used inotropic support (adrenaline and milrinone) and 48 in FS (1.9), 28% use inotropic support, 21 patients died after IABP (3 RT and 18 FS). Incidence of perioperative VA-ECMO for the PCS treatment was 13 and 4 with IABP, 9 RT (0.2%) and 4 FS approach (0.15%), 12 patients died after VA-ECMO. CONCLUSION: Minimally invasive mitral valve surgery is a safe and reproducible approach associated with low mortality and morbidity. ECMO and IABP incidence for the treatment of PCS was 0.2% and for Low cardiac output syndrome (LCOS) was 1.6% in elective mitral valve surgery is very low. The patients that use the perioperative IABP in minimally invasive mitral valve surgery (MIMVS) trough RT reported a reduced mortality compared to FS in relation to the operative risk and surgical technique. Low incidence of VA-ECMO was found in RT and FS approach, only one patient survived after VA-ECMO after minimally invasive mitral valve surgery.

[Role of fractional flow reserve for invasive functional evaluation in surgical myocardial revascularization: available evidence and state of the art]. / Ruolo della valutazione funzionale mediante riserva frazionale di flusso nella rivascolarizzazione miocardica chirurgica: evidenze disponibili e stato dell'arte.

Fractional flow reserve (FFR) is the ratio of distal to proximal pressure during maximal hyperemia and indirectly estimates the blood flow across a stenotic coronary artery and the related degree of myocardial ischemia. Several studies have investigated the role of FFR in the setting of percutaneous myocardial revascularization and further research is ongoing. However, current evidence on FFR-guided surgical myocardial revascularization is controversial and limited. The main scientific interest is to clarify whether FFR-guided coronary artery bypass surgery is associated with clinical benefits in terms of mortality, myocardial infarction, major adverse cardiovascular events, minimally invasive surgical access compared with sternotomy and off-pump surgery. Furthermore some data suggest that conduit selection for coronary artery bypass grafting and surgical technique might be affected by FFR value. The aim of this article is to review the most recent available evidence about FFR-guided coronary artery bypass grafting and to discuss clinical implications and future perspectives.

Left ventricular surgical remodeling 2.0.

Left ventricular surgical remodeling has been, for a long time, the procedure applied for large dyskinetic, or akinetic, areas as a consequence of a myocardial infarction, mainly located in the left anterior descending area. Many surgical techniques were developed, aimed to a pure reduction of the volume of the left ventricular (LV) cavity or to add to volume reduction a more physiologic conical shape. The expansion of interventional procedures invaded most of the fields before treated only by cardiac surgeons. In this issue, Pillay describes a hybrid technique, involving both interventional cardiologists and cardiac surgeons, aimed to LV volume reduction after an anterior myocardial infarction. A series of internal (right ventricular septum) and external (anterior wall) anchors are implanted to approximate the LV free wall to the anterior septum, consequently excluding the scarred myocardium. Although some limitations of this study, the authors have to be commended for having revitalized a procedure almost eliminated from the surgical scenario.

An observational, prospective study on surgical treatment of secondary mitral regurgitation: The SMR study. Rationale, purposes, and protocol.

The natural history of secondary mitral regurgitation (MR) is unfavorable. Nevertheless, there are no evidence that its correction can improve the outcome. If from one side the original cause of secondary MR can be such to limit the possibilities of improvement, from the other side it is possible that the surgical technique widely applied to repair, restrictive mitral annuloplasty, is not adequate to correct the regurgitation. The addition of valvular and/or subvalvular techniques has been considered a possible technical solution. However, we do not know the prevalence of each technique, how many times mitral replacement is used to correct secondary MR. This aspect is of particular importance, as we know that a successful mitral repair causes a better left ventricular systolic remodeling than a unsuccessful repair or replacement. This study is a prospective, observational registry, conceived to understand what is done in the real world. Any surgeon will use the technique he thinks the most suitable for the patient. Every year, for 5 years, patients will have a clinical and echocardiographic follow-up, to evaluate the risk factors for a worse result (death, rehospitalization for heart failure, reoperation for MR return, moderate, or more MR return). This knowledge will give us the possibility to understand which is the technique, or the strategy, more efficient to treat this disease and the real efficacy of the surgical treatment.

Intermittent Antegrade Warm Blood Cardioplegia: What Is Next?

The introduction of warm heart surgery was a radical change in the concept of myocardial protection. In 1992, we applied a protocol for intermittent antegrade warm blood cardioplegia (CPL), which acquired some popularity for its simplicity and effectiveness. The possibility to deliver the warm blood CPL intermittently using the antegrade route attracted the attention of the scientific world, as the surgical procedure was less complicated. In this report, our aim is to focus on the changes that the protocol underwent over time and the reasons why these changes were made.

Left thoracotomy approach for off-pump coronary artery bypass grafting surgery: 15 years of experience in 2500 consecutive patients.

OBJECTIVES: Our goal was to describe the experience at 2 centres with off-pump coronary artery bypass grafting using a left thoracotomy. METHODS: From January 2002 to December 2017, a total of 2528 consecutive patients (578 women, mean age 62.3 ± 9.1 years) were operated on using this technique. Data were collected prospectively and analysed retrospectively. RESULTS: There were no conversions to median sternotomy and 6 patients (0.2%) were converted to on-pump CABG. The mean number of grafts per patient was 2.8 ± 0. 9. The 30-day mortality rate was 1.0% (25 patients). Most patients were extubated in the operating theatre (97.3%), and 47 patients (1.9%) needed re-exploration for bleeding. Seven patients (0.3%) experienced a cerebrovascular event; 4 (0.3%) had a postoperative myocardial infarction; and 84 (3.4%) had new-onset atrial fibrillation. A total of 1510 patients (61.1%) were discharged from the hospital in the first 48 h after surgery. Long-term survival rates were 98.8%, 93.6% and 69.1% at 1, 5 and 10 years, respectively (central image). During the follow-up period, 60 patients (2.9%) were re-examined for recurrence of angina with a new coronary angiogram; of those, 24 (1.2%) required percutaneous coronary intervention and 11 (0.5%) had redo surgery. CONCLUSIONS: A left thoracotomy is a safe alternative to a median sternotomy for coronary artery bypass grafting on the beating heart, with low early complications and good mid- and long-term results.