Pharmacological inhibition of hydroxysteroid 11-beta dehydrogenase type 1 (11-βHSD1) after myocardial infarction preserves cardiac function in a translational mini-pig model Sara Al Disi, Raimondo Ascione, Shazia Khan, Thomas Johnson, Eva Sammut, Vito Domenico Bruno, Daniel Baz Lopez, Carol‐Anne James, Joanna Simpson, Natalie Z. Homer, Michael Millar, Trisha Singh, Alex von Kreigsheim, Nick L. Mills, Brian R. Walker, Ruth Andrew, Scott P. Webster, Andrew Whittaker, Adrian Freeman, Gillian A. Gray British Journal of Pharmacology, 2026 Background and Purpose Plasma glucocorticoids increase acutely after MI, thereafter tissue levels are amplified selectively within cells expressing 11‐ ß hydroxysteroid dehydrogenase type 1 (11‐ßHSD1) that regenerates active glucocorticoids from circulating metabolites. Glucocorticoids initially protect cardiomyocytes and prevent excessive inflammation after MI but can also suppress wound repair leading to functional decline. We investigate 11‐ßHSD1 inhibition after MI to prevent deterioration of cardiac function and its impact on wound repair. Experimental Approach Adult female Gottingen mini‐pigs underwent percutaneous balloon MI/reperfusion and were randomised to receive either oral 11‐ßHSD1 inhibitor AZD8329 (n = 11) or vehicle (n = 9), from 2 until 27 days later, with concurrent administration of relevant therapeutic intervention (anti‐platelet, statin and ACE inhibitor). Key Results AZD8329 treatment increased plasma accumulation of cortisone substrate showing successful 11‐ßHSD1 inhibition. Gadolinium‐enhanced magnetic resonance imaging (MRI) showed equivalent infarct size in both groups prior to commencing treatment. Twenty‐eight days after MI cardiac function and left ventricle area were preserved in the AZD8329 treated group relative to vehicle. There was no impact of 11‐ßHSD1 inhibitor on neovascularisation or infarct area. Mass spectrometry imaging revealed AZD8329 binding to the healing infarct and altered regulation of extracellular matrix processing was highlighted by birefringence microscopy and proteomic analysis. Conclusions and Implications Pharmacological inhibition of 11‐ßHSD1 after MI prevents deterioration of cardiac function and detrimental remodelling. 11‐ßHSD1 inhibitors have safely reached Phase 2 clinical trials in diabetes and dementia, and could be repurposed as an addition to standard care after MI to prevent the development of heart failure.
Prognostic Impact of Untreated Chronic Coronary Artery Obstruction After Surgery for Aortic Regurgitation Xin Li, Vito Domenico Bruno, Yi Jiang, Yunxing Xue, Dongjin Wang Journal of Cardiovascular Development and Disease, 2026 Background: The optimal management strategy for 50–70% chronic coronary artery stenosis in patients undergoing aortic valve surgery for aortic regurgitation (AR) remains controversial. This study evaluates the prognostic impact of chronic coronary obstruction severity on surgical outcomes and mid-term survival. Methods: This retrospective cohort study included 717 patients undergoing aortic valve surgery for AR, grouped by coronary stenosis into <50% (n = 641) and 50–70% (n = 76). Following 1:1 propensity score matching (72 patients per group), the primary outcome of major adverse cardiovascular events (MACE) and the secondary outcome of all-cause death were compared. Results: No intergroup differences emerged in perioperative mortality (1.32% vs. 1.56%, p = 1.000) or complication rate. With a median follow-up of 2.53 years, 50–70% coronary obstruction does not increase MACE (HR = 2.050; 95% CI 0.375–11.197; log-rank p = 0.397) and all-cause mortality (HR = 0.710; 95% CI 0.200–2.522; log-rank p = 0.595). Similar results were obtained in the competing risk regression and multivariable analyses. Conclusions: In patients with AR, 50–70% chronic coronary obstruction does not increase perioperative complications, MACE, and all-cause mortality.
Evaluation of three-dimensional right ventricular function and reverse remodelling in patients undergoing percutaneous mitral valve repair for functional mitral regurgitation: insights from a multicentre Italian registry Tommaso Viva, Jessica Zannoni, Antonio Popolo Rubbio, Laura Lupi, Eustachio Agricola, Elena Biagini, Marianna Adamo, Cristina Giannini, Alessandra Berardini, Salvatore Scandura, Carmelo Grasso, Sara Boveri, Paolo Denti, Anna S. Petronio, Chiara Marcelli, Vito D. Bruno, Francesco Sturla, Nicola R. Pugliese, Nedy Brambilla, Luca Testa, Patrizio Lancellotti, Francesco Bedogni, Maurizio Tusa Acta Cardiologica, 2026 BACKGROUND: The predictive role of right ventricular dysfunction (RVD) in patients with functional mitral regurgitation (FMR) undergoing transcatheter edge-to-edge repair (TEER), as well as RV remodelling following the procedure, remains uncertain. We evaluated the prognostic impact of pre-procedural three-dimensional (3D) right ventricular ejection fraction (RVEF) in patients with FMR. Additionally, we assessed the RV reverse remodelling (RVRR) based on 3D volumes and ejection fraction six months after the procedure. METHODS: = 11). RESULTS: < 0.05). CONCLUSIONS: RVD was common among patients undergoing mitral TEER for FMR. Those with pre-procedural SRVD had worse mid-term survival compared to patients with MRVD and No-RVD. The group with MRVD was the only one to demonstrate an RVRR six months after the procedure.
Mitochondrial accumulation of GRK2 as a protective mechanism against hypoxia-induced endothelial dysfunction Cristina Gatto, Maria Rosaria Rusciano, Daniela Sorriento, Paola Di Pietro, Angela Carmelita Abate, Valeria Visco, Nicola Montone, Pasquale Mone, Daniele Di Napoli, Pierpaolo Chivasso, Vito Domenico Bruno, Vincenza Valerio, Paolo Poggio, Guido Iaccarino, Gaetano Santulli, Carmine Vecchione, Albino Carrizzo, Michele Ciccarelli Cell Death Discovery, 2025 Hypoxia, a condition characterized by a temporary lack of oxygen, causes mitochondrial damage, which in turn leads to endothelial dysfunction. G-protein-coupled receptor kinase 2 (GRK2) plays a key role in vascular homeostasis and remodeling, influencing endothelial function through various pathways. GRK2 moves within the cellular compartments and is linked to mitochondrial function and biogenesis, promoting ATP production and protecting against oxidative stress and cell death. The present study examined how mitochondrial GRK2 accumulation affects vascular reactivity and endothelial function in transient hypoxic conditions. Using a cloning strategy, we employed a small peptide (10aa) TAT-conjugated based on the pleckstrin homology domain of GRK2 to redirect GRK2 from the plasma membrane to the mitochondria. Mitochondrial accumulation of GRK2 increases vasodilatory responses in isolated swine artery segments, indicating potential therapeutic applications for cardiovascular disorders. Furthermore, in endothelial cells, GRK2 accumulation within mitochondria protects membrane potential, mitochondrial mass and prevents oxidative damage and cell death caused by transient hypoxia. Our findings show that GRK2 accumulation in mitochondria represents a potential therapeutic target to prevent transient hypoxia-induced damage.
Artificial intelligence in the diagnosis and management planning of bicuspid aortic valvular disease: a case series Tommaso Viva, Alessandro Masini, Michele Gallazzi, Vito Domenico Bruno, Antonio Miceli, Mattia Glauber, Daniele Andreini, Edoardo Conte European Heart Journal Case Reports, 2025 Background Bicuspid aortic valve (BAV) is the most common congenital heart anomaly, often leading to significant aortic stenosis (AS) or aortic regurgitation (AR), which may require surgical intervention. Echocardiography is typically used for the diagnosis of BAV, and the integration of artificial intelligence (AI) can enhance diagnostic accuracy and guide surgical decisions. Case summary We present two patients with BAV: a 17-year-old male football player with isolated AR due to prolapse undergoing aortic valve repair and a 68-year-old male with combined AS and AR, candidate for aortic valve replacement. Artificial intelligence-based tools assisted in characterizing the valvular disease and assessing its haemodynamic impact by estimating and averaging transvalvular gradients and velocity-time integrals, reconstructing three-dimensional valve anatomy, and automatically calculating left ventricular volumes, ejection fraction, and global longitudinal strain. This comprehensive assessment improved prognostic evaluation and helped tailor the treatment plan. Conclusion Artificial intelligence in echocardiography holds great potential for diagnosis and planning the treatment of BAV disease. By enhancing image analysis and automating key diagnostic steps, AI can reduce diagnostic times and optimize patient outcomes. As AI-based tools continue to evolve and gain clinical validation, their integration into everyday practice will likely lead to a more efficient and accurate care for patients with valvular heart disease.
In-Situ Vascular Regeneration by Host Cells of Acellular Human Saphenous Vein Implanted in Porcine Carotid Artery Andrew Bond, Vito Bruno, Nadiah Sulaiman, Jason Johnson, Sarah George, Raimondo Ascione International Journal of Molecular Sciences, 2025 Small vascular graft engineering may help reduce early vein graft failure. We assessed the feasibility, safety, and in vivo vascular regeneration potential of the decellularised human saphenous vein (D-hSV) with and without pre-seeding with porcine endothelial-like cells (ELCs) following grafting in porcine carotid artery (CA). A total of 14 pigs received CA grafting of control D-hSVs (n = 7) or D-hSVs seeded with ELCs (SD-hSV; n = 7). Ultrasound vascular Doppler was undertaken before and after grafting, and at 4 weeks. Outcome measures included patency, intimal thickening (IT), in situ vascular regeneration, endothelial cell (EC) coverage, neo-angiogenesis, mesenchymal–EC transition, and contractile cells. All animals reached the predefined culling point in good health, with no feasibility/safety concerns. Mild graft dilatation occurred at 4 weeks vs. baseline, with no difference between groups. In total, 9/14 grafts (64.3%) remained patent at 4 weeks (4/7 (57.1%) vs. 5/7 (71.4%) in the D-hSV and SD-hSV groups, respectively). IT increased from 17.1 ± 4.7% at baseline to 54.1 ± 12.2% at 4 weeks. Vascular regeneration occurred in all patent grafts with EC coverage, an increase in collagen and elastin, vimentin, SM-MHC-11, and calponin, with no difference between groups. The D-hSV for arterial vascular grafting is feasible and safe and associated with signs of in situ vascular regeneration by host cells at 4 weeks. Pre-seeding with ELCs did not add benefits.
Preoperative consecutive treatment with isoprenaline and adenosine is safe and reduces ischaemia-reperfusion injury in a porcine model of cardiac surgery with recent acute myocardial infarction Sarah Smith, Igor Khaliulin, Ettorino Di Tommaso, Vito D Bruno, Thomas W Johnson, Eva Sammut, Daniel Baz-Lopez, Julia Deutsch, M-Saadeh Suleiman, Raimondo Ascione European Journal of Cardio Thoracic Surgery, 2025 OBJECTIVES The goal of this study was to assess the feasibility, safety and efficacy of consecutive treatment with isoprenaline/adenosine (ISO/ADE) in a pig model of myocardial infarction and cardiac surgery. METHODS The final ISO/ADE dose was selected from a pilot study (n = 8). In the subsequent randomized trial, 16 pigs underwent cardiac magnetic resonance imaging 4 weeks after a myocardial infarction, then were randomized to either the ISO/ADE (n = 8) or the control (n = 8) group before undergoing cardiac surgery with 1 h recovery. Feasibility and safety end points included the method of ISO/ADE delivery, serial blood pressure, heart rate, pH, HCO3-, circulating lactate levels, troponin levels and arrhythmias. Biomarkers of efficacy included serial lactate levels and serial pO2 mean arterial-to-venous functional ratio along with histologic levels of glycogen, protein carbonyls, O2, CO2, HCO3- and fibrosis. Postoperative rates of low cardiac output and death were also recorded. RESULTS Cardiac magnetic resonance measures of myocardial infarction did not differ between the groups. The selected method of ISO/ADE delivery was feasible. At no time were all safety outcomes measured in the ISO/ADE group worse than those in the control group. ISO/ADE reduced circulating lactate levels, preserved the serial pO2 mean arterial-to-venous functional ratio and reduced tissue-based glycogen and protein carbonylation. No other differences were observed. Low cardiac output and death occurred in 3/8 (37.5%) and 2/8 (25%) control animals versus 0% in the ISO/ADE group. CONCLUSIONS The therapy was feasible and safe and improved biomarkers of efficacy. ISO/ADE was not associated with any postoperative low cardiac output and deaths versus 37.5% and 25%, respectively, in the control group. A pilot human study is warranted.
The German Registry of Acute Aortic Dissection Type A score for 30-day mortality prediction in Type A Acute Aortic Dissection surgery: a systematic review and meta-analysis Marco Gemelli, Thanakorn Rojanathagoon, Jef van den Eynde, Enrico G Italiano, Tea Lena, Michel Pompeu Sá, Vito D Bruno, Manraj Sandhu, Robert Pruna-Guillen, Aung Y Oo, Martin Czerny, Michele Gallo, Mark S Slaughter, Vincenzo Tarzia, Eltayeb Mohamed Ahmed, Cha Rajakaruna, Gino Gerosa European Journal of Cardio Thoracic Surgery, 2025 OBJECTIVES The German Registry of Acute Aortic Dissection Type A (GERAADA) score is a risk score for predicting 30-day mortality after an operation for type A acute aortic dissection (TAAAD). This meta-analysis sought to assess the performance of the GERAADA model and compare it to the performance of the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). METHODS A systematic search of 3 online databases was conducted to identify studies that externally validated the GERAADA score. A random-effect meta-analysis was conducted, pooling area under the curve (AUC) data, operative mortality observed/expected (O/E) ratios and observed-expected (O-E) differences—of the GERAADA model in all studies and of the EuroSCORE II when available. RESULTS Eleven studies were selected, including a total of 10 360 patients. The observed in-hospital mortality rate was 12.2%. Pooled expected mortality rates estimated by the GERAADA score and the EuroSCORE II were 18.4% and 5.8%, respectively. The pooled analyses for the GERAADA scores showed moderate discrimination [AUC 0.70, 95% confidence interval (CI) 0.66–0.73] and good calibration [observed-expected (O-E) differences −12.3, 95% CI −27.1 to 2.58; O/E ratio 0.81, 95% CI 0.57–1.05]. Results from 5 studies (2133 patients) investigating both scores simultaneously revealed similar AUC results (P = 0.50), significantly lower O-E differences (P = 0.03) and a trend towards O/E ratios closer to 1 (P = 0.08) with the GERAADA score compared to the EuroSCORE II. CONCLUSIONS The GERAADA score seemed to offer a better calibration for predicting 30-day postoperative death following TAAAD operations, even though further studies are needed to confirm these findings. The moderate discriminatory capacity of both scores highlights the challenges of predicting outcomes in complex cardiovascular conditions like TAAAD.
Reporting of surrogate endpoints in randomised controlled trial reports (CONSORT-Surrogate): Extension checklist with explanation and elaboration Anthony Muchai Manyara, Philippa Davies, Derek Stewart, Christopher J Weir, Amber E Young, Jane Blazeby, Nancy J Butcher, Sylwia Bujkiewicz, An-Wen Chan, Dalia Dawoud, Martin Offringa, Mario Ouwens, Asbjørn Hróbjartssson, Alain Amstutz, Luca Bertolaccini, Vito Domenico Bruno, Declan Devane, Christina D C M Faria, Peter B Gilbert, Ray Harris, Marissa Lassere, Lucio Marinelli, Sarah Markham, John H Powers, Yousef Rezaei, Laura Richert, Falk Schwendicke, Larisa G Tereshchenko, Achilles Thoma, Alparslan Turan, Andrew Worrall, Robin Christensen, Gary S Collins, Joseph S Ross, Rod S Taylor, Oriana Ciani BMJ, 2024
Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration Anthony Muchai Manyara, Philippa Davies, Derek Stewart, Christopher J Weir, Amber E Young, Jane Blazeby, Nancy J Butcher, Sylwia Bujkiewicz, An-Wen Chan, Dalia Dawoud, Martin Offringa, Mario Ouwens, Asbjørn Hróbjartssson, Alain Amstutz, Luca Bertolaccini, Vito Domenico Bruno, Declan Devane, Christina D C M Faria, Peter B Gilbert, Ray Harris, Marissa Lassere, Lucio Marinelli, Sarah Markham, John H Powers, Yousef Rezaei, Laura Richert, Falk Schwendicke, Larisa G Tereshchenko, Achilles Thoma, Alparslan Turan, Andrew Worrall, Robin Christensen, Gary S Collins, Joseph S Ross, Rod S Taylor, Oriana Ciani BMJ, 2024
A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials Oriana Ciani, Anthony M. Manyara, Philippa Davies, Derek Stewart, Christopher J. Weir, Amber E. Young, Jane Blazeby, Nancy J. Butcher, Sylwia Bujkiewicz, An-Wen Chan, Dalia Dawoud, Martin Offringa, Mario Ouwens, Asbjørn Hróbjartssson, Alain Amstutz, Luca Bertolaccini, Vito Domenico Bruno, Declan Devane, Christina D.C.M. Faria, Peter B. Gilbert, Ray Harris, Marissa Lassere, Lucio Marinelli, Sarah Markham, John H. Powers, Yousef Rezaei, Laura Richert, Falk Schwendicke, Larisa G. Tereshchenko, Achilles Thoma, Alparslan Turan, Andrew Worrall, Robin Christensen, Gary S. Collins, Joseph S. Ross, Rod S. Taylor Eclinicalmedicine, 2023
The need for custom made frozen elephant trunk: when and where Pierpaolo Chivasso, Paolo Masiello, Mario Miele, Vito Domenico Bruno, Alba Chiara Genovino, Ivana Iesu, Donato Triggiani, Mario Colombino, Francesco Cafarelli, Rocco Leone, Generoso Mastrogiovanni, Severino Iesu Cardiovascular Diagnosis and Therapy, 2022
Frozen elephant trunk technique in acute type a aortic dissection: Is it for all? Pierpaolo Chivasso, Generoso Mastrogiovanni, Mario Miele, Vito Domenico Bruno, Antonio Rosciano, Antonio Pio Montella, Donato Triggiani, Mario Colombino, Francesco Cafarelli, Rocco Leone, Paolo Masiello, Severino Iesu Medicina Lithuania, 2021
MicroRNAs as potential biomarkers in congenital heart surgery Serban C. Stoica, Dan M. Dorobantu, Antonella Vardeu, Giovanni Biglino, Kerrie L. Ford, Domenico V. Bruno, Mustafa Zakkar, Andrew Mumford, Gianni D. Angelini, Massimo Caputo, Costanza Emanueli Journal of Thoracic and Cardiovascular Surgery, 2020
Effectiveness and Safety of Aprotinin Use in Thoracic Aortic Surgery Pierpaolo Chivasso, Vito D. Bruno, Roberto Marsico, Anilkumar Sankanahalli Annaiah, Alexander Curtis, Carlo Zebele, Gianni D. Angelini, Alan J. Bryan, Cha Rajakaruna Journal of Cardiothoracic and Vascular Anesthesia, 2018
Prior Percutaneous Coronary Intervention and Mortality in Patients Undergoing Surgical Myocardial Revascularization Giovanni Mariscalco, Stefano Rosato, Giuseppe F. Serraino, Daniele Maselli, Magnus Dalén, Juhani K.E. Airaksinen, Daniel Reichart, Marco Zanobini, Francesco Onorati, Marisa De Feo, Riccardo Gherli, Giuseppe Santarpino, Antonino S. Rubino, Giuseppe Gatti, Francesco Nicolini, Francesco Santini, Andrea Perrotti, Vito D. Bruno, Vito G. Ruggieri, Fausto Biancari, Aamer Ahmed, Nicola Masala, Carmelo Dominici, Saverio Nardella, Sorosh Khodabandeh, Peter Svenarud, Helmut Gulbins, Matteo Saccocci, Giuseppe Faggian, Ilaria Franzese, Ciro Bancone, Ester E. Della Ratta, Francesco Musumeci, Laszlo Gazdag, Theodor Fischlein, Carmelo Mignosa, Aniello Pappalardo, Tiziano Gherli, Antonio Salsano, Guido Olivieri, Karl Bounader, Jean P. Verhoye, Sidney Chocron, Tuomas Tauriainen, Eeva-Maija Kinnunen Circulation Cardiovascular Interventions, 2018
Safety andmid-term outcome of catheter ablation of ventricular tachycardia in octogenarians Antonio Frontera, Sandeep Panniker, Alexander Breitenstein, Vito Domenico Bruno, Georgia May Connolly, David Wilson, Teresa Rio, Mehul B. Dhinoja, Wajid Hussain, Richard J. Schilling, Glyn Thomas, Tom Wong, Ross J. Hunter, Frederic Sacher, Pierre Jaïs, Edward Duncan Europace, 2017