Publications by authors named "Fabio Miraldi"

57 Publications

3D morphometric analysis of ascending aorta as an adjunctive tool to predict type A acute aortic dissection.

J Thorac Dis 2021 Jun;13(6):3443-3457

Department of Clinical, Internal Medicine, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.

Background: Acute type A aortic dissection (AAAD) is a pathological process that implicates the ascending aorta and represents a surgical emergency burdened by high mortality if not promptly treated in the first hours of onset. Despite best efforts, the annual incidence rates of aortic dissection has remained stable over the past decades. We measured aortic dimensions (aortic diameters, area, length and volume) using 3D multiplanar reconstruction imaging with the purpose of refining the risk- morphology for AAAD.

Methods: Computerized tomography angiography studies of three groups were compared retrospectively: patients affected by AAAD (AAAD group; n=71), patients affected by aortic aneurysm and subsequently subjected to ascending aorta replacement (Aneurysm, n=77) and a healthy aorta's group (Control, n=75).

Results: Mean diameters of AAAD (4.9 cm) and Aneurysm (5.1 cm) aortas were significantly larger than those of the control group (3.4 cm). In AAAD patients, an ascending aorta diameter greater than 5.5 cm was observed in 18% of patients. Multiple comparisons showed statistically significant differences among mean of the ratio of aortic root area to height between the three groups (P<0.001). In frontal and sagittal planes, the length of the ascending aorta was significantly greater in patients affected by aortic pathology (AAAD and aneurysm) than in the control group (P<0.001). Significant differences were confirmed when indexing the aortic length to patient's height and BSA, and the aortic volume to patient's BSA.

Conclusions: Maximum transverse diameter, considered separately, is not the best predictor of aortic dissection. In our opinion, the introduction into clinical practice of measurements of the area, length, and volume of the aorta, as absolute or indexed values, could improve the selection of patients who would benefit from preventive surgical aortic replacement.
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http://dx.doi.org/10.21037/jtd-21-119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264695PMC
June 2021

Impact of chronic use of heat-not-burn cigarettes on oxidative stress, endothelial dysfunction and platelet activation: the SUR-VAPES Chronic Study.

Thorax 2021 06 19;76(6):618-620. Epub 2021 Apr 19.

IRCCS NeuroMed, Pozzilli, Italy.

Tobacco habit still represents the leading preventable cause of morbidity and mortality worldwide. Heat-not-burn cigarettes (HNBCs) are considered as an alternative to traditional combustion cigarettes (TCCs) due to the lack of combustion and the absence of combustion-related specific toxicants. The aim of this observational study was to assess the effect of HNBC on endothelial function, oxidative stress and platelet activation in chronic adult TCC smokers and HNBC users. The results showed that both HNBC and TCC display an adverse phenotype in terms of endothelial function, oxidative stress and platelet activation. Future randomised studies are strongly warranted to confirm these data.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215900DOI Listing
June 2021

Beating vs Arrested Heart Isolated Tricuspid Valve Surgery: Long-term Outcomes.

Ann Thorac Surg 2021 Apr 5. Epub 2021 Apr 5.

Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Background: Isolated tricuspid valve (TV) surgery is a rare procedure generally considered at high risk of perioperative mortality and poor long-term outcomes. Surgical treatment can be performed with either an arrested heart (AH) or beating heart (BH) technique. Aim of this study is to compare the outcomes of isolated tricuspid surgery with two different approaches.

Methods: The SUR-TRI study is a multicenter international retrospective study enrolling adult patients who underwent isolated tricuspid valve procedures (n=406, 56±16 years; 56% female) at 13 international sites. AH and BH strategies were performed in 253 and 153 cases, respectively. Propensity score-matched analysis was used to compare groups.

Results: After matching, 129 pairs were obtained and analyzed. The 30-day mortality rate was 6.2 vs 5.0% in the AH and BH groups, respectively (p=0.9). The rates of acute renal failure requiring replacement therapy (3 vs 10%, p=0.02) and stroke (0 vs 1.8%, p=0.08) were numerically higher in the AH group. The 6-year survival rate was 67±6 vs 78±5% in the AH and BH groups, respectively (p=0.18), while freedom from cardiac death was 75±5 vs 84±4% (p=0.21). The six-year composite cardiac endpoint of cardiac death and reoperation rate was 60±9 vs 86±5% (p=0.024) comparing AH-TV replacement and BH-TV repair groups.

Conclusions: Isolated tricuspid valve surgery performed with a beating heart strategy is a safe option and resulted in a trend of increased long-term survival and freedom from reoperation when compared with the standard arrested heart technique. Patients undergoing beating heart valve repair had the best long-term outcome.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.070DOI Listing
April 2021

Cardiac surgery practice during the COVID-19 outbreak: a multicentre national survey.

Eur J Cardiothorac Surg 2021 04;59(4):901-907

Cardiac Surgery Unit, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy.

Objectives: Healthcare systems worldwide have been overburdened by the coronavirus disease 2019 (COVID-19) outbreak. Accordingly, hospitals had to implement strategies to profoundly reshape both non-COVID-19 medical care and surgical activities. Knowledge about the impact of the COVID-19 pandemic on cardiac surgery practice is pivotal. The goal of the present study was to describe the changes in cardiac surgery practices during the health emergency at the national level.

Methods: A 26-question web-enabled survey including all adult cardiac surgery units in Italy was conducted to assess how their clinical practice changed during the national lockdown. Data were compared to data from the corresponding period in 2019.

Results: All but 2 centres (94.9%) adopted specific protocols to screen patients and personnel. A significant reduction in the number of dedicated cardiac intensive care unit beds (-35.4%) and operating rooms (-29.2%), along with healthcare personnel reallocation to COVID departments (nurses -15.4%, anaesthesiologists -7.7%), was noted. Overall adult cardiac surgery volumes were dramatically reduced (1734 procedures vs 3447; P < 0.001), with a significant drop in elective procedures [580 (33.4%) vs 2420 (70.2%)].

Conclusions: This national survey found major changes in cardiac surgery practice as a response to the COVID-19 pandemic. This experience should lead to the development of permanent systems-based plans to face possible future pandemics. These data may effectively help policy decision-making in prioritizing healthcare resource reallocation during the ongoing pandemic and once the healthcare emergency is over.
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http://dx.doi.org/10.1093/ejcts/ezaa436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989504PMC
April 2021

Susceptibility to ischaemic heart disease: Focusing on genetic variants for ATP-sensitive potassium channel beyond traditional risk factors.

Eur J Prev Cardiol 2020 Jun 2. Epub 2020 Jun 2.

Department of Clinical, Internal, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Italy.

Aims: Ischaemic heart disease is classically associated with coronary artery disease. Recent evidences showed the correlation between coronary microvascular dysfunction and ischaemic heart disease, even independently of coronary artery disease. Ion channels represent the final effectors of blood flow regulation mechanisms and their genetic variants, in particular of Kir6.2 subunit of the ATP-sensitive potassium channel (KATP), are reported to be involved in ischaemic heart disease susceptibility. The aim of the present study is to evaluate the role of KATP channel and its genetic variants in patients with ischaemic heart disease and evaluate whether differences exist between coronary artery disease and coronary microvascular dysfunction.

Methods: A total of 603 consecutive patients with indication for coronary angiography due to suspected myocardial ischaemia were enrolled. Patients were divided into three groups: coronary artery disease (G1), coronary microvascular dysfunction (G2) and normal coronary arteries (G3). Analysis of four single nucleotide polymorphisms (rs5215, rs5216, rs5218 and rs5219) of the KCNJ11 gene encoding for Kir6.2 subunit of the KATP channel was performed.

Results: rs5215 A/A and G/A were significantly more represented in G1, while rs5215 G/G was significantly more represented in G3, rs5216 G/G and C/C were both more represented in G3, rs5218 C/C was more represented in G1 and rs5219 G/A was more represented in G1, while rs5219 G/G was significantly more represented in G2. At multivariate analysis, single nucleotide polymorphism rs5215_G/G seems to represent an ischaemic heart disease independent protective factor.

Conclusions: These results suggest the potential role of KATP genetic variants in ischaemic heart disease susceptibility, as an independent protective factor. They may lead to a future perspective for gene therapy against ischaemic heart disease.
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http://dx.doi.org/10.1177/2047487320926780DOI Listing
June 2020

Von Willebrand factor with increased binding capacity is associated with reduced platelet aggregation but enhanced agglutination in COVID-19 patients: another COVID-19 paradox?

J Thromb Thrombolysis 2021 Jul 2;52(1):105-110. Epub 2021 Jan 2.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Patients with Coronavirus-associated disease-2019 (COVID-19) display alterations of the hemostatic system and the presence of a prothrombotic status frequently leading to vascular complications. However, the impact of COVID-19 on platelet activity, aggregation and agglutination still needs to be clarified. We measured total levels of von Willebrand factor (vWF) and vWF binding to the platelet glycoprotein (Gp) complex (GPIb-IX-V), in a cohort of COVID-19 patients admitted to the intensive care unit of our Institution. Moreover, we evaluated platelet aggregation in response to agonists (ADP, collagen, arachidonic acid) and platelet agglutination in response to ristocetin. We found that levels of vWF antigen and the active form of vWF binding to platelets (vWF:RCo), were markedly increased in these patients. These results were associated with higher agglutination rates induced by ristocetin, thereby indirectly indicating an increased capability of vWF to bind to platelets. Conversely, we found that platelet aggregation in response to both ADP and collagen was lower in COVID-19 patients compared to healthy volunteers. This study shows that COVID-19 is associated with increased vWF-induced platelet agglutination but reduced platelet responsivity to aggregation stimuli. Our findings have translational relevance since platelet adhesion to vWF may represent a marker to predict possible complications and better delineate therapeutic strategies in COVID-19 patients.
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http://dx.doi.org/10.1007/s11239-020-02339-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778414PMC
July 2021

Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome.

Eur Heart J 2021 04;42(16):1609-1617

Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy.

Aims: Necrotizing coronary vasculitis (NCV) is a rare entity usually associated to myocarditis which incidence, cause, and response to therapy is unreported.

Methods And Results: Among 1916 patients with biopsy-proven myocarditis, 30 had NCV. Endomyocardial samples were retrospectively investigated with immunohistochemistry for toll-like receptor 4 (TLR4) and real-time polymerase chain reaction (PCR) for viral genomes. Serum samples were processed for anti-heart autoantibodies (Abs), IL-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α. Identification of an immunologic pathway (including virus-negativity, TLR4-, and Ab-positivity) was followed by immunosuppression. Myocarditis-NCV cohort was followed for 6 months with 2D-echo and/or cardiac magnetic resonance and compared with 60 Myocarditis patients and 30 controls. Increase in left ventricular ejection fraction ≥10% was classified as response to therapy. Control endomyocardial biopsy followed the end of treatment. Twenty-six Myocarditis-NCV patients presented with heart failure; four with electrical instability. Cause of Myocarditis-NCV included infectious agents (10%) and immune-mediated causes (chest trauma 3%; drug hypersensitivity 7%; hypereosinophilic syndrome 3%; primary autoimmune diseases 33%, idiopathic 44%). Abs were positive in immune-mediated Myocarditis-NCV and virus-negative Myocarditis; Myocarditis-NCV patients with Ab+ presented autoreactivity in vessel walls. Toll-like receptor 4 was overexpressed in immune-mediated forms and poorly detectable in viral. Interleukin-1β was significantly higher in Myocarditis-NCV than Myocarditis, the former presenting 24% in-hospital mortality compared with 1.5% of Myocarditis cohort. Immunosuppression induced improvement of cardiac function in 88% of Myocarditis-NCV and 86% of virus-negative Myocarditis patients.

Conclusion: Necrotizing coronary vasculitis is histologically detectable in 1.5% of Myocarditis. Necrotizing coronary vasculitis includes viral and immune-mediated causes. Intra-hospital mortality is 24%. The immunologic pathway is associated with beneficial response to immunosuppression.
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http://dx.doi.org/10.1093/eurheartj/ehaa973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088814PMC
April 2021

Interplay between Nox2 Activity and Platelet Activation in Patients with Sepsis and Septic Shock: A Prospective Study.

Oxid Med Cell Longev 2020 27;2020:4165358. Epub 2020 Oct 27.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls.

Methods And Results: Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls ( = 10, age 67.8 ± 3.2, male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, < 0.001), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, < 0.001), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, < 0.001), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, < 0.001). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed.

Conclusions: Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock.
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http://dx.doi.org/10.1155/2020/4165358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641261PMC
May 2021

Clinical Conundrum: Three Management Strategies for Three-Vessel Coronary Artery Disease?

J Cardiovasc Pharmacol 2020 11;76(5):489-491

Unità Operativa Complessa di UTIC, Emodinamica e Cardiologia, Ospedale Santa Maria Goretti, Latina, Italy.

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http://dx.doi.org/10.1097/FJC.0000000000000900DOI Listing
November 2020

Comparative Indoor Pollution from Glo, Iqos, and Juul, Using Traditional Combustion Cigarettes as Benchmark: Evidence from the Randomized SUR-VAPES AIR Trial.

Int J Environ Res Public Health 2020 08 19;17(17). Epub 2020 Aug 19.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy.

Modified risk products (MRP) such as electronic vaping cigarettes (EVC) and heat-not-burn cigarettes (HNBC) are appealing alternatives to combustion cigarettes. Limited between- and within-device comparative data are available on MRP. We aimed at comparing indoor particulate matter (PM) emissions measured in a randomized trial enforcing standardized smoking sessions, testing different devices and flavors of MRP, using traditional combustion cigarettes (TCC) as benchmark. Overall, MRP yielded significantly lower levels of indoor PM in comparison to TCC (with median PM levels during smoking for MRP < 100 μg/m, and for TCC > 1000 μg/m). Despite this, significant differences among MRP were found, with Iqos appearing associated with a significantly lower burden of emissions for all the monitored fractions of PM, including total PM (all < 0.05). Precisely, during use, PM ≤1 µm (PM) emissions were 28 (16; 28) μg/m for Glo, 25 (15; 57) μg/m for Iqos, and 73 (15; 559) μg/m for Juul ( < 0.001 for Glo vs. Iqos, < 0.001 for Glo vs. Juul, and = 0.045 for Iqos vs. Juul). Exploratory within-MRP analyses suggested significant differences between flavors, favoring, for instance, Ultramarine for Glo, Bronze for Iqos, and Mango for Juul, even if results varied substantially according to individual smoker. In conclusion, leading MRP have significantly less intense and persistent effects on indoor pollution in comparison to TCC. Yet, when focusing solely on MRP, between-product and between-flavor differences appear, with quantitative estimates suggesting lower polluting effects with Iqos. These results, if confirmed externally, could be used to individualize product and flavor choice to minimize the untoward effects of EVC and HNBC on indoor pollution.
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http://dx.doi.org/10.3390/ijerph17176029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504617PMC
August 2020

Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review.

Nutrients 2020 Jun 8;12(6). Epub 2020 Jun 8.

Department of Public Health and Infectious Diseases, Sapienza, University of Rome, 00185 Rome, Italy.

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) global pandemic is a devastating event that is causing thousands of victims every day around the world. One of the main reasons of the great impact of coronavirus disease 2019 (COVID-19) on society is its unexpected spread, which has not allowed an adequate preparation. The scientific community is fighting against time for the production of a vaccine, but it is difficult to place a safe and effective product on the market as fast as the virus is spreading. Similarly, for drugs that can directly interfere with viral pathways, their production times are long, despite the great efforts made. For these reasons, we analyzed the possible role of non-pharmacological substances such as supplements, probiotics, and nutraceuticals in reducing the risk of Sars-CoV-2 infection or mitigating the symptoms of COVID-19. These substances could have numerous advantages in the current circumstances, are generally easily available, and have negligible side effects if administered at the already used and tested dosages. Large scientific evidence supports the benefits that some bacterial and molecular products may exert on the immune response to respiratory viruses. These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19. However, there are no specific data available, and rigorous clinical trials should be conducted to confirm the putative benefits of diet supplementation, probiotics, and nutraceuticals in the current pandemic.
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http://dx.doi.org/10.3390/nu12061718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352781PMC
June 2020

Susceptibility to ischaemic heart disease: Focusing on genetic variants for ATP-sensitive potassium channel beyond traditional risk factors.

Eur J Prev Cardiol 2020 Jun 2:2047487320926780. Epub 2020 Jun 2.

Department of Clinical, Internal, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Italy.

Aims: Ischaemic heart disease is classically associated with coronary artery disease. Recent evidences showed the correlation between coronary microvascular dysfunction and ischaemic heart disease, even independently of coronary artery disease. Ion channels represent the final effectors of blood flow regulation mechanisms and their genetic variants, in particular of Kir6.2 subunit of the ATP-sensitive potassium channel (K), are reported to be involved in ischaemic heart disease susceptibility. The aim of the present study is to evaluate the role of K channel and its genetic variants in patients with ischaemic heart disease and evaluate whether differences exist between coronary artery disease and coronary microvascular dysfunction.

Methods: A total of 603 consecutive patients with indication for coronary angiography due to suspected myocardial ischaemia were enrolled. Patients were divided into three groups: coronary artery disease (G1), coronary microvascular dysfunction (G2) and normal coronary arteries (G3). Analysis of four single nucleotide polymorphisms (rs5215, rs5216, rs5218 and rs5219) of the gene encoding for Kir6.2 subunit of the K channel was performed.

Results: rs5215 A/A and G/A were significantly more represented in G1, while rs5215 G/G was significantly more represented in G3, rs5216 G/G and C/C were both more represented in G3, rs5218 C/C was more represented in G1 and rs5219 G/A was more represented in G1, while rs5219 G/G was significantly more represented in G2. At multivariate analysis, single nucleotide polymorphism rs5215_G/G seems to represent an ischaemic heart disease independent protective factor.

Conclusions: These results suggest the potential role of K genetic variants in ischaemic heart disease susceptibility, as an independent protective factor. They may lead to a future perspective for gene therapy against ischaemic heart disease.
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http://dx.doi.org/10.1177/2047487320926780DOI Listing
June 2020

Extracorporeal membrane oxygenation for critically ill patients with coronavirus-associated disease 2019: an updated perspective of the European experience.

Minerva Cardioangiol 2020 Oct 27;68(5):368-372. Epub 2020 Apr 27.

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.

Background: Infection due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), i.e. coronavirus-associated disease 2019 (COVID-2019), may occasionally lead to acute respiratory distress syndrome (ARDS), requiring in the most severe cases extracorporeal membrane oxygenation (ECMO). Yet, limited data, if any, are currently available on the role of ECMO in critically ill patients with COVID-19. We aimed at providing a snapshot analysis of ECMO for COVID-19 in Europe.

Methods: Freely available data on ECMO in COVID-19 patients reported by the European Extracorporeal Life Support Organization (EuroELSO) were extracted and analyzed after conversion into long format. The primary outcome was the incidence of death during ECMO. Bootstrapping and logistic regression were used for inferential estimates.

Results: Details from a total of 333 patients treated in 90 institutions spanning 17 countries were obtained, with 22% women and mean age of 52 years. Death rate was 17.1% (95% confidence interval: 13.1% to 21.1%), even if significant between-center differences were found, with some institutions reporting 100% case fatality. Exploratory inferential analysis showed no nominally statistically significant association between death and gender (P=0.788), but a significant association was found with age, mainly due to increased case fatality in subjects >60 years (odds ratio: 4.80 [95% confidence interval 1.64 to 14.04], P=0.004).

Conclusions: ECMO may play an important role in critically ill patients with COVID-19 refractory to less invasive treatments. The increased risk of early death in older patients may be used to prioritize ECMO indication in resource-conscious settings, if confirmed externally.
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http://dx.doi.org/10.23736/S0026-4725.20.05328-1DOI Listing
October 2020

Deep sternal wound infection following cardiac surgery: A comparison of the monolateral with the bilateral pectoralis major flaps.

Int Wound J 2020 Jun 17;17(3):683-691. Epub 2020 Feb 17.

Department of Plastic Reconstructive and Aesthetic Surgery, Sapienza Università di Roma, Rome, Italy.

Deep sternal wound infections are a serious complication following sternotomy for cardiothoracic surgery. "Conventional" treatment provides debridement and secondary closure or closed catheter irrigation. The combination of the Negative Pressure Therapy with flap coverages is an accepted technique and one or both Pectoralis Major muscles could be chosen. A multistep protocol was adopted. One hundred and sixty seven patients were treated with the combination of Negative Pressure Therapy with the Pectoralis Major muscle flap: 86 monolateral flap and 81 bilateral flap reconstruction. The main complications (hematoma, seroma, dehiscence, and re-infection), the need for re-intervention, mortality rates, Intensive Care Unit, and hospitalisation time were assessed. The mono-pectoralis group had fewer complications and need for revision, with a shorter hospital stay. A statistically significant difference emerged for the hematoma rate (P = .0079). Monolateral flap should to be preferred because with the same coverage effectiveness, it guarantees the saving of controlateral muscle with its functionality and the possibility of its use in case of failure. Furthermore, as the technique is less invasive, it can be reserved for more fragile patients.
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http://dx.doi.org/10.1111/iwj.13324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948840PMC
June 2020

Ascending aorta disruption after thoracic blunt trauma.

Chin J Traumatol 2020 Feb 21;23(1):32-33. Epub 2019 Nov 21.

Cardiac Department, Sapienza University, Rome, Italy.

Blunt traumatic aortic injury is the second leading cause of death after motor vehicle accidents. The most frequent localisation of aortic lesion is the isthmus, especially in those who survived the accident. Here we report a case of blunt traumatic aortic injury with unusual localisation and modality. A 31 years old man sustained a motorcycle accident, being run over by a car. Computed tomography scan showed an atypical ascending aorta lesion, confirmed by intraoperative finding. The patient underwent emergency ascending aorta replacement with Dacron tubular graft. The patient was discharged uneventfully on 35th postoperative day, after multiple maxillofacial surgeries for concomitant injuries.
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http://dx.doi.org/10.1016/j.cjtee.2019.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049597PMC
February 2020

Echocardiography and Correction of Mitral Regurgitation: An Unbreakable Link.

Cardiology 2020;145(2):110-120. Epub 2019 Dec 3.

Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological, and Geriatric Sciences, Sapienza University, Rome, Italy.

Background: Degenerative mitral valve (MV) disease causing mitral regurgitation (MR) is the most common organic valve pathology and is classified based on leaflet motion. MV repair is indicated as the preferred technique (Class I indication) when the results are expected to be durable. Therefore, a detailed and systematic evaluation of MV apparatus is pivotal in allowing the proper surgical planning, as well as the screening for trans catheter-based treatment when surgery is not indicated.

Aim: The aim of the present review is to describe the crucial role of both Transthoracic Echocardiography (TTE) and Transesophageal Echocardiography (TEE) in the decisional process and the guidance of MV repair procedures. TTE is the main investigation and the first approach used to make diagnosis of MR, to assess the severity and to describe the underlying mechanism, while TEE, especially with 3D echocardiography, has been shown to be useful for clarifying complicated valvular anatomy, assessing the surgical result and detecting complications. The surgical treatment of MR takes advantage of ultrasound evaluation of MV apparatus at any stage of the process, thus making the link between surgery and echocardiography unbreakable throughout the perioperative phase.
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http://dx.doi.org/10.1159/000504248DOI Listing
November 2020

On the Road to Regeneration: "Tools" and "Routes" Towards Efficient Cardiac Cell Therapy for Ischemic Cardiomyopathy.

Curr Cardiol Rep 2019 10 31;21(11):133. Epub 2019 Oct 31.

Department of Medical Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100, Latina, Italy.

Purpose Of Review: Cardiac regenerative medicine is a field bridging together biotechnology and surgical science. In this review, we present the explored surgical roads to cell delivery and the known effects of each delivery method on cell therapy efficiency. We also list the more recent clinical trials, exploring the safety and efficacy of delivery routes used for cardiac cell therapy approaches.

Recent Findings: There is no consensus in defining which way is the most suitable for the delivery of the different therapeutic cell types to the damaged heart tissue. In addition, it emerged that the "delivery issue" has not been systematically addressed in each clinical trial and for each and every cell type capable of cardiac repair. Cardiac damage occurring after an ischemic insult triggers a cascade of cellular events, eventually leading to heart failure through fibrosis and maladaptive remodelling. None of the pharmacological or medical interventions approved so far can rescue or reverse this phenomenon, and cardiovascular diseases are still the leading cause of death in the western world. Therefore, for nearly 20 years, regenerative medicine approaches have focused on cell therapy as a promising road to pursue, with numerous preclinical and clinical testing of cell-based therapies being studied and developed. Nonetheless, consistent clinical results are still missing to reach consensus on the most effective strategy for ischemic cardiomyopathy, based on patient selection, diagnosis and stage of the disease, therapeutic cell type, and delivery route.
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http://dx.doi.org/10.1007/s11886-019-1226-5DOI Listing
October 2019

Get out of trouble during redo surgery for false aneurysm of the ascending aorta.

Asian Cardiovasc Thorac Ann 2020 Feb 11;28(2):104-107. Epub 2019 Oct 11.

Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological, and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1177/0218492319883528DOI Listing
February 2020

Comparative spallation performance of silicone versus Tygon extracorporeal circulation tubing.

Interact Cardiovasc Thorac Surg 2019 11;29(5):685-692

Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Rome, Italy.

Objectives: Reports ranged from mixed to marginal tubing wear and spallation effects as a complication of roller pumps in cardiopulmonary bypass (CPB). Because the rollers constantly compress part of the tubing, we sought to determine whether circuit materials behave differently under a 3-h simulation of CPB.

Methods: Two different tubing materials (silicone and Tygon) were tested with a customized experimental circuit, designed to allow in vitro simulation of CPB with priming volumes, pressures, revolutions per minute and temperatures equivalent to the clinical scenario. Samples were analysed with optical and field-emission scanning electron microscopy. We collected 200-ml fluid samples at 4 different times: before starting the CPB (T0), when the predicted revolutions per minute corresponded to about 2 min of CPB (T1), at 90 min (T2) and at 180 min (T3). At the end of CPB, we harvested 2 samples of tubing. Lastly, optical investigations and field-emission scanning electron microscopy observations were used for qualitative and quantitative analysis of circulating fragments.

Results: T2 and T3 fluid samples showed more particles than T1 samples. Significant differences in terms of particle numbers were detected: silicone tubing released more fragments per millilitre than Tygon tubing, with both materials releasing particles from 5 to 500 µm. Silicone tubing was associated with a time-dependent increase in small particles released (P = 0.04), whereas this did not apply to large particles or to Tygon tubing. Yet, bootstrap estimates suggested that silicone tubing was associated with the release of more small particles whereas Tygon tubing released more large particles (both P < 0.01). Unlike silicone, Tygon samples taken from the portion of the circuit not subjected to the action of the roller pump did not show any erosion on their surfaces. Samples of both materials taken from the portion subjected to the compression of the roller pump showed signs of significant deterioration.

Conclusions: Silicone showed a worse spallation performance than Tygon, thus appearing less safe for more complex surgery of prolonged duration or for patients with a prior cerebral ischaemic event. Additional risk and cost-effectiveness comparisons to determine the potential benefits of one type of tubing material over the other are warranted to further expand our findings.
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http://dx.doi.org/10.1093/icvts/ivz170DOI Listing
November 2019

Vacuum-Assisted Closure Therapy for the Treatment of Poststernotomy Wound Dehiscence in Neonates and Infants.

Thorac Cardiovasc Surg 2020 01 19;68(1):92. Epub 2019 Apr 19.

Umberto I Policlinico di Roma, Roma, Italy.

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http://dx.doi.org/10.1055/s-0039-1685543DOI Listing
January 2020

Giant right atrium and subvalvular pulmonary stenosis: A case report of an interesting combination.

Echocardiography 2019 May 14;36(5):992-995. Epub 2019 Mar 14.

Department of Cardiovascular, Respiratory, Geriatric, Anesthesiologic and Nephrologic Sciences, Sapienza University of Rome, Rome, Italy.

A 20-year-old Congolese woman presented with presyncope, dyspnea, and anasarca. Past medical history was unremarkable. Echocardiography revealed a rare combination of giant right atrium (RA), a dilated and hypertrophied right ventricle, subvalvular pulmonary stenosis (subPS), severe tricuspid regurgitation (TR), pericardial effusion and what appeared to be a spontaneously closed ventricular septal defect (VSD). Cardiac Magnetic Resonance and Cardiac Computed Tomography confirmed the findings excluding the presence of intra-cardiac and extra-cardiac shunt and other associated congenital anomalies. The patient underwent subPS resection, right atrioplasty, and tricuspid annuloplasty. Multimodality approach facilitated the detection of the abnormalities and provided clarity when determining the optimal surgical strategy.
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http://dx.doi.org/10.1111/echo.14311DOI Listing
May 2019

Right atrial function by speckle tracking echocardiography in atrial septal defect: Prediction of atrial fibrillation.

Clin Cardiol 2018 Oct 16;41(10):1341-1347. Epub 2018 Oct 16.

Cardiac Department, Sapienza University, Rome, Italy.

Background: Most antiarrhythmic interventional therapies for atrial fibrillation (AF) have been provided with special focus on the treatment of left-sided valvular disease and enlarged left atrium but few studies have assessed AF associated with congenital heart disease and dilated right atrium.

Hypothesis: We hypothesized that right atrial (RA) function assessed by two-dimensional (2DSTE) and three-dimensional (3DSTE) speckle-tracking echocardiography in patients with atrial septal defect (ASD) before and after percutaneous trancatheter closure could predict paroxysmal atrial fibrillation (PAF) development.

Methods: Seventy-three patients with hemodynamically significant secundum ASD were prospectively studied and followed up for 6 months after occluder insertion and compared with a normal age-matched group (n = 73). A subgroup of 17 patients who developed PAF after device implantation was also studied. RA peak global longitudinal strain (PS) was determined using 2DSTE. Standard deviations (SDs) of times to peak strain (TPS) were calculated as indices of dyssynchrony. RA volumes, emptying fraction (EF), and expansion index (EI) were determined using 3DSTE.

Results: RA-PS, EF, and EI (pre-closure values) were reduced in patients with atrial devices compared with controls, and further reductions were observed in patients with PAF. Pre-closure 3D-RA-EI (P = 0.009) and RA-TPS (P = 0.023) were independent predictors of PAF by multivariate analysis after adjustment for age and left atrial dysfunction. The areas under the ROC-curve (AUC) for 3D-RA-EI, RA-PS, RA-TPS (pre-closure values) showed high discriminative values(from 0.76 to 0.85) in predicting PAF. By combining 3D-RA-EI and RA-TPS, the AUC increased to 0.90.

Conclusions: Two-dimensional and three-dimensional speckle tracking echocardiography was clinically helpful in ASD patients in revealing right atrial dilatation and dysfunction pre-existent to device closure and associated with PAF development. RA parameters had a higher association with PAF compared to both the size of the implanted device and left atrial indices.
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http://dx.doi.org/10.1002/clc.23051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489743PMC
October 2018

Foetal bovine serum-derived exosomes affect yield and phenotype of human cardiac progenitor cell culture.

Bioimpacts 2016 28;6(1):15-24. Epub 2016 Mar 28.

Department of Molecular Medicine, "Sapienza" University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.

Introduction: Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects. According to their potential, many researchers have focused on characterizing exosomes derived from specific cell types, but, up until now, only few studies have analyzed the possible in vitro effects of bovine serum-derived exosomes on cell proliferation or differentiation.

Methods: The aim of this study was to analyse, from a qualitative and quantitative point of view, the in vitro effects of bovine serum exosomes on human CPCs cultured either as cardiospheres or as monolayers of cardiosphere-forming cells.

Results: Effects on proliferation, yield and molecular patterning were detected. We show, for the first time, that exogenous bovine exosomes support the proliferation and migration of human cardiosphere-forming cells, and that their depletion affects cardiospheres formation, in terms of size, yield and extra-cellular matrix production.

Conclusion: These results stress the importance of considering differential biological effects of exogenous cell culture supplements on the final phenotype of primary human cell cultures.
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http://dx.doi.org/10.15171/bi.2016.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916547PMC
June 2016

Analysis of pregnancy-associated plasma protein A production in human adult cardiac progenitor cells.

Biomed Res Int 2013 10;2013:190178. Epub 2013 Nov 10.

Department of Gynaecology, Obstetrics and Urologic Sciences, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.

IGF-binding proteins (IGFBPs) and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A) is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs) and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays, we firstly report that PAPP-A is produced and secreted in surprisingly high amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A is secreted in relevant concentrations in haCPC-conditioned media, while the enzymatically inactive PAPPA/proMBP complex is not detectable in the same media. Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as cell associated, suggesting that the previously described complex formation at the cell surface does not occur easily, thus positively affecting IGF signalling. Therefore, our results strongly support the importance of PAPP-A for the IGFs/IGFBPs/PAPP-A axis in CPCs biology.
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http://dx.doi.org/10.1155/2013/190178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842074PMC
June 2014

Double aortic arch: postnatal obliteration of the left aortic arch. Is arterial duct closure responsible?

Cardiol Young 2014 Jun 29;24(3):534-6. Epub 2013 May 29.

1 Department of Cardiocirculatory Pathophysiology, Anesthesiology, and General Surgery, Sapienza University of Rome, Rome, Italy.

We present a case of double aortic arch with a predominant right and a double arterial duct detected by echocardiogram in a 28-week gestation foetus. The first evaluation revealed that both arches were perfused; the 1-month postnatal echocardiogram showed the closure of both arterial ducts and the partial obliteration of the left aortic arch between the left subclavian artery and the dorsal aorta. In our case, the postnatal obliteration of the left arch in a double aortic arch was probably due to the closure of the left-sided arterial duct.
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http://dx.doi.org/10.1017/S104795111300070XDOI Listing
June 2014

Long-term survival after resection of a primary leiomyosarcoma of the innominate vein Report of a case.

Ann Ital Chir 2012 Oct 29;2012. Epub 2012 Oct 29.

Leiomyosarcoma of the innominate vein is a rare but usually lethal disease. We report the case of a 50-year-old woman, undergoing a curative resection of the tumor. She is alive and free of disease at 88-month follow-up. Surgical excision remains the current optimal treatment able to provide a chance of cure. KEY WORDS: Late survival, Venous leiomyosarcoma.
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October 2012

TGFβ-dependent epithelial-to-mesenchymal transition is required to generate cardiospheres from human adult heart biopsies.

Stem Cells Dev 2012 Nov 7;21(17):3081-90. Epub 2012 Aug 7.

Department of Molecular Medicine, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.

Autologous cardiac progenitor cells (CPCs) isolated as cardiospheres (CSps) represent a promising candidate for cardiac regenerative therapy. A better understanding of the origin and mechanisms underlying human CSps formation and maturation is undoubtedly required to enhance their cardiomyogenic potential. Epithelial-to-mesenchymal transition (EMT) is a key morphogenetic process that is implicated in the acquisition of stem cell-like properties in different adult tissues, and it is activated in the epicardium after ischemic injury to the heart. We investigated whether EMT is involved in the formation and differentiation of human CSps, revealing that an up-regulation of the expression of EMT-related genes accompanies CSps formation that is relative to primary explant-derived cells and CSp-derived cells grown in a monolayer. EMT and CSps formation is enhanced in the presence of transforming growth factor β1 (TGFβ1) and drastically blocked by the type I TGFβ-receptor inhibitor SB431452, indicating that TGFβ-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGFβ is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs.
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http://dx.doi.org/10.1089/scd.2012.0277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146498PMC
November 2012

Late MitraClip failure: removal technique for leaflet-sparing mitral valve repair.

J Card Surg 2012 Sep 4;27(5):543-5. Epub 2012 Jul 4.

Department of Cardiocirculatory Pathophysiology, Anesthesiology, and General Surgery, Sapienza University of Rome, Rome, Italy.

MitraClip system has been recently introduced in clinical practice for percutaneous mitral valve repair in selected patients. In the case of early or late detachment of the device dedicated tools, either with percutaneous or surgical approach, have been developed. We describe a novel technique to atraumatically remove the MitraClip.
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http://dx.doi.org/10.1111/j.1540-8191.2012.01483.xDOI Listing
September 2012

Aortic valve 'kissing' vegetation: mitral valve endocarditis with functional aortic stenosis.

J Heart Valve Dis 2011 Nov;20(6):715-7

Sapienza University, Rome, Italy.

The case is reported of giant mitral valve vegetation that was wedged into the aortic valve plane (aortic valve 'kissing' vegetation), causing obstruction to the left ventricular outflow tract. In such a case, echocardiography plays a key role in the assessment of vegetation morphology, risk of embolization, impact on valvular function and indication for surgery. Because of its size, the obstructive hemodynamics, and the potential to induce aortic valve endocarditis, aortic 'kissing' vegetation requires surgical intervention to preserve the integrity of the valve and improve the hemodynamic status.
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November 2011
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