Publications by authors named "Carlo Pellegrini"

36 Publications

Extracorporeal Membrane Oxygenation for COVID-19 respiratory distress syndrome: an Italian Society for Cardiac Surgery Report.

ASAIO J 2021 Jan 18. Epub 2021 Jan 18.

Division of Cardiac Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy Cardio-Thoracic Surgery Unit, Heart and Vascular Centre, Maastricht University Medical Centre (MUMC), Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands. Cardiac Surgery Department, IRCCS San Matteo, Pavia, Italy Cardiothoracic Surgery Department, Città della Scienza, University of Turin, Turin, Italy Cardiac Surgery Department, Ospedale dell'Angelo, Mestre, Italy Cardiac Surgery Department, Hospital Clinic, University of Barcelona, Barcelona, Spain Cardiothoracic Department, University of Padua, Padua, Italy Cardiac Surgery Department, Ca Foncello Hospital, Treviso, Italy Cardiac Surgery Department, Sant'Ambrogio Hospital, University of Milan, Milan, Italy Cardiac Surgery Department, San Martino Hospital, University of Genova, Genova, Italy Cardiac Surgery Department, AOUP, University of Pisa, Pisa, Italy Cardiac Surgery Department, San Camillo-Forlanini Hospital, Rome, Italy Cardiac Surgery Department, San Bortolo Hospital, Vicenza, Italy UOC Cardiac Surgery and Translational Research, IRCCS San Donato and University of Milan, San Donato Milanese, Italy.

An increased need of Extracorporeal Membrane Oxygenation (ECMO) support is going to become evident as treatment of SARS-CoV-2 respiratory distress syndrome. This is the first report of Italian Society for Cardiac Surgery (SICCH) on preliminary experience with COVID-19 patients receiving ECMO support. Data from 12 Italian hospitals participating in SICCH were retrospectively analyzed. Between March 1st and September 15th, 2020, a veno-venous (VV) ECMO system was installed in 67 patients (94%) and a veno-arterio-venous (VAV) ECMO in four (6%). Five patients required VA ECMO after initial weaning from VV ECMO. Thirty (42.2%) patients were weaned from ECMO, while 39 (54.9%) died on ECMO, and six (8.5%) died after ECMO removal. Overall hospital survival was 36.6% (n=26). Main causes of death were multiple organ failure (n=14, 31.1%) and sepsis (n=11, 24.4%). On multivariable analysis, predictors of death while on ECMO support were older age (p=0.048), elevated pre-ECMO C-reactive protein level (p=0.048), higher positive end-expiratory pressure on ventilator (p=0.036) and lower lung compliance (p=0.032). If the conservative treatment is not effective, ECMO support might be considered as life-saving rescue therapy for COVID-19 refractory respiratory failure. However warm caution and thoughtful approaches for timely detection and treatment should be taken for such a delicate patients population.
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http://dx.doi.org/10.1097/MAT.0000000000001399DOI Listing
January 2021

Calcineurin Inhibitor-Based Immunosuppression and COVID-19: Results from a Multidisciplinary Cohort of Patients in Northern Italy.

Microorganisms 2020 Jun 30;8(7). Epub 2020 Jun 30.

Department of Respiratory Diseases, University of Pavia and IRCCS Policlinico S. Matteo Foundation of Pavia, 27100 Pavia, Italy.

The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to April 28 2020. Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy. Selected patients were referred from the North of Italy. The aim of our study was to evaluate the clinical course of COVID-19 in this setting. We evaluated 385 consecutive patients (220 males, 57%; median age 61 years, IQR 48-69); 331 (86%) received solid organ transplantation and 54 (14%) had a RMD. CNIs were the only immunosuppressant administered in 47 patients (12%). We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%). Twelve patients were hospitalized and two of them died, both with severe comorbidities. No patients developed acute respiratory distress syndrome or infectious complications. The surviving 10 patients are now fully recovered. The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low.
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http://dx.doi.org/10.3390/microorganisms8070977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409165PMC
June 2020

Development and validation of a combined enzymatic-digestion/mass spectrometry assay for Tacrolimus quantitation in cardiac biopsies.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Sep 21;1152:122215. Epub 2020 Jun 21.

Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address:

Recent studies report strategies for analysing immunosuppressive drugs in brain, liver and renal tissue, mostly in animals: we developed and validated a two steps combined enzymatic digestion/mass spectrometry assay to quantify Tacrolimus (TAC) in heart biopsies. Our aims were to avoid sample loss and sample contamination during the laboratory preparation, and to limit matrix effects in the electrospray ionization source (ESI) of the mass spectrometer. Enzymatic tissue digestion followed by a liquid-liquid drug extraction in the same vial of reaction allowed us to reach both our aims. The assay was assessed for selectivity, matrix effect, linearity, Lower Limit of Quantification (LLOQ) and Detection (LOD), accuracy and precision, according to the "Guideline on Bioanalytical Method Validation (EMA). A stable isotopically labelled (SIL) analogue (CD-TAC) was used as internal standard. The chromatographic separation of the analyte took 6 min. The observed linear range of quantification was 0.0162-0.520 ng in terms of TAC added to the biopsies (by 50 μL of the corresponding working solutions). The limit of detection and the lower limit of quantification (LLOQ) were 0.008 and 0.0162 ng, respectively. Both the mobile phases contained ammonium acetate and formic acid that promote the formation of ammoniated precursor ions that can be easily fragmented ([M + NH], TAC m/z 821.3; CD-TAC m/z 824.3). The calibration curves were generated by plotting analyte-to-internal standard peak area ratios versus TAC amount (ng) added to the biopsies, and using a weighted (1/x) linear regression. Curves were not forced to pass through the origin. Swine hearts were employed as blank matrix for all the analytical method validation procedures but, after approval by the ethics committee (by "Fondazione IRCCS Policlinico San Matteo": Protocol 20190032933), TAC was also quantified in endomyocardial biopsies from informed and consenting heart transplant patients. The study was funded by Fondazione IRCCS Policlinico San Matteo (RC08017617), as a part of the clinical studies on the maintenance of immunosuppressive therapy in cardiac transplant patients. Tacrolimus concentrations in patients biopsies were expressed as ratio between the detected amount of TAC (ng) in the tissue and the weight of the tissue itself (mg).
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http://dx.doi.org/10.1016/j.jchromb.2020.122215DOI Listing
September 2020

Myocardial localization of coronavirus in COVID-19 cardiogenic shock.

Eur J Heart Fail 2020 05 11;22(5):911-915. Epub 2020 Apr 11.

Transplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 69-year-old patient with flu-like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous-arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low-grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.
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http://dx.doi.org/10.1002/ejhf.1828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262276PMC
May 2020

Long-Term Effects of the Replacement of Calcineurin Inhibitors With Everolimus and Mycophenolate in Patients With Calcineurin Inhibitor-Related Nephrotoxicity.

Transplant Proc 2020 Apr 27;52(3):836-842. Epub 2020 Feb 27.

Division of Cardiology, Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Background: There is little evidence on the long-term effects of calcineurin inhibitor (CNI) withdrawal and substitution with everolimus and mycophenolate mofetil in maintenance therapy of patients who have received heart transplants and have concurrent CNI nephrotoxicity. Aims of this study were to evaluate the progression of renal dysfunction after discontinuation of CNIs and to monitor for major adverse events after therapy change.

Methods: Data from 41 patients who underwent heart transplant and have different degrees of renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m), without evidence of proteinuria, and in whom CNI therapy was replaced by everolimus, were analyzed. At the time of CNI withdrawal, clinical parameters, echocardiographic data, blood tests of renal function, and monitoring of adverse events were recorded. The median follow-up period was 5 years ± 28 months.

Results: In 52% of patients, there was a clear improvement in renal function (10.5 mL/min/1.73 m of extra eGFR on average). The former were characterized by less advanced age and a short time from the heart transplant. The echocardiographic parameters showed a significant reduction in septum thickness (11.58 ± 2 mm vs 10.29 ± 2 mm; P = .0001) and in left ventricle posterior wall thickness (10.74 ± 1 mm vs 9.74 ± 1 mm; P = .0004). The incidence of late acute rejection and cardiac allograft vasculopathy was similar in our population compared to literature data.

Conclusions: A therapeutic switch from CNIs to everolimus and mycophenolate mofetil can improve renal function in patients with CNI nephrotoxicity, especially in those with a shorter time period from transplantation, without exposing them to a higher incidence of late acute rejection and cardiac allograft vasculopathy.
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http://dx.doi.org/10.1016/j.transproceed.2020.01.030DOI Listing
April 2020

An experimental model of veno-venous arterial extracorporeal membrane oxygenation.

Int J Artif Organs 2020 Apr 6;43(4):268-276. Epub 2019 Nov 6.

UOC Anestesia e Rianimazione, IRCCS Policlinico San Matteo, Pavia, Italy.

Introduction: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure.

Aim: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump-driven circuit.

Methods: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels.

Results: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min.

Conclusion: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings.
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http://dx.doi.org/10.1177/0391398819882024DOI Listing
April 2020

Advanced native-kidney carcinoma in a heart- and kidney-transplanted patient: a case report.

CEN Case Rep 2018 May 31;7(1):132-136. Epub 2018 Jan 31.

Institute of Radiology, IRCCS Policlinico San Matteo, University of Pavia, Viale Golgi 19, 27100, Pavia, Italy.

Malignancies are one of the leading causes of death in long-term surviving transplant recipients. Dose and prolonged durations of immunosuppressive regimens are considered the main cause, through a direct oncogenic effect and a renowned interaction on physiological anti-viral and anti-oncogenic immune response. Specific neoplasms are known to occur with different frequencies according to the transplanted organ. As a consequence, imaging screenings have been implemented in many graft surveillance programs, although a wide consensus on the timing and modality has not been concurred. There are little data available in the literature regarding incidence of de-novo malignancies in multi-organ recipients. We report the case of a 66-year-old man who developed a renal mass 10 years after a combined heart-kidney transplant.
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http://dx.doi.org/10.1007/s13730-018-0310-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886941PMC
May 2018

Veno-venous ECMO during surgical repair of tracheal perforation: A case report.

Int J Surg Case Rep 2018 24;42:64-66. Epub 2017 Nov 24.

1st Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Introduction: Extracorporeal membrane oxygenation (ECMO) is used extensively in cardiothoracic surgery both for hemodynamic and respiratory support. It has proven to be a valuable tool to maintain adequate oxygenation during tracheal surgery. Airway lesion may be an indication for veno-venous ECMO both in case of conservative management and in case of surgical repair. Here we report the case of a patient with a iatrogenic tracheal injury, successfully operated with the support of veno-venous extracorporeal oxygenation.

Presentation Of Case: A 39-year-old female underwent an elective laparoscopic adhesiolysis. At the end of the procedure, the patient had developed subcutaneous emphysema. A CT-scan showed mediastinal and subcutaneous emphysema and left pneumothorax with a laceration of the membranous portion of the middle third of the trachea. A left pleural drain was inserted and a bronchoscopy showed a 2-cm long tear of the membranous portion in the middle third of the trachea. Veno-venous ECMO was established and surgical repair of the tracheal lesion was performed. Post-operative recovery was uneventful and the patient was discharged on 8th postoperative day.

Discussion: The use of Veno-venous ECMO allowed a safe intubation with optimal oxygenation. A selective intubation with a small tube was performed to prevent further tracheal injury and allow an adequate surgical space for tracheal repair.

Conclusion: The use of ECMO support represents a safe and effective way to manage patients with ITI when surgical repair with minimally invasive ventilation is needed. Since this is a case report larger studies are needed to validate the technique.
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http://dx.doi.org/10.1016/j.ijscr.2017.11.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734871PMC
November 2017

Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients: Results of the Prospective Randomized Study EVERHEART.

Transplantation 2018 03;102(3):493-501

Cardiac Surgery Unit, Hospital Molinette, Turin, Italy.

Background: Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization.

Methods: This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion, pleural effusion needing drainage, and renal insufficiency events (estimated glomerular filtration rate ≤30/mL/min per 1.73 m) in de novo HTx recipients receiving immediate everolimus (EVR-I) (≤144 hours post-HTx) or delayed everolimus (EVR-D) (4-6 weeks post-HTx with mycophenolate mofetil as a bridge) with reduced-dose cyclosporine A. Cumulative incidence of biopsy-proven rejection ≥ 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint.

Results: Overall, 181 patients were randomized to the EVR-I (n = 89) or EVR-D (n = 92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P = 0.191), mainly driven by a higher rate of pericardial effusion (33.7% vs 19.6%; P = 0.04); wound healing delays, acute renal insufficiency events, and pleural effusion occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm versus EVR-D arm (37.1% vs 28.3%; P = 0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm versus EVR-D arm (P = 0.02).

Conclusions: Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy.
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http://dx.doi.org/10.1097/TP.0000000000001945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828375PMC
March 2018

A case of veno-venous extracorporeal membrane oxygenation for severe respiratory failure in a superobese patient.

Clin Case Rep 2016 12 24;4(12):1147-1150. Epub 2016 Oct 24.

Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche Anaesthesiology of Università degli Studi di Pavia Pavia Italy; S.C. Anestesia e Rianimazione 2 Fondazione IRCCS Policlinico San Matteo Pavia Italy.

After risk assessment, veno-venous extracorporeal membrane oxygenation (ECMO) has been achieved in a superobese adult patient as a bridge to recovery of respiratory failure, despite the weight-related difficulties. Early v-v ECMO implantation could be considered to support and to conduct weaning both from sedation and from invasive mechanical ventilation, with the goal to perform physiokinesitherapy during awake ECMO.
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http://dx.doi.org/10.1002/ccr3.732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134152PMC
December 2016

Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics.

J Am Coll Cardiol 2016 09;68(10):1037-50

Center for Inherited Cardiovascular Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Foundation University Hospital Policlinico San Matteo, Pavia, Italy. Electronic address:

Background: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%.

Objectives: This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients.

Methods: In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations.

Results: Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively.

Conclusions: Screening probands with clinically suspected AFD significantly increased diagnostic yield. The heart was the organ most commonly involved, independent of the clinical setting in which the patient was first evaluated.
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http://dx.doi.org/10.1016/j.jacc.2016.05.090DOI Listing
September 2016

A brief clinical case of monitoring of oxygenator performance and patient-machine interdependency during prolonged veno-venous extracorporeal membrane oxygenation.

J Clin Monit Comput 2017 Oct 24;31(5):1027-1033. Epub 2016 Aug 24.

S.C. Anestesia e Rianimazione 2, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Monitoring veno-venous extracorporeal membrane oxygenation (vvECMO) during 76 days of continuous support in a 42-years old patient with end-stage pulmonary disease, listed for double-lung transplantation. Applying a new monitor (Landing, Eurosets, Medolla, Italy) and describing how measured and calculated parameters can be used to understand the variable interdependency between artificial membrane lung (ML) and patient native lung (NL). During vvECMO, in order to understand how the respiratory function is shared between ML and NL, ideally we should obtain data about oxygen transfer and CO removal, both by ML and NL. Measurements for NL can be made on the mechanical ventilator. Measurements for ML are typically made from gas analysis on blood samples drawn from the ECMO system before and after the oxygenator, and therefore are non-continuous. Differently, the Landing monitor provides a continuous measurement of the oxygen transfer from the ML, combined with hemoglobin level, saturation of drained blood and saturation of reinfused blood. Moreover, the Landing monitor provides hemodynamics data about circulation through the ECMO system, with blood flow, pre-oxygenator pressure and post-oxygenator pressure. Of note, measurements include the drain negative pressure, whose monitoring may be particularly useful to prevent hemolysis. Real-time monitoring of vvECMO provides data helpful to understand the complex picture of a patient with severely damaged lungs on one side and an artificial lung on the other side. Data from vvECMO monitoring may help to adapt the settings of both mechanical ventilator and vvECMO. Data about oxygen transfer by the oxygenator are important to evaluate the performance of the device and may help to avoid unnecessary replacements, thus reducing risks and costs.
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http://dx.doi.org/10.1007/s10877-016-9927-4DOI Listing
October 2017

Venoarterial Extracorporeal Membrane Oxygenation for Acute Fulminant Myocarditis in Adult Patients: A 5-Year Multi-Institutional Experience.

Ann Thorac Surg 2016 Mar 27;101(3):919-26. Epub 2015 Oct 27.

Cardiac Surgery Unit, Niguarda Hospital, Milan, Italy.

Background: Acute fulminant myocarditis (AFM) may represent a life-threatening event, characterized by rapidly progressive cardiac compromise that ultimately leads to refractory cardiogenic shock or cardiac arrest. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides effective cardiocirculatory support in this circumstance, but few clinical series are available about early and long-term results. Data from a multicenter study group are reported which analyzed subjects affected by AFM and treated with VA-ECMO during a 5-year period.

Method: From hospital databases, 57 patients with diagnoses of AFM treated with VA-ECMO in the past 5 years were found and analyzed. Mean age was 37.6 ± 11.8 years; 37 patients were women. At VA-ECMO implantation, cardiogenic shock was present in 38 patients, cardiac arrest in 12, and severe hemodynamic instability in 7. A peripheral approach was used with 47 patients, whereas 10 patients had a central implantation or other access.

Results: Mean VA-ECMO support was 9.9 ± 19 days (range, 2 to 24 days). Cardiac recovery with ECMO weaning was achieved in 43 patients (75.5%), major complications were observed in 40 patients (70.1%), and survival to hospital discharge occurred in 41 patients (71.9%). After hospital discharge (median follow-up, 15 months) there were 2 late deaths. The 5-year actual survival was 65.2% ± 7.9%, with recurrent self-recovering myocarditis observed in 2 patients (at 6 and 12 months from the first AFM event), and 1 heart transplantation.

Conclusions: Cardiopulmonary support with VA-ECMO provides an invaluable tool in the treatment of AFM, although major complications may characterize the hospital course. Long-term outcome appears favorable with rare episodes of recurrent myocarditis or cardiac-related events.
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http://dx.doi.org/10.1016/j.athoracsur.2015.08.014DOI Listing
March 2016

Endomyocardial Biopsy in acute cardiogenic shock: Diagnosis of pheochromocytoma.

Int J Cardiol 2016 Jan 9;202:897-9. Epub 2015 Oct 9.

Centre for Inherited Cardiovascular Diseases, Transplant Research Area. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2015.10.053DOI Listing
January 2016

Heart transplantation in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

J Heart Lung Transplant 2014 Aug 24;33(8):842-50. Epub 2014 Feb 24.

Department of Cardiovascular and Thoracic Surgery, Hôpital de la Pitié-Salpêtrière, APHP, Université Pierre-et-Marie-Curie, Paris, France.

Background: Heart involvement is the leading cause of death of patients with eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) and is more frequent in anti-neutrophil cytoplasm antibody (ANCA)-negative patients. Post-transplant outcome has only been reported once.

Methods: We conducted a retrospective international multicenter study. Patients satisfying the criteria of the American College of Rheumatology and/or revised Chapel Hill Consensus Conference Nomenclature were identified by collaborating vasculitis and transplant specialists, and the help of the Churg-Strauss Syndrome Association.

Results: Nine ANCA(-) patients who received transplants between October 1987 and December 2009 were identified. The vasculitis and cardiomyopathy diagnoses were concomitant for 5 patients and separated by 12 to 288 months for the remaining 4 patients. Despite ongoing immunosuppression, histologic examination of 7 (78%) patients' explanted hearts showed histologic patterns suggestive of active vasculitis. The overall 5-year survival rate was low (57%), but rose to 80% when considering only the 6 patients transplanted during the last decade. After survival lasting 3 to 60 months, 4 (44%) patients died sudden deaths.

Conclusions: The search for EGPA-related cardiomyopathy is mandatory early in the course of this type of vasculitis. Indeed, prompt treatment with corticosteroids and cyclophosphamide may achieve restore cardiac function. Most patients in this series were undertreated. For patients with refractory EGPA, heart transplantation should be performed, which carries a fair prognosis. No optimal immunosuppressive strategy has yet been identified.
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http://dx.doi.org/10.1016/j.healun.2014.02.023DOI Listing
August 2014

Long-term survival following surgery for endomyocardial fibrosis.

J Card Surg 2013 Nov 30;28(6):675-7. Epub 2013 Jun 30.

Department of Cardiac Surgery, Fondazione IRCCS Policlinico "San Matteo, ", Pavia, Italy.

We report a successful follow-up after 28 years of a woman with obliterative restrictive endomyocardial fibrosis (EMF) that underwent complete surgical decortication with simultaneous mitral and tricuspid bioprosthetic valve replacement in 1982 and underwent successful reoperation for the structural failure of biological prostheses after 25 years.
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http://dx.doi.org/10.1111/jocs.12159DOI Listing
November 2013

Kinetics of T-lymphocyte subsets and posttransplant opportunistic infections in heart and kidney transplant recipients.

Transplantation 2012 Jan;93(1):112-9

Virology and Microbiology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Background: The potential use of T-lymphocyte measurements as infection risk markers after solid organ transplant has not been fully investigated. We analyzed the kinetics of T-lymphocyte subsets within the first 8 months posttransplant and their correlation with opportunistic infections (OIs) in solid organ transplant recipients.

Methods: Serial measurement of CD4 and CD8 T cells was performed retrospectively in 48 heart transplant recipients (HTR) and 42 kidney transplant recipients (KTR). Generalized estimating equation models were used to analyze longitudinal data separately for HTR and KTR.

Results: An initial CD4 T-cell drop (at months 1 and 2, in HTR and KTR, respectively) coincided with the peak of OIs. HTR with a low nadir CD4 T-cell count (≤ 200/μL) showed poor CD4 T-cell recovery (175 ± 277 cells/μL at baseline vs 242 ± 99 cells/μL at month 8) and their CD8 T cells increased from 153 ± 194 cells/μL at baseline to 601 ± 399 cells/μL at month 8. KTR with a low nadir CD4 T-cell count (≤ 200/μL) showed a modest CD4 T-cell recovery (138 ± 46 cells/μL at baseline vs. 440 ± 448 cells/μL at month 8), and their CD8 T cells increased from 90 ± 41 cells/μL at baseline to 450 ± 242 cells/μL at month 8. HTR developing OIs had lower CD4 (P<0.001) and CD8 T cells (P=0.001) than those without infections, whereas in KTR the risk for OIs seemed restricted to patients with low CD8 T cells. HTR with OIs had a low CD4/CD8 T-cell ratio, whereas KTR had a high CD4/CD8 T-cell ratio.

Conclusions: Determination of T-lymphocyte subsets is a simple and effective parameter to identify patients at risk of developing OIs.
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http://dx.doi.org/10.1097/TP.0b013e318239e90cDOI Listing
January 2012

Long-term patency of saphenous vein patch plasty for left main coronary artery ostial disease.

J Card Surg 2011 Nov 27;26(6):629. Epub 2011 Sep 27.

Cardiac Surgery Unit, Istituto Clinico Humanitas IRCCS, Rozzano, Milano, Italy.

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http://dx.doi.org/10.1111/j.1540-8191.2011.01317.xDOI Listing
November 2011

Heart rate and cardiac allograft vasculopathy in heart transplant recipients.

J Heart Lung Transplant 2011 Dec 15;30(12):1368-73. Epub 2011 Aug 15.

Divisione di Cardiologia, Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Montescano, Montescano, (Pavia), Italy.

Background: Elevated heart rate (HR) has been indicated as risk factor for cardiovascular disease. Experimental data support a role of HR in the progression and severity of atherosclerotic lesions. Sinus tachycardia is common in heart transplant patients due to the lack of autonomic control. This study assessed the role of HR in the development of cardiac allograft vasculopathy (CAV) in heart transplant recipients.

Methods: Data from 244 allograft recipients were analyzed. Known factors affecting CAV and mean HR obtained from 24-hour recordings at 1 year (dichotomized at ≥90 beats/min) were tested in univariate and multivariable Cox analysis.

Results: During a median of 96 months, 60 patients (25%) experienced CAV. Surprisingly, HR < 90 but not ≥90 beats/min was significantly associated with an increased CAV development. Univariate analysis showed several predictors were associated with the end point; however, at multivariable analysis, only donor's age, chronic renal failure, and left ventricular end-diastolic wall thickness were significant predictors of CAV, with hazard ratios of 1.02 (95% confidence interval, 1.00-1.04), 1.90 (1.13-3.21), and 1.11 (1.00-1.22), respectively. A highly statistically significant difference in donor's age was found among patients with mean heart rate ≥90 or <90 beats/min (30 ± 13 vs 40 ± 14 years, p < 0.0001).

Conclusions: In the denervated heart, sinus tachycardia is not a risk factor for coronary atherosclerosis. HR in heart transplant recipients reflects "intrinsic heart rate" and is a simple epiphenomenon of the donor's age.
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http://dx.doi.org/10.1016/j.healun.2011.07.009DOI Listing
December 2011

Minimally invasive aortic valve replacement in a transplanted heart.

Ann Thorac Surg 2010 Nov;90(5):1688-90

Department of Cardiothoracic Surgery, Foundation IRCCS Policlinico S.Matteo, Pavia University School of Medicine, Pavia, Italy.

Heart transplantation is subject to a number of chronic complications that may limit graft survival and be detrimental to the patient's quality of life. Aortic valve stenosis is a rare complication found after cardiac transplantation, which we believe has never been described on a tricuspid normal aortic valve. In the present study, we report a case of successful aortic valve replacement performed 16 years after cardiac transplantation on an extensively calcified tricuspid valve. Surgery was performed by using a minimally invasive approach with a reverse T upper mini-sternotomy, and the aortic valve was replaced by a biological prosthesis. The postoperative course was uneventful and the patient was discharged 7 days after the operation.
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http://dx.doi.org/10.1016/j.athoracsur.2010.08.013DOI Listing
November 2010

Aortic valve replacement by ministernotomy in redo patients with previous left internal mammary artery patent grafts.

Ann Thorac Cardiovasc Surg 2010 Jun;16(3):181-6

University of Pavia, Pavia, Italy.

Objective: Aortic valve surgery with a patent left internal mammary artery (LIMA) on the left anterior descending (LAD) coronary artery is challenging in terms of myocardial protection and graft injury. Minimally invasive techniques may require minimal dissection of adhesions and may eventually decrease the risk of injuries.

Methods: Since 1997, more than 1000 ministernotomies have been performed by our surgical unit. Of these, 16 patients (14 males, 2 females, mean age: 68.7 years) had a patent LIMA graft on LAD. Fourteen underwent native aortic valve replacement, and in 2 a previously implanted prosthesis was replaced. A miniresternotomy was performed using either a "J" (15 patients) or a "reversed-T" method (1 patient).

Results: Cardiopulmonary bypass (CPB) was achieved by either femoral vein (12 patients) or right atrium (4 patients); arterial inflow was achieved either by ascending aorta (12 patients) or by femoral artery (4 patients). Mean CPB time was 119.7 ± 38.1 minutes (range: 50-235). Mean cooling body temperature was 27.4 °C. Antegrade cold crystalloid cardioplegia was delivered to all the patients. Mean aortic cross-clamp time was 72 ± 20 minutes (range: 45-125). No damage to LIMA occurred in any of the patients. No intra- or perioperative myocardial infarction (MI) occurred. Neither a conversion to full sternotomy nor a reoperation for bleeding was needed. Mean postoperative bleeding was 426 ± 474 ml (range: 120-1950). A blood transfusion was necessary in 7 patients. Mean postoperative ICU stay was 1.6 ± 1.1 days. Mean postoperative hospital stay was 7.5 ± 2.6 days. Postoperative course was totally uneventful in 10 patients (58.8%). Follow-up was complete for a total of 928 patient/months (range: 11-124), and there were four late deaths, two of which were related to cardiac problems. Nine of the 12 survivors are in NYHA CLASS I . II. Prosthesis-related morbidity did not occur either early or late during follow-up.

Conclusions: This experience may represent the feasibility of an alternative surgical approach to a standard full-length median sternotomy in patients with previous coronary revascularization and with a patent LIMA on the LAD, requiring new surgery on the aortic valve.
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June 2010

Port-access surgery as elective approach for mitral valve operation in re-do procedures.

Eur J Cardiothorac Surg 2010 Apr 25;37(4):920-5. Epub 2009 Nov 25.

Division of Cardiac Surgery, San Giovanni Battista Hospital "Molinette", University of Torino, 10126 Turin, Italy.

Background: Re-do mitral valve procedures performed through median sternotomy carry substantial mortality and morbidity. To avoid complications of sternal re-entry and to provide adequate mitral valve exposure, antero-lateral thoracotomy has been suggested by some authors.

Methods: From October 1997 to January 2007, 677 mitral valve operations have been performed in our centre using port-access video-assisted right mini-thoracotomy. Among these, 241 (35.6%) were performed on patients who had undergone one or more previous cardiac surgery procedures.

Results: Mean cardio-pulmonary bypass time and endo-clamp time were 117+/-46 min and 71+/-31 min, respectively. Arterial cannulation was performed either on the ascending aorta, with the endo-direct cannula (112 patients, 46.5%), or peripherally with a femoral artery approach (129 patients, 53.5%). Conversion to median sternotomy was necessary in only two patients (0.8%) due to aortic dissection (one case) and left ventricle free wall rupture (one case). Median intensive care unit stay was 24h, median mechanical ventilation time was 12h; median hospital stay was 8 days. Bleeding requiring surgical revision occurred in 12 patients (4.9%). Hospital mortality was 4.9% (12/241 patients).

Conclusions: Port-access video-assisted right mini-thoracotomy allows good results in a difficult subset of patients; it allows minimal adhesion dissection, short ICU and hospital stay. In our practice, this technique has become the treatment of choice for mitral valve re-do surgery.
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http://dx.doi.org/10.1016/j.ejcts.2009.10.011DOI Listing
April 2010

Two-year follow-up of the pharmacokinetics of immunosuppressive drugs in a neonate who underwent heart transplantation.

J Matern Fetal Neonatal Med 2009 ;22 Suppl 3:108-10

Unit of Clinical Pharmacokinetics, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

The pharmacokinetic properties of immunosuppressive drugs are quite different in newborns than in adults and few studies describe the pharmacokinetics of these drugs in pediatric heart transplant recipients. We report on the two-year follow up of a neonate who underwent heart transplantation for Hypoplastic Left Heart Syndrome on day of life 9. Two different immunosuppressive regimens were used: cyclosporine, azathioprine and prednisone in the early postoperative period, followed by the routine tacrolimus and mycophenolate mofetil combination plus prednisone from post-transplant day 22. Our findings demonstrate marked variability in immunosuppressive pharmacokinetic profiles early post-transplant. Frequent monitoring of drug levels is required to ensure that they remain within the therapeutic range. After the first 2-3 months post-transplant, changes in immunosuppressive drug levels are less marked and correlate more with the administered dosage.
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http://dx.doi.org/10.1080/14767050903181278DOI Listing
May 2010

Port-access minimally invasive surgery for atrial septal defects: a 10-year single-center experience in 166 patients.

J Thorac Cardiovasc Surg 2010 Jan 25;139(1):139-45. Epub 2009 Aug 25.

Cardiac Surgery Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Objective: We assessed the surgical results and the benefits to the patient of a minimally invasive surgical approach for atrial septal defects.

Methods: Between May 1998 and May 2008, 166 patients (median age, 44 years) had surgery for atrial septal defects in our institution. Of these patients, 118 (71%) had a patent foramen ovale (associated with atrial septal aneurysm in 48 cases), 33 (20%) had a wide ostium secundum defect, 6 (3.6%) had an ostium primum defect, 6 (3.6%) had a sinus venosus defect with abnormal pulmonary vein connection, and 1 (0.6%) had a coronary sinus defect. In 2 cases (1.2%) patients were referred to our department for surgical correction after failure of interventional occluder placement. All patients were operated on via a right minithoracotomy (mean incision, 5.5 + or - 1 cm) in the fourth intercostal space and under cardiopulmonary bypass.

Results: The HeartPort access system was used in 106 patients (64%), with an endoaortic clamp (central kit in 50 cases and peripheral kit in 56). In the remaining patients (36%), we preferred the Portaclamp system (37 cases) or the Chitwood clamp (23 cases). Average crossclamp time was 38.4 + or - 22.2 minutes with a mean cardiopulmonary bypass time of 64.9 + or - 34.5 minutes. There was no conversion in classic sternotomy. There were no early or late hospital deaths. Surgical revision was performed in 6 patients for bleeding from the thoracic wall. The mean hospital stay was 5.8 days. At 51 months mean follow-up, 4 patients died of non-cardiac-related causes.

Conclusions: Port-access minimally invasive surgery for atrial septal defects is a safe, less-invasive, reproducible, and cosmetic operation, providing an excellent outcome and an effective correction, and could be now considered the standard approach for this type of patient.
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http://dx.doi.org/10.1016/j.jtcvs.2009.07.022DOI Listing
January 2010

Should we perform heart retransplantation in early graft failure?

Transpl Int 2010 Jan 12;23(1):47-53. Epub 2009 Aug 12.

Department of Cardiac Surgery and Thoracic Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Cardiac retransplantation represents the gold standard treatment for a failing cardiac graft but the decision to offer the patient a second chance is often made difficult by both lack of donors and the ethical issues involved. The aim of this study was to evaluate whether retransplantation is a reasonable option in case of early graft failure. Between November 1985 and June 2008, 922 patients underwent cardiac transplantation at our Institution. Of these, 37 patients (4%) underwent cardiac retransplantation for cardiac failure resulting from early graft failure (n = 11) or late graft failure (acute rejection: n = 2, transplant-related coronary artery disease: n = 24). Survival at 1, 5 and 10 years of patients with retransplantation was 59%, 50% and 40% respectively. An interval between the first and the second transplantation of less than (n = 11, all in early graft failure) or more than (n = 26) 1 month was associated with a 1-year survival of 27% and 73%, and a 5-year survival of 27% and 65% respectively (P = 0.01). The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation only in patients with transplant-related coronary artery disease. Early graft failure is a significant risk factor for survival after cardiac retransplantation and should be considered as an exclusion criteria.
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http://dx.doi.org/10.1111/j.1432-2277.2009.00945.xDOI Listing
January 2010

Antibody cases.

Clin Transpl 2006 :483-8

Regenerative Medicine Department, Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena, Milan, Italy.

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May 2008

Minimally invasive video-assisted surgery for iatrogenic aortic root-to-right atrium fistula after incomplete percutaneous occlusion of patent foramen ovale: case report and review of the literature.

J Card Surg 2008 Jan-Feb;23(1):75-8

Department of Cardiac Surgery, University of Pavia, Pavia, Italy.

Background: The foramen ovale remains patent in about 25% of the population. Paradoxical embolism through a patent foramen ovale (PFO) may produce ischemic events. The closure of a PFO may prevent recurrence of cerebrovascular events. Percutaneous closure of a PFO is now-a-days a standard procedure and it appears to carry a low rate of complications. A surgical approach, in some cases, may be needed.

Methods: A patient underwent percutaneous closure of PFO. There was a residual shunt after the procedure and a fistula between the aortic root-to-right atrium was subsequently discovered. Surgery was carried out using a "Port-Access technique" through a right anterior minithoracotomy.

Results: Postoperative course was uneventful. Complete obliteration of the fistula was achieved.

Conclusion: Minimally invasive surgery may be effective to treat PFO or even complications after previous percutaneous attempts of closure. An aesthetically acceptable conclusion, especially in young female patients, and a very low rate of morbidity may be accomplished.
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http://dx.doi.org/10.1111/j.1540-8191.2007.00483.xDOI Listing
July 2008

Arrow CorAide left ventricular assist system: initial experience of the cardio-thoracic surgery center in Pavia.

Ann Thorac Surg 2007 Jan;83(1):279-82

Department of Cardiac Surgery, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Purpose: The aim of the present study is to describe our preliminary experience with the Arrow CorAide left ventricular assist system (LVAS).

Description: The Arrow CorAide LVAS is a small implantable, continuous flow centrifugal pump, with a fully suspended rotating assembly, intended as a bridge to transplant device, bridge to recovery, and for long-term use.

Evaluation: Since April 2005 we have implanted the CorAide LVAS in 2 male patients, with a patient follow-up of more than 6 months. Surgical procedures were uneventful, and both patients had an uneventful postoperative course, with fast weaning from mechanical ventilation and inotropic support. No thromboembolic events, infective complication, hemolysis, or mechanical failure occurred. To date, both patients are in New York Heart Association class I.

Conclusions: In our initial experience the CorAide LVAS blood pump is nonthrombogenic, nonhemolytic, and easy to implant. Both patients have improved their functional status. Further follow-up is needed to assess long-term results.
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http://dx.doi.org/10.1016/j.athoracsur.2006.05.026DOI Listing
January 2007

Diagnostic imaging of lung cancer after heart transplantation.

Tumori 2006 Sep-Oct;92(5):429-32

Department of Radiology, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.

Aims And Background: In heart transplant recipients pulmonary neoplasms are among the most frequent solid tumors; they have a rapid and aggressive course, and therefore require an early diagnosis. We describe the role that diagnostic imaging plays in different diagnostic moments of this disease.

Methods: We evaluated the incidence and diagnosis of lung cancer in patients who underwent heart transplants at our institution. Taking into account the few different diagnostic imaging techniques (chest X-ray, high-resolution computed tomography [CT], staging CT and CT-guided biopsy) used in standard surveillance protocols or indicated by clinical symptoms, we evaluated their diagnostic accuracy, their efficacy in tumor staging, and their impact on the therapeutic choices.

Results: Seventeen neoplasms in a total of 712 patients were diagnosed (2.4%). In 16 of these 17 cases chest X-ray (routinely performed as follow-up in 11 cases, indicated by symptoms in 5 cases) was diagnostic. In another 11 cases chest X-ray was false positive. The diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of chest X-ray was 98%, 91%, 98%, 50%, and 99%, respectively. Total-body CT correctly staged the tumors and provided information as to whether surgery was indicated or not (stage II or advanced).

Conclusions: Chest X-ray is still the surveillance radiological technique in heart transplant recipients. Considering its low specificity and sensitivity, we propose high-resolution CT imaging during follow-up to identify pulmonary lesions as soon as possible and enable a differential diagnosis with parenchymal inflammation. The use of CT-guided fine-needle biopsy and culture examinations permits to differentiate neoplastic from inflammatory parenchymal opacities. Use of CT in cancer staging is effective for subsequent treatment choices.
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December 2006