Spotlight: Gino Gerosa, MD.
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Cardiology↗
Biomedical subjects
Gino Gerosa
Publications and source records attributed to Gino Gerosa.
An alternative technique for aortic root remodeling in patients with bicuspid aortic valve.
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Adult↗
Early and long-term prognostic value of Troponin-I after cardiac surgery in newborns and children.
BACKGROUND: Troponin-I (Tn-I) is a well-recognized early postoperative marker for myocardial damage in adults and children. The present prospective study was undertaken to investigate whether a postoperative Tn-I value higher than 35 microg/l is able to predict long-term outcome as it does in early postoperative course, after surgery for congenital heart defects (CHD). MATERIALS AND METHODS: Five hundred and twenty patients (median age 11 months; male 54.7%: 284 patients) undergoing congenital heart defect repair on cardiopulmonary by-pass were prospectively updated in our database including postoperative Tn-I values. Seventy of them (13.4%) (mean age 2.6+/-5.8 months) (70/520) experienced low output syndrome in the early postoperative period. According to the complexity of their malformations, we have arbitrarily divided these patients into two groups: group A included atrial and ventricular septal defects (13 patients), while group B included hypoplastic left heart syndrome, atrio-ventricular canal, transposition of great vessels, tetralogy of Fallot, double outlet right ventricle, truncus arteriosus, total anomalous venous return, and other combined diseases (57 patients). These patients are the object of our study. We reviewed clinical, laboratory, and echocardiographic data performed in the immediate postoperative course (within 24 h) and in the follow-up. RESULTS: In this study, 13 patients died (13/70 patients; 18.5%), 12 in group B and 1 in group A. In deceased patients, mean Tn-I value was 130+/-175 microg/l (CK-MB 570+/-280 microg/l). Conversely, survivors showed a lower mean Tn-I value (25.5+/-28.9 microg/l; CK-MB 76+/-86 microg/l). Overall, Tn-I peak value was higher than 35 microg/l in 19 patients (19/70; 27.2%); among these, 9 died (median Tn-I was 163+/-186 microg/l), whereas in survivors it was 73.4+/-37 microg/l (p=0.37). The remaining four patients who died had a median Tn-I value of 21 microg/l. When Tn-I exceeded 35 microg/l (>100 microg/l in two cases), at echocardiogram a severely depressed cardiac function was evident. Nevertheless, at long-term follow-up (12+/-6 months), the echocardiogram showed an enhanced cardiac performance with an ejection fraction of 70+/-8.5% in all; none of these patients presented with worsened ventricular function. CONCLUSION: Cardiac Tn-I is a specific and sensitive marker of myocardial injury after cardiac surgery and it may predict early in-hospital outcomes. However, by long-term echocardiographic analysis, cardiac Tn-I value looses its prognostic significance and therefore it is not a predictor of long-term ventricular dysfunction.
Adolescent↗
Coronary flow velocity pattern and coronary flow reserve by contrast-enhanced transthoracic echocardiography predict long-term outcome in heart transplantation.
BACKGROUND: We assessed coronary flow velocity pattern and coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) as markers of major adverse cardiac events (MACE) related to cardiac allograft vasculopathy (CAV) after heart transplantation (HT). METHODS AND RESULTS: Deceleration time of diastolic flow velocity (DDT) and CFR were measured in the left anterior descending coronary artery (LAD) by CE-TTE in 66 consecutive HT patients (follow-up 19+/-5 months). CFR was calculated as the ratio of hyperemic to basal diastolic flow velocity. Angiographies were analyzed by a qualitative grading system; CAV was defined as changes grade II or higher. MACE were cardiac death, stent implantation, and heart failure. Patients with MACE had higher CAV incidence (P=0.004) and grade (P=0.008), shorter DDT (P=0.006), and lower CFR (P=0.008). A receiver-operating characteristic-derived DDT cutpoint < or = 840 ms (area under the curve 0.793; P=0.01) was 75% specific and 86% sensitive for predicting MACE, with positive predictive value (PPV) and negative predictive value (NPV) of 33% and 97%, respectively (P=0.002). A CFR cutpoint of < or =2.6 (area under the curve 0.746; P=0.01) was 62% specific and 91% sensitive for predicting MACE (PPV =32%, NPV =97%) (P=0.001). Patients with CFR < or = 2.6 and patients with DDT < or = 840 ms had a lower survival free from MACE (P=0.006 and P=0.009, respectively). By Cox regression, only a lower CFR predicted the risk of MACE (relative risk 3.1; 95% CI, 1.26 to 7.9; P=0.01). CONCLUSIONS: In HT patients, shorter DDT and lower CFR by CE-TTE are reliable markers for CAV-related MACE. CFR is the main independent predictor of MACE.
Adolescent↗
Similar efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS, myfortic) compared with mycophenolate mofetil (MMF) in de novo heart transplant recipients: results of a 12-month, single-blind, randomized, parallel-group, multicenter study.
BACKGROUND: Enteric-coated mycophenolate sodium (EC-MPS, myfortic) is an advanced formulation that delays the release of mycophenolic acid (MPA). Its efficacy and safety has been proven in several clinical trials in renal transplantation. METHODS: In a single-blind, multicenter trial, a total of 154 de novo heart transplant patients were randomized to either EC-MPS 1,080 mg twice daily or mycophenolate mofetil (MMF) 1,500 mg twice daily. Eligible patients included men or women aged 18 to 65 years, undergoing primary heart transplantation, who were treated with cyclosporine microemulsion and corticosteroids as basic immunosuppression. The primary study objective was to investigate the incidence of biopsy-proven and treated acute rejection, graft loss or death (defined as treatment failure) for EC-MPS vs MMF during the first 6 months of treatment in de novo heart transplant recipients. Secondary objectives included assessment of the overall safety and tolerability of EC-MPS vs MMF in the study population. RESULTS: The primary efficacy variable, treatment failure at 6 months, was similar for both treatments: 52.6% for EC-MPS and 57.9% for MMF (2-sided 95% confidence interval [CI]: -21.0% to 10.4%). At 12 months, treatment failure was 57.7% for EC-MPS and 60.5% for MMF (2-sided 95% CI: -18.4 to 12.7), and death and graft loss rate was 5.1% vs 9.2% for EC-MPS and MMF at 12 months, respectively (2-sided 95% CI: -12.2 to 4.1). The overall safety profile was similar for both groups. Significantly more patients on MMF had two or more study medication dose reductions during the treatment period. CONCLUSIONS: These 6- and 12-month results show that EC-MPS is therapeutically similar to MMF in de novo heart transplant recipients and has a comparable safety profile.
Adolescent↗
How to deal with recipients of valves prone to structural failure in the 2000s: Padua experience with the TRI Technologies valve.
BACKGROUND: TRI Technologies (TT) valves evidenced a propensity to structural failure, consisting in fracture of the pivoting system, leading to leaflet escape. At our institution, between 2000 and 2002, 36 TT valves were implanted in 34 patients. Here we report the final results of the Tritech survey program. METHODS: In February 2002, the first valve-related death occurred. After the event, patients were enrolled in the TT valve survey program and strictly followed up. The option of a reintervention was advised to each patient and weighed against the redo operative risk. The prophylactic TT valve replacement program took place in two time frames, dependent on each patient's personal choice: between September 2002 and October 2003 (first phase), and between September 2004 and October 2004 (second phase). Overall, 22 (10 women, 12 men) patients underwent reoperation. Mean time interval between TT valve implantation and replacement was 23 +/- 11 months. Patients' mean age was 59 +/- 11 years (median age, 64 years). RESULTS: All recipients adhering to the program successfully underwent reoperation. Operative mortality was 0%. CONCLUSIONS: We believe that the timing of the second surgery was fundamental for the favorable outcome of each patient and the absence of operative mortality. We are convinced that the tailored programming of the reintervention, together with the strong motivation of each patient, contributed in minimizing the risks related to surgery. The circumscribed cohort of patients involved was compatible with a tailored therapeutic plan. We strongly advise prophylactic reoperation of recipients of TT valves.
Aged↗
Inappropriate surgical technique or prosthesis malfunctioning?
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Aortic Valve↗
Small aortic annulus: the hydrodynamic performances of 5 commercially available tissue valves.
BACKGROUND: In vivo comparison of the performance of heart valve prostheses is confounded by several factors, such as different nominal size, patients' characteristics and hemodynamics, surgical techniques, and study design. The aim of this study was to compare the in vitro hydrodynamic performances of 5 different tissue valves that would fit a 21-mm-diameter valve holder of the Sheffield pulse duplicator. METHODS: Three samples of 5 supra-annular production-quality tissue valves, including the sewing ring cuffs, were tested in the aortic chamber of the Sheffield pulse duplicator. The prostheses fitting a 21-mm valve holder, which is comparable with a 21-mm aortic annulus, were as follows: 20-mm Sorin Soprano, 21-mm Carpentier-Edwards Magna, 21-mm SJM-Biocor-Epic-Supra, 21-mm Medtronic Mosaic, and 23-mm Mitroflow. The tests were carried out at a fixed pulse rate (70 beats/min) and at increasing cardiac outputs of 2, 4, 5, and 7 L/min. Each valve was tested 10 times for each different cardiac output. This resulted in a total of 40 tests for each valve and 120 tests for each valve model. Forward flow pressure decrease, effective orifice area, stroke work loss, and total regurgitant, closing, and leakage volumes were recorded while the valve operated under each cardiac output. RESULTS: Pericardial valves showed significantly lower transvalvular gradients than porcine valves, unlike the SJM-Biocor-Epic-Supra valve at 2 L/min of cardiac output. Although the Carpentier-Edwards Magna valve provided the best performance at 2 and 4 L/min, the Mitroflow valve exhibited the lowest mean and peak gradients at 5 to 7 L/min. Total regurgitant and leakage volumes were higher for the Carpentier-Edwards Magna valve and lower for the SJM-Biocor-Epic-Supra and Mitroflow valves. Between 2 and 4 L/min, the calculated effective orifice area and stroke work loss were better for the Carpentier-Edwards Magna valve, whereas between 5 and 7 L/min, they were significantly superior with the Mitroflow prosthesis. Among the porcine bioprostheses, the SJM-Biocor-Epic-Supra valve showed significantly better results when compared with the Medtronic Mosaic valve at each cardiac output. CONCLUSION: Assuming that the valve holder is comparable with a defined aortic annulus of 21 mm in which a spread of supra-annular tissue valves could be fitted, this hydrodynamic evaluation model allows comparison of the efficiency of currently available bioprostheses with a definite tissue annulus diameter. Pericardial valves exhibited the best performances, and the Mitroflow valve showed the lowest gradients and stroke work loss at increasing cardiac output.
Aortic Valve↗
Early antithrombotic therapy after aortic valve replacement with tissue valves: when the practice diverges from the guidelines.
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Aortic Valve↗
Clinical results of Hancock II versus Hancock Standard at long-term follow-up.
OBJECTIVE: We performed a multi-institutional study to compare the long-term structural valve deterioration of isolated Hancock Standard versus Hancock II bioprostheses. METHODS: From 1983 to 2002, 714 Hancock Standard and 1293 Hancock II bioprostheses were implanted at hospitals of the Venetian territory (Padova, Treviso, and Venice). Follow-up on January 1, 2003, included 14,749 patient-years with a median of 12 years and was 96% complete: 115 Hancock Standard and 53 Hancock II bioprostheses were at risk at 15 years. The 2 series were nonconcomitant, and many covariates differed (Table 1). Survival was analyzed with Cox analysis, and durability was analyzed with Weibull analysis. Balancing analysis with the logistic propensity score model was performed. RESULTS: Perioperative mortality was 6% in Hancock II and 12% in Hancock Standard operations. The overall unadjusted 15-year survival was identical (39.7% +/- 2.3% vs 39.9% +/- 2.4%, respectively), but age-adjusted survival at 15 years was 46% versus 25% (P < .001). Late survival was unrelated to the prosthetic model, whereas it was adversely affected by older age, previous operations, aortic regurgitation, male sex, higher New York Heart Association class, atrial fibrillation, and coronary artery bypass grafting. In Hancock II patients aged 65 years and older, the cumulative hazard of structural valve deterioration at 15 years was 6%, versus 17.5% in Hancock Standard patients. In younger patients, it was 18% and 37%, respectively. Analysis of 541 propensity-balanced patients showed a hazard ratio of the Hancock Standard prosthesis of 2 and a risk reduction of older age of approximately 10% every 10 years. CONCLUSION: After balancing risk factors and calibrating age effects, Hancock II propensity-matched bioprostheses showed similar survival but definitely increased durability.
Adult↗
Fifteen-year results with the Hancock II valve: a multicenter experience.
OBJECTIVES: The purpose of this multi-institutional study was to review the 15-year outcome of patients who received isolated aortic or mitral valve replacement with the Hancock II bioprosthesis. METHODS: From 1983 through 2002, 1274 patients underwent 1293 isolated valve replacements, 809 aortic valve replacements and 484 mitral valve replacements, at hospitals in the Venetian area (Padova, Treviso, and Venice). Mean age was 68 +/- 8 years in patients undergoing aortic valve replacement and 66 +/- 9 years in patients undergoing mitral valve replacement; 52% of patients undergoing aortic valve replacement and 63% of patients undergoing mitral valve replacement were in New York Heart Association class III or greater. Coronary artery disease was present in 32% of patients who had undergone aortic valve replacement and 18% of patients who had undergone mitral valve replacement. Follow-up included 8520 patient-years, with a median of 12 years, and was 97% complete. RESULTS: Overall 15-year survival was 39.7% +/- 2.4%, similar in both the aortic and mitral positions. Multivariable analysis of late survival showed the incremental risk of male sex, higher New York Heart Association class, coronary artery disease, and mitral position. Freedom from embolism was higher in the aortic position (81% +/- 2.9% in aortic vs 72% +/- 4.7% in mitral valve replacements). Freedom from endocarditis was similar in the aortic and mitral position (95% +/- 1.2% vs 94% +/- 1.7%). Freedom from reoperation (82% +/- 3.7% vs 71% +/- 5.0%) and from valve-related morbidity-mortality (52% +/- 3.6% vs 36% +/- 4.4%) was higher in patients who had undergone AVR. Actual freedom from structural valve deterioration for patients 60 years and older who had undergone aortic valve replacement was 96.5% +/- 1.3% versus 88% +/- 3.2% for patients who had undergone mitral valve replacement and 70% +/- 7.5% versus 77.5% +/- 5.3%, respectively, in younger patients. Multivariable Weibull analysis showed structural valve deterioration related to younger age and preoperative valve incompetence and inversely related to coronary artery disease. CONCLUSION: Optimal 15-year durability can be expected in male patients 60 years and older who have undergone aortic valve replacement and in male patients 65 years and older who have undergone mitral valve replacement, extending safely the age limits for the use of this valve.
Aged↗
Commissural dehiscence: a rare and peculiar cause of porcine valve structural deterioration.
OBJECTIVE: Calcification is the main cause of structural valve deterioration; however, other causes of failure have been identified, and among them, dehiscence of a commissure from the stent has been reported in several models of porcine valves. The aim of this study was to analyze the rate and mode of occurrence of this complication in first- and second-generation porcine bioprosthetic explants. METHODS: Among 586 porcine xenografts explanted and analyzed at the Institute of Pathological Anatomy of the University of Padua, 17 (2.9%) have been replaced for incompetence because of commissural dehiscence. All these explants were in the mitral position, with the exception of a Carpentier-Edwards supra-annular aortic valve prosthesis. RESULTS: Dehiscence was observed in 9 (1.9%) of 455 Hancock standard explants, in 1 (3.2%) of 31 Hancock II, in 3 (8.6%, 2 standard and 1 supra-annular) of 35 Carpentier-Edwards, in 1 (2.4%) of 42 Bioimplants, and in 3 (50%) of 6 Xenotech after a mean time function of 157 +/- 50, 156, 96 +/- 29, 143, and 130 +/- 8 months, respectively. Dehiscence was the sole cause of incompetence in 6 cases. An impending commissural dehiscence caused by blood creeping was observed in one case. This might be an explanation for the dehiscence other than excessive trimming of the aortic wall. CONCLUSIONS: Commissural dehiscence is an uncommon and peculiar mode of failure of porcine valves implanted in the mitral position and was observed earlier and more frequently with Carpentier-Edwards porcine explants (P < .05). We speculate that pericardial strip protection of the suture between the Dacron fabric and porcine aortic wall, as used in the Biocor porcine valve, might prevent this complication.
Aged↗
Differential availability/processing of decorin precursor in arterial and venous smooth muscle cells.
The existence of specific differentiation markers for arterial smooth muscle (SM) cells is still a matter of debate. A clone named MM1 was isolated from a library of monoclonal antibodies to adult porcine aorta, which in vivo binds to arterial but not venous SM cells, except for the pulmonary vein. MM1 immunoreactivity in Western blotting involved bands in the range of M(r) 33-226 kDa, in both arterial and venous SM tissues. However, immunoprecipitation experiments revealed that MM1 bound to a 100-kDa polypeptide that was present only in the arterial SM extract. By mass spectrometry analysis of tryptic digests from MM1-positive 130- and 120-kDa polypeptides of aorta SM extract, the antigen recognized by the antibody was identified as a decorin precursor. Using a crude decorin preparation from this tissue MM1 reacted strongly with the 33-kDa polypeptide and this pattern did not change after chondroitinase ABC treatment. In vitro, decorin immunoreactivity was found in secreted grainy material produced by confluent arterial SM cells, although lesser amounts were also seen in venous SM cells. Western blotting of extracts from these cultures showed the presence of the 33-kDa band but not of the high-molecular-weight components, except for the 100-kDa monomer. The 100/33-kDa combination was more abundant in arterial SM cells than in the venous counterpart. In the early phase of neointima formation, induced by endothelial injury of the carotid artery or vein-to-artery transposition, the decorin precursor was not expressed, but it was up-regulated in the SM cells of the media underlying the neointima in both models. Collectively, these data suggest a different processing/utilization of the 100-kDa monomer of proteoglycan decorin in arterial and venous SM cells, which is abolished after vein injury.
Animals↗
Identification and localization of adrenomedullin-storing cardiac mast cells.
Adrenomedullin (AM), a potent vasodilatory hypotensive peptide, is expressed in the heart, where it is known to play a protective action. Light-microscopy immunocytochemistry (ICC) demonstrated the presence of AM immunoreactivity not only in the coronary-vessel wall and ventricular myocytes of the human and rat heart, but also in sparse voluminous cells located in the perivascular space. These cells displayed the same location of toluidine blue-positive mast cells, and electron microscopy ICC showed AM-immunogold staining over the granules of rat cardiac mast cells. The incubation of rat left ventricle fragments with the mast-cell histamine releaser compound 48/80 evidenced groups of AM-positive cells undergoing degranulation and caused an increase of approximately 50% in the AM concentration in the incubation medium. Collectively, our findings provide evidence that at least a subset of cardiac mast cells are able to synthesize and store AM, and upon stimulation to release it near coronary arterioles and venules.
Adrenomedullin↗
Prolonged durability of a Kay-Shiley mechanical valve prosthesis.
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Adult↗
Moray mouth heart.
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Abnormalities, Multiple↗
Amniotic mesenchymal cells autotransplanted in a porcine model of cardiac ischemia do not differentiate to cardiogenic phenotypes.
OBJECTIVE: Transplantation of stem cells in the acute ischemic myocardium (AMI) may play a role in the recovery of cardiac function. Here, we investigated the ability of amniotic fluid-derived mesenchymal cells (AFC) for phenotypic conversion to vascular cells and cardiomyocytes (CM) when autotransplanted in a porcine model of AMI. METHODS: Single AFC preparations were taken from 12 fetuses 3 days before normal delivery. AFC were expanded in vitro and stored separately until animals of the original litter weighed 22-25 kg. A new model of AMI, i.e. 45-min circumflex coronary occlusion followed by wall dissection, was used to assess AFC differentiation potential. CMFDA-labeled AFC were autogenically transplanted in the ischemic area 1 week after AMI induction. Thirty days later, pigs were sacrificed and the phenotypic profile of transplanted AFC was assessed and compared to the corresponding pre-injection pattern. RESULTS: AFC showed in vitro to be of mesenchymal type also expressing markers of 'embryonic stem' cells (SSEA4 and Oct-4), as well as endothelial (von Willebrand factor, VE-cadherin) and smooth muscle (SM alpha-actin, SM22) cells. Thirty days after transplantation, in the survived AFC (5+/-1%) 'embryonic stem' cell markers disappeared and mesenchymal cell markers were down regulated with the exception of smooth muscle and endothelial antigens. No evidence for expression of cardiac troponin I was found. CONCLUSIONS: In the conditions used in this study, AFC were able to transdifferentiate to cells of vascular cell lineages but not to CM. Thus, porcine AFC may require further ex vivo re-programming to be suitable for therapeutic use in AMI.
Amniotic Fluid↗
Moderate-to-severe ischemic mitral regurgitation and multivessel coronary artery disease: Impact of different treatment on survival and rehospitalization.
BACKGROUND: The outcome of moderate-to-severe ischemic mitral regurgitation with multivessel coronary artery disease is still debated. We analysed the effect of different treatments, i.e. medical therapy (MT), coronary artery by-pass grafting (CABG) alone and CABG with mitral valve surgery (MVS), on the survival and rehospitalization of these patients. METHODS: Between 1990 and 2002, we identified 111 consecutive patients, aged 73+/-8 years, with chronic moderate-to-severe mitral regurgitation and multivessel coronary artery disease at cardiac catheterization, in absence of primary valve disease. Twenty-two patients were treated by MT, 50 by CABG and 39 by CABG+MVS. Overall, the median clinical and echocardiographic follow-ups were 34.9 and 14.6 months, respectively. RESULTS: Groups differed significantly (p < 0.03) for left ventricular end-diastolic volume index (MT 153+/-54, CABG 125+/-35, CABG + MVS 129+/-38, ml/m2), ejection fraction (MT 35+/-14, CABG 38+/-13, CABG + MVS 50+/-14, %) and mammary artery graft use (CABG 60, CABG + MVS 74, %). While in-hospital mortality was higher in surgical patients (MT 13.6, CABG 18, CABG + MVS 17.9, %, p=0.09), 7-years mortality showed a trend in favour of CABG + MVS compared to other groups (MT 100, CABG 57, CABG + MVS 29, %, p = 0.1). After adjusting for baseline differences, CABG alone or with MVS had a 57% (HR 0.43, p = 0.005) and 53% (HR 0.47, p = 0.02) risk reduction of combined cardiac death and rehospitalization rate compared to MT. However, only CABG + MVS independently predicted mortality (risk reduction 65%, HR 0.35, p = 0.027). CONCLUSIONS: In moderate-to-severe ischemic mitral regurgitation and multivessel coronary artery disease, surgery reduced total cardiac events but only a concomitant MVS significantly improved survival.
Aged↗