Objectives: Age-related degenerative heart-valve disease is a health issue in the present era. Octogenarians are frequently affected by concomitant diseases and, with the present lack of resources, the risk/benefit of valvular replacement therapy poses serious medical, economical and political challenge. We analysed the long-term survival of 346 octogenarians who underwent 352 operations between 1 January 1987 and 1 January 2009 and we compared it with the survival of the general population, matched for age, sex and operative year. Methods: The total follow-up was of 1352 years, maximum 15.7 years and was nearly complete except for a single foreigner. Heart diseases, concomitant pathologies, complications and actuarial survival of this study group were compared with 4649 younger counterparts, who received 5416 operations during the same time frame. Octogenarians were sorted by age, sex and operative year and the expected survival was calculated by applying US survival rate and added to the Kaplan-Meier plot for visual comparison. Results: A total of 279 aortic, 38 mitral and 35 mitro-aortic valves were replaced or repaired using 357 bioprostheses, 18 mechanical prostheses, 12 reparative operations and 24 re-operations. A total of 75% of patients were younger than 84 years, 95% were younger than 87 years and 99% younger than 90 years. Sex prevalence was 215 female versus 131 male. Operative (30 days) mortality was 5.5% and overall survival was 84.3% at 1 year, 65.4% at 5 years, 27.3% at 10 years and 5.4% at 15 years. The expected survival of the age-, sex-, operative year-matched population was 26.9% at 10 years and 7.9% at 15 years. Female operative mortality was 5.9% and survival was respectively 86.3%, 70.2%, 27.5% and 9.1%, male mortality was 4.5% and survival was respectively 81%, 56.7%, 28.8% and 0%(p=0.16). Expected female survival was 30% at 10 years and 10% at 15 years versus 22% and 5.6%, respectively, in males. Six octogenarians underwent re-operation, with one death. Conclusions: Despite the highest prevalence of concomitant diseases and the requirement of additional resources for the detection and neutralisation of risk factors, heart-valve operations in octogenarians offer excellent results that compare favourably with the expected survival of the age-, sex- and operative year-matched population, particularly after primary operations.

Bileaflet mechanical heart valves, which exhibit hemodynamic performance fairly similar to that of native valves, can be investigated by the analysis of their closing sounds. Signal spectra calculated from the closing sounds are characterized by specific features that are suitable for the functional evaluation of the valves. Five commercial bileaflet mechanical heart valves were studied under different conditions that were simulated in vitro using a Sheffield pulse duplicator for the aortic position. The closing sounds were acquired by means of a phonocardiographic apparatus, analyzed by a specifically implemented algorithm, and were statistically compared. This article was aimed at classifying the investigated valves on the basis of their signal spectra: different profiles were identified, depending on the working conditions; moreover, closing sound reproducibility and intensity allowed the ranking of valve performances with respect to the "noise" produced by valve closure. In particular, results demonstrated which valves were characterized by the lowest noise (i.e., the Medtronic Advantage and St. Jude Regent valves) and which were characterized by the highest reproducibility (OnX, Medtronic Advantage, and St. Jude Regent valves) under the examined experimental conditions.

OBJECTIVES: Our aim was to assess the safety and feasibility of the retrograde trans-subclavian approach to transcatheter aortic valve implantation (TAVI) in selected high-risk patients with aortic stenosis (AS) and severe peripheral vasculopathy. BACKGROUND: TAVI is an emerging therapeutic option to treat inoperable/high-risk patients affected by symptomatic AS. However, these patients are also often affected by severe iliac-femoral arteriopathy, rendering the transfemoral approach unemployable for percutaneous revalving procedure. METHODS: From among those patients in our department between May 2007 and December 2008, who were refused surgical aortic valve replacement because of high surgical risk and were ineligible for transfemoral percutaneous aortic valve replacement, we scheduled 3 for TAVI by the subclavian approach. Procedures were performed by a combined team of cardiologists, cardiac surgeons, and anesthetists in the catheterization laboratory. The III generation CoreValve Revalving System (CoreValve Inc., Irvine, California) with an 18-F delivery system was introduced in all cases by the left subclavian artery. RESULTS: Prosthetic valves were successfully implanted in all 3 cases, leading to a fall in transvalvular gradient without significant paravalvular regurgitation. No intraprocedural or periprocedural complications occurred. Two patients developed an atrioventricular block requiring the implantation of a permanent pacemaker. All patients were discharged in asymptomatic status, with good prosthesis performance. No adverse events occurred within the 3-month follow-up. CONCLUSIONS: TAVI by subclavian retrograde approach seems safe and feasible in inoperable/high-risk patients with AS and peripheral vasculopathy, who are neither eligible for surgical valve replacement nor transfemoral percutaneous aortic valve implantation. Further studies are needed to evaluate the long-term efficacy of this new therapy.

BACKGROUND.: Pharmacokinetic modeling supports trough monitoring of everolimus, but prospective data comparing this approach versus mycophenolate mofetil (MMF) in de novo cardiac transplant recipients are currently unavailable. METHODS.: In a 12-month multicenter open-label study, cardiac transplant patients received everolimus (trough level 3-8 ng/mL) with reduced cyclosporine A (CsA) or MMF (3 g/day) with standard CsA, both with corticosteroids+/-induction therapy. RESULTS.: In total, 176 patients were randomized (everolimus 92, MMF 84). Mean creatinine clearance was 72.5+/-27.9 and 76.8+/-32.1 mL/min at baseline, 65.4+/-24.7 and 72.2+/-26.2 mL/min at month 6, and 68.7+/-27.7 and 71.8+/-29.8 mL/min at month 12 with everolimus and MMF, respectively. The primary endpoint was not met since calculated CrCl at month 6 posttransplant was 6.9 mL/min lower with everolimus, exceeding the predefined margin of 6 mL/min. However, by month 12 the between-group difference had narrowed versus baseline (3.1 mL/min). All efficacy endpoints were noninferior for everolimus versus MMF. The 12-month incidence of biopsy-proven acute rejection International Heart and Lung Transplantation grade more than or equal to 3A was 21 of 92 (22.8%) with everolimus and 25 of 84 (29.8%) with MMF. Adverse events were consistent with class effects including less-frequent cytomegalovirus infection with everolimus (4 [4.4%]) than MMF (14 [16.9%], P=0.01). CONCLUSION.: Concentration-controlled everolimus with reduced CsA results in similar renal function and equivalent efficacy compared with MMF with standard CsA at 12 months after cardiac transplantation.

The potential for in vitro colonization of decellularized valves by human bone marrow mesenchymal stem cells (hBM-MSCs) towards the anisotropic layers ventricularis and fibrosa and in homo- vs. heterotypic cell-ECM interactions has never been investigated. hBM-MSCs were expanded and characterized by immunofluorescence and FACS analysis. Porcine and human pulmonary valve leaflets (p- and hPVLs, respectively) underwent decellularization with Triton X100-sodium cholate treatment (TRICOL), followed by nuclear fragment removal. hBM-MSCs (2x10(6)cells/cm(2)) were seeded onto fibrosa (FS) or ventricularis (VS) of decellularized PVLs, precoated with FBS and fibronectin, and statically cultured for 30 days. Bioengineered PVLs revealed no histopathological features but a reconstructed endothelium lining and the presence of fibroblasts, myofibroblasts and SMCs, as in the corresponding native leaflet. The two valve layers behaved differently as regards hBM-MSC repopulation potential, however, with a higher degree of 3D spreading and differentiation in VS than in FS samples, and with enhanced cell survival and colonization effects in the homotypic ventricularis matrix, suggesting that hBM-MSC phenotypic conversion is strongly influenced in vitro by the anisotropic valve microstructure and species-specific matching between extracellular matrix and donor cells. These findings are of particular relevance to in vivo future applications of valve tissue engineering.

Heart valve disorders, caused by congenital defects, rheumatic fever, calcification, myocardial infarction and other cardiovascular diseases, often require native valves to be replaced by bio-prosthetic devices or mechanical heart valves (MHVs). Among MHVs, bileaflet valves are usually preferred for their hemodynamic features, similar to physiological ones, and their durability, but they are prone to complications due to thromboembolic events. Due to the asynchronous closure of the leaflets, bileaflet MHVs are also known to produce closing sounds typically characterized by the presence of two peaks in the time domain. The detection of this “double click” in the signal may be useful for the early diagnosis of bileaflet MHV malfunction. The closing sound is actually a non-stationary signal that can be properly explored by means of time-frequency analysis. This paper describes a preliminary approach to the investigation of bileaflet MHV closing sounds performed by Continuous Wavelet Transform (CWT) analysis. Signals were collected from 3 patients immediately after surgery by means of the Myotis 3C, which is a traditional phonocardiographic apparatus. Signals were analyzed by two algorithms: one embedded in the Myotis 3C, based on the Fast Fourier Transform (FFT); and one specifically created for the purposes of the present study, based on CWT. The performance of these algorithms was compared and the results showed that the proposed CWT technique correctly classifies as ''double'' a large number of clicks that are recognized as ''single'' by the Myotis 3C.

BACKGROUND: Determination of coronary flow reserve (CFR) is increasingly being used in cardiac allograft vasculopathy (CAV). We aimed to identify determinants of CFR in heart transplantation (HT). METHODS: CFR was measured by transthoracic echocardiography in 119 HT recipients (97 men, 22 women; 50 +/- 12 years of age at HT and 8 +/- 5 years post-HT). CFR was expressed as the ratio of hyperemic (adenosine infusion at a rate of 0.14 mg/kg) to basal diastolic flow velocity. Rejection scores (RS) on endomyocardial biopsy were calculated. Angiographic CAV was analyzed using a qualitative grading system. The coronary tree was divided into 17 traits and a CAV severity/diffusion index (SDI) was calculated for each patient, summing the scores assigned to all lesions. RESULTS: Upon multivariate analysis, CFR was related to CAV (p = 0.001), interventricular septum thickness (p = 0.01), ischemic heart disease pre-HT (p = 0.02) and SDI and SDI/segment number (p < 0.0001 and p = 0.003, respectively). In patients without CAV, CFR was related only to RS for severe grades (p = 0.01). CONCLUSIONS: Left ventricular hypertrophy, CAV and its severity/diffusion independently contribute to reduced CFR. In patients without angiographic CAV, CFR was only independently related to RS. Because a high rejection burden is associated with increased risk of CAV, CFR reduction may be an early marker of CAV. Microvascular dysfunction may contribute to the late morbidity and mortality seen in HT.

Cardiac involvement is very frequent and underestimated in systemic sclerosis, but few reports have been published on the surgical treatment of patients with systemic sclerosis. We describe herein two cases of valve replacement because of aortic stenosis.