Andrea De Martino

High concentration of C-type natriuretic peptide promotes VEGF-dependent vasculogenesis in the remodeled region of infarcted swine heart with preserved left ventricular ejection fraction.

BACKGROUND Vasculogenesis is a hallmark of myocardial restoration. Post-ischemic late remodeling is associated with pathology and function worsening. At the same time, neo-vasculogenesis helps function improving and requires the release of vascular endothelial growth factor type A (VEGF-A). The vasculogenic role of C-type natriuretic peptide (CNP), a cardiac paracrine hormone, is unknown in infarcted hearts with preserved left ventricular (LV) ejection fraction (EF). We explored whether myocardial VEGF-dependent vasculogenesis is affected by CNP. METHODS AND RESULTS To this end, infarcted swine hearts were investigated by magnetic resonance imaging (MRI), histological and molecular assays. At the fourth week, MRI showed that transmural myocardial infarction (MI) affected approximately 13% of the LV wall mass without impairing global function (LVEF>50%, n=9). Increased fibrosis, metalloproteases and capillary density were localized to the infarct border zone (BZ), and were associated with increased expression of CNP (p=0.03 vs. remote zone (RZ)), VEGF-A (p<0.001 vs. RZ), BNP, a marker of myocardial dysfunction (p<0.01 vs. RZ) and the endothelial marker, factor VIII-related antigen (p<0.01 vs. RZ). In vitro, CNP 1000 nM promoted VEGF-dependent vasculogenesis without affecting the cell growth and survival, although CNP 100 nM or a high concentration of VEGF-A halted vascular growth. CONCLUSIONS CNP expression is locally increased in infarct remodeled myocardium in the presence of dense capillary network. The vasculogenic response requires the co-exposure to high concentration of CNP and VEGF-A. Our data will be helpful to develop combined myocardial delivery of CNP and VEGF-A genes in order to reverse the remodeling process.

Surgery for prosthetic valve endocarditis: a retrospective study of a national registry

OBJECTIVES We described clinical-epidemiological features of prosthetic valve endocarditis (PVE) and assessed the determinants of early surgical outcomes in multicentre design. METHODS Data regarding 2823 patients undergoing surgery for endocarditis at 19 Italian Centers between 1979 and 2015 were collected in a database. Of them, 582 had PVE: in this group, the determinants of early mortality and complications were assessed, also taking into account the different chronological eras encompassed by the study. RESULTS Overall hospital (30-day) mortality was 19.2% (112 patients). Postoperative complications of any type occurred in 256 patients (44%). Across 3 eras (1980-2000, 2001-08 and 2009-14), early mortality did not significantly change (20.4%, 17.1%, 20.5%, respectively, P  = 0.60), whereas complication rate increased (18.5%, 38.2%, 52.8%, P  < 0.001), consistent with increasing mean patient age (56 ± 14, 64 ± 15, 65 ± 14 years, respectively, P  < 0.001) and median logistic EuroSCORE (14%, 21%, 23%, P  = 0.025). Older age, female sex, preoperative serum creatinine >-2 mg/dl, chronic pulmonary disease, low ejection fraction, non-streptococcal aetiology, active endocarditis, preoperative intubation, preoperative shock and triple valve surgery were significantly associated with mortality. In multivariable analysis, age (OR = 1.02; P  = 0.03), renal insufficiency (OR = 2.1; P  = 0.05), triple valve surgery (OR = 6.9; P  = 0.004) and shock (OR = 4.5; P  < 0.001) were independently associated with mortality, while streptococcal aetiology, healed endocarditis and ejection fraction with survival. Adjusting for study era, preoperative shock (OR = 3; P  < 0.001), Enterococcus (OR = 2.3; P  = 0.01) and female sex (OR = 1.5; P  = 0.03) independently predicted complications, whereas ejection fraction was protective. CONCLUSIONS PVE surgery remains a high-risk one. The strongest predictors of early outcome of PVE surgery are related to patients haemodynamic status and microbiological factors.

The Mosaic Mitral Valve Bioprosthesis: A Long-Term Clinical and Hemodynamic Follow-Up

We reviewed the cases of 100 patients (mean age, 73 ± 10 yr; 64 men) who had mitral valve replacement with a Medtronic Mosaic porcine bioprosthesis from 1995 through 2011. The mean New York Heart Association (NYHA) class was 3 ± 0.7, and 52 patients were in atrial fibrillation. Prosthetic sizes were chiefly 27 mm (50 patients) and 29 mm (40 patients). Follow-up ended in December 2012 and is 97% complete, with a cumulative duration of 611 patient-years (mean duration, 6 ± 4.6 yr; maximum, 17.7 yr). The early mortality rate was 10% (6% in elective patients); late deaths occurred in 31 patients (5 valve-related). Actuarial survival rates at 5, 10, and 15 years were 74% ± 5%, 50% ± 6%, and 37% ± 8%. The mean NYHA class in survivors was 1.4 ± 0.6 (P <0.0001). Thromboembolic episodes occurred in 4 patients, with an actuarial freedom at 15 years of 91% ± 5%. No cases of endocarditis were observed. Four patients needed reoperation, 2 for structural failure, and 1 each for perivalvular leakage and valve thrombosis. Actuarial freedom from structural failure and from reoperation, respectively, was 93% ± 5% and 91% ± 5% at 15 years. Echocardiographic follow-up in 24 patients with 27-mm prostheses showed a mean gradient of 5 ± 1.7 mmHg and an effective orifice area of 1.57 ± 0.3 cm(2); in 16 patients with 29-mm prostheses, the mean gradient was 4.5 ± 1.9 mmHg, and the effective orifice area, 1.63 ± 0.4 cm(2). During nearly 17 years of follow-up, the Mosaic bioprosthesis has shown good overall clinical and hemodynamic performance after mitral valve replacement.

Lipomatous hamartoma-like lesion of a bicuspid aortic valve: an incidental surgical finding

Cardiac valve lipomatous hamartomas are very rare lesions with preferential localization on the pericardium, followed by the endocardial surfaces. We report a quite unique case of a lipomatous hamartoma-like lesion involving a bicuspid aortic valve. The lesion was incidentally found in a young patient undergoing cardiac surgery for aortic regurgitation, and the diagnosis was done by histology. It cannot be excluded that the lipomatous hamartoma-like lesion might have contributed to aortic valve regurgitation.

Durability of the Mitroflow Pericardial Prosthesis: Influence of Patient–Prosthesis Mismatch and New Anticalcification Treatment

BACKGROUND  The Mitroflow pericardial bioprosthesis (MPB) has been recently associated with a high incidence of early structural failures, questioning its validity as cardiac valve substitute. We have therefore reviewed our experience with this device. MATERIALS AND METHODS  A total of 398 patients with a mean age of 75 ± 7 years (58% above the age of 75 years) had aortic valve replacement with a Mitroflow prosthesis (2005-2015). Most patients had calcific aortic stenosis (86%) and were in sinus rhythm (89%). Mean EuroSCORE II was 5.5 ± 6.2. Mean follow-up was 4 ± 2 years (range: 4 months to 10 years), which was 100% complete. RESULTS  Hospital mortality was 6.5%; at discharge, 25% of patients had a moderate patient-prosthesis mismatch and none had a severe mismatch. Cumulative incidence of structural valve deterioration in the entire series was 2% (95% confidence interval [CI]: 1-4) at 5 years and 7% (95% CI: 4-14) at 8 years. Significant factors influencing MPB durability were age ≤ 65 years (p < 0.001) and the presence of patient-prosthesis mismatch (p = 0.01). No cases of structural valve deterioration were observed in patients with the new prosthetic model incorporating an anticalcification treatment the first 4 years of follow-up. CONCLUSIONS  The Mitroflow prosthesis has shown satisfactory results in the first decade of use. Durability appears adversely influenced by patient age and patient-prosthesis mismatch. Thus, a careful valve size selection and implantation in patients >65 years of age appears to be associated with excellent valve durability in the aortic position. Whether the new anticalcification treatment will provide a more durable prosthesis must be verified at a longer follow-up.

Repair of a giant left ventricular pseudoaneurysm with rupture of the interventricular septum

Presence of two combined mechanical complications of acute myocardial infarction is extremely rare and still associated with a high-operative mortality. We describe a 73-year-old male patient who presented with a giant left ventricular pseudoaneurysm associated with rupture of the interventricular septum. Surgical repair of both lesions was successfully accomplished.

Novel use of the AngioVac system

The Vortex Medical AngioVac Cannula was employed in a 71-year-old man with a renal neoplasm with occlusion of the inferior vena cava and involvement of the right atrial cavity. Due to the presence of diffuse metastases, surgery was not indicated, and the AngioVac system was employed to remove the free-floating mobile atrial mass, thus minimizing the risk of pulmonary embolism and as a bioptic tool to allow a correct histological diagnosis. This novel use of this system may be advantageous in other similar cases.

Cell differentiation in cardiac myxomas: confocal microscopy and gene expression analysis after laser capture microdissection

Cardiac myxomas are rare tumors with a heterogeneous cell population including properly neoplastic (lepidic), endothelial and smooth muscle cells. The assessment of neoplastic (lepidic) cell differentiation pattern is rather difficult using conventional light microscopy immunohistochemistry and/or whole tissue extracts for mRNA analyses. In a preliminary study, we investigated 20 formalin-fixed and paraffin-embedded cardiac myxomas by means of conventional immunohistochemistry; in 10/20 cases, cell differentiation was also analyzed by real-time RT-PCR after laser capture microdissection of the neoplastic cells, whereas calretinin and endothelial antigen CD31 immunoreactivity was localized in 4/10 cases by double immunofluorescence confocal microscopy. Gene expression analyses of α-smooth muscle actin, endothelial CD31 antigen, alpha-cardiac actin, matrix metalloprotease-2 (MMP2) and tissue inhibitor of matrix metalloprotease-1 (TIMP1) was performed on cDNA obtained from either microdissected neoplastic cells or whole tumor sections. We found very little or absent CD31 and α-Smooth Muscle Actin expression in the microdissected cells as compared to the whole tumors, whereas TIMP1 and MMP2 genes were highly expressed in both ones, greater levels being found in patients with embolic phenomena. α-Cardiac Actin was not detected. Confocal microscopy disclosed two different signals corresponding to calretinin-positive myxoma cells and to endothelial CD31-positive cells, respectively. In conclusion, the neoplastic (lepidic) cells showed a distinct gene expression pattern and no consistent overlapping with endothelial and smooth muscle cells or cardiac myocytes; the expression of TIMP1 and MMP2 might be related to clinical presentation; larger series studies using also systematic transcriptome analysis might be useful to confirm the present results.

Splenectomy and Valve Replacement in Patients With Infective Endocarditis and Splenic Abscesses

In patients with infective endocarditis (IE), splenic involvement is a rare but well-known adverse event. The treatment of patients with IE and splenic abscesses is still challenging and controversial. We report 3 patients with IE and splenic abscesses who underwent successful valve replacement and splenectomy. Our experience confirms that in such a patient, a valve operation combined with splenectomy can be performed with excellent results during the same hospitalization. The timing of splenectomy and the type of surgical approach should be based mainly on the stability of a patients hemodynamic condition.