Laura Bergamasco

Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function.

OBJECTIVES The aim of this study was to compare the prevalence of silent cerebral ischemia (SCI) and cognitive performance in patients with paroxysmal and persistent atrial fibrillation (AF) and controls in sinus rhythm. BACKGROUND Large registries have reported a similar risk for symptomatic stroke in both paroxysmal and persistent AF. The relationship among paroxysmal and persistent AF, SCI, and cognitive impairment has remained uncharted. METHODS Two hundred seventy subjects were enrolled: 180 patients with AF (50% paroxysmal and 50% persistent) and 90 controls. All subjects underwent clinical assessment, neurological examination, cerebral magnetic resonance, and the Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS At least 1 area of SCI was present in 80 patients (89%) with paroxysmal AF, 83 (92%) with persistent AF (paroxysmal vs. persistent, p = 0.59), and 41 (46%) controls (paroxysmal vs. controls and persistent vs. controls, p < 0.01). The number of areas of SCI per subject was higher in patients with persistent AF than in those with paroxysmal AF (41.1 ± 28.0 vs. 33.2 ± 22.8, p = 0.04), with controls reporting lower figures (12.0 ± 26.7, p < 0.01 for both). Cognitive performance was significantly worse in patients with persistent and paroxysmal AF than in controls (Repeatable Battery for the Assessment of Neuropsychological Status scores 82.9 ± 11.5, 86.2 ± 13.8, and 92.4 ± 15.4 points, respectively, p < 0.01). CONCLUSIONS Patients with paroxysmal and persistent AF had a higher prevalence and number of areas of SCI per patient than controls and worse cognitive performance than subjects in sinus rhythm.

Impact of TAVI on mitral regurgitation: a prospective echocardiographic study.

Objective: This study aims to assess changes in mitral regurgitation (MR) severity after transcatheter aortic valve implantation (TAVI). Background: Existing data on MR after TAVI are contradictory. Methods: Thirty‐five patients with MR graded ≥ 2+ were followed after undergoing TAVI with either the Edwards Sapien or CoreValve device. Echocardiography was performed the week before and 3 months after the procedure. MR was graded on a scale of 0 to 4+, classified as organic or functional, and the effective regurgitant orifice area (EROA) and MR index were calculated. Results: At baseline, MR was graded 4+ in 4 (11.4%) patients, 3+ in 10 (28.6%), and 2+ in 21 (60%). At follow‐up, MR was graded at 3+ in 4 (11.4%) patients, 2+ in 8 (22.9%), and 1+ in 19 (54.3%); 4 (11.4%) exhibited no MR. EROA (24.4 ± 11.5 mm2 pre‐TAVI vs. 11.2 ± 10.3 mm2 post‐TAVI, P < 0.001) and MR index (1.9 ± 0.3 pre‐TAVI vs. 1.3 ± 0.7 post‐TAVI, P < 0.001) were reduced with TAVI, independent of the etiology. MR decreased by at least 1 grade in 28 (80%) patients, with a reduction ≥2 grades in 10 (28.6%) patients; no patient showed a worsened condition. Subgroup analyses showed that the reduction in MR was significant in patients treated with the Edwards Sapien device but not in patients treated with the CoreValve device. Conclusions: This multiparametric echocardiographic evaluation showed that MR improved significantly after TAVI and that this result may be related to the type of valve implanted.

Fontan circulation causes early, severe liver damage. Should we offer patients a tailored strategy?

BACKGROUND In patients with Fontan circulation, the liver is profoundly affected by chronic venous stasis. Little is known about early hepatic changes in this population. METHODS We performed echocardiography, abdominal ultrasound, liver elastography, cardiac catheterization, esophago-gastro-duodenoscopy and calculated MELD-XI score in 64 Fontan patients (69% minors), at an interval of 1-15years since Fontan. RESULTS Cardiac output remained stable in the first 5years after Fontan, then significantly decreased (r=-0.45, p(r=0)=0.003). NYHA class significantly increased after Fontan. Patients in NYHA class II/III (n=21, 14 minors) had significantly higher hepatic pressures, but normal ventricular function and pulmonary vascular resistances (PVR). Patients with pulmonary arterial pressure (PAP) ≥15mmHg (n=12, 6 minors) and those with PVR≥2WU*m(2) (n=27, 25 minors), had higher hepatic pressures (p<0.0001), a higher incidence of liver collaterals and/or esophageal varices (p<0.0001) and splenomegaly (p<0.02). Liver stiffness (LS) was elevated in most patients (median, 25th-75th percentile:17.3KPa, 14.1-21.4). It rapidly increased during the first 5-years after Fontan, compared to the following 5-years (from 12.2KPa, 9.8-14.1 to 17.5KPa, 14.3-24.5, p=0.007), then remained stable (19.1KPa, 16.9-22.6, p=0.60). MELD-XI score increased linearly with the time interval since Fontan (r=0.31, p(r=0)=0.01). For patients above 12years we found a linear correlation between LS and MELD-XI score in the 6-15years period after Fontan (r=0.40. p(r=0)=0.04). The overall incidence of established liver cirrhosis was 22%. CONCLUSIONS This is the largest study showing that Fontan circulation prompts early, progressive and eventually irreversible liver damage. Precautions should be taken immediately after Fontan, to protect this fragile population.

Digital breast tomosynthesis as an adjunct to digital mammography for detecting and characterising invasive lobular cancers: a multi-reader study

AIM To examine the interpretive performance of digital breast tomosynthesis (DBT) as an adjunct to digital mammography (DM) compared to DM alone in a series of invasive lobular carcinomas (ILCs) and to assess whether DBT can be used to characterise ILC. MATERIALS AND METHODS A retrospective, multi-reader study was conducted of 83 mammographic examinations of women with 107 newly diagnosed ILCs ascertained at histology. Consenting women underwent both DM and DBT acquisitions. Twelve radiologists, with varying mammography experience, interpreted DM images alone, reporting lesion location, mammographic features, and malignancy probability using the Breast Imaging-Reporting and Data System (BI-RADS) categories 1-5; they then reviewed DBT images in addition to DM, and reported the same parameters. Statistical analyses compared sensitivity, false-positive rates (FPR), and interpretive performance using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), for reading with DM versus DM plus DBT. RESULTS Multi-reader pooled ROC analysis for DM plus DBT yielded AUC=0.89 (95% confidence interval [CI]: 0.88-0.91), which was significantly higher (p<0.0001) than DM alone with AUC=0.84 (95% CI: 0.82-0.86). DBT plus DM significantly increased pooled sensitivity (85%) compared to DM alone (70%; p<0.0001). FPR did not vary significantly with the addition of DBT to DM. Interpreting with DBT (compared to DM alone) increased the correct identification of ILCs depicted as architectural distortions (84% versus 65%, respectively) or as masses (89% versus 70%), increasing interpretive performance for both experienced and less-experienced readers; larger gains in AUC were shown for less-experienced radiologists. Multifocal and/or multicentric and bilateral disease was more frequently identified on DM with DBT. CONCLUSION Adding DBT to DM significantly improved the accuracy of mammographic interpretation for ILCs and contributed to characterising disease extent.

PPARγ in coronary atherosclerosis: In vivo expression pattern and correlations with hyperlipidemic status and statin treatment

OBJECTIVE Peroxisome proliferator-activated receptor-γ (PPARγ) is involved in regulation of macrophage inflammation and in atherosclerosis. Herein we investigate the influence of statin treatment on PPARγ expression in coronary artery disease. METHOD PPARγ expression was investigated in coronary atherosclerotic atherectomies (N=48) and arteries (N=12) from patients with stable or unstable coronary syndromes or undergoing cardiac transplantation for end-stage ischemic cardiomyopathy, respectively, by immunohistochemistry. Plaque components and tissue factor immunoreactivity were also investigated. Atherectomies were obtained from de novo culprit lesions of hypercholesterolemic (16 statin-treated and 16 untreated) and normolipidemic (N=16) patients. Furthermore, PPARγ expression was evaluated in patients peripheral blood monocytes and in monocytic U937 cells after atorvastatin incubation, by Western blot analysis. RESULT PPARγ expression was higher in coronary plaques and peripheral blood monocytes of statin-treated patients, and it significantly increased in monocytes after 24h atorvastatin incubation (p<0.05). Intra-plaque macrophage content, atheroma, neoangiogenesis and hemorrhage, and circulating CRP levels were lower in statin-treated than untreated hypercholesterolemic patients and comparable with normolipidemic subjects. PPARγ immunoreactivity was localized to neointima and media, its distribution pattern being different from that of tissue factor. CONCLUSION PPARγ expression was enhanced in statin-treated patients with different distribution and behavior as compared to atheroma, macrophage content, tissue factor immunoreactivity and serum CRP. In vitro studies showed increased PPARγ expression in monocytes after atorvastatin incubation. These findings provide further evidence as to the protective role of statins in coronary artery disease and their influence on PPARγ expression in coronary plaques and on the inflammatory status of patients.

Myocardial Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 Gene Expression in Failing Hearts Harvested From Patients Undergoing Cardiac Transplantation

Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding proteins (IGFBPs) might play a pathogenic role in heart failure. We showed significantly increased myocardial IGFBP-3 expression (investigated by real-time polymerase chain reaction) and apoptosis (detected by flow cytometry) in 23 failing hearts from patients undergoing cardiac transplantation for end-stage dilated or ischemic cardiomyopathy, when compared with 10 controls. Higher IGF-1 mRNA levels were shown only in end-stage dilated cardiomyopathy.

Endothelin inhibitors lower pulmonary vascular resistance and improve functional capacity in patients with Fontan circulation

Objectives: To evaluate the effects of endothelin inhibitors (ERAs) on hemodynamic and functional parameters in patients post‐Fontan procedure with high pulmonary vascular resistance (PVR). Methods: Among our cohort of patients with Fontan circulation, 8 children, 8 adolescents, and 8 adults had PVR ≥2 WU*m2. These patients were treated with ERAs (minors with bosentan, adults with macitentan) and reevaluated after 6 months. Pre‐ and posttreatment hemodynamic variables were assessed by cardiac catheterization. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). Our primary endpoint was to obtain a reduction of PVR; the secondary endpoint was to obtain an improvement of functional capacity. Results: Under treatment, New York Heart Association class improved for adolescents and adults. PVR decreased (P = .01) in all groups: in children from the median value 2.3 (interquartile range 2.0–3.1) to 1.9 (1.4–2.3) WU*m2, in adolescents from 2.3 (2.1–2.4) to 1.7 (1.4–1.8) WU*m2, and in adults from 2.8 (2.0–4.7) to 2.1 (1.8–2.8)WU*m2. In 71% of patients, PVR fell to less than 2 WU*m2. Cardiac index increased in adolescents from 2.6 (2.4–3.3) to 3.6 (3.4–4.3) L/min/m2, P = .04, and in adults from 2.1 (2.0–2.3) to 2.8 (2.3–4.7) L/min/m2, P = .03. CPET showed that only adolescents displayed a significant functional improvement. Anaerobic threshold improved from 17 (13–19) to 18 (13–20) mL/kg/min, P = .03; oxygen consumption and VO2 max increased from 1.3 (1.0–1.6) to 1.7 (1.1–1.9) L/min, P = .02 and from 25 (21–28) to 28 (26–31) L/min, P = .02, respectively. Oxygen pulse increased from 7.9 (5.7–10.4) to 11.2 (8.2–13.0) L/beat, P = .01. Conclusions: This is the first study that assesses by cardiac catheterization and CPET the effects of ERA in patients with Fontan circulation with increased PVR. These results suggest that ERAs might provide most pronounced hemodynamic and functional improvement in adults and adolescents.

Bleeding rate during oral surgery of oral anticoagulant therapy patients with associated systemic pathologic entities: a prospective study of more than 500 extractions.

PURPOSE Oral anticoagulant therapy (OAT) patients have international normalized ratio (INR) safety windows for oral surgery, the lower limit of which is determined by the thromboembolic risk, with the upper limit typically 3.0. We sought to assess whether these limits will also be true with comorbidities that favor bleeding, such as diabetes, liver disease, and chronic renal failure. MATERIALS AND METHODS The study was designed for 500 consecutive extractions. Patients with an INR greater than 3.0 were switched to heparin and used as controls. The primary outcome was the incidence of bleeding with the need for reoperation, in connection with 3 principal predictors: the INR, reasons for OAT, and comorbidity type. Continuous variables were analyzed using the Mann-Whitney U test and categorical variables using χ2 or Fishers exact test. Statistical significance was set at P < .05. The reliability of the INR as a bleeding predictor was assessed using receiver operating characteristic (ROC) curves. RESULTS Extractions in patients receiving OAT without comorbidities had a success rate of 99.7% against severe bleeding. Despite equivalent INR values, patients with comorbidities had a significantly lower rate (81.3%, P < .001). For these patients, the ROC curve procedure indicated lower INR upper limits, 2.8 for mechanical heart prosthesis subjects and 2.3 for all others. Among the comorbidities, diabetes was associated with the greatest frequency of bleeding (31%) compared with liver disease (15%) and kidney failure (11%). CONCLUSIONS Patients with comorbidities should be advised to bring their INR within narrower safety windows (upper limit of 2.5 to 2.8 for mechanical prosthesis and 2.0 to 2.3 otherwise) or be switched to heparin. Alternatively, we propose applying to the socket, a platelet-rich growth factor preparation to foster hemostasis.

Failure risk estimates after dental implants placement associated with plasma rich in growth factor-Endoret in osteoporotic women under bisphosphonate therapy

AbstractThere is disagreement as to whether it is safe to place implants in patients under bisphosphonates (BPs) therapy owing to the risk for developing BP-related osteonecrosis of the jaws (BRONJ). The American Association of Oral and Maxillofacial Surgeons recommends that dental implants should be avoided in oncologic patients treated with intravenous BPs. Conversely, for patients receiving oral BPs, dental implant placement is not explicitly contraindicated even if a cautious approach is suggested. The aim of the current study was to assess the risk level as related to adverse events such as implant failure and BRONJ in a large cohort of osteoporotic patients submitted to implant placement and concomitant application of plasma rich in growth factor (PGRF)-Endoret. The clinical charts of 235 middle-aged women under oral BPs therapy for osteoporosis, who underwent positioning of 1267 dental implants, were reviewed. The implants were always positioned in association with PRGF-Endoret. The outcomes were implant failure and BRONJ. A model based on personal risk factors distribution was used for risk assessment. Sixteen implants were lost in 16 patients up to 120 months of follow-up, leading to a survival of 98.7% and 93.2% on an implant basis and patient basis, respectively. No cases of BRONJ were reported. In line with the current literature, the present data show that the risk for developing BRONJ associated to dental implant surgery remains low for patients receiving oral BPs. The use of procedures that could enhance and support healing, such as platelet concentrates, should be recommended.

Prostate Cancer Detection Rate with Koelis Fusion Biopsies versus Cognitive Biopsies: A Comparative Study

Objective: Targeted fusion biopsies have led to an improved prostate cancer (PCa) detection rate (CDR). Our aim was to assess if device-assisted fusion biopsies are superior to cognitive ones in terms of CDR. The association between multiparametric MRI parameters and PCa was also evaluated. Methods: We retrospectively enrolled 50 patients who underwent transrectal biopsy with elastic fusion (Koelis; group KB, n = 25) or cognitive approach (group CB, n = 25). Targeted biopsies were done on targets, while a variable number of random biopsies were performed depending on the clinical case. Results: The groups did not significantly differ in terms of age, prostate-specific antigen, prostate volume and previous biopsies. Mean number of random cores was significantly inferior in KB group (8.4 vs. 12.1) and mean number of targeted biopsies was significantly higher (3.6 vs. 2.6). CDR was higher in fusion biopsies (64 vs. 40%), with the gap becoming significant when considering CDR of MRI targets only (59 vs. 27%). The difference was marked for lesions ≤10 mm, where CDR was 52% in KB against 21% in CB group. Conclusions: According to our study, elastic fusion biopsies performed with Koelis achieve an increased per-patient and per-lesion CDR as compared to cognitive biopsies, especially in the case of lesions ≤10 mm.