Local inhibition of ornithine decarboxylase reduces vascular stenosis in a murine model of carotid injury.

OBJECTIVES: Polyamines are organic polycations playing an essential role in cell proliferation and differentiation, as well as in cell contractility, migration and apoptosis. These processes are known to contribute to restenosis, a pathophysiological process often occurring in patients submitted to revascularization procedures. We aimed to test the effect of α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, on vascular cell pathophysiology in vitro and in a rat model of carotid arteriotomy-induced (re)stenosis. METHODS: The effect of DFMO on primary rat smooth muscle cells (SMCs) and mouse microvascular bEnd.3 endothelial cells (ECs) was evaluated through the analysis of DNA synthesis, polyamine concentration, cell viability, cell cycle phase distribution and by RT-PCR targeting cyclins and genes belonging to the polyamine pathway. The effect of DFMO was then evaluated in arteriotomy-injured rat carotids through the analysis of cell proliferation and apoptosis, RT-PCR and immunohistochemical analysis of differential gene expression. RESULTS: DFMO showed a differential effect on SMCs and on ECs, with a marked, sustained anti-proliferative effect of DFMO at 3 and 8 days of treatment on SMCs and a less pronounced, late effect on bEnd.3 ECs at 8 days of DFMO treatment. DFMO applied perivascularly in pluronic gel at arteriotomy site reduced subsequent cell proliferation and preserved smooth muscle differentiation without affecting the endothelial coverage. Lumen area in DFMO-treated carotids was 49% greater than in control arteries 4 weeks after injury. CONCLUSIONS: Our data support the key role of polyamines in restenosis and suggest a novel therapeutic approach for this pathophysiological process.

Lack of definite indication criteria for choosing between transcatheter implantation and surgical replacement of the aortic valve.

AIMS: Age over 75 years and logistic Euroscore over 20% have been jointly proposed by European scientific associations as the criteria for aortic valve stenosis patients to be considered 'high-risk' for surgical aortic valve replacement (AVR) and candidates for transcatheter aortic valve implantation (TAVI). We aimed to verify traditional AVR outcomes in the presence of the above criteria. METHODS: Between January 2001 and January 2011, 180 patients with severe aortic valve stenosis (mean aortic valve area = 0.4±0.1 cm/m), with age range 75-88 years (mean 78.2±3), logistic Euroscore between 4.5 and 40% (mean 12.6±7.4%), underwent surgical AVR. The patient population was divided into group A (118 patients between 75 and 79 years of age), further divided into subgroups A1 (76 patients) and A2 (42 patients) with logistic Euroscore, respectively, less than 20% and at least 20%; and group B (62 patients between 80 and 88 years of age), subdivided into B1 (34 patients) and B2 (28 patients) with logistic Euroscore, respectively, less than 20% and at least 20%. Hospital outcomes were retrospectively evaluated. Univariate and multivariate analyses, including age and logistic Euroscore, were performed to individuate predictors of hospital mortality. RESULTS: Overall observed/expected mortality ratio was 0.4. Hospital mortality was 5.3% in group A1, 4.8% in A2, 5.9% in B1, 3.6% in B2 (P=NS). Mortality with age over 75 and Euroscore at least 20% was 4.3%. As regards postoperative morbidity, atrio-ventricular bock indicating pacemaker implantation occurred in four patients, pneumonia in three, stroke in two, perioperative myocardial infarction in one. Age and Euroscore were not independent predictors of mortality, morbidity or composite endpoint in multivariable analysis. CONCLUSION: Age and logistic Euroscore might be inadequate criteria for the identification of patients with severe aortic stenosis unsuitable for AVR and addressable to TAVI.

Coronary artery bypass grafting associated to aortic valve replacement in the elderly: survival and quality of life.

Myocardial ischemia is often associated to aortic valve stenosis in the elderly. Aim of this study was to evaluate the impact on survival and quality of life of CABG associated to aortic valve replacement in the septuagenarians and octogenarians.Between January 1991 and January 2010, 520 patients ageing > 70 years underwent aortic valve replacement with a mechanical prosthesis in two Institutions. They were divided into 2 groups: Group A included 406 patients undergoing isolated aortic valve replacement; Group B 114 patients receiving aortic valve replacement and CABG. A comparative analysis of long-term survival and quality of life (SF-36 test) was performed.Mean age was 74.2 ± 3.6 years (74.3 ± 3.6 in Group A, 74 ± 3.3 in Group B; p = 0.33). Hospital mortality was 9.5% (46 patients). Twenty-nine (7.8%) in Group A and 17 in Group B (15.2%)(p = 0.019). Actuarial survival was 88.5% ± 0.015 at 1 year, 81.9% ± 0.02 at 5 years, 76.6% ± 0.032 at 10 and 57.3 ± 0.1 at 15 years. Ten-year survival was 77% ± 0.034 in Group A and 77.8% ± 0.045 in Group B (p = 0.2). Multivariate analysis did not reveal associated CABG as a predictor of long term mortality. The scores obtained in the SF-36 test were similar in the two groups and significantly higher than those of the general population matched for country, age and sex (p < 0.001 in all domains).Associated CABG determines a significant increase of hospital mortality in the elderly undergoing aortic valve replacement. Survivors did not show differences in long-term outcome and quality of life according to the presence of associated CABG.

Is post-sternotomy mediastinitis still devastating after the advent of negative-pressure wound therapy?

In this study, we reviewed a 15-year experience with the treatment of a severe sequela of cardiac surgery: post-sternotomy mediastinitis. We compared the outcomes of conventional treatment with those of negative-pressure wound therapy, focusing on mortality rate, sternal reinfection, and length of hospital stay.We reviewed data on 157 consecutive patients who were treated at our institution from 1995 through 2010 for post-sternotomy mediastinitis after cardiac surgery. Of these patients, 74 had undergone extensive wound débridement followed by negative-pressure wound therapy, and 83 had undergone conventional treatment, including primary wound reopening, débridement, closed-chest irrigation without rewiring, topical application of granulated sugar for recurrent cases, and final plastic reconstruction with pectoral muscle flap in most cases.The 2 study groups were homogeneous in terms of preoperative data and operative variables (the primary cardiac surgery was predominantly coronary artery bypass grafting). Negative-pressure wound therapy was associated with lower early mortality rates (1.4% vs 3.6%; P = 0.35) and significantly lower reinfection rates (1.4% vs 16.9%; P = 0.001). Significantly shorter hospital stays were also observed with negative pressure in comparison with conventional treatment (mean durations, 27.3 ± 9 vs 30.5 ± 3 d; P = 0.02), consequent to the accelerated process of wound healing with negative-pressure therapy.Lower mortality and reinfection rates and shorter hospital stays can result from using negative pressure rather than conventional treatment. Therefore, negative-pressure wound therapy is advisable as first-choice therapy for deep sternal wound infection after cardiac surgery.

Evolution in the treatment of mediastinitis: single-center experience.

This study aimed to evaluate our 30-year experience in the treatment of deep sternal wound infection after cardiac surgery. Between 1979 and 2009, deep sternal wound infections occurred in 200 of 22,366 (0.89%) patients who underwent sternotomy. The study population was divided into 3 groups. In group A (62 patients; 1979-1994), an initial attempt at conservative antibiotic therapy was the rule, followed by surgery in case of failure. In group B (83 patients; 1995-2002), the treatment was in 3 steps: wound debridement and closed irrigation for 10 days; in case of failure, open dressing with sugar and hyperbaric treatment; delayed healing and negative wound cultures mandated plastic reconstruction. In group C (2002-2009), the treatment was based on early surgical debridement, vacuum application, and reconstruction using pectoralis muscle flap. Hospital mortality in group A was significantly higher than that in groups B and C. Hospital stay, time for normalization of white blood cell count and C reactive protein, and time for defervescence were significantly shorter in group C. In our experience, early surgical debridement and vacuum application followed by plastic reconstruction provided a satisfactory rate of healing and a good survival rate.

Role of vacuum in methicillin-resistant deep sternal wound infection.

Between January 2002 and January 2009, 39 patients with post-cardiotomy staphylococcal deep sternal wound infection were treated primarily by a vacuum-assisted closure method (group A). Results were compared with those of 30 patients with staphylococcal deep sternal wound infection who received closed mediastinal irrigation with antibiotics (group B). The prevalence of methicillin-resistance was similarly high in both groups (64.1% in A, 56.7% in B). One group B patient died during treatment. The median healing time was significantly shorter at 13 days in group A (mean, 13.5 +/- 3.2 days) compared to 18 days (mean, 21.2 +/- 16.4 days) in group B. Deep sternal wound infection did not recur after vacuum treatment, while 7 (24%) patients in group B suffered a recurrence. Hospital stay was significantly shorter in group A (median, 30.5 days; mean, 32.2 +/- 11.3 days vs. median, 45 days; mean, 49.2 +/- 19.3 days). The significantly shorter healing time with vacuum-assisted closure was confirmed in both methicillin-sensitive (12 vs. 17 days) and methicillin-resistant infections (14 vs. 21 days). Hospital stay remained significantly shorter in group A (35 vs. 46 days) when only methicillin-resistant deep sternal wound infection was considered.

DNA damage and repair in a model of rat vascular injury.

Restenosis rate following vascular interventions still limits their long-term success. Oxidative stress plays a relevant role in this pathophysiological phenomenon, but less attention has been devoted to its effects on DNA damage and to the subsequent mechanisms of repair. We analysed in a model of arteriotomy-induced stenosis in rat carotids the time-dependent expression of DNA damage markers and of DNA repair genes, together with the assessment of proliferation and apoptosis indexes. The expression of the oxidative DNA damage marker 7,8-dihydro-8-oxo-2'-deoxyguanosine was increased at 3 and 7 days after arteriotomy, with immunostaining distributed in the injured vascular wall and in perivascular tissue. The expression of the DNA damage marker phospho-H2A.X was less relevant but increasing from 4 hrs to 7 days after arteriotomy, with immunostaining prevalently present in the adventitia and, to a lesser extent, in medial smooth muscle cells at the injury site. RT-PCR indicated a decrease of 8 out of 12 genes of the DNA repair machinery we selected from 4 hrs to 7 days after arteriotomy with the exception of increased Muyth and Slk genes (p<0.05). Western Blot revealed a decrease of p53 and catalase at 3 days after arteriotomy (p<0.05). A maximal 7% of BrdU-positive cells in endothelium and media occurred at 7 days after arteriotomy, while the apoptotic index peaked at 3 days after injury (p<0.05). Our results highlight a persistent DNA damage presumably related to a temporary decreased expression of the DNA repair machinery and of the antioxidant enzyme catalase, playing a role in stenosis progression.

Arterial tortuosity syndrome in two Italian paediatric patients.

BACKGROUND: Arterial tortuosity syndrome (ATS) (OMIM #208050) is a rare autosomal recessive connective tissue disorder characterized by tortuosity and elongation of the large and medium-sized arteries, propensity to aneurysms formation, vascular dissection, and pulmonary arteries stenosis. ATS is caused by mutations in SLC2A10 gene, encoding for the facilitative glucose transporter 10 (GLUT10). So far, 17 SLC2A10 mutations have been reported in 32 families, two of which were Italian with a total of five patients. Here we present the clinical and molecular characterization of two novel Italian paediatric ATS patients. METHODS: The exons and intronic flanking regions of SLC2A10 gene were amplified and direct sequencing was performed. RESULTS: In both patients, the involvement of major- and medium-sized arteries was characteristic; the nonvascular connective tissue manifestations were mild and not pathognomic of the disorder. Both patients, born from non-consanguineous parents, were heterozygous for two different SLC2A10 mutations, three of which were recurrent and one was novel (p.Arg231Trp). This mutation is localized at the endofacial loop between the transmembrane domains 6 and 7 of GLUT10. CONCLUSION: Two novel ATS patients were characterized at clinical and molecular level. Overall, four ATS unrelated families are known in Italy so far. Though ATS clinical delineation improved in the last years, further works in the comprehension of disease presentation and complications onset, particularly in paediatric age, and on ATS molecular basis are needed to add new insights for diagnosis and prevention strategies for related complications.

Noninvasive positive-pressure ventilation for extubation failure after cardiac surgery: Pilot safety evaluation.

OBJECTIVE: Extubation failure is a serious complication after cardiac surgery. The role of noninvasive positive-pressure ventilation for acute respiratory failure in patients undergoing cardiac surgery is unknown. This study aimed to assess the safety of implementing noninvasive positive-pressure ventilation in this setting and its impact on lung function and operative outcomes. METHODS: In a 6-month pilot prospective survey, the study population comprised 43 patients (32 were male with a mean age of 65.73 +/- 9 years; 3 heart transplantations, 18 coronary artery bypass grafts, 5 aortic dissections, and 17 valvular procedures; 34 active smokers, 25 with medically treated chronic obstructive pulmonary disease, 21 emergency/urgency procedures) who required noninvasive positive-pressure ventilation for acute respiratory failure after initial weaning from a respirator. The cause of acute respiratory failure (classified as post-cardiopulmonary bypass lung injury in 48.8% [21 patients], cardiogenic edema in 30.2% [13 patients], and pneumonia in 21% [9 patients]), length of noninvasive positive-pressure ventilation support, respiratory ratios (arterial oxygen tension/fraction of inspired oxygen assessed immediately before noninvasive positive-pressure ventilation, and every 6 hours after institution of pressure ventilation), and need for reintubation along with a set of predefined safety parameters were recorded. RESULTS: The mean length of noninvasive positive-pressure ventilation support was 33.8 +/- 24.04 hours. Plotting respiratory ratios with length of noninvasive positive-pressure ventilation supports a significant improvement was already evident within the first 6-hour frame (133.6 +/- 39.5 vs 205 +/- 65.7; P < .001) for all causes. Noninvasive positive-pressure ventilation prevented intubation in 74.4% of the patients, with satisfactory recovery for post-cardiopulmonary bypass lung injury and cardiogenic dysfunction (90.5% and 69.2%, respectively) and poor results (55% reintubated) in those treated for pneumonia. Noninvasive positive-pressure ventilation safety approached 97.7%. CONCLUSION: In appropriate candidates, noninvasive positive-pressure ventilation exerts favorable effects on lung function, preventing reintubation. The cost-effectiveness of its systematic use in this setting should be assessed.

Prosthesis-patient mismatch in the elderly: survival, ventricular mass regression, and quality of life.

BACKGROUND: Evaluation of the impact of prosthesis-patient mismatch (PPM) on long-term outcome and quality of life (QOL) in elderly patients who underwent implantation of small size bileaflet prostheses for aortic stenosis. METHODS: Between September 1988 and September 2006, 377 patients aged greater than 70 years underwent aortic valve replacement with a small size bileaflet prosthesis (17, 19, and 21 mm) in one Institution. The study population's survivors (345 patients) were divided into three groups according to the indexed effective orifice area (EOAI): Group A included patients with EOAI less than 0.60 cm(2)/m(2); group B included patients with EOAI ranging between 0.61 and 0.84 cm(2)/m(2); and group C included patients with EOAI 0.85 cm(2)/m(2) or greater. Cumulative and comparative analyses of long-term outcomes and of left ventricular mass regression were performed. The QOL was evaluated with the 36-Item Short Form Health Survey (SF-36) questionnaire. RESULTS: Overall hospital mortality was 8.5% (32 patients). Group A included 33 patients (9.6%), group B 175 (50.7%), and group C 137 (39.7%). Actuarial survival was 88.8% +/- 0.016 at 1 year, 82.1% +/- 0.022 at 5 years, and 76.7% +/- 0.032 at 10 years. No difference emerged among the three groups. A significant reduction in left ventricular mass was observed in all groups and in all patient subsets of prosthetic size. The scores obtained in the SF-36 test were similar in the three groups and significantly higher than those of the general population (p < 0.001 in all domains). CONCLUSIONS: Incidence of severe PPM is low after aortic valve replacement. Presence of severe or moderate PPM, did not influence long-term outcome, left ventricular mass regression and QOL in a population of septuagenarians.

Echocardiographic follow-up after implanting 17-mm Regent mechanical prostheses.

The aim of this study was to evaluate midterm echocardiographic results and changes in quality of life after aortic valve replacement with 17-mm St. Jude Medical Regent mechanical prostheses in patients with aortic valve stenosis. The study population was 34 women and 2 men, aged 31-83 years. Echocardiographic follow-up was 100% complete at 4.1 +/- 1.8 years. Hospital mortality was 5.6%. Actuarial 5-year survival was 88.5% +/- 0.067%. Postoperative echocardiography showed significant regression of left ventricular mass index and significant reductions of peak gradient, mean gradient and mean effective orifice area index. All survivors were interviewed using the 36-item Short Form Health Survey questionnaire. Scores obtained in 7 of the 8 domains of the test were significantly higher than preoperative values. In our experience, implantation of this prosthesis allowed regression of left ventricular mass index and improved the perceived quality of life.

Aortic valve replacement with 19-mm bileaflet prostheses in the elderly: left ventricular mass regression and quality of life.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate left ventricular mass (LVM) regression, survival and quality of life in elderly patients after aortic valve replacement (AVR) with small-sized bileaflet prostheses. METHODS: Between September 1988 and September 2005, a total of 147 patients aged > 70 years underwent AVR with 19-mm bileaflet prostheses for aortic stenosis. In order to evaluate the impact of prosthesis-patient mismatch (PPM) on long-term outcome, survivors were allocated to two groups according to the effective orifice area index (EOAI): group A, with EOAI < 0.85 cm2/m2, and group B with EOAI > or = 0.85 cm2/m2. Hospital survivors were interviewed using the SF-36 questionnaire, and the scores compared with those of age- and gender-matched members of the general Italian population. RESULTS: The mean patient age was 74.5 +/- 3.5 years, body surface area (BSA) 1.68 +/- 0.15 m2, and EOAI 0.73 +/- 0.2 cm2/m2. Hospital mortality was 8.8% (n = 13). Actuarial survival was 87.1 +/- 0.028% at one year, 81.3 +/- 0.035% at five years, and 77.2 +/- 0.044% at eight years. Eight-year survival was 74.0 +/- 0.062% in group A and 82.5 +/- 0.064% in group B (p = 0.29). Echocardiographic follow up showed a significant regression of LVM. Scores obtained in the SF-36 test were similar in the two groups, and significantly higher than those of the general Italian population matched for age and gender (p < 0.001 in all domains). CONCLUSION: The implantation of 19-mm bileaflet mechanical prostheses in the elderly allowed LVM regression and a good perceived quality of life. PPM did not influence the long-term survival of these patients.

Hybrid approach in a case of arterial tortuosity syndrome.

Arterial tortuosity syndrome is a rare connective tissue disorder characterised by elongation, tortuosity, stenosis and aneurysms of the large and middle-sized arteries. The symptomatology is correlated to the artery affected by the pathology with correlated stenosis. We describe our hybrid surgical procedure in the treatment of a case of kinking of the pulmonary branches with significant gradient and hypertension. Aortic arch and supraaortic vessels presented various deviousness without hemodynamic alterations.

Tissue versus mechanical prostheses: quality of life in octogenarians.

BACKGROUND: The aim of this study was to determine whether changes in prognosis and quality of life (QOL) after aortic valve replacement (AVR) in octogenarians differ depending on the choice of mechanical (MP) or tissue (BP) valves. METHODS: Between July 1992 and September 2006, 160 consecutive octogenarians underwent AVR with (18.8%) or without concomitant coronary artery bypass grafting. At follow-up (mean 3.4 +/- 2.8 years, 552 patient-years, 98.3% complete), 121 were still alive and answered the Medical Outcomes Study Short-Form 36 Health Survey (SF-36) QOL questionnaire. RESULTS: Group BP had 62 patients. Group MP had 98 patients. Preoperative risk factors were comparable except group BP was older. Global hospital mortality was 8.8%. There were 21 late deaths, 61.9% of which were not valve- or anticoagulation-related. A significant difference emerged in 1-, 3-, 5- and 8-year actuarial survival rates (BP: 86.4% +/- 0.04%, 76.9% +/- 0.06%, 58.1% +/- 0.1%, 46.5% +/- 0.14%, respectively, vs MP: 91.3% +/- 0.03%, 88.6% +/- 0.03%, 81.6% +/- 0.05%, 70% +/- 0.67%; p = 0.025) but not in terms of 8-year freedom from valve-related complications (82.6% +/- 0.1% vs 87% +/- 0.053%, p = 0.55). One anticoagulant-related hemorrhage occurred in group MP; one stroke occurred in group BP. Survivors had significant improvement in New York Heart Association functional class compared with preoperatively (1.1 vs 2.8, p < 0.001) Mean QOL scores were satisfactory and substantially comparable between the two groups; in seven domains, scores were higher than those of the age- and sex-matched general Italian population. CONCLUSIONS: Long-term survival after AVR in selected octogenarians was similar to that of the general elderly population. The device type exerted no influence on QOL.

Best site on right ventricle for open-chest biventricular pacing.

Cardiac resynchronization therapy is effective in patients with a low ejection fraction and left bundle branch block, but 20%-30% do not respond despite selection of the optimal site for pacing on the left ventricle. We investigated whether optimizing the site for placement of the pacing lead on the right ventricle could further improve left ventricular function during cardiac resynchronization in 19 patients (mean age, 63 +/- 5 years) undergoing coronary artery bypass with post-ischemic dilated myocardiopathy (ejection fraction, 25.8% +/- 2%) and left bundle branch block. The hemodynamic response to pacing was tested with the right ventricular lead positioned at the interventricular septum, atrioventricular junction, acute margin, and the pulmonary trunk. Biventricular stimulation improved left ventricular function. When the right ventricular lead was sited at the interventricular septum, a significant improvement in all hemodynamic parameters compared to the other sites was obtained. Biventricular pacing is important to optimize cardiac resynchronization. Although further studies are needed to confirm these findings, accurate lead placement is recommended for cardiac resynchronization therapy in patients with poor cardiac function and left bundle branch block.