Andrea Sala

Impaired Arteriogenic Response to Acute Hindlimb Ischemia in CD4-Knockout Mice

Background—T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. Methods and Results—One week after ischemia, CD4−/− mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4−/− mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. Conclusions—These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.

Acute Kidney Injury: A Relevant Complication After Cardiac Surgery

Acute kidney injury (AKI) occurs in as many as 40% of patients after cardiac surgery and requires dialysis in 1% of cases. Acute kidney injury is associated with an increased risk of mortality and morbidity, predisposes patients to a longer hospitalization, requires additional treatments, and increases the hospital costs. Acute kidney injury is characterized by a progressive worsening course, being the consequence of an interplay of different pathophysiologic mechanisms, with patient-related factors and cardiopulmonary bypass as major causes. Recently, several novel biomarkers have emerged, showing reasonable sensitivity and specificity for AKI prediction and protection. The development and implementation of potentially protective therapies for AKI remains essential, especially for the relevant impact of AKI on early and late survival.

CD8+ T Lymphocytes Regulate the Arteriogenic Response to Ischemia by Infiltrating the Site of Collateral Vessel Development and Recruiting CD4+ Mononuclear Cells Through the Expression of Interleukin-16

Background— Previous studies have demonstrated that macrophages and CD4+ T lymphocytes play pivotal roles in collateral development. Indirect evidence suggests that CD8+ T cells also play a role. Thus, after acute cerebral ischemia, CD8+ T cells infiltrate the perivascular space and secrete interleukin-16 (IL-16), a potent chemoattractant for monocytes and CD4+ T cells. We tested whether CD8+ T lymphocytes contribute to collateral vessel development and whether the lack of circulating CD8+ T cells prevents IL-16 expression, impairs CD4+ mononuclear cell recruitment, and reduces collateral vessel growth after femoral artery ligation in CD8−/− mice. Methods and Results— After surgical excision of the femoral artery, laser Doppler perfusion imaging demonstrated reduced blood flow recovery in CD8−/− mice compared with C57/BL6 mice (ischemic/nonischemic limb at day 28, 0.66±0.04 versus 0.87±0.04, respectively; P<0.01). This resulted in greater calf muscle atrophy (mean fiber area, 785±68 versus 1067±69 &mgr;m2, respectively; P<0.01) and increased fibrotic tissue content (10.8±1.2% versus 7±1%, respectively; P<0.01). Moreover, CD8−/− mice displayed reduced IL-16 expression and decreased CD4+ T-cell recruitment at the site of collateral vessel development. Exogenous CD8+ T cells, infused into CD8−/− mice immediately after femoral artery ligation, selectively homed to the ischemic hind limb and expressed IL-16. The restoration of IL-16 expression resulted in significant CD4+ mononuclear cell infiltration of the ischemic limb, faster blood flow recovery, and reduced hindlimb muscle atrophy/fibrosis. When exogenous CD8+ T cells deficient in IL-16 (IL-16−/−) were infused into CD8−/− mice immediately after femoral artery ligation, they selectively homed to the ischemic hind limb but were unable to recruit CD4+ mononuclear cells and did not improve blood flow recovery. Conclusions— These results demonstrate that CD8+ T cells importantly contribute to the early phase of collateral development. After femoral artery ligation, CD8+ T cells infiltrate the site of collateral vessel growth and recruit CD4+ mononuclear cells through the expression of IL-16. Our study provides further evidence of the significant role of the immune system in modulating collateral development in response to peripheral ischemia.

The Italian study of the Mitroflow postoperative results (ISTHMUS): a 20-year, multicenter evaluation of Mitroflow pericardial bioprosthesis

OBJECTIVE A multicentre experience with the Mitroflow pericardial bioprosthesis has been evaluated longitudinally over a 20-year period. METHODS From 1988 through 2008, 1591 patients (mean age, 75.3±6.8 years, and 60.1% female) from 12 centres had a Mitroflow in the aortic position. Concomitant coronary artery bypass was performed in 41.9% (n=666) of patients, urgency/emergency surgery in 9.5% (n=152) and replacement of degenerated prosthesis in 2.3% (n=36). Follow-up (7.447 patient-years) was 99.2% complete. Median follow-up was 61.9 months (interquartile range (IQR) 30.8-90.9 months). The study was carried out following American Association for Thoracic Surgery/Society for Thoracic Surgeons/European Association for Cardio-Thoracic Surgery (AATS/STS/EACTS) Guidelines for reporting valve morbidity and mortality. RESULTS The early (30-day) mortality was 6.5% (n=104). Actuarial survival rates at 10, 15 and 18 years were 53%, 34% and 27%, respectively (2.2 patient/year). Re-operation was required in 96 patients (5.9%), of whom 59 patients (3.7%) for structural valve degeneration. Actuarial freedom from prosthetic valve degeneration at 18 years was 65.5% (78% in patients>70 years) with a linearised rate of 1.4 patient/year (0.8 patient/year in patients>70 years). At 18 years, freedom from embolism was 82% (0.9 patient/year), freedom from valve endocarditis was 89% (0.6 patient/year) and freedom from bleeding episodes was 95% (0.2 patient/year), respectively. CONCLUSIONS This independent multicentre study indicates that the Mitroflow pericardial bioprosthesis provides favourable long-term postoperative results with a low rate of valve-related events and need of re-intervention, particularly in patients older than 70 years.

Preoperative n-3 Polyunsatured Fatty Acids Are Associated With a Decrease in the Incidence of Early Atrial Fibrillation Following Cardiac Surgery

Background: Atrial fibrillation (AF) after cardiac surgery is associated with increased mortality, morbidity, and expenditure. Controversial data exist on possible preventive effects of n-3 polyunsatured fatty acids (PUFAs) against postoperative AF. We investigated whether preoperative PUFA therapy is effective in reducing AF after cardiac surgery during the surgical hospitalization and/or the cardiac rehabilitation period. Methods: Over a 4-year period, 530 patients (363 men, 68.5%) with a mean age of 66.4 ± 10.9 years, undergoing cardiac surgery were monitored for ‘‘early AF’’ and ‘‘late AF’’ defined as AF documented in the surgical department or during the rehabilitation program, respectively. Results: The overall incidence of early AF in the whole study sample was 44.7%, whereas late AF occurred in 14.7% patients. Patients with AF had a longer length of hospital and rehabilitation stay (10.4 ± 9.8 vs 9.5 ± 9.2 days, P = .025 and 24.2 ± 15.3 vs 21.1 ± 8.3 days, P = .008, respectively). Early AF occurred in 31.0% of the patients with preoperative PUFAs compared with 47.3% of those without them (P = .006). Conversely, late AF was not influenced by preoperative PUFA regimen (11.9% vs 15.2%, P = .43). Preoperative PUFAs were independently associated with a 46% reduction in risk of early AF development (OR 0.54, 95% CI 0.31-0.92), after propensity score analysis. Conclusion: Preoperative PUFA therapy is associated with a decreased incidence of early AF after cardiac surgery but not late AF. Patients undergoing cardiac surgery may benefit from a preventive PUFA approach.

Papillary Fibroelastoma: Insight to a Primary Cardiac Valve Tumor

Abstract  Papillary fibroelastomas are rare benign cardiac tumors. Although they have minimal hemodynamic effects, their propensity for embolization can result in serious morbidity. The pathophysiology and management of these tumors is the subject of this review. (J Card Surg 2010;25:198‐205)

Post-infarction cardiac rupture: surgical treatment

OBJECTIVE Rupture of ventricular free wall (VFWR) may complicate acute myocardial infarction and accounts for high mortality. Surgical repair is the only therapeutic option. A review of our surgical experience is presented. METHODS Seventeen patients (11 men, mean age 68 years) underwent surgery for VFWR. Patch covering technique was used in 13 patients, infarctectomy with patch reconstruction in three patients, direct suture without patch in one patient. Coronary artery bypass grafting was performed in eleven patients. RESULTS Hospital mortality was 17.6% (three patients). Three patients died of cancer during the follow-up. The remaining 11 patients are in good condition after a mean follow-up of 45.8 months (range 7.5-84.2). CONCLUSIONS Postinfarction rupture of ventricular free wall treated surgically gives excellent long-term results. Our first choice for repair is the covering technique with a large pericardial patch anchored with biological glue and epicardial sutures.

Culture of skeletal myoblasts from human donors aged over 40 years: dynamics of cell growth and expression of differentiation markers.

BackgroundLocal myogenesis, neoangiogenesis and homing of progenitor cells from the bone marrow appear to contribute to repair of the infarcted myocardium. Implantation into heart tissues of autologous skeletal myoblasts has been associated with improved contractile function in animal models and in humans with acute myocardial ischemia. Since heart infarction is most prevalent in individuals of over 40 years of age, we tested whether culture methods available in our laboratory were adequate to obtain sufficient numbers of differentiated skeletal myoblasts from muscle biopsy specimens obtained from patients aged 41 to 91.Methods and resultsNo matter of donor age, differentiated skeletal muscle cells could be produced in vitro in amounts adequate for cellular therapy (≥300 millions). Using desmin as a cytoplasmic marker, about 50% cultured cells were differentiated along myogenic lineages and expressed proteins proper of skeletal muscle (myosin type I and II, actin, actinin, spectrin and dystrophin). Cytogenetic alterations were not detected in cultured muscle cells that had undergone at least 10 population doublings. Molecular methods employed for the screening of persistent viral infections evidenced that HCV failed to replicate in muscle cells cultured from one patient with chronic HCV infection.ConclusionThe proposed culture methods appear to hold promise for aged patients not only in the field of cardiovascular medicine, but also in the urologic and orthopedic fields.

Type 2 Diabetes Mellitus Is Associated With Faster Degeneration of Bioprosthetic Valve Results From a Propensity Score–Matched Italian Multicenter Study

BACKGROUND The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration. METHODS AND RESULTS Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score-matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM (P<0.001), respectively. Seven-year freedom from valve deterioration was significantly lower in patients with DM (73.2% [95% confidence interval, 61.6-85.5] versus 95.4% [95% confidence interval, 83.9-100], P<0.001). In Cox regression models with robust SEs that accounted for the clustering of matched pairs, DM was the strongest predictor of structural valve degeneration (hazard ratio 2.39 [95% confidence interval 2.28-3.52]). When we allowed for interaction between type 2 DM and other key risk factors, DM remained a significant predictor beyond any potentially associated variable. CONCLUSIONS Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.Background— The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration. Methods and Results— Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score–matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM ( P <0.001), respectively. Seven-year freedom from valve deterioration was significantly lower in patients with DM (73.2% [95% confidence interval, 61.6–85.5] versus 95.4% [95% confidence interval, 83.9–100], P <0.001). In Cox regression models with robust SEs that accounted for the clustering of matched pairs, DM was the strongest predictor of structural valve degeneration (hazard ratio 2.39 [95% confidence interval 2.28–3.52]). When we allowed for interaction between type 2 DM and other key risk factors, DM remained a significant predictor beyond any potentially associated variable. Conclusions— Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration. # Clinical Perspective {#article-title-46}

Mitral valve surgery in emergency for severe acute regurgitation: analysis of postoperative results from a multicentre study.

OBJECTIVE To evaluate postoperative outcome of emergency surgery for acute severe mitral regurgitation (ASMR) from a multicentre experience. METHODS In six centres, 279 patients (mean age 62+/-14 years, 62% female) undergoing emergency surgery for ASMR from December 1986 to March 2007 were analysed and followed up. Aetiology included acute myocardial infarction (AMI) in 126 patients (group 1, 45%), degenerative mitral valve disease in 74 (group 2, 26%), and acute endocarditis (AE) in 79 (group 3, 28%). Preoperatively, all patients were in haemodynamic instability, with 185 patients in cardiogenic shock (66%), 184 (66%) intubated, and 61 (22%) on IABP, respectively. Valve repair was performed in 76 (27%), whereas 203 (73%) underwent valve replacement. Median follow-up (98% complete) was 70.8 months (inter-quartile range 59.8-86.66 months). RESULTS Overall 30-day mortality was 22.5% (63/279). Early death was significantly lower in group 2 (p<0.001 and p=0.005 vs group 1 and 3, respectively) whereas no difference was detected between group 1 and 3. At logistic regression analysis AMI, AE, shock, left ventricular dysfunction, and coronary artery disease were predictors of early death. Overall 15-year survival was 67+/-10%. Survival was lower in group 1 (39+/-11%) than in group 2 (75+/-9%) and group 3 (77+/-10%). Cox regression found AMI, and associated coronary artery disease to be predictors of late death. Overall 15-year actuarial and actual freedom from cardiac-related events were 44+/-9% and 28+/-10%, respectively, with the worst outcome in the presence of AE. Associated coronary artery disease, AE, AMI, preoperative atrial fibrillation, and chronic renal failure were independent predictors of cardiac-related events. CONCLUSIONS Emergency surgery for ASMR remains a surgical challenge for high incidence of early and late cardiac-related events, particularly in patients with associated coronary artery disease and acute endocarditis. Apparently, type of mitral valve surgical approaches (repair or replacement) did not provide any influence on postoperative outcome.