Secretory products from epicardial adipose tissue of patients with type 2 diabetes mellitus induce cardiomyocyte dysfunction.

BACKGROUND: Secreted factors from epicardial adipose tissue (EAT) have been implicated in the development of cardiomyocyte dysfunction. This study aimed to assess whether alterations in the secretory profile of EAT in patients with type 2 diabetes mellitus (DM2) affect contractile function and insulin action in cardiomyocytes. METHODS AND RESULTS: Contractile function and insulin action were analyzed in primary adult rat cardiomyocytes incubated with conditioned media (CM) generated from explants of EAT biopsies obtained from patients without and with DM2. CM from subcutaneous and pericardial adipose tissue biopsies from the same patients served as the control. Cardiomyocytes treated with CM (EAT) from DM2 patients showed reductions in sarcomere shortening, cytosolic Ca(2+) fluxes, expression of sarcoplasmic endoplasmic reticulum ATPase 2a, and decreased insulin-mediated Akt-Ser473-phosphorylation as compared with CM from the other groups. Profiling of the CM showed that activin A, angiopoietin-2, and CD14 selectively accumulated in CM-EAT-DM2 versus CM-EAT in patients without DM2 and CM from the other fat depots. Accordingly, EAT biopsies from DM2 patients were characterized by clusters of CD14-positive monocytes. Furthermore, SMAD2-phosphorylation, a downstream target of activin A signaling, was elevated in cardiomyocytes treated with CM (EAT) from DM2 patients, and the detrimental effects of CM (EAT) from DM2 patients were partially abolished in cardiomyocytes pretreated with a neutralizing antibody against activin A. Finally, both recombinant activin A and angiopoietin-2 reduced cardiomyocyte contractile function, but only activin A reduced the expression of sarcoplasmic endoplasmic reticulum ATPase 2a. CONCLUSIONS: Collectively, our data implicate DM2-related alterations in the secretory profile of EAT in the pathogenesis of diabetes mellitus-related heart disease.

Twenty years' single-center experience with mechanical heart valves: a critical review of anticoagulation policy.

BACKGROUND AND AIM OF THE STUDY: Since January 1990, a variety of mechanical valves (St. Jude Medical, CarboMedics, ATS Medical) have been implanted routinely at the authors' institution. The study aim was to analyze, retrospectively, the 20-year clinical results of those mechanical valves, and to challenge the anticoagulation policy employed over the years. METHODS: Between January 1990 and December 2008, a total of 2,108 mechanical valves was inserted into 1,887 consecutive patients (1,346 aortic, 725 mitral, 27 tricuspid, 10 pulmonary). The mean age of the patients was 63 +/- 13.2 years, and the majority (61%) were males. Preoperatively, 71% the patients were in NYHA class > or = III (average 3.01). The most frequent comorbidities included: atrial fibrillation (n = 594), coronary disease (n = 567) and diabetes (n = 398). The follow up (99% complete) totaled 13,721 patient-years (pt-yr), and ranged from 12 to 241 months (average 84 months). RESULTS: In-hospital mortality was 5.2% (n = 98, 14 valve-related). Of the 629 late deaths, the majority were cardiac (n = 276). Survival (Kaplan-Meier estimation) was significantly better for aortic valve patients compared to mitral or multiple valve replacement (Mantel-Cox, p < 0.0001). The overall linearized incidences (as %/pt-yr) were: valve thrombosis 0.31, thromboembolism 1.08, and bleeding 0.91. However, as repeated events occurred in several patients, the hazard function was not constant. Multivariate analysis (Cox regression model) showed age > 70 years (p < 0.0001), NYHA class > or = III (p < 0.0001), non-sinus rhythm (p = 0.001), concomitant coronary artery bypass grafting (p = 0.008) and higher International Normalized Ratio (INR) values (p = 0.013) as significant risk factors for death, with a trend for redo operations (p = 0.052). Multivariate analysis found variable INR, non-sinus rhythm and NYHA class > II as significant risk factors for thromboembolism, while long-acting coumadin and NYHA class > II were significant risk factors for bleeding. CONCLUSION: This 20-year experience demonstrated excellent clinical outcomes for patients with mechanical prostheses, with no valve structural failure and an acceptable incidence of adverse events. INR values between 2-2.5 for aortic valve patients, and 3-3.5 for mitral valve patients, yielded the fewest major adverse events.

A giant post-dissection aneurysm of the ascending aorta in an octogenarian.

Aneurysm formation is a well-known complication of untreated long-standing dissection of the aorta. Despite numerous advances in cardiac surgery, intrinsic diseases of the ascending aorta and aortic arch requiring surgical therapy, remain a technical challenge. However, surgery is the only option for effective treatment of ascending aorta aneurysm but carries an increased risk of severe morbidity and mortality, particularly in the elderly. We report on the successful repair of a giant ascending aorta aneurysm due to chronic dissection in an elderly woman with dyspnoea as main symptom.

Ten years single-centre experience with intra-aortic balloon pump.

OBJECTIVES: The objective of this study was to investigate the patient characteristics and outcomes in 1406 patients undergoing intra-aortic balloon pump (IABP) counterpulsation. METHODS: Between 1998 and 2008, 1406 consecutive patients were recorded in a prospective database. Based on the main clinical indication for IABP use, we defined 3 groups: group A, 630 cases of coronary ischaemia or infarction without serious left ventricular (LV) dysfunction; group B, 466 patients with left ventricular failure or cardiogenic shock; group C, 310 patients where IABP was used for miscellaneous procedures such as weaning from cardiopulmonary bypass or during high-risk angioplasty or surgery. RESULTS: Global mortality was 28% (n = 390), with a significant difference between group A (15%, n = 95) and group B (41%, n = 191) (P < 0.001). Mortality in group C was 34% (n = 104). Most insertions were done in the catheterization laboratory (n = 943) with subsequent mortality of 23% whereas 199 balloons were inserted in the operation room with 34% mortality. 170 balloons inserted in the intensive care unit resulted in 46% mortality (P < 0.001). Major IABP-induced complications were 6.8% with no statistical differences between the three groups. Advanced age, left ventricular failure and low BMI were identified as prognostic risk factors for early mortality. CONCLUSIONS: IABP deployed at an early clinical stage yields the best results, especially for acute coronary patients with preserved LV function whereas LV failure and late insertion result in worse outcome.

Late presentation of left main stem occlusion after blunt chest trauma.

Blunt chest trauma is a rare but known cause of acute coronary lesions. Commonly, the left anterior descending artery is involved which results in an anterior myocardial infarction, diagnosed within a variable time span of 24 hours to 6 months.We report on an unusual case of left main stem occlusion in a young adult patient presenting with evolving angina 5 years after an apparently minor chest trauma.

Fifteen years' single-center experience with the ATS bileaflet valve.

BACKGROUND AND AIM OF THE STUDY: Since its introduction in May 1992, the bileaflet ATS Open Pivot valve has been implanted routinely at the authors' institution. The study aim was to analyze, retrospectively, the 15-year clinical results of these implanted ATS valves. METHODS: Between May 1992 and December 2005, a total of 1,160 ATS valves (749 aortic, 381 mitral, 21 tricuspid, nine pulmonary) was implanted in 1,047 consecutive patients (655 males, 392 females; mean age 62.1 +/- 12.4 years). Preoperatively, 75% of the patients were in NYHA class III or higher (mean 3.1). The most frequent comorbidities included atrial fibrillation (n = 381), coronary disease (n = 288) and diabetes (n = 172). RESULTS: The mean follow up was 78 months (range: 24-183 months); the total follow up was 6,887 patient-years (pt-yr) and was 99.8% complete. In-hospital mortality was 4% (n = 43; three valve-related). Survival (Kaplan-Meier) at five and 10 years was significantly better for aortic than for mitral valve patients (84% and 65% versus 75% and 41%, respectively) (Mantel-Cox, p < 0.001). A log rank analysis detected no statistical difference in the incidence of thromboembolism (p = 0.182) or bleeding (p = 0.375) between both groups. The overall linearized incidences were: thromboembolism 1.08%/pt-yr; bleeding 0.91%/pt-yr; endocarditis 0.22%/pt-yr; paravalvular leakage 0.33%/pt-yr; and valve thrombosis 0.21%/pt-yr. Multivariate analysis (Cox regression) indicated age > 70 years (p < 0.0001), NYHA class > or = III (p < 0.0001), non-sinus rhythm (p = 0.001), concomitant CABG (p = 0.008) and higher INR values (p = 0.013) to be significant risk factors for death. CONCLUSION: This 15-year experience with the ATS bileaflet prosthesis showed excellent clinical outcomes for patients, with no structural failure and an acceptable incidence of adverse events.

Reappraisal of a single-centre policy on the contemporary surgical management of active infective endocarditis.

OBJECTIVES: We studied a contemporary cohort of adult patients treated surgically for infective endocarditis (IE) in order to evaluate the surgical approach and predictors of outcomes, in relation to the intercurrent adaptation of the 2006 ACC/AHA guidelines. METHODS: One hundred and eighty-six consecutive patients operated on for active IE from August 1999 to September 2012 were reviewed retrospectively. Clinical presentation, surgical management and outcomes in the two study periods before and after January 2007 were compared (Period 1: n = 95 and Period 2: n = 91). RESULTS: The mean (SD) follow-up was 4.3 (3.8) years and was 99.5% complete. Patients in Period 2 had more frequently associated coronary artery disease (31 vs 18%, P = 0.06), while the microbiology revealed more Staphylococcus species (43 vs 26%, P = 0.02), predominantly Staphylococcus aureus (31 vs 19%; P = 0.07), and less culture-negative cases (7 vs 17%; P = 0.05). The median delay between diagnosis and surgery was 7 days in Period 2 compared with 14 days in Period 1 (P = 0.001). Surgery in Period 2 included more root replacements for aortic valve endocarditis (11 vs 2%; P = 0.02) and mitral valve repairs (18 vs 5%; P = 0.01), while the use of homografts for aortic valve endocarditis was almost abandoned (1 vs 15%; P = 0.001). Hospital mortality was 13% and did not change significantly over both periods (P = 0.66). The independent predictors of hospital mortality were age (P = 0.03), female gender (P = 0.02), previous cardiac surgery (P = 0.02), preoperative serum creatinine level >2 mg/dl (P = 0.05), S. aureus infection (P = 0.02), emergent or salvage operation (P = 0.001) and concomitant coronary artery bypass grafting (P = 0.03). The 1-, 3-, 5- and 10-year survival were 84, 72, 64 and 57%, respectively. Late survival was negatively influenced by S. aureus endocarditis (P < 0.001) and peripheral vascular disease (P = 0.03), whereas associated coronary artery disease (P = 0.07) had a strong impact. CONCLUSIONS: Adaptation of the 2006 ACC/AHA guidelines in the contemporary management of IE led to a shorter interval between diagnosis and surgery. Despite a more extensive and earlier operative approach, IE caused by S. aureus still remains a major determinant of early and late outcomes.

Twenty-year single-center experience with the medtronic open pivot mechanical heart valve.

BACKGROUND: Since May 1992 the Medtronic Open Pivot mechanical heart valve has been implanted routinely at the authors' institution. The study aim was to analyze, retrospectively, the 20-year clinical results of the valve. METHODS: Between May 1992 and December 2011 a total of 1,520 valves was inserted into 1,382 consecutive patients (1,012 aortic, 473 mitral, 26 tricuspid, 9 pulmonary). The mean age of the patients was 61±13.2 years. Preoperatively, 65% of the patients were in New York Heart Association (NYHA) class III or greater. Frequent comorbidities included atrial fibrillation (n=419), coronary disease (n=357), and diabetes (n=255). The 99% complete follow-up totaled 10,527 patient-years (range 12 to 244 months). RESULTS: Ninety-day mortality was 5.2% (n=73, 8 valve related). Of the 550 total deaths, 240 were cardiac and 56 valve related. Multivariate analysis selected age, NYHA III or greater, concomitant coronary revascularization, and respiratory insufficiency as risk factors for death. Renal failure was considered a risk factor in the aortic and atrial fibrillation in the mitral subgroup. Erratic international normalized ratio (INR), NYHA class III or greater, and non-sinus rhythm were risk factors for thromboembolism; likewise redo operations in the aortic subgroup. Erratic INR and age were risk factors for bleeding as were over-coagulation and coronary revascularization in the aortic subgroup and redo operations and renal failure in mitral patients. CONCLUSIONS: This 20-year experience demonstrated excellent clinical outcomes with no structural valve failure. Odds ratio defined aortic patients as the lowest risk for adverse events. By contrast atrial fibrillation and elderly age, in combination with instable anticoagulation, yielded the worst long-term results.

Ultrasound-guided thoracotomy for implantation of an epicardial left ventricular lead after left pneumonectomy.

Surgical placement of a left ventricular epicardial pacing lead is a valuable alternative to the standard approach of endovascular placement of a pacing lead in the coronary sinus for cardiac resynchronization therapy. Despite higher perioperative morbidity, surgically placed leads perform well with lower revision and dislocation rates. Moreover, surgery is the only option when an endovascular approach proves to be unsuccessful. We report a successful implantation of an epicardial left ventricular lead through an ultrasound-guided lateral left mini-thoracotomy in a patient with a severely disturbed thoracic anatomy due to left pneumonectomy.

Endogenous oestradiol and cardiovascular disease in healthy men: a systematic review and meta-analysis of prospective studies.

CONTEXT: The literature provides no clear answer as to whether total oestradiol (E2) concentrations increase the risk of incident cardiovascular disease (CVD) in healthy men. OBJECTIVE: The authors conducted a systematic review and meta-analysis to estimate the predictive value of E2 for CVD, and to identify study features explaining conflicting results. DATA SOURCES: Articles were identified by a Medline and Embase search and citation tracking. STUDY SELECTION: Eligible articles were prospective population-based cohorts and nested case-control studies on E2 and incident cardiovascular disease (CVD), including myocardial infarction, stroke or death from coronary heart disease. DATA-EXTRACTION: Independent researchers re-expressed associations of E2 and incident CVD in a uniform manner to be used in meta-regression analyses for identification of study features explaining conflicting results, and to estimate the predictive value of E2 for CVD. RESULTS AND CONCLUSIONS: 14 studies out of 128 electronically identified articles were eligible. Data to be used for meta-analysis could be calculated in seven cases, and in the remaining seven cases, data of three more became available by contacting those authors. Overall, a non-significant association was found with an estimated summary RR of 0.98 for a change of >75th versus <25th percentile in E2 (95% CI 0.74 to 1.31). Mean body mass index (BMI) of the study population (ßs -0.8, p<0.004), and quality of E2 assay (ßs -0.6, p<0.08) may have modified the relationship between E2 and incident CVD. The present systematic review does not provide evidence for a pronounced harmful or beneficial effect of E2 on risk for incident CVD in healthy men. If present, an effect of E2 on risk for CVD might be modulated by BMI.

Short-term systolic and diastolic ventricular performance after surgical ventricular restoration for dilated ischemic cardiomyopathy.

OBJECTIVE: Based on the adverse relationship between left ventricular (LV) remodeling and clinical outcome in ischemic cardiomyopathy, surgical ventricular restoration (SVR) is proposed as a valuable adjunct procedure. This study reports on the short-term clinical and hemodynamical performance of SVR. METHODS: Using end-systolic LV volume as indication for SVR, 78 patients with ischemic cardiomyopathy are divided in two groups: group 1 comprised 55 patients treated by coronary revascularization and mitral annuloplasty, group 2 comprised 23 patients undergoing additional SVR. Hemodynamic investigation included echocardiographic assessment of systolic and diastolic function. Clinical follow-up focused on survival and functional status with exercise performance. RESULTS: Both surgical approaches resulted in improvement of NYHA class (2.9-1.6 in group 1; 3.3-1.5 in group 2, p<0.001), achieving similar exercise performance (peak VO2 13.7 vs 15.4 ml/kgmin in groups 1 and 2, p=0.25) and plasma BNP values (group 1: 1350 pg/ml and group 2: 767 pg/ml, p=0.23). SVR provided additional benefit as patients basically had a worse NYHA class (2.9 in group 1 vs 3.3 in group 2, p=0.03). Within mean follow-up of 20 months, survival rate was 84% in group 1 and 74% in group 2 (p=0.11), including operative mortality of 7% and 13% (p=0.42). Through effective volume reduction (LVEDVI 41%; LVESVI 49%) systolic function improved immediately after SVR (LVEF 27-39% in group 2, p<0.05). Worsening of diastolic function was specifically observed after SVR within the first year (E/A-ratio 1.38-1.74 cm/s, p=0.02). Recurrent mitral regurgitation (p=0.004) and secondary remodeling (p=0.01) were major determinants of decreasing LV compliance. Clinical outcome in terms of cardiac events and survival was compromised by restrictive diastolic function (p=0.02) and increased LV volumes (p=0.04). CONCLUSION: SVR in addition to coronary revascularization and restrictive mitral annuloplasty results in significant clinical improvement in selected patients with advanced ischemic heart disease and severely dilated ventricles. SVR entails immediate improvement of systolic function, which remains sustained during short-term follow-up. Serial assessment of diastolic function is mandatory as LV compliance seems more sensitive to early changes induced by recurrence of mitral regurgitation and secondary ventricular dilation. Moreover, worsening of diastolic dysfunction should be timely recognized because of its adverse clinical impact.

Midterm assessment of the reconstructed arteries after the arterial switch operation.

BACKGROUND: The arterial switch operation is the preferred treatment for transposition of the great arteries (TGA), but there are concerns on the fate of the neoarterial trunks. METHODS: Ninety-three children were reviewed for functional and morphologic assessment of both reconstructed arteries after the arterial switch operation. Longitudinal analysis focused on neoaortic valve function, neoaortic obstruction, and neopulmonary stenosis as well as on the time-related size changes of both roots, with its clinical implications. RESULTS: Within a mean follow-up of 4.8 +/- 3.9 years, aortic regurgitation of 2 or greater developed in 10% in TGA with intact ventricular septum (IVS) versus 23% in TGA with ventricular septal defect (VSD). A VSD and major pulmonary to aortic annulus size discrepancy were main precursors of early neoaortic valve dysfunction, whereas development of aortic regurgitation of 2 or greater was additionally promoted by the duration of follow-up. Presence of a VSD enhanced neoaortic root enlargement, resulting in a mean root z-score of 3.25 in TGA/VSD versus 1.96 in TGA/IVS. Root dilation was more severe in case of aortic regurgitation of 2 or greater (z = 3.38). Neoaortic obstruction occurred in 8%, mostly at the neosinotubular anastomosis, and correlated with prior pulmonary to aortic ratio greater than 1.5. Concerning the neopulmonary tract, increased flow velocity was observed in 24%, primarily at the supravalvular level. Two patients with pulmonary annulus hypoplasia (z < -2) required early reintervention. Regarding clinical outcome, freedom from reintervention at 1, 5, and 10 years was, respectively, 98%, 96%, and 96% for TGA/IVS, versus 65%, 63%, and 63% for TGA/VSD. A VSD and aortic arch obstruction were significant predictors for reintervention. CONCLUSIONS: After arterial switch operation, the neoaortic root is usually enlarged, but with a growth pattern comparable to that of a normal population. The association of a VSD and major arterial root size discrepancy predisposes to both neoaortic valve dysfunction and root enlargement. Severe root dilation appears to be closely related to significant neoaortic valve regurgitation, mainly as a result of a time-depending and reciprocal process. Neopulmonary stenosis is a frequent finding, but rarely has clinical consequences. Because the factor "time" is the principal determinant of late neoaortic valve dysfunction and root dilation, strict serial surveillance after arterial switch operation is mandatory.