Reduced Permanent Pacemaker Implantation in Patients With Stentless Freedom SOLO Compared With Stented Perimount Magna Aortic Bioprostheses: A Propensity Score Weighted Analysis.

OBJECTIVES: Postoperative permanent pacemaker implantation (PPI) after conventional aortic valve replacement (AVR), due to new-onset severe conduction system disorders, is required in approximately 7% of patients. This study investigated the need for PPI after AVR with conventional stented Perimount Magna compared with the Freedom SOLO (FS) stentless valve (Sorin Group, Saluggia, Italy), now LivaNova plc (London, UK) that uses a strictly supra-annular, subcoronary running suture implantation technique, sparing the vulnerable interleaflet triangles in the region of the septum membranaceum. METHODS: A total of 413 consecutive patients (71.4±9.2 yrs, 178 [43.1%] female) underwent isolated AVR using the stented Perimount Magna (n=264) or the stentless FS (n=149) bioprosthesis. Propensity score weighted analysis was used to account for patient-specific and procedural-specific variables, and to identify the prosthesis-specific need for early postoperative PPI within 30 days of AVR. RESULTS: Twenty (20) patients required PPI, which was associated with longer intensive care unit (2.1±1.7 vs 1.5±3.0 days, p<0.001) and overall hospital stays (13.8±5.2 vs 10.7±5.3 days, p<0.001) compared with no PPI. Propensity weighted logistic regression including cross-clamp times identified that use of the stented Perimount Magna was associated with increased need for PPI, as compared with the FS, with an odds ratio 5.8 (95% CI, 1.09-30.76; p=0.039). CONCLUSIONS: After corrections for all plausible confounders, AVR with the stented Perimount valve was associated with an odds ratio of almost 6 for an increased early postoperative need for pacemaker implantation compared with the FS stentless valve. This finding can be explained by the conventional implantation technique, which is potentially associated with mechanical trauma to the conducting system.

A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes in Healthy Humans and Their Effects on Homocysteine, Oxidative Stress, and Antioxidant Levels.

The vitamin B complex comprises 8 different water-soluble constituents that humans must sequester from the diet. This pilot study compared natural versus synthetic vitamin B complexes for their bioavailability, accumulation, and their impact on antioxidants, homocysteine levels, and oxidative stress. We conducted a double-blind randomized clinical trial with thirty healthy participants. They were randomly assigned to group N (natural) and group S (synthetic). Vitamin B was ingested daily for 6 weeks in the range of about 2.5 times above the recommended daily allowance. Blood samples were taken at baseline, 1.5 h, 4 h, 7 h (diurnal), 6 w (discontinuation of supplements), and 8 w (washout). Blood levels of thiamine (B1), riboflavin (B2), pyridoxine (B6), folic acid (B9), cobalamin (B12), homocysteine, total antioxidants, peroxidase activity, polyphenols, and total peroxides were determined. Compared to initial values, serum levels of each B vitamin increased at the end of the supplementation period: i.e., B1 (+23% N; +27% S), B2 (+14% N; +13% S), B6 (+101% N; +101% S), B9 (+86% N; +153% S), and B12 (+16% N) (p < 0.05). Homocysteine (-13% N) decreased, while peroxidase activity (+41% S) and antioxidant capacity increased (+26% N). Short-term effects were already observed after 1.5 h for B9 (+238% N; +246% S) and after 4 h for vitamin B2 (+7% N; +8% S), B6 (+59% N; +51% S), and peroxidase activity (+58% N; +58% S). During the washout period, serum levels of B vitamins decreased except for thiamine and peroxidase activity, which increased further. This clinical pilot study revealed comparable bioavailability for both natural and synthetic B vitamins but did not show statistically noticeable differences between groups despite some favourable tendencies within the natural vitamin group, i.e., sustained effects for cobalamin and endogenous peroxidase activity and a decrease in homocysteine and oxidative stress levels.

Freedom SOLO-Associated Thrombocytopaenia is Valve-Dependent and Not Due to In Vitro Pseudothrombocytopaenia.

BACKGROUND: Use of the Freedom SOLO (FS) stentless aortic bioprosthesis is limited by a unique and as yet unexplained severe decrease in postoperative platelet count in the absence of FS-related excess bleeding or thromboembolism. We investigated whether anticoagulant-associated pseudothrombocytopaenia could explain this complication. METHODS: Thirty consecutive patients (mean age 75.4±7.7 years, 11 [36.7%] female) underwent elective aortic valve replacement (AVR) with either the stented bovine Mitroflow (MF, n=18) or the stentless bovine FS (n=12) aortic valve bioprostheses. Serial platelet counts were performed simultaneously with sampling tubes containing tripotassium (K3-)-EDTA, trisodium (Na3)-citrate, or novel alternative magnesium sulfate (MgSO4, ThromboExact™)-based anticoagulant, respectively. RESULTS: Postoperative platelet counts decreased compared with preoperative values in all patients (p<0.001), but were significantly lower in patients receiving FS compared to MF at all measurement time points until the end of observation (day 9). Lowest platelet counts were seen on the first postoperative day for MF (mean reduction: -41.5%) and on the second postoperative day for FS (mean reduction: -59.9%). Postoperative platelet counts did not correlate with any of the anticoagulants, thereby indicating no pseudothrombocytopaenia in the study population. There was no interaction between anticoagulant and type of valve. Only 1% of variance in platelet counts was caused by the anticoagulant, 46% by the day of measurement relative to baseline, and 20% was caused by the type of valve. CONCLUSIONS: The platelet-lowering effect in patients receiving the FS is valve-dependent and is not caused by systemic preanalytical (laboratory) measurement error such as anticoagulant-dependent pseudothrombocytaemia, particularly with EDTA and citrate.

The Freedom Solo pericardial stentless valve: Single-center experience, outcomes, and long-term durability.

OBJECTIVES: To report our institutional experience and long-term results with the Freedom Solo bovine pericardial stentless bioprosthesis (Sorin Group, Saluggia, Italy). METHODS: Between January 2005 and November 2009, 149 patients (mean age, 73.6 ± 8.7 years; 68 [45.6%] female) underwent isolated (n = 75) or combined (n = 74) aortic valve replacement (AVR) using the Solo in our institution. Follow-up was 100% complete with an average follow-up time of 5.9 ± 2.6 years (maximum, 9.6 years) and a total of 885.3 patient years. RESULTS: Operative (30-day) mortality was 2.7% (1.3% for isolated AVR [n = 1] and 4.0% for combined procedures [n = 3]). All causes of death were not valve-related. Preoperative peak (mean) gradients of 74.2 ± 23.0 mm Hg (48.6 ± 16.3 mm Hg) decreased to 15.6 ± 5.4 mm Hg (8.8 ± 3.0 mm Hg) after AVR, and remained low for up to 9 years. The postoperative effective orifice area was 1.6 ± 0.57 cm(2), 1.90 ± 0.45 cm(2), 2.12 ± 0.48 cm(2), and 2.20 ± 0.66 cm(2) for the valve sizes 21, 23, 25, and 27, respectively, with absence of severe prosthesis-patient mismatch and 0.7% (n = 1) experienced moderate prosthesis-patient mismatch. During follow-up, 26 patients experienced structural valve deterioration (SVD) and 14 patients underwent explantation. Kaplan-Meier estimates for freedom from death, explantation, and SVD at 9 years averaged 0.57 (range, 0.47-0.66), 0.82 (range, 0.69-0.90), and 0.70 (range, 0.57-0.79), respectively. CONCLUSIONS: The Freedom Solo stentless aortic valve is safe to implant and shows excellent early and midterm hemodynamic performance. However, SVD was observed in a substantial number of patients after only 5-6 years and the need for explantation increased markedly, suggesting low durability.

Pitfalls and premature failure of the Freedom SOLO stentless valve.

OBJECTIVES: This study reports a series of pitfalls, premature failures and explantation of the third-generation Freedom SOLO (FS) bovine pericardial stentless valve. METHODS: A total of 149 patients underwent aortic valve replacement using the FS. Follow-up was 100% complete with an average observation time of 5.5 ± 2.3 years (maximum 8.7 years) and a total of 825 patient-years. Following intraoperative documentation, all explanted valve prostheses underwent histological examination. RESULTS: Freedom from structural valve deterioration (SVD) at 5, 6, 7, 8 and 9 years was 92, 88, 80, 70 and 62%, respectively. Fourteen prostheses required explantation due to valve-independent dysfunction (n = 5; i.e. thrombus formation, oversizing, aortic dilatation, endocarditis and suture dehiscence) or valve-dependent failure (acute leaflet tears, n = 4 and severe stenosis, n = 5). Thus, freedom from explantation at 5, 6, 7, 8 and 9 years was 95, 94, 91, 81 and 72%, respectively. An acute vertical tear along the non-coronary/right coronary commissure to the base occurred at a mean of 6.0 years (range 4.3-7.3 years) and affected size 25 and 27 prostheses exclusively. Four FS required explantation after a mean of 7.5 years (range 7.0-8.3 years) due to severe functional stenosis and gross calcification that included the entire aortic root. CONCLUSIONS: The FS stentless valve is safe to implant and shows satisfying mid-term results in our single institution experience. Freedom from SVD and explantation decreased markedly after only 6-7 years, so that patients with FS require close observation and follow-up. Exact sizing, symmetric positioning and observing patient limitations are crucial for optimal outcome.

Clinical experience with the freedom SOLO stentless aortic valve in 277 consecutive patients.

BACKGROUND: The Sorin Freedom SOLO (FS) bovine pericardial stentless valve prosthesis is designed for supraannular, subcoronary implantation. We report our experience and results with 277 consecutively implanted FS bioprostheses. METHODS: 277 patients (mean age, 74.2 ± 7.3 years; 139 (50.2%) female) underwent aortic valve replacement (AVR) with the FS stentless bioprosthesis. The hemodynamic performance was investigated with transthoracic echocardiography at discharge, 6 months later, and yearly thereafter. Follow-up was 100% complete, with an average observation time of 2.6 ± 1.7 years and a total of 697.3 patient-years. RESULTS: The overall 30-day mortality was 4.3%. The mortalities for isolated AVR and combined procedures were 1.9% and 7.3%, respectively. No causes of death were valve-related. Preoperative peak (74.2 ± 23.0 mm Hg) and mean (48.6 ± 16.3 mm Hg) gradients decreased to 15.6 ± 5.4 mm Hg and 8.8 ± 3.0 mm Hg postoperatively and remained unchanged for as long as 5 years. The postoperative mean effective orifice area (EOA) for valve sizes 19, 21, 23, 25, and 27 were 1.49 ± 0.32 cm(2), 1.67 ± 0.40 cm(2), 1.92 ± 0.38 cm(2), 2.01 ± 0.42 cm(2), and 2.13 ± 0.36 cm(2), respectively. Severe prosthesis-patient mismach (PPM) was completely absent, and moderate PPM occurred in 17 patients (6.1%). In isolated AVR, 0.8% of patients with preoperative sinus rhythm required a permanent pacemaker before hospital discharge. There was 100% freedom from structural valve deterioration, 99.6 % freedom from endocarditis and reoperation, and 97.3% freedom from thromboembolism at 5 years. CONCLUSIONS: The FS stentless aortic valve is safe to implant, and it shows excellent hemodynamic performance and early and midterm results. Owing to the favorable EOA, the valve appears particularly attractive for patients at risk for PPM.

Mid-term results of aortic root replacement using a self-assembled biological composite graft.

OBJECTIVES: To report the mid-term results of aortic root replacement using a self-assembled biological composite graft, consisting of a vascular tube graft and a stented tissue valve. METHODS: Between January 2005 and December 2011, 201 consecutive patients [median age 66 (interquartile range, IQR, 55-77) years, 31 female patients (15.4%), median logistic EuroSCORE 10 (IQR 6.8-23.2)] underwent aortic root replacement using a stented tissue valve for the following indications: annulo-aortic ectasia or ascending aortic aneurysm with aortic valve disease in 162 (76.8%) patients, active infective endocarditis in 18 (9.0%) and acute aortic dissection Stanford type A in 21 (10.4%). All patients underwent clinical and echocardiographic follow-up. We analysed survival and valve-related events. RESULTS: The overall in-hospital mortality rate was 4.5%. One- and 5-year cardiac-related mortality rates were 3 and 6%, and overall survival was 95 ± 1.5 and 75 ± 3.6%, respectively. The rate of freedom from structural valve failure was 99% and 97 ± 0.4% at the 1- and 5-year follow-up, respectively. The incidence rates of prosthetic valve endocarditis were 3 and 4%, respectively. During a median follow-up of 28 (IQR 14-51) months, only 2 (1%) patients required valve-related redo surgery due to prosthetic valvular endocarditis and none suffered from thromboembolic events. One percent of patients showed structural valve deterioration without any clinical symptoms; none of the patients suffered greater than mild aortic regurgitation. CONCLUSIONS: Aortic root replacement using a self-assembled biological composite graft is an interesting option. Haemodynamic results are excellent, with freedom from structured valve failure. Need for reoperation is extremely low, but long-term results are necessary to prove the durability of this concept.

Antioxidant supplementation attenuates oxidative stress in patients undergoing coronary artery bypass graft surgery.

Ischemia-reperfusion has been reported to be associated with augmented oxidative stress in the course of surgery, which might be causally involved in the onset of atrial fibrillation (AF), the most common arrhythmia after cardiac surgery. We hypothesized that supplementation of antioxidants and n-3 polyunsaturated fatty acids (n-3 PUFAs) might lower the incidence of AF following coronary artery bypass graft (CABG) surgery. In the present study, by monitoring oxidative stress in the course of CABG surgery, we analyzed the efficacy of vitamins (ascorbic acid and α-tocopherol) and/or n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid). Subjects (n = 75) were divided into 4 subgroups: control, vitamins, n-3 PUFAs, and a combination of vitamins and n-3 PUFAs. Fluorescent techniques were used to measure the antioxidative capacity, i.e. ability to inhibit oxidation. Total peroxides, endogenous peroxidase activity, and antibodies against oxidized LDL (oLAb) were used as serum oxidative stress biomarkers. Post-operative increase in oxidative stress was associated with the consumption of antioxidants and a simultaneous onset of AF. This was confirmed through an increased peroxide level and a decreased oLAb titer in control and n-3 PUFAs groups, indicating the binding of antibodies to oxidative modified epitopes. In both subgroups that were supplemented with vitamins, total peroxides decreased, and the maintenance of a constant IgG antibody titer was facilitated. However, treatment with vitamins or n-3 PUFAs was inefficient with respect to AF onset and its duration. We conclude that the administration of vitamins attenuates post-operative oxidative stress in the course of CABG surgery.

Type A aortic dissection after nonaortic cardiac surgery.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass is associated with mechanical manipulation of the ascending aorta that occasionally leads to type A aortic dissection (AAD). METHODS AND RESULTS: One hundred three patients with surgical repair for AAD following nonaortic cardiac surgery were identified. With the use of logistic regression modeling, coronary artery bypass surgery (CABG), either isolated or combined with another procedure in the initial operation, was associated with significantly higher operative mortality in comparison with patients with non-CABG procedures at the time of AAD repair both for all patients (odds ratio, 2.90; 95% confidence interval, 1.09-7.72; P=0.033) and for patients with acute and chronic AAD≥30 days after the initial operation (odds ratio, 3.62; 95% confidence interval, 1.13-11.54; P=0.03). In patients who developed AAD late after the initial operation, operative mortality was highest in patients without preoperative coronary angiography and appropriate management of their native coronary artery disease and graft disease (odds ratio, 5.36; 95% confidence interval, 1.68-17.0; P=0.002). Nearly all the intimal dissection tears were located at sites of previous surgical trauma. Most of the ascending aortas that had dissected initially had a diameter≥40 mm with histological evidence of medial degeneration in resected tissue samples. CONCLUSIONS: In patients who have undergone previous cardiac surgery, preexisting aortic wall pathology contributes to AAD with typical intimal damage at sites of mechanical trauma. The operative mortality was the highest in patients with previous CABG in comparison with patients with non-CABG procedures. Preoperative coronary angiography and operative management of native coronary and graft disease were significantly associated with outcome in patients with previous CABG.

Enzymatic and non-enzymatic antioxidative effects of folic acid and its reduced derivates.

A great part of the population appears to have insufficient folate intake, especially subgroups with higher demand, as determined through more sensitive methods and parameters currently in use. As the role of folate deficiency in congenital defects, e.g. in cardiovascular and neurodegenerative diseases, and in carcinogenesis has become better understood, folate has been recognized as having great potential to prevent these many disorders through folate supplementation or fortification for the general population. Folates are essential cofactors in the transfer and utilization of one-carbon groups in the process of DNA-biosynthesis with implications for genomic repair and stability. Folate acts indirectly to lower homocysteine levels and insures optimal functioning of the methylation cycle. Homocysteine was shown to be an independent risk factor for neurodegenerative and cardiovascular disease, which includes peripheral vascular disease, coronary artery disease, cerebrovascular disease and venous thrombosis. In fact, it was long believed that the beneficial effects of folate on vascular function and disease are related directly to the mechanism of homocysteine-diminution. Recent investigations have, however, demonstrated beneficial effects of folates unrelated to homocysteine-diminution, suggesting independent properties. One such mechanism could be free radical scavenging and antioxidant activity, as it is now recognized that free radicals play an important role in the oxidative stress leading to many diseases. It was found that folic acid and, in particular, its reduced derivates act both directly and indirectly to produce antioxidant effects. Folates interact with the endothelial enzyme NO synthase (eNOS) and, exert effects on the cofactor bioavailability of NO and thus, on peroxynitrite formation. Folate metabolism provides an interesting example of gene-environmental interaction.

Severe non-valve-related hemolytic anemia following aortic root replacement.

Aortic interposition grafting combined with aortic root replacement (conduit) is widely performed to manage thoracic aortic aneurysms. Intravascular hemolysis without clinical significance is occasionally observed as a complication after prosthetic valve replacement. Symptomatic lysis of red blood cells (RBCs) is rare and primarily attributed to mechanical damage as result of high shear stress, turbulent flow, and physical interaction. We report a case of severe hemolytic anemia shortly after mechanical conduit implantation. The RBC damage was not related to the valve prosthesis and resolved completely after replacement of a section of the kinked Dacron tube graft to correct a fold.

Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and treatment recommendations.

In Europe, neuropsychiatric diseases currently make up approximately a third of the total burden of disease. In 2004, 27% of the overall population was affected by at least one of the most frequent neuropsychiatric diseases such as Alzheimer's dementia, Parkinson's disease, stroke or depression. The annual costs of care exceed those of cancer, cardiovascular conditions and diabetes. In order to delay the onset or course of neurodegenerative diseases, the available potential should be utilized. As well as improving quality of life of patients and relatives, this may reduce the great financial burden caused by neurodegenerative disorders. However, the availability of established drugs or therapeutic agents is very limited. This paper reviews the state of current knowledge as to how homocysteine metabolism is relevant for neurodegenerative and other neuropsychiatric diseases, with particular emphasis on the evidence for prophylactic and therapeutic strategies. In the European countries, many people do not take the recommended daily minimum amount of folate and vitamin B12. Deficiency of these vitamins and secondary changes in the concentrations of associated metabolites, such as methylmalonic acid and homocysteine, may contribute to the onset and progression of neuropsychiatric diseases. This paper reviews the evidence regarding whether substitution of folate and vitamin B12 is beneficial, for example, in cerebrovascular disease, dementia and depression.

Immunohistochemical detection of N-homocysteinylated proteins in humans and mice.

N-homocysteinylation of epsilon-amino group of protein lysine residues by homocysteine (Hcy) thiolactone has been implicated in vascular disease in humans. We have previously generated polyclonal rabbit anti-N-Hcy-protein IgG antibodies that specifically recognize the Nepsilon-Hcy-Lys epitope on N-homocysteinylated proteins. The present work was undertaken to examine the utility of these antibodies for the immunohistochemical detection of N-homocysteinylated proteins in biological samples. We found that the rabbit antibody specifically detected N-Hcy-protein in a dot-blot assay, that the signal resulting from the reaction of the antibody with N-Hcy-protein depended on the amount of the antigen, and that the sensitivity of the assay was protein-dependent. The rabbit anti-N-Hcy-protein IgG also specifically detected Nepsilon-Hcy-Lys epitopes in human tissues, as shown by positive immunohistochemical staining of myocardium and aorta samples from cardiac surgery patients, and a lack of staining when the antibody was pre-adsorbed with N-Hcy-albumin. We also observed increased immunohistochemical staining for N-Hcy-proteins in aortic lesions from ApoE-/- mice with hyperhomocysteinemia induced by a high methionine diet, relative to ApoE-/- mice fed a control chow diet. In conclusion, polyclonal rabbit anti-N-Hcy-protein antibody can detect and monitor N-homocysteinylated proteins in human and mouse tissues with good sensitivity and specificity.

Surgical treatment of coronary multivessel disease.

Coronary artery bypass grafting has had a significant impact on the treatment of angina, and has been the 'gold standard' since 1969. Its use and efficacy has been increased by revascularization in cardiac arrest and the use of the internal mammary artery. In parallel, catheter techniques have evolved by means of balloon dilatation and additional stenting. This has effected the referral to surgery despite the development of new arterialization techniques and minimally invasive surgery. As competing techniques, an acceptable equilibrium between surgery and stenting will be found within the next years.