Efficacy of losartan vs. atenolol for the prevention of aortic dilation in Marfan syndrome: a randomized clinical trial.

AIMS: To determine the efficacy of losartan vs. atenolol in aortic dilation progression in Marfan syndrome (MFS) patients. METHODS AND RESULTS: A phase IIIb, randomized, parallel, double-blind study was conducted in 140 MFS patients, age range: 5-60 years, with maximum aortic diameter <45 mm who received losartan (n = 70) or atenolol (n = 70). Doses were raised to a maximum of 1.4 mg/kg/day or 100 mg/day. The primary end-point was the change in aortic root and ascending aorta maximum diameter indexed by body surface area on magnetic resonance imaging after 36 months of treatment. No serious drug-related adverse effects were observed. Five patients presented aortic events during a follow-up (one in the losartan and four in the atenolol groups, P = 0.366). After 3 years of follow-up, aortic root diameter increased significantly in both groups: 1.1 mm (95% CI 0.6-1.6) in the losartan and 1.4 mm (95% CI 0.9-1.9) in the atenolol group, with aortic dilatation progression being similar in both groups: absolute difference between losartan and atenolol -0.3 mm (95% CI -1.1 to 0.4, P = 0.382) and indexed by BSA -0.5 mm/m2 (95% CI -1.2 to 0.1, P = 0.092). Similarly, no significant differences were found in indexed ascending aorta diameter changes between the losartan and atenolol groups: -0.3 mm/m2 (95% CI -0.8 to 0.3, P = 0.326). CONCLUSION: Among patients with MFS, the use of losartan compared with atenolol did not result in significant differences in the progression of aortic root and ascending aorta diameters over 3 years of follow-up.

Activation of peroxisome proliferator-activated receptor-alpha and -gamma in auricular tissue from heart failure patients.

OBJECTIVE: Peroxisome proliferator-activated receptors (PPARs), key transcriptional regulators of lipid and energy metabolism in cardiomyocytes, have recently been proposed to modulate cardiovascular pathophysiological responses in experimental models. However, there is little information about the functional activity of PPARs in human heart failure. AIMS: To investigate PPAR-alpha and -gamma expression and activity, and the association with ET-1 production and fibrosis, in cardiac biopsies from patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) in comparison and from non-failing donor hearts. All samples were obtained during cardiac transplantation. METHODS AND RESULTS: Morphological analysis (by Masson trichrome and image analysis) did not detect fibrosis in the left atrium from non-failing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21+/-1.15, FLA: 1.63+/-0.83, FLV: 14.5+/-3.45%; n = 9, P<0.05). By RT-PCR, preproET-1 expression was similar in the non-failing and failing atrium but was significantly higher in the ventricles from failing hearts (NFLA: 1.00+/-0.06, FLA: 1.08+/-0.11, FLV: 1.74+/-0.19; n = 9, P<0.05). PPAR-alpha and PPAP-gamma mRNA (by RT-PCR) and protein (by Western blot) levels were higher in the ventricles from failing hearts compared with the atrium from failing and non-failing hearts. Electrophoretic mobility shift assays showed that PPAR-alpha and PPAP-gamma were not activated in the ventricles (NFLA: 1.00+/-0.11, FLA: 1.89+/-0.24, FLV: 0.95+/-0.07; n = 9, P<0.05). CONCLUSIONS: These data suggest that PPAR-alpha and PPAP-gamma are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.

Assessment of cardiac viability by thallium 201 redistribution and dobutamine echocardiography.

OBJECTIVE: Dobutamine echocardiography and thalium 201 are useful in the assessment of myocardial viability, but both techniques frequently yield conflicting results. The objective of this study was to determine the minimum mass of viable myocardium that each test could detect and compare the agreement of dobutamine echocardiography and thallium 201 to detect viability. METHODS: Dobutamine echocardiography and thallium 201 were performed in 10 patients scheduled for cardiac transplantation. In each patient, 15 segments were studied. After transplantation these segments were analyzed by the pathologist measuring by a computer system the total area of each segment, the necrotic + fatty mass, and area (%) of viable myocytes per segment. The percentage of viable tissue was estimated ([Total mass - (Necrotic + Fatty tissue)]/Total mass x 100) on each segment, which was compared with the result (viable or not viable) obtained by echocardiography or thallium 201. RESULTS: Dobutamine echocardiography defined 90 segments (60%) as viable versus 117 (78%) in thallium (kappa 0.49, 95% CI 0.36-0.63). The minimum percent of viable tissue per segment defined as viable by thallium was 43% versus 49% by echocardiography. With use of thallium, the highest accuracy of the test to detect viability was when the percent of necrotic tissue of the segment analyzed was 40% (positive and negative likelihood ratio 2.2 and 3.6, respectively). By use of echocardiography, the highest accuracy of the test was observed when the percent of necrotic tissue of the segment analyzed was 31% (positive and negative likelihood ratio 5.5 and 7.7, respectively). CONCLUSION: The discrepant results of dobutamine echocardiography and thallium 201 are due to differences in the minimum mass of live myocytes required by each technique to detect viability.

Left ventricular-coronary sinus/right ventricular fistula late after mitral valve replacement.

Development of an intracardiac fistula is a rare complication after mitral valve replacement. In the literature we have found six cases of left ventricular-coronary sinus fistula and another one of left ventricular-coronary sinus and right atrial fistula. We report the history and course of a patient in whom a left ventricular-coronary sinus and right ventricular fistula developed late after mitral valve replacement. The current study examines this type of intracardiac shunt, and presents our report on a left ventricular-coronary sinus and right ventricular fistula complication.

Paravalvular leak and other events in silzone-coated mechanical heart valves: a report from AVERT.

BACKGROUND: The Artificial Valve Endocarditis Reduction Trial (AVERT) was designed to compare endocarditis rates in Silzone versus conventional valves. Recruitment ended January 21, 2000, because of higher rates of paravalvular leakage in patients receiving the Silzone prosthesis. The present analysis determined late event rates that might be used in the management of approximately 36,000 patients who have received the Silzone prosthesis. METHODS: A total of 807 patients in 19 centers in North America and Europe were randomized. Mean age was 61+/-11 years; 41% were women. Operations included aortic valve replacement in 59%, mitral valve replacement in 32%, and aortic and mitral valve replacements in 9%; 41% had concomitant operations (26% coronary artery bypass grafting). RESULTS: Major paravalvular leakage (followed by repair, explant, or mortality) occurred in 18 of 403 patients receiving Silzone valves and 4 of 404 patients without Silzone valves (2-year event-free rates: 91.1% versus 98.9% conventional, p < 0.003). Similarly, 2-year freedom from any explant was lower in the Silzone arm (19 versus 2 events; 90.1% versus 99.4%, p = 0.0002). Rates of mortality and stroke were similar during follow-up. CONCLUSIONS: Continued follow-up of AVERT supports the conclusion that the Silzone prosthesis has increased risk of paravalvular leakage requiring reoperation. Overall survival is similar in the two groups.

Should aortic valve reimplantation be offered to patients with a large aorto-ventricular junction?

OBJECTIVES: Large aortic root aneurysms might increase leaflet stress and compromise aortic valve durability after the reimplantation technique. We analysed the impact of the preoperative aorto-ventricular junction (AVJ) diameter on the durability of the valve. METHODS: Between March 2004 and January 2012, 150 patients underwent the David operation on the aortic root. We identified 47 patients with a preoperative AVJ >28 mm (Group A) and 103 patients with a diameter ≤ 28 mm (Group B). The mean follow-up was 44 ± 27 months. Both groups were compared regarding mortality, freedom from moderate or severe aortic valve regurgitation and freedom from reoperation. RESULTS: Early mortality was 1.3%. Actuarial survival at 1, 3 and 5 years was 97 ± 2, 94 ± 3 and 94 ± 3% for Group A, and 99 ± 1, 97 ± 1 and 94 ± 3% for Group B, respectively (P = 0.3). Two patients in Group B were reoperated for severe aortic regurgitation (AR). Actuarial freedom from reoperation at 1, 3 and 5 years was 100% for Group A, and 98 ± 1, 98 ± 1 and 96 ± 2% for Group B, respectively (P = 0.3). During the follow-up, 6 patients (3 in each group) developed AR ≥ Grade II. Therefore, actuarial freedom from AR grade II or greater at 1.3 and 5 years was 97 ± 2, 94 ± 4 and 87 ± 7% for Group A, and 99 ± 1, 97 ± 1 and 95 ± 2% for Group B (P = 0.3). CONCLUSIONS: The reimplantation technique shows excellent results. Medium-term stability of the aortic valve repair was not influenced by the preoperative aorto-ventricular junction diameter.

[Aortic valve sparing in 120 patients with aortic root aneurysms]. / Cirugía de preservación valvular en 120 pacientes con aneurismas de la raíz aórtica.

INTRODUCTION AND OBJECTIVES: Several aortic valve sparing techniques have been described for the treatment of aortic root aneurysms. We report our experience using the reimplantation technique in 120 patients. METHODS: Between March 2004 and October 2010, 120 patients with aortic root aneurysms underwent David operations. Of these, 51 were diagnosed with Marfan syndrome. Mean patient age was 31 ± 12 years. The mean diameter of the sinuses of Valsalva was 51 ± 5 mm and moderate/severe aortic regurgitation was present in 16% of these patients. In the other 69 patients mean age was 56 ± 14 years, the mean diameter of the sinuses of Valsalva was 53 ± 7 mm and moderate/severe aortic regurgitation was present in 66%. A bicuspid aortic valve was presented in 14 cases. RESULTS: Hospital mortality was 1.7%. Mean follow-up was 37 ± 21 months; 94% of the patients survived and 96% had an aortic regurgitation below grade II during 5 years of follow-up. One patient required re-operation because of severe aortic regurgitation. No endocarditis or thromboembolic complications have been documented, and 96% of the patients did not receive any anticoagulation therapy. CONCLUSIONS: Short- and mid-term results with the reimplantation technique for aortic root aneurysms are excellent. This technique prevents the need for chronic anticoagulation treatment as well as the complications arising from mechanical prostheses, and it should be the treatment of choice for young patients.

Staphylococcus aureus poststernotomy mediastinitis: description of two distinct acquisition pathways with different potential preventive approaches.

OBJECTIVE: Determining the acquisition routes of infection is crucial to designing specific preventive approaches against Staphylococcus aureus poststernotomy mediastinitis. METHODS: From 2002 to 2004, a nasal sample was obtained from patients before cardiac surgery. We collected clinical and microbiologic data of all episodes of S aureus poststernotomy mediastinitis. A case-control study (3:1) was performed to confirm the role of previous preoperative nasal colonization by S aureus as a risk factor for S aureus poststernotomy mediastinitis. Pulsed field gel electrophoresis molecular analysis of nasal and surgical site S aureus isolates was performed to analyze their relatedness in each patient with poststernotomy mediastinitis and with other patients of the study cohort. RESULTS: S aureus nasal cultures were positive in 228 (15.9%) of 1432 patients: methicillin-susceptible S aureus in 222 (15.5%) and meticillin-resistant S aureus in 6 (0.4%). S aureus poststernotomy mediastinitis was diagnosed in 17 (1.2%) of 1432 patients: 9 (3.95%) of 228 in colonized patients versus 8 (0.66%) of 1204 in noncolonized patients (P < .0001). Seven of 9 patients (1.2%) with methicillin-susceptible S aureus had an identical isolate by pulsed field gel electrophoresis in preoperative nasal and surgical-site cultures, but no clonal relatedness was shown among the isolates from these 9 patients. None of the 8 patients with methicillin-resistant S aureus poststernotomy mediastinitis had an identical isolate by pulsed field gel electrophoresis in preoperative nasal and surgical-site cultures, and the same clone of methicillin-resistant S aureus was responsible for all these cases. CONCLUSIONS: Endogenous [corrected] nasal colonization often precedes methicillin-resistant S aureus poststernotomy mediastinitis, which suggests that preoperative [corrected] decontamination is adequate for preventing methicillin-susceptible [corrected] S aureus poststernotomy mediastinitis, whereas hospital infection control measures seem to be the major factor for preventing methicillin-resistant S aureus poststernotomy mediastinitis.