Genome-Wide Association Studies in Sunflower: Towards Sclerotinia sclerotiorum and Diaporthe/Phomopsis Resistance Breeding.

Diseases caused by necrotrophic fungi, such as the cosmopolitan Sclerotinia sclerotiorum and the Diaporthe/Phomopsis complex, are among the most destructive diseases of sunflower worldwide. The lack of complete resistance combined with the inefficiency of chemical control makes assisted breeding the best strategy for disease control. In this work, we present an integrated genome-wide association (GWA) study investigating the response of a diverse panel of sunflower inbred lines to both pathogens. Phenotypic data for Sclerotinia head rot (SHR) consisted of five disease descriptors (disease incidence, DI; disease severity, DS; area under the disease progress curve for DI, AUDPCI, and DS, AUDPCS; and incubation period, IP). Two disease descriptors (DI and DS) were evaluated for two manifestations of Diaporthe/Phomopsis: Phomopsis stem canker (PSC) and Phomopsis head rot (PHR). In addition, a principal component (PC) analysis was used to derive transformed phenotypes as inputs to a univariate GWA (PC-GWA). Genotypic data comprised a panel of 4269 single nucleotide polymorphisms (SNP), generated via genotyping-by-sequencing. The GWA analysis revealed 24 unique marker-trait associations for SHR, 19 unique marker-trait associations for Diaporthe/Phomopsis diseases, and 7 markers associated with PC1 and PC2. No common markers were found for the response to the two pathogens. Nevertheless, epistatic interactions were identified between markers significantly associated with the response to S. sclerotiorum and Diaporthe/Phomopsis. This suggests that, while the main determinants of resistance may differ for the two pathogens, there could be an underlying common genetic basis. The exploration of regions physically close to the associated markers yielded 364 genes, of which 19 were predicted as putative disease resistance genes. This work presents the first simultaneous evaluation of two manifestations of Diaporthe/Phomopsis in sunflower, and undertakes a comprehensive GWA study by integrating PSC, PHR, and SHR data. The multiple regions identified, and their exploration to identify candidate genes, contribute not only to the understanding of the genetic basis of resistance, but also to the development of tools for assisted breeding.

Bentall procedure after previous aortic valve or complete root replacement: Usefulness of self-assembled aortic valve conduit.

OBJECTIVES: The aim of this study was to evaluate surgical results of complete aortic root replacement using self-assembled valve composite graft in the setting of destroyed aortic annulus after previous valve replacement. METHODS: Aortic root pathology being addressed by complete root replacement was combined with partial or complete absence of annular tissue in 112 consecutive patients. Eighty-eight had undergone a previous replacement of the aortic valve and 24 had undergone root replacement with a valved conduit. Altogether, 31 patients (27.7%) presented with acute endocarditis, which was the indication for surgery in 75% of patients with prior root replacement. In all patients, the root replacement or re-replacement was performed with a self-assembled valved conduit using mechanical (n = 74) or, in patients with an advanced age, biological (n = 38) valve prostheses. RESULTS: In-hospital mortality was 11.6%, including a 30-day mortality of 6.3%. Resternotomy for bleeding was necessary in 5.4% of patients and about one-quarter did not need any blood transfusion. Estimated survival at 1, 5, and 10 years was 84.8% ± 3.4%, 75.7% ± 4.3%, and 57.1% ± 6.5%, respectively. Freedom from any valve-related events at 10 years was 86.2% ± 4.1%. During the follow-up time (mean, 63 ± 47 months), there was only 1 reoperation necessary 9 years after surgery (replacement of deteriorated biological valve prosthesis within the vascular tube leaving the conduit untouched). CONCLUSIONS: A self-assembled composite graft allows safe proximal fixation of the conduit in patients with destroyed aortic annulus, resulting in sufficient proximal anastomosis and a very low incidence of aorta-related reoperations.

Bio-Bentall procedure versus isolated biological aortic valve replacement: a case-match study.

OBJECTIVES: The aim of the study was to evaluate whether a complete aortic root replacement using a composite graft with biological valve prosthesis carries a higher early or late postoperative risk than isolated valve replacement. METHODS: Between 1998 and 2008, 182 consecutive patients underwent complete aortic root and ascending aorta replacement using a self-assembled composite graft with a biological valve prosthesis located within the vascular tube (modified Bentall procedure). In the same period, 1959 patients received an isolated aortic valve replacement using a biological valve prosthesis. After matching the patients using five variables (sex, age-by 5-year increments, aortic valve defect, concomitant coronary surgery and the year of surgery), 79 perfectly matched pairs were found. Regarding other clinically essential but unmatched preoperative characteristics, there were no relevant differences between the groups. RESULTS: There was no statistically significant difference in the early postoperative mortality (30-day and/or in-hospital), which was 5.1% (4 patients) in the Root Group (RG) and 3.8% (3 patients) in the Valve Group (VG). The follow-up was complete for all patients and contained 499 patient-years in the RG versus 488 in the VG. In total, there were 23 deaths in each group during the follow-up time, which was 6.2 ± 2.8 years for the RG and 6.2 ± 3.2 years for the VG. Hence, the linearized death rate and actuarial survival at 10 years were almost identical. They were 4.66%/year and 63.2 ± 8.3%, respectively, in the RG; compared with 4.71%/year and 58.5 ± 9.3% in the VG. Also the rates of valve-related morbidities were similar except for the tendency of a lower rate of cerebral embolism in the RG. CONCLUSIONS: Complete aortic root replacement with a biological composite graft can be performed by experienced surgeons with an operative risk similar to that of an isolated biological aortic valve replacement. Starting with comparable operative outcomes, both procedures offer almost identical long-term survival. The rates of valve-related events after complete aortic root replacement and isolated valve replacement are also comparable, apart from cerebral embolism, which seems to be less frequent after aortic root replacement.

Long-term results after aortic root replacement using self-assembled valve composite grafts in patients with small aortic annulus.

OBJECTIVES: The study was aimed to evaluate operative and long-term results after complete root replacement using self-assembled valve composite grafts in patients with a small aortic annulus. METHODS: Among 547 consecutive patients who received the Bentall procedure between 2000 and 2012, a total of 29 patients (61 ± 10; range 42-79 years) had an annulus of ≤20 mm (mean 19.0 ± 0.9). Patients with a native aortic valve (22) suffered from stenosis, insufficiency or mixed defect in 10, 10 and 2 cases, respectively. Among the remaining 7 patients with an artificial aortic valve, there were 3 symptomatic prosthesis-patient mismatches, 3 valve prosthesis deteriorations (1 structural and 2 none-structural) and 1 paravalvular leak. Indication for aortic root replacement was true or false aneurysm, porcelain aorta and intraoperative aortic wall injury in 17, 6 and 6 patients, respectively. RESULTS: The composite graft for complete aortic root replacement was assembled using a mechanical (26) or biological (3) valve prosthesis placed inside a vascular graft with a median size of 24 (range 22-26) mm. The margin of the tube beneath the valve was anastomosed to the aortic annulus, and coronary ostia were implanted in the usual manner. The mean transvalvular gradient at discharge was 10.8 ± 3.9 mmHg and remained virtually unchanged at the follow-up completed for all patients. Early mortality was 0. During the mean follow-up of 95.8 ± 43.7 months, 2 patients died (54 and 146 months after surgery) due to pulmonary embolism and myocardial infarction, respectively. CONCLUSIONS: In patients with a small aortic annulus who need complete aortic root replacement, an oversizing of the valve can be easily achieved using modified, self-assembled composite grafts. Offering excellent haemodynamic characteristics, these grafts lead to prevention of prosthesis-patient mismatch and result in very good and durable functional and clinical results.

Cardiac surgery in patients with a porcelain aorta in the era of transcatheter valve implantation.

OBJECTIVES: New surgical and perfusion techniques allow the avoidance of deep hypothermia during open aortic arch surgery, which is generally necessary in patients with an unclampable porcelain aorta. The aim of the study was to evaluate operative and long-term results in patients with a porcelain aorta who underwent conventional cardiac surgery using current surgical and perfusion techniques. METHODS: Between November 2003 and February 2012, 30 consecutive patients (mean age 68 ± 11 years, 10 patients had previous cardiac surgery with use of glue in 5 of them) with porcelain aorta diagnosed by computed tomography and defined as a severe circular calcification of the proximal thoracic aorta were referred for cardiac surgery. All patients underwent conventional surgery with arterial cannulation of the innominate (8) or a carotid artery (22) for arterial return. During mild hypothermic circulatory arrest, unilateral cerebral perfusion through the arterial line was performed for cerebral protection. The valve surgery consisted of aortic, mitral or double valve repair in 23, 3 and 4 cases, respectively. Aortic surgery (17 complete root replacements with valve composite grafts and 22 arch replacements) and coronary revascularization due to coronary heart disease (15) were the most frequent concomitant procedures. RESULTS: Thirty-day mortality was 3.3% (1 patient died of bowel ischaemia caused by severe stenosis of the celiac and upper mesenteric arteries) and the rate of permanent neurological deficit was 3.3% as well. Two further patients died during the follow-up at age 91 and 82 years, respectively; however, no death was cardiac or valve related. The actuarial survival at 5 years was 87.3 ± 7.2%. There were no cardiac reoperations, new interventions or aortic- or valve-related events noted during the median follow-up of 45 months (range 0.1-106.0). CONCLUSIONS: Conventional cardiac and aortic surgery offers definitive repair and can be performed safely using current perfusion and operative techniques. Although more invasive, this surgical technique provides mortality and morbidity rates that do not exceed those reported for transcatheter valve implantation. The curative replacement of the pathological proximal aorta, which is one of the most main sources of cerebral embolism, leads to excellent neurological outcome during mid- to long-term follow-up.