Massimiliano Mariani

Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes in familial cases of bicuspid aortic valve

BackgroundThe purpose of our study was to investigate the potential contribution of germline mutations in NOTCH1, GATA5 and TGFBR1 and TGFBR2 genes in a cohort of Italian patients with familial Bicuspid Aortic Valve (BAV).MethodsAll the coding exons including adjacent intronic as well as 5′ and 3′ untranslated (UTR) sequences of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes were screened by direct gene sequencing in 11 index patients (8 males; age = 42 ± 19 years) with familial BAV defined as two or more affected members.ResultsTwo novel mutations, a missense and a nonsense mutation (Exon 5, p.P284L; Exon 26, p.Y1619X), were found in the NOTCH1 gene in two unrelated families. The mutations segregated with the disease in these families, and they were not found on 200 unrelated chromosomes from ethnically matched controls. No pathogenetic mutation was identified in GATA5, TGFBR1 and TGFBR2 genes.ConclusionsTwo novel NOTCH1 mutations were identified in two Italian families with BAV, highlighting the role of a NOTCH1 signaling pathway in BAV and its aortic complications. These findings are of relevance for genetic counseling and clinical care of families presenting with BAV. Future studies are needed in order to unravel the still largely unknown genetics of BAV.

Free triiodothyronine: a novel predictor of postoperative atrial fibrillation

OBJECTIVE Despite improved perioperative management, atrial fibrillation (AF) after coronary artery bypass grafting (CABG) remains a relevant clinical problem, whose pathogenetic mechanisms remain incompletely explained. A reduced incidence of postoperative AF has been described in CABG patients receiving IV tri-iodothyronine (T3). This study was designed to define the role of thyroid metabolism on the genesis of postoperative AF. METHODS AND RESULTS Free T3 (fT3), free thyroxine (fT4), and thyroid stimulating hormone were assayed at admission in 107 consecutive patients undergoing isolated CABG surgery. Patients with thyroid disease or taking drugs known to interfere with thyroid function were excluded. A preoperative rhythm other than sinus rhythm was considered an exclusion criterion. Thirty-three patients (30.8%) had postoperative AF. An older age (P=0.03), no therapy with beta-blockers (P=0.08), chronic obstructive pulmonary disease (P=0.08), lower left ventricle ejection fraction (P=0.09) and lower fT3 concentration (P=0.001), were univariate predictors of postoperative AF. On multivariate analysis, low fT3 concentration and lack of beta-blocking therapy were independently related with the development of postoperative AF (odds ratio, OR, 4.425; 95% confidence interval, CI, 1.745-11.235; P=0.001 and OR 3.107; 95% CI 1.087-8.875; P=0.03, respectively). Postoperative AF significantly prolonged postoperative hospital stay (P=0.002). CONCLUSIONS Low basal fT3 concentration can reliably predict the occurrence of postoperative AF in CABG patients.

Sizing the aortic annulus

Transcatheter aortic valve implantation (TAVI) is a valuable alternative for aortic valve replacement in selected high-risk candidates. Accurate preoperative assessment of the aortic annular dimensions is crucial for the success of TAVI, since choice of an incorrectly sized prosthesis may result in catastrophic complications. These complications include annular rupture and coronary arterial obstruction, if the prosthesis is too big, or prosthesis migration and severe paravalvular leakage, if the prosthesis is too small. According to current recommendations, the choice of prosthesis size is based on transoesophageal echocardiography (TEE) measurements. However, TEE results are dependent on operator experience. Moreover, recent research has shown that TEE can significantly underestimate annular dimensional measurements. Alternative sizing methods based on Multidetector Computed Tomography (MDCT) or manometry during balloon aortic valvuloplasty have therefore been developed. We present a brief overview of the imaging modalities available for preoperative assessment of annular size and discuss their potential advantages and limitations.

Mitral valve repair for degenerative disease: is pericardial posterior annuloplasty a durable option?

OBJECTIVE Biological and prosthetic rings are available for supporting mitral valve repair (MVR). Contrasting data are reported on the durability of pericardial ring annuloplasty. This retrospective study was undertaken to assess the durability of MVR for degenerative regurgitation with posterior annuloplasty performed with glutaraldehyde-treated autologous pericardium. METHODS From August 1995 through December 2000, 133 patients underwent mitral repair for degenerative regurgitation (86 men, age 62.9+/-11.5 years). Thirty patients (22.6%) underwent combined coronary artery bypass graft and fourteen (10.5%) underwent tricuspid annuloplasty. Associated aortic disease, previous cardiac surgery and endocarditis were considered exclusion criteria. RESULTS Seventy-seven patients (57.9%) received a Carpentier-Edwards ring and 56 received (42.1%) an autologous pericardium ring. Thirty-day mortality was 3.8%. Mean follow-up, 98.3% complete, was of 35.6+/-18.7 months. Five-year freedom from reoperation and recurrence of mitral regurgitation> or =3+/4+ was significantly higher in the prosthetic ring group (90.1% - CL90%: 81.9-98.3%) compared with the pericardial ring group (62.6% - CL90%: 43.1-82.1%; P=0.027). Prosthetic ring implantation (P=0.004; RR=0.11) and preoperative New York Heart Association (NYHA) class< or =II (P=0.011; RR=0.16) were independently related to a lower risk of reoperation and recurrence of mitral regurgitation> or =3+/4+, by multivariate analysis. Five-year overall survival was 91.4% (CL90%: 87.9.7-95%). A higher preoperative left ventricular end-diastolic diameter (P=0.006; RR=1.17) and the severity of associated coronary artery disease (P=0.021; RR=2.00) were independent predictive factors for poor survival by multivariate analysis. CONCLUSIONS Posterior pericardial annuloplasty can jeopardize reproducibility and durability of MVR for degenerative regurgitation.

Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves

OBJECTIVE The angiotensin-converting enzyme (ACE) is highly expressed in the aneurysmal vascular wall, in both animal models and human disease. Genetic variations in ACE could be crucial in determining the risk of thoracic aortic aneurysm (TAA). The aim of the present study was to examine the role of ACE insertion/deletion polymorphism on the risk of TAA in patients with bicuspid aortic valves or tricuspid aortic valves. METHODS We enrolled 216 patients (158 men; age, 58.9±14.9 years) with TAA, associated with bicuspid aortic valves (n=105) and tricuspid aortic valves (n=111) compared with 312 patients (252 men; age, 54.6±11.0 years) with angiographically proven coronary artery disease and 300 healthy controls (91 men; age, 40.4±10.5 years). RESULTS The genotype distribution of ACE insertion/deletion was significantly different between the patients with TAA compared with both the control group (P=.0005) and the coronary artery disease group (P=.03). The genotypes were not different between the control group and the coronary artery disease group (P=.3). Compared with the controls, both the bicuspid aortic valve patients (P=.0008) and tricuspid aortic valve patients (P<.0001) had a greater frequency of allele D. The aortic diameters were significantly different among the three genotypes (48.3±6.6, 45.3±8.9, 39.9±8.7 for the DD, DI, and II genotypes, respectively; P=.0002). A synergistic effect between the ACE D allele and hypertension was found for both an increased aortic diameter (P=.003) and the risk of TAA (P<.001). On multivariate logistic regression analysis, D allele (odds ratio, 3.0; 95% confidence interval, 1.1-8.1; P=.03) was a significant predictor of TAA. CONCLUSIONS ACE insertion/deletion polymorphism represents a genetic biomarker for TAA. These findings could have a significant effect on both the early detection and effective pharmacologic treatment of aortic disease.

A New Vacuum-Assisted Probe for Minimally Invasive Radiofrequency Ablation

PURPOSE The Cobra Adhere XL (Estech, San Ramon, CA) is a multiple-electrode, temperature-controlled, monopolar radiofrequency probe with a vacuum-assisted stabilization system. We evaluated this new technology for epicardial ablation of atrial fibrillation in mitral valve patients through a right mini-thoracotomy. DESCRIPTION Between June and August 2008, 12 patients underwent minimal invasive surgery for mitral disease and ablation for atrial fibrillation with the Cobra Adhere XL (Estech). Three patients had paroxysmal atrial fibrillation. Off-pump pulmonary vein isolation was performed with an epicardial oval lesion parallel to the mitral plane. In 10 patients, an endocardial lesion to the mitral annulus was added. EVALUATION There were no operative deaths or major postoperative complications. At a mean follow-up of 8.76 +/- 1.0 months, 11 patients (91.67%) were in stable sinus rhythm. Echocardiography underscored a complete recovery of atrial transport function in most of these patients (90.91%). No major cardiac and cerebrovascular events occurred during follow-up. CONCLUSIONS Left-side ablation combined with minimally invasive surgery for mitral disease can be easily, safely, and effectively performed with the Cobra Adhere XL probe.

Predictive value of less than moderate residual mitral regurgitation as assessed by transesophageal echocardiography for the short-term outcomes of patients with mitral regurgitation treated with mitral valve repair

BackgroundTraditionally, in patients with mitral regurgitation (MR) a successful mitral valve repair is considered when residual MR by post-pump transesophageal echocardiography (TEE) is less than moderate or absent. Little is known about the prognostic value of less than moderate (mild or mild-to-moderate) residual MR for the early outcome of patients treated with mitral valve repair.MethodsEligible for this study were patients undergoing isolated mitral valve repair. Patients with moderate or severe residual MR after valve repair were excluded. The primary endpoint of the study was the composite of death or need of reintervention.ResultsA total of 98 patients (54 with no residual MR-Group 1, and 44 with less than moderate residual MR-Group 2) were analyzed. Of these, 72% presented with New York Heart Association (NYHA) 3/4, and 38% were women. The primary endpoint of the study occurred in 3 (5.5%) patients in Group 1 and 6 (13.6%) patients in Group 2 MR (P = 0.31). There was a trend toward a higher incidence of use of inotropic drugs post-interventional (P = 0.12), and a longer hospital stay among patients with less than moderate residual MR (P = 0.18).ConclusionIn our study population, patients with less than moderate residual MR had a trend toward a higher risk of early adverse outcomes as compared with patients with no residual MR by post-pump TEE. Studies with a larger patient population and longer follow-up data may be useful to better define the clinical significance of residual mild MR after mitral vale repair.

The non-thyroidal illness syndrome after coronary artery bypass grafting: a 6-month follow-up study

Abstract The non-thyroidal illness syndrome (NTIS) is considered a transient and completely reversible phenomenon, but it has been shown that it may last for several days postoperatively after coronary artery bypass grafting (CABG) surgery. This study was undertaken to assess thyroid function 6 months after uncomplicated CABG. The thyroid profile was evaluated in 40 consecutive patients undergoing CABG preoperatively, at 0, 12, 48, and 120h postoperatively, and at 6-month follow-up. Triiodothyronine (T 3), free T 3 (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were assayed using a microparticle enzyme immunoassay. T 4 and total serum thyroid hormone-binding capacity (T-uptake) were measured on the same samples using a fluorescence polarization immunoassay. Patients with severe systemic illness and patients treated with amiodarone were excluded. All patients were euthyroid at admission. Mean age was 67.4±9.0years. There were 31 (77.5%) men. Typical NTIS was observed in all patients, and the FT 3 concentration was still reduced by postoperative day 5 (p<0.0001). At 6-month follow-up, all patients were free from cardiac symptoms, and no new cardiac events were recorded. The thyroid profile was normal in 35 patients (87.5%). One patient (4.5%) had developed overt hypothyroidism. Two patients had isolated low T 3 and FT 3 levels with normal TSH. Two patients had moderately increased FT 3 levels with suppressed TSH. In most uncomplicated patients, thyroid function returns to normal 6months after CABG. However, we observed significant alterations of the thyroid profile in 5 out of 40 patients. Further studies are needed to define the long-term consequences of postoperative NTIS.

Hybrid Repair of a Kommerell's Diverticulum Aneurysm

Abstract  Aneurysms of the right aortic arch with an aberrant left subclavian artery are rare. We report the case of a 77‐year‐old woman with a Kommerells diverticulum aneurysm, who underwent a successful hybrid repair, combining surgical off‐pump bypass of the aortic arch vessels followed by endovascular aneurysm repair. (J Card Surg 2010;25:67‐69)

Aortic arch replacement with prophylactic aortic arch debranching during type A acute aortic dissection repair: initial experience with 23 patients.

OBJECTIVE To improve the long-term results of acute type A dissection repair, we developed a technique that combines radical surgical resection, and, at the same time, creates a safe and long landing zone for subsequent endovascular procedure on the descending aorta. METHODS Since November 2006, 23 patients (62 ± 13 years) underwent aortic arch replacement concomitant with prophylactic debranching of the supra-aortic vessels, with a specially designed arch graft. The technique consists of replacing the ascending aorta and the aortic arch, and, at the same time, relocating the origin of the supra-aortic vessels just above the sinotubular junction creating a long and safe proximal landing zone for subsequent stent-graft deployment. Perfusion was antegrade through the ascending aorta during cooling and through the vascular prosthesis during rewarming. Distal arch anastomosis was performed under moderate hypothermic circulatory arrest for 25 ± 7 min and antegrade selective cerebral perfusion (46 ± 14 min). Cardiopulmonary bypass and aortic cross-clamp time were 138 ± 46 and 63 ± 22 min. RESULTS Hospital mortality was 4.3% (1/23). Postoperative morbidity includes five acute renal failures and four lung failures. No major neurological complications were observed. At follow-up (22±10 months), survival was 100% and two patients required an endovascular thoracic aorta repair for aneurysmal enlargement. In both cases, the stent grafts were successfully released in the landing zone created at the time of primary repair. CONCLUSIONS Our technique extends the suitability of endovascular therapies during type A acute dissection repair, creating a long and stable landing zone that allows safe performance of a second endovascular step if needed, both in the short- and long term.