Closure of patent foramen ovale or medical therapy alone for secondary prevention of cryptogenic cerebrovascular events.

AIMS: About one-third of ischemic stroke are cryptogenic. Paradoxical embolism through patent foramen ovale (PFO) has been identified as a possible cause of cryptogenic stroke. Therefore, PFO closure has been considered for secondary prevention of cryptogenic stroke. However, randomized clinical trials (RCTs) comparing PFO closure versus medical therapy led to conflicting results. Our objectives were to examine if PFO closure is superior to medical therapy alone for secondary prevention of cryptogenic stroke and to investigate whether PFO closure is associated with an increased incidence of atrial fibrillation/atrial flutter (AFL). METHODS: The authors systematically searched MEDLINE for RCTs that compared PFO closure with medical therapy. Efficacy outcome was cerebrovascular event (CVE) recurrence and safety outcome was new-onset atrial fibrillation/AFL. The outcomes of interest were investigated according to device type with subgroup analyses and meta-regression. RESULTS: The authors included eight RCTs constituting 4114 patients. Patients who underwent PFO closure had a lower risk of CVE recurrence compared with medically treated patients [relative risk (RR): 0.56; 95% confidence interval (CI) 0.40-0.80; P = 0.001; I = 30%]. This protective effect was consistent across the different device types. Patients who underwent PFO closure developed more frequently atrial fibrillation/AFL (RR 4.96; 95% CI 2.74-8.99; P < 0.00001; I = 0%), which was mainly transient and within 1 month. Atrial fibrillation/AFL risk was consistent according to device types, although marginally significant in the Amplatzer subgroup. CONCLUSION: PFO closure might have a role in secondary CVE prevention of patients with PFO and cryptogenic stroke. However, it is associated with an increased incidence of new-onset atrial fibrillation/AFL especially within 1 month.

[Valve-in-valve treatment of a degenerated supra-annular stentless bioprosthesis using a balloon-expandable transcatheter valve in a patient at high risk for coronary occlusion]. / Trattamento valve-in-valve con protesi balloon-expandable di bioprotesi chirurgica stentless sovra-anulare degenerata con alto rischio di occlusione coronarica.

Transcatheter valve-in-valve treatment of degenerated supra-annular stentless bioprostheses may be challenging and associated with a high risk of coronary occlusion. Preprocedural imaging evaluation is a key step to assess feasibility and to minimize or prevent coronary occlusion. We report the case of a degenerated Freedom Solo valve, treated with a balloon-expandable valve and a previously deflated stent positioned at the level of both coronary ostia. The procedure was successful but stent inflation at the right coronary ostium was required due to slow flow that occurred after valve implantation.

Disappearance of Electrocardiographic Abnormalities Associated with the Arrhythmic Pattern of a Barlow Disease After Surgical Mitral Valve Repair.

We describe the case of a 46-year old female with a Barlow's disease (MVP) characterized by systolic curling of posterior left ventricular (LV) wall + significant mitral annular disjunction + complex ventricular arrhythmias + syncope + inverted T waves in inferolateral leads in whom a successful surgical mitral valve rapair determined the disappearance not only of the echocardiographic but also the electrocar-diographic abnormalities (in particular the inferolateral T waves inversion on basal electrocardiogram and the complex basal arrhythmic pattern). This case demonstrates that electrocardiographic abnormalities may disappear after the surgical correction of the mechanical stretch imposed on the inferior LV free wall by the prolapsing mitral valve leaflets. Electrocardiographic changes remain an important and easy marker to recognize for the identification of a high-risk subgroup of MVP patients.

Analysis of ENG and ACVRL1 genes in 137 HHT Italian families identifies 76 different mutations (24 novel). Comparison with other European studies.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder causing vascular dysplasias. About 70-80% of HHT patients carries mutations in ENG or ACVRL1 genes, which code for a TGFbeta receptor type III and I respectively. Molecular data on a large cohort of Italian HHT patients are presented, discussing the significance of missense and splice site mutations. Mutation analysis in ENG and ACVRL1 genes was performed using single strand conformation polymorphisms (SSCP), denaturing high performance liquid chromatography (DHPLC) and subsequent direct sequencing. Overall, 101 mutations were found, with ACVRL1 involved in 71% of cases. The highest number of mutations (28/101 subjects, 14/76 different mutations referring to both genes) was in ACVRL1, exon 3. Mutation analysis was then extended to a total of 356 family members, and 162 proven to carry the mutation. New polymorphisms were identified in both genes, and evidence that ENG P131L change is not a disease-causing mutation was also provided. An in silico analysis was performed in order to characterize splice-site mutations. These results were compared to other European national studies and data from Italy, France and Spain were consistent for an higher incidence of ACVRL1 mutations.

Aortic dimensions in Turner's syndrome: two-dimensional echocardiography versus magnetic resonance imaging.

BACKGROUND: Patients with Turner's syndrome have an increased risk of cardiac death caused by aortic disease. Consensus has not been reached about the best method to image the aorta in this syndrome. AIM: This present study aimed: (i) to evaluate thoracic and abdominal aortic dimensions by two-dimensional echo (2-DE) and magnetic resonance imaging (MRI) and (ii) to assess agreement between 2-DE and MRI measurements. MATERIAL AND METHODS: Among 75 kariotypically proven Turner's syndrome patients, 59 (79%) (mean age: 22 +/- 7 years) underwent a 2-DE and an MRI study of the thoracic and proximal abdominal aorta. The aortic root (AR), the sino-tubular aortic junction (STJ), the first part of the ascending thoracic aorta (AscTA), the aortic arch (AArch), the descending thoracic aorta (DTAp) a few centimetres below the isthmus and the abdominal aorta (AbA) were analysed. The Bland and Altman method and Lin's concordance correlation coefficient were utilized to compare 2-DE and MRI aortic dimensions. RESULTS: Compared to MRI, feasibility of aortic imaging by 2-DE was identical at AR level, but lower when measuring distal aorta (88% at DTAp and 91.5% at AbA level versus 100%). The 2-DE and MRI showed a very slight difference between measurements and a high concordance correlation coefficient at the level of AR and AscTA; correlations were weaker at the other aortic levels. Absolute differences calculated at each measurement level showed that concordance (defined as differences within 1 mm between 2-DE and MRI absolute measures) was highest at AR (45.6%) and AscTA (28%) level and lowest at STJ (12.2%) level. The 2-DE overestimated aortic arch diameters in approximately 70% of cases, whereas at the remaining aortic levels MRI measurements were usually 1 mm higher compared to the corresponding 2-DE values. CONCLUSIONS: Concordance between 2-DE and MRI was found to be very good at the AR and AscTA levels. Because the risk of aortic complication is higher when AR and proximal thoracic aorta are dilated, 2-DE may be considered a useful method to screen for aortic disease and a good choice to follow proximal aortic dimensions over time in Turner's syndrome patients.

Prospective evaluation of aortic dimensions in Turner syndrome: a 2-dimensional echocardiographic study.

BACKGROUND: The prevalence of aortic disease, including dilatation of the proximal aorta, is higher in patients with Turner syndrome (TS) compared with healthy female control subjects, but there are no data regarding the prospective evaluation of aortic dimensions in this syndrome. OBJECTIVE: This study was undertaken to assess the: (1) prevalence of aortic root (AR) and proximal thoracic aorta enlargement by 2-dimensional echocardiography; and (2) evolution of aortic diameters over time. METHODS: In all, 78 patients with kariotypically proven TS (mean age 21.5 +/- 9 years) underwent a 2-dimensional echocardiographic study of the proximal thoracic aorta at baseline and yearly thereafter, during a median follow-up period of 37 months (25th-75th percentile: 25-51). We investigated the AR, sinotubular aortic junction, and tubular portion of the ascending thoracic aorta. Linearity of the relationship between AR dimensions and body surface area allowed us to use Roman nomograms to identify patients with or without an enlarged AR. RESULTS: At baseline, 62 of 78 patients (80%) presented normal AR dimensions compared with 16 of 78 (20%) with AR dilatation. Mean AR diameter was 24.5 +/- 3.6 versus 30.9 +/- 4.6 mm (P = .0001), sinotubular aortic junction was 18.0 +/- 4.0 versus 21.7 +/- 5.2 mm (P = .015), and ascending thoracic aorta was 21.1 +/- 4.1 versus 26.6 +/- 6.0 mm, respectively (P = .003). The incidence of AR dilatation was similar in patients younger than 18 years or 18 years and older. During follow-up, we observed a similar significant, albeit minor, increase in aortic diameters in all patients. However, the absolute entity of this increase was not clinically relevant. Lymphedema at birth was the only significant clinical variable observed more frequently in patients with AR enlargement compared with those with normal AR. CONCLUSIONS: Proximal aortic dimensions in patients with TS did not change rapidly in our medium-term follow-up study. The progression of AR dimensions was similar in patients with (20%) or without baseline AR dilatation. Age did not affect the pattern and evolution of aortic disease in TS.

Treatment of epistaxis in hereditary hemorrhagic telangiectasia patients by argon plasma coagulation with local anesthesia.

BACKGROUND: Recurrent epistaxis is the most common manifestation of hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to determine the role and efficacy of argon plasma coagulation (APC) in the management of epistaxis caused by HHT. METHODS: From 1997 to 2004, 43 patients with diagnosed HHT were treated for recurrent epistaxis with APC in our department. RESULTS: Thirty-six patients reported substantial reduction of bleeding after treatment. Of the 18 patients who previously needed blood transfusions, 13 reported substantial reduction of bleeding after treatment and no blood transfusions were necessary. CONCLUSION: APC allows a control of epistaxis in HHT patients and guarantees a long time free from blood transfusions. This treatment modality can be performed with local anesthesia, is not invasive, is well tolerated, is inexpensive, and can be used as a first step even in patients who need to undergo several blood transfusions for their epistaxis.

Two novel and one known mutation of the TGFBR2 gene in Marfan syndrome not associated with FBN1 gene defects.

TGF-beta-receptor 2 (TGFBR2) gene defects have been recently associated with Marfan syndrome (MFS) with prominent cardio-skeletal phenotype in patients with negative fibrillin-1 (FBN1) gene screening. Four mutations have been identified to date in five unrelated families. We screened TGFBR2 gene by direct automated sequencing in two adult patients diagnosed with MFS according to Ghent criteria, and in one girl clinically suspected as affected on the basis of a major cardiovascular criterion and skeletal involvement, all proven not to carry mutations in the exon-intron boundaries of FBN1 gene. We identified two novel and one known TGFBR2 gene mutations in the three unrelated probands. The D446N was identified in a 4-year-old girl with de novo disease characterized by severe cardiovascular disease and skeletal involvement. The M425V and R460H mutations were identified in two familial, autosomal dominant MFSs, both characterized by major cardio-skeletal signs and absence of major ocular signs. The mutation R460H has been recently reported in a family with thoracic aortic aneurysms and dissection. The three mutations are absent in 192 controls and affect evolutionarily conserved residues of the serine/threonine kinase domain (exon 5). Our data support the recently reported association between TGFBR2 gene and MFS without major ocular signs (MFS2). The number of genotyped cases however is too low to confirm that major ocular signs are characteristically absent in MFS2. Accordingly, all patients proven or suspected to be affected by MFS with negative FBN1 gene screening could benefit from rapid investigation of the TGFBR2 gene.

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies.

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.

Two simple echo-Doppler measurements can accurately identify pulmonary hypertension in the large majority of patients with chronic heart failure.

BACKGROUND: The assessment of pulmonary hypertension in patients with heart failure is of great clinical importance not only for diagnostic purposes but also for prognostication. The present study was undertaken on a consecutive basis with a group of patients with chronic heart failure. Patients were evaluated for their suitability for heart transplantation: (1) to explore the diagnostic accuracy of several echo Doppler parameters of pulmonary hemodynamics in predicting the presence of elevated pulmonary artery pressure (defined as pulmonary artery systolic pressure > or =35 mmHg and mean pulmonary artery pressure >20 mmHg); (2) to assess the diagnostic ability of the same parameters to identify patients with elevated pulmonary vascular resistance; and (3) to evaluate the influence of right ventricular function and degree of tricuspid regurgitation in modifying diagnostic accuracy. METHODS: Echo Doppler examination and right heart catheterization were performed consecutively within 24 hours in 86 patients. The optimal cut-off value for a series of echo Doppler parameters capable of identifying patients with pulmonary hypertension was obtained by dividing the entire sample into 2 groups; the optimal threshold (highest sensitivity and specificity) of the echo and Doppler parameters used to classify patients with and without pulmonary hypertension was determined in 67% of cases by means of the receiver operating characteristic (ROC) curve: this was the testing sample. The proportion of cases classified correctly according to the selected cut-off was computed. The remaining 33% of cases represented the validation sample: sensitivity, specificity and predictive values (and their 95% confidence intervals [CIs]) for identifying pulmonary hypertension were calculated from the proposed cut-offs in this second sample. Finally, the overall performance of the echo Doppler parameters was assessed over the whole sample by considering the extent of the area under the ROC curve (A-ROC) and its 95% CI, for the dichotomic measurement. RESULTS: On right heart catheterization, a pulmonary artery systolic (PAPs) pressure > or =35 mmHg plus a mean pressure (mean PAP) >20 mmHg was documented in 49 of 86 cases (57%), for whom mean values were 56 +/- 17 and 38 +/- 11 mmHg, respectively. The proportion of cases identified correctly as having pulmonary hypertension was highest for PAPs (88%) and mean PAP (85%) in addition to acceleration time of pulmonary artery systolic flow (ACT) (79%) and pulmonary artery diastolic pressure obtained utilizing the early phase of the tricuspid regurgitation spectral flow (PAPd/TR) (75%). PAPd/TR performed better in the validating sample in terms of diagnostic ability, with high sensitivity and specificity (100% and 60%) and positive and negative predictive values (PPV 80%, NPV 100%). PAPs, mean PAP, ACT and PAPd/TR confirmed their prevailing diagnostic ability (A-ROC from 0.74 to 0.86) in identifying pulmonary hypertension with fair to high feasibility (67% to 91%) and an odds ratio (OR) indicative of strong association. ACT and PAPd/TR, the 2 parameters with the highest feasibility, allowed us to identify 46 of 49 (94%) hypertensive cases. The same parameters did not perform well in identifying patients with increased vascular resistance, with A-ROC ranging from 0.55 to 0.69. Heterogeneity of effect, due to right ventricular function or tricuspid regurgitation degree, could not be demonstrated in the ability of the echo Doppler measurements to identify pulmonary hypertension. CONCLUSIONS: ACT, PAPd/TR, PAPs and mean PAP have been shown to accurately classify patients with chronic heart failure with or without pulmonary hypertension. In particular, ACT and PAPd/TR alone allowed reliable and accurate definition of pulmonary hypertension in 94% of patients, regardless of right ventricular function or degree of tricuspid regurgitation. Non-invasive pulmonary pressure assessment by the referred method might be useful in the evaluation of heart transplant candidates.