Quantification of aortic flow by phase-contrast magnetic resonance in patients with bicuspid aortic valve.

AIMS: Bicuspid aortic valve (BAV) causes complex flow patterns in the ascending aorta (AAo), which may compromise the accuracy of flow measurement by phase-contrast magnetic resonance (PC-MR). Therefore, we aimed to assess and compare the accuracy of forward flow measurement in the AAo, where complex flow is more dominant in BAV patients, with flow quantification in the left ventricular outflow tract (LVOT) and the aortic valve orifice (AV), where complex flow is less important, in BAV patients and controls. METHODS AND RESULTS: Flow was measured by PC-MR in 22 BAV patients and 20 controls at the following positions: (i) LVOT, (ii) AV, and (iii) AAo, and compared with the left ventricular stroke volume (LVSV). The correlation between the LVSV and the forward flow in the LVOT, the AV, and the AAo was good in BAV patients (r = 0.97/0.96/0.93; P < 0.01) and controls (r = 0.96/0.93/0.93; P < 0.01). However, in relation with the LVSV, the forward flow in the AAo was mildly underestimated in controls and much more in BAV patients [median (inter-quartile range): 9% (4%/15%) vs. 22% (8%/30%); P < 0.01]. This was not the case in the LVOT and the AV. The severity of flow underestimation in the AAo was associated with flow eccentricity. CONCLUSION: Flow measurement in the AAo leads to an underestimation of the forward flow in BAV patients. Measurement in the LVOT or the AV, where complex flow is less prominent, is an alternative means for quantifying the systolic forward flow in BAV patients.

Phylloid pattern of hypomelanosis closely related to chromosomal abnormalities in the 13q detected by SNP array analysis.

Phylloid hypomelanosis is a distinct type of pigmentary mosaicism characterized by congenital hypochromic macules resembling a floral ornament with various elements such as round or oval patches, asymmetrical macules similar to begonia leaves, or oblong lesions. It has been found to be predominantly associated with abnormalities in chromosome 13 and sometimes as-sociated with different extracutaneous abnormalities. Here, we report 2 new cases of phylloid hypomelanosis due to mosaicism involving chromosome 13. The first one is a mosaicism for a supernumerary marker belonging to chromosome 13 and the second one is the first report of phylloid hypomelanosis associated with a mosaic deletion of 13q. Because of the extremely low level of mosaicism in these 2 cases, SNP array analysis on skin fibroblasts was carried out, showing a 13q21.33-q34 duplication (71,024,411-115,103,529) and a 13q13.3-q34 (38,368,012-115,103,529) deletion. Both cases underline on the one hand the strict connection between phylloid hypomelanosis and anomalies of chromosome 13, and on the other hand the relevance of the SNP array analysis on skin fibroblasts in the detection of low-level mosaicism.

Two Novel COH1 Mutations in an Italian Patient with Cohen Syndrome.

Cohen syndrome (CS) is an autosomal recessive disease caused by mutations in the COH1 gene. It is characterized by intellectual disability, hypotonia, joint hyperlaxity, severe myopia, characteristic facial dysmorphisms and, in some cases, intermittent isolated neutropenia. We investigated an Italian patient with CS together with his family. Genetic analysis disclosed 2 novel mutations: the first is an intronic mutation (c.8697-9A>G) creating a new splice site 8 nucleotides upstream, and the second is a duplication of 1 base (c.10156dupA) generating a premature stop codon. The compound heterozygous mutations explain the proband's phenotype and improved the knowledge of genotype-phenotype correlation.

Identification of a New Mutation (L46P) in the Human NOG Gene in an Italian Patient with Symphalangism Syndrome.

Proximal symphalangism (SYM1) is a joint morphogenesis disorder characterized by stapes ankylosis, proximal interphalangeal joint fusion, skeletal anomalies and conductive hearing loss. Noggin is a bone morphogenetic protein (BMP) antagonist essential for normal bone and joint development in humans and mice. Autosomal dominant mutations have been described in the NOG gene, encoding the noggin protein. We analyzed an Italian sporadic patient with SYM1 due to a novel NOG mutation (L46P) based on a c.137T>C transition. A different pathogenic mutation in the same codon (L46D) has been previously described in an in vivo chicken model. An in silico model shows a decreased binding affinity between noggin and BMP7 for both L46D and L46P compared to the wild type. Therefore, this codon should play an important role in BMP7 binding activity of the noggin protein and consequently to the joint morphogenesis.

De novo 911 Kb interstitial deletion on chromosome 1q43 in a boy with mental retardation and short stature.

Patients with distal deletions of chromosome 1q have a recognizable syndrome that includes microcephaly, hypoplasia or agenesis of the corpus callosum, and psychomotor retardation. Although these symptoms have been attributed to deletions of 1q42-1q44, the minimal chromosomal region involved has not yet defined. In this report, we describe a 7 years old male with mental retardation, cryptorchid testes, short stature and alopecia carrying only an interstitial de novo deletion of 911 Kb in the 1q43 region (239,597,095-240,508,817) encompassing three genes CHRM3, RPS7P5 and FMN2.

Current applications of contrast echocardiography.

Transthoracic echocardiography is a practical, widely available non-invasive imaging technique examining cardiac structure and function at rest and during stress. However, diagnostically useful images are not provided in a non-negligible proportion of patients, mainly because of obesity and lung disease. The use of echo-contrast agents (microbubbles consisting of high molecular weight gas encapsulated in a outer shell which have ultrasound characteristics distinctly different from those of the surrounding blood cells and heart tissue) solves these issues, providing cardiac chamber opacification and improving endocardial border definition, consequently allowing a more accurate quantification of left ventricular function. Besides improving the assessment of left ventricular function, echo-contrast agents may be used also to assess the myocardial perfusion at the capillary level, providing useful information about myocardial blood flow. Aim of the present paper is to provide an overview of the main clinical applications of contrast echocardiography, i.e. left ventricular opacification and myocardial contrast echocardiography.

Estimates of lifetime attributable risk of cancer after a single radiation exposure from 64-slice computed tomographic coronary angiography.

AIMS: To estimate the life attributable risk (LAR) of cancer incidence over a wide range of dose radiation exposure and a large spectrum of possible diagnostic computed tomographic coronary angiography (CTCA) scenarios. METHODS: This study included 561 consecutive patients who underwent a successful prospective ECG-gating CTCA protocol (low-dose group) 64-slice CTCA and 188 patients who underwent retrospective ECG-gating CTCA with ECG-triggered dose modulation CTCA (high-dose group). LAR was computed, given the organ equivalent dose, for all cancers in both sexes. LAR was tabulated for each decile of dose-length product by 10-year age classes, separately for each sex. RESULTS: Estimates of LAR of any cancer for an exposure at age < or =40 year were lower in males than in females for any given quantile. At age >/ or =50 years, LAR was similar between sexes only at the lowest exposure doses, whereas at higher dosage, it was, in general, higher for women. At the median age of this case series (62 years) and for a radiation exposure ranging from 1.33 to 3.81 mSv, LAR was 1 in 4329 (or 23.1 per 10(5) persons exposed) and 1 in 4629 (or 21.6 per 10(5) persons) in men and women, respectively. For an exposure ranging from 10.34 to 18.97 mSv at the same median age, the LAR of cancer incidence was 1 in 1336 (or 74.8 per 10(5) persons) in men and doubled (1 in 614 or 162.8 per 10(5) persons) in women. CONCLUSIONS: This study provided an estimate of the LAR of cancer in middle-aged patients of both sexes after a single diagnostic CTCA, providing an easy-to-read table.

Relation between coronary atherosclerotic plaques and traditional risk factors in people with no history of cardiovascular disease undergoing multi-detector computed coronary angiography.

AIMS: To prospectively investigate the prevalence of coronary artery plaques (CAP) as detected by computed tomography-based angiography in a large number of consecutive individuals with no history of coronary artery disease (CAD) or acute coronary syndrome; to evaluate whether traditional risk factors are related to prevalence of CAP and to the expected 10-year risk of first major or fatal cardiovascular event (CVE). DESIGN: Prospective, single-centre, cross-sectional study. SETTING: The division of Cardiology at Fondazione Cardiocentro Ticino Lugano, Switzerland. METHODS: We prospectively included 920 consecutive individuals with no history of CAD who underwent computed tomography coronary angiography (CTCA). Risk estimation of fatal and non-fatal CVE was assessed using Global Assessment Risk (GAR) and Systematic Coronary Risk Evaluation (SCORE), respectively. Logistic regression was used to assess the association of risk factors with the prevalence of CAP. RESULTS: CAP was found in 459 (49.9%) individuals. Older age, higher body mass index, male gender, diabetes, hypertension and dyslipidaemia all increased the likelihood of the CAP burden at univariable analysis (p<0.001). At the multivariable analysis older age, male gender, hypertension and diabetes independently increased the likelihood of CAP burden (p<0.001). An increase in likelihood of CAP was observed in the presence of one, two and three or more risk factors and with an increasing value of GAR and SCORE. Notably, about 18% of subjects with CAP did not report any traditional risk factors and among individuals without CAPs, 12% had three or more risk factors. CONCLUSIONS: A direct relation between the prevalence of CAP, number of risk factors and the related 10-year risk of CVE was found. 18% of subjects without risk factors had CAP. In these individuals CTCA may help in further optimising the risk reduction strategies on an individual basis.

Microwave ablation of atrial fibrillation in conjunction with treatment of early postoperative massive left atrial thrombosis.

Left atrial thrombosis is a rare complication of both atrial fibrillation and mitral valve surgery. A patient with a massive atrial thrombosis associated with symptoms of severe heart failure is presented. Restoration of rhythmical ventricular contraction and, ultimately, atrial contractility is of great benefit for providing relief from symptoms and for preventing thrombus recurrence. We present an approach to surgically treat atrial fibrillation using a new microwave energy source in a patient with left atrial thrombosis who requires a mitral valve prosthesis replacement.

[Clinical usefulenss of a saggital ultrasonography study of the left atrium: report of a case]. / Utilità clinica di una sezione ecocardiografica sagittale dell'auricola sinistra: descrizione di un caso.

Multiplane transesophageal echocardiography allows a more complete image of the complex anatomy of the left atrial appendage. In this study we describe a clinical case in which a "sagittal echocardiographic section" revealed a thrombus not imaged with the usual horizontal and longitudinal echocardiographic planes.

[Posterior echocardiography windows: usefulness in clinical practice]. / Le finestre ecocardiografiche posteriori: utilità nella pratica clinica.

Posterior cardiac structures cannot always be imaged by means of standard transthoracic echocardiography. Left pleural effusion leading to pulmonary atelectasis and/or to displacement of air-filled pulmonary tissue displacement, allows ultrasound transmission from a patient's back to his heart through a liquid interface. In this study we present the clinical usefulness of echocardiographic posterior windows for the diagnosis of constrictive pericarditis and aortic dissection in 2 patients in whom the standard transthoracic approach did not permit diagnostic imaging. We conclude that, in the case of left pleural effusion, the use of posterior windows should be encouraged.

Safety, feasibility, and diagnostic accuracy of accelerated high-dose dipyridamole stress echocardiography.

Protocols for dipyridamole stress testing have evolved in the last 16 years in the neverending quest of optimal diagnostic accuracy and user friendliness. Higher dipyridamole dose in a shorter infusion time provides higher sensitivity, but concern over safety is still controversial. An accelerated high-dose (0.84 mg/kg in 6 minutes without atropine) dipyridamole stress test was performed on 1,295 patients in 2 echocardiographic laborotories: Institute of Clinical Physiology of Pisa and Niguarda Hospital of Milan. During testing, there were no deaths and no patients had ventricular fibrillation. Major adverse reactions occurred in 3 cases (1 every 431 studies): 1 myocardial infarction, 1 brief cardiac asystole, and 1 transient ischemic attack. Overall feasibility was 97%. In 66 patients with normal function at rest who were evaluated off therapy, with coronary angiography performed independently of test results, the accelerated high-dose protocol showed a sensitivity of 85% (confidence interval [CI] 73% to 92%) and a specificity of 93% (CI 83% to 97%) for angiographically assessed coronary artery disease (quantitatively assessed diameter reduction > or = 50%). Diagnostic accuracy of the accelerated high dose was 89% (CI 79% to 95%). Thus, accelerated high-dose dipyridamole stress echocardiography was reasonably safe and well tolerated. This protocol is especially appealing for its excellent diagnostic accuracy coupled with the short imaging time and no need for drug cocktails.

Relationship of unrecognised myocardial infarction, diabetes mellitus and type of surgery to postoperative cardiac outcomes in vascular surgery.

OBJECTIVES: to evaluate preoperative clinical, surgical and instrumental variables as predictors of postoperative cardiac events in patients undergoing different types of elective major vascular surgery. MATERIAL AND METHODS: on the basis of an algorithm including clinical and test echocardiographic data, we prospectively stratified 604 consecutive patients into low, intermediate and high-risk groups. The value of the variables in predicting postoperative cardiac events was assessed by means of multivariate analysis. RESULTS: there were 16 major postoperative cardiac events and six of 16 postoperative deaths were cardiac related (1%). Significant predictors of cardiac complications were unrecognised myocardial infarction (odds ratio - (OR) 5.6), coronary artery disease (OR 2.5), severe hypertension (OR 2.1) and peripheral vascular surgery (OR 1.9). In the intermediate-risk group, the best correlates with cardiac complications were unrecognised myocardial infarction (OR 3.3) and diabetes (OR 2.5). CONCLUSIONS: our results suggest the importance of identifying patients with unrecognised ischaemic heart disease and of using aggressive perioperative protocols for managing diabetic patients undergoing peripheral vascular procedures.

Incorrect echocardiographic diagnosis in patients with mechanical prosthetic valve dysfunction: correlation with surgical findings.

PURPOSE: To identify the rate of occurrence and type of incorrect echocardiographic diagnoses in patients with mechanical valve prostheses. PATIENTS AND METHODS: We studied 170 consecutive patients (73 women and 97 men) with a total of 208 prostheses who underwent surgery for mitral (n = 136) or aortic (n = 72) valve dysfunction between January 1991 and December 1997. Preoperative echocardiographic data were compared with surgical findings. Any major discrepancy between the echocardiographic reports and surgery was judged to be unconfirmed when the preoperative echocardiographic diagnosis was not confirmed at surgery, but the prosthesis was found to be dysfunctioning; and was judged to be erroneous when the preoperative echocardiographic diagnosis was not confirmed, and surgical inspection failed to reveal any other prosthetic abnormality. RESULTS: There were 25 (12%) diagnostic errors. Of the 136 mitral prostheses, there were 9 unconfirmed diagnoses of paravalvular regurgitation (6 had a fibrous tissue overgrowth, 1 had a thrombus with fibrous tissue overgrowth, 1 had endocarditis vegetations, and 1 had a ball variance) and 5 erroneous diagnoses. Eleven diagnostic errors were made in the 72 aortic prostheses: there were 9 unconfirmed diagnoses (paravalvular regurgitation was diagnosed as transvalvular in 7, and transvalvular regurgitation as paravalvular in 2 cases), and 2 erroneous diagnoses. CONCLUSIONS: Although echocardiography has gained great credibility among clinicians, special care should be taken when assessing patients in whom prosthetic valve dysfunction is suspected.