Long-Term Outcomes and Complications of Intracardiac Echocardiography-Assisted Patent Foramen Ovale Closure in 1,000 Consecutive Patients.

BACKGROUNDS: Long-term fate of patients submitted to patent foramen ovale (PFO) closure is still unclear. The aim of the study was to evaluate the incidence of atrial fibrillation (AF), aortic or atrial free wall erosion, device thrombosis (DT), new onset or worsening of mitral valve regurgitation (MVR), and recurrent cerebral ischemic events in the long-term follow up after intracardiac echocardiography (ICE)-aided PFO closure in a large population. METHODS: We reviewed the medical and instrumental data of 1,000 consecutive patients (mean age 47.3 ± 17.1 years, females) prospectively enrolled in 2 centres over a 13 years period (February 1999-February 2012) for R-to-L shunt ICE-aided catheter-based closure using different devices. RESULTS: Immediate success was 99.8%. Implanted devices were Amplatzer PFO Occluder in 463 patients (46.3%), Amplatzer ASD Cribriform Occluder in 420 patients (42.0%), Premere Occlusion System in 95 patients (9.5%), and Biostar Occluder in 22 patients (2.2%). On a mean follow-up of 12.3 ± 0.6 years (minimum 4- maximum 17 years), permanent AF occurred in 0.5%, DT was apparent in 0.5%, new onset or worsening of MVR was observed in 0.2%, whereas recurrent cerebral ischemic events were 0.8%. Occlusion rate was 93.8%. No aortic or atrial free wall erosion has been observed. CONCLUSION: ICE-aided closure of PFO using different devices, appeared very safe and effective on very long-term follow up with low incidence of erosion, DT, recurrent ischemic events, MVR new onset or worsening, and permanent AF.

Residual shunt after patent foramen ovale closure: preliminary results from Italian patent foramen ovale survey.

BACKGROUND: Percutaneous patent foramen ovale (PFO) closure is accepted as treatment for cryptogenic ischemic stroke/transient ischemic attack in young subjects. However, a thorough evaluation of residual right-to-left shunt (rRLS) after PFO closure is needed. Our aims were to analyze the characteristics related to PFO diagnosis and closure, focusing on rRLS and clinical recurrences until 24-month follow-up. Data were extrapolated from the 12-month Italian PFO Survey. METHODS: In all, 1035 patients were included. PFO diagnosis and right-to-left shunt (RLS) were assessed by contrast-enhanced transesophageal and/or transthoracic echocardiography and/or transcranial Doppler. RESULTS: PFO diagnosis with RLS data were available in 894 of 1035 (86.4%) patients. rRLS was investigated in 49.6% (6 months), 27.1% (12 months), and 3.5% (24 months), and observed in 19.5% (6 months) and 18.2% (12 months) of subjects. Large permanent rRLS was observed in less than 3% of RLS-positive patients after 1 year. Eleven of 14 and 3 of 14 neurological recurrences were observed in 10 of 444 (2.25%) and 2 of 243 (0.8%) patients within the 6- and 12-month follow-up, respectively. Among these, no large rRLS was reported. There were no neurological events at 2-year follow-up. Forty of 444 subjects had non-neurological complications, mostly cardiac arrhythmias within the sixth month. CONCLUSIONS: PFO closure is a safe procedure. rRLS is not uncommon but large rRLS is rare. Clinical complications, mostly related to cardiac arrhythmias, are not unusual. Evaluation of the data of the whole survey is underway.

Funnel technique for EVAR: "a way out" for abdominal aortic aneurysms with ectatic proximal necks.

BACKGROUND: To describe an endovascular technique for proximal stent-graft fixation in patients with an abdominal aortic aneurysm and an ectatic aortic neck. METHODS: We describe a method in which using currently available devices in a hybrid assembly offers another option for circumventing the limitations of problematic proximal fixation. CONCLUSIONS: Through four examples, we illustrate the feasibility of placing a straight endograft as proximal extension of a bifurcated or aorto-uni-iliac graft in patients with a dilated proximal aortic neck. It appears secure and effective, with no type I endoleak or migration over a midterm follow-up.

Echocardiographic guidance of percutaneous patent foramen ovale closure: head-to-head comparison of transesophageal versus rotational intracardiac echocardiography.

BACKGROUND: Transesophageal (TEE) and intracardiac (ICE) echocardiography are commonly used to guide percutaneous patent foramen ovale (PFO) closure. The study aim was to perform a head-to-head comparison between TEE and rotational ICE echocardiography in the measurement of the fossa ovalis and device selection. METHODS: In 45 patients with cryptogenic stroke or peripheral embolism and PFO with large right-to-left shunt, fossa ovalis dimensions were assessed preoperatively by TEE and intraoperatively by rotational ICE. The Amplatzer devices, deployed on the basis of ICE, were compared with those that would have been selected by TEE. RESULTS: A good correlation between TEE and rotational ICE was observed for both longitudinal and transverse fossa ovalis dimensions (TEE four-chamber vs. ICE four-chamber: r = 0.75; TEE bicaval vs. ICE four-chamber: r = 0.77; TEE aorta vs. ICE aorta: r = 0.59; P < 0.001 for all). However, no such correlation was found in 13 patients with atrial septal aneurysm (ASA) (TEE four-chamber vs. ICE four-chamber: r = 0.33; TEE bicaval vs. ICE four-chamber: r = 0.49; TEE aorta vs. ICE aorta: r = 0.05; P = NS for all). At Bland-Altman analysis, slight systematic differences with wide limits of agreement for each comparison were observed, particularly in patients with ASA, suggesting that the two imaging modalities cannot be used interchangeably. As regards device selection, a moderate agreement was found between TEE- and ICE-guided device size (72%, κ = 0.53, P < 0.001), except in patients with ASA (36%, κ = 0.02, P = NS). CONCLUSIONS: Our study suggests a significant disagreement between TEE and rotational ICE in measuring fossa ovalis and selecting the device for PFO closure, particularly in patients with ASA.

Exon 11 deletion in the myocyte enhancer factor (MEF)2A and early onset coronary artery disease gene in a Sicilian family.

AIMS: We investigated the prevalence of the myocyte enhancer factor (MEF)2A exon 11 deletion, a putative coronary artery disease (CAD) susceptibility gene, in patients referred for coronary angiography. METHODS AND RESULTS: In total, 1079 consecutive patients referred for coronary angiography in the GENICA Study were genotyped and 301 low-risk subjects were used as controls. One patient with early onset three vessels CAD, carrying the MEF2A deletion was found in the GENICA Study cohort and none in the control group. CONCLUSION: In a cohort of patients undergoing coronary angiography for suspected CAD the MEF2A exon 11 deletion occurred in 0.09%.

Aneurysm sac "thrombization" and stabilization in EVAR: a technique to reduce the risk of type II endoleak.

PURPOSE: To evaluate the reduction in type II endoleak risk after introducing a new prevention method, "thrombization" or clotting of the aneurysm sac, during endovascular aneurysm repair (EVAR) versus the standard EVAR technique. METHODS: From September 1999 to December 2008, 469 consecutive patients underwent EVAR for AAA at our institution. In 2003, the injection of fibrin glue with or without microcoils into the aneurysm sac was added to the EVAR treatment plan ("thrombization" technique). Patients who did not meet the inclusion criterion (at least 1-year follow-up imaging) were censored at the end of 2007, leaving 404 patients eligible for the study: 224 patients (210 men; mean age 71.9+/-8.5 years, range 25-88) undergoing EVAR alone from September 1999 to May 2003 (group 1) compared to 180 patients (161 men; mean age 72.6+/-8 years, range 46-89) who underwent EVAR + thrombization from June 2003 to December 2006 (group 2). RESULTS: The 2 treatment groups were similar with regard to aneurysm morphology. No allergic or anaphylactic reactions were encountered related to the fibrin glue. Over median follow-up times of 72 months in group 1 and 26 months in group 2, there were 34 (15.2%) endoleaks in group 1 versus 4 (2.2%) in group 2 (p<0.0001). The incidence of type II endoleak was 0.25/100 person-months for group 1 versus 0.07/100 person-months for group 2. The preventive sac thrombization technique was significantly associated with a reduced risk of type II endoleak (HR 0.13, 95% CI 0.05 to 0.36; p<0.0001) regardless of the type of stent-graft fixation (infrarenal versus suprarenal). CONCLUSION: The preventive method of intrasac "thrombization" using fibrin glue injection with or without the insertion of coils proves to be a simple, low cost, safe, and effective technique to significantly reduce the risk of type II endoleaks irrespective of the endograft used.

Plasma adiponectin for prediction of cardiovascular events and mortality in high-risk patients.

CONTEXT: The prognostic value of plasma levels of adiponectin, an adipocytokine with antiatherogenic, antiinflammatory, and insulin-sensitizing effects, is contentious. OBJECTIVE: The objective of the study was to investigate whether plasma adiponectin levels predict cardiovascular (CV) events and mortality in high-risk coronary artery disease (CAD) patients. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURE: We measured plasma adiponectin and examined its impact on the incidence of CV deaths and events at follow-up in the context of all potentially relevant background covariates in 712 high-risk patients of the Genetic and ENvironmental factors in Coronary Atherosclerosis study who underwent coronary angiography for suspected CAD. Based on the population plasma adiponectin median (6.38 microg/ml, interquartile range 4.2-10.2), we split the patients in a high- and a low-plasma adiponectin subgroup. After a median follow-up of 3.8 years (interquartile range 3.3-4.3 yr), outcome data were obtained in 100% of the patients and 45 CV deaths (6.4%) were recorded. Kaplan-Meier analysis unexpectedly showed a higher CV death rate in high-plasma adiponectin than low-plasma adiponectin patients. By contrast, multivariate Cox regression analysis, in which potential confounders, including ongoing medical treatment, were considered, showed no impact of plasma adiponectin on CV death. Similar negative results were obtained using the propensity score that considered all relevant covariables and medical treatment rate, which differed between the high- and low-plasma adiponectin group. CONCLUSIONS: In high-risk CAD patients, plasma adiponectin above the median (6.38 microg/ml) implies a paradoxical higher risk of CV death. However, when relevant covariates that differ between high- and low-plasma adiponectin groups are considered, this association wanes, indicating that the clustering of plasma adiponectin with other covariates can abolish its impact on CV prognosis.

[Short and medium term functional capacity after single cycle of controlled physical training in subjects with claudication]. / Risultati a breve e medio termine dei parametri funzionali dopo singolo ciclo di training fisico controllato in soggetti con claudicatio.

BACKGROUND: Previous studies have shown the positive effect of exercise rehabilitation in patients with claudication, but uncertainties remain surrounding the optimal exercise program strategy and the persistence of the benefits over time. The purpose of the present study has been to prospectively assess the feasibility of short-course intensive supervised exercise training beyond pain threshold and to verify the maintenance of walking capacity during a medium term follow-up. METHODS: Ninety patients with intermittent claudication due to peripheral artery disease were enrolled in a supervised intensive exercise training. Seventy six of them (67 +/- 7 years, 64 male and 12 female, 48 with bilateral claudication) performed a graded treadmill testing at baseline and after 3 months. Sixty patients completed also a specific questionnaire (Walking Impairement Questionnarie). After a mean follow-up of 2.6 years, fifty six patients repeated treadmill testing and 24 patients repeated the questionnaire. RESULTS: After training, the patients showed a 91% and 53% increase in the initial and absolute claudication distance time, respectively (p = 0.0000). At follow-up there was no change in the initial claudication distance time, whereas absolute claudication distance time was reduced by only 13% (p = 0.0001). All items of the questionnaire showed a statistically significant improvement after training (from 30 to 71%) and remained unchanged at follow-up. Sixty seven percent of the patients were considered responder, 15% partial responder and 18% no-responder to exercise training, whereas at follow-up these percentages were 55%, 13% and 32%, respectively. These results after training and at follow-up were independent from age, sex, smoke, hypertension, coronary artery disease and diabetes. CONCLUSIONS: Our findings confirm that a short supervised exercise therapy in the form of walking out over pain threshold is effective in maximizing the walking time of the majority of patients with intermittent claudication, independently of demographic data and their associated cardiac risk factors or comorbidities. After a mean follow-up of 2.6 years there was only a minor reduction of absolute claudication distance time and no modification of initial claudication distance time and questionnaire's score, despite the fact that none of these patients were contacted by the rehabilitation centre after their physical training period.

A collaborative study by the Working Group on Hemostasis and Thrombosis of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) on the interference of haemolysis on five routine blood coagulation tests by evaluation of 269 paired haemolysed/non-haemolysed samples.

INTRODUCTION: Haemolysis is the leading cause of sample rejection in laboratory haemostasis. Most studies focused on artificially haemolysed samples. The aim of this study was a prospective assessment of spontaneous haemolysis on haemostasis tests, by comparing results of haemolysed (H) versus new, non-haemolysed (NH) specimens, collected within 4hrs. As new coagulometers can identify interfering substances, visual assessment of haemolysis was also compared with instrumental haemolysis index and stratified in subclasses. MATERIALS AND METHODS: Two hundred and sixty nine paired samples were collected and analysed using ACL TOP750-CTS (Instrumentation Laboratory, Bedford, USA), for prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer (DD), fibrinogen (Fib) and antithrombin (AT). Bias between H and NH was calculated and compared with the respective critical difference (CD). RESULTS: Mean bias was - 0.1 s for PT (P = 0.057), - 1.1 s for aPTT (P < 0.001), 1025 ng/mL for DD (P < 0.001), - 0.04 g/L for Fib (P = 0.258) and 1.4% for AT (P = 0.013). Bias exceeding the CD varied according to the method, with larger differences for aPTT (36.1%) and DD (17.1%) and < 8% for PT, Fib and AT. No correlation emerged between free haemoglobin values and difference in haemostasis tests in H and NH samples for any tests. Moderate/severe haemolysis involved > 95% of samples. The agreement between visual assessment and instrumental evaluation of haemolysis was 0.62. CONCLUSION: Spurious haemolysis deeply influences aPTT and DD, and to a lesser extent AT and Fib. Prothrombin time seems only slightly influenced, suggesting that PT can be accepted also in haemolysed samples. Although a good inter-observer correlation of haemolysis evaluation was found, the instrumental assessment of haemolysis seems recommendable.

[Is obesity still a coronary risk factor?]. / L'obesità è ancora un fattore di rischio coronarico?

Although obesity and, in particular, abdominal obesity is clearly a risk factor for developing coronary artery disease, once coronary artery disease has been established, the correlation of obesity with total mortality, cardiovascular mortality, myocardial infarction, and revascularization is unclear and still remains a matter of debate. The relationship between obesity and mortality in patients with coronary artery disease has so far only been investigated by posthoc analysis of cohort studies, which have produced contradictory results. When a higher percentage body fat has been found to be a strong independent predictor of event-free survival, the phenomenon has been described as an 'obesity paradox' or 'reverse epidemiology'. A recent meta-analysis, appearing in the August 19 issue of Lancet on 250,152 patients with documented coronary artery disease, suggests that after grouping 40 cohort studies with adjusted risks, overweight patients were consistently associated with a better survival and lower cardiovascular events than patients with a low body mass index, whereas obesity was associated with a higher total mortality only in patients with history of coronary artery bypass graft, and severe obesity was associated with a significantly higher cardiovascular mortality but not with an increased risk for total mortality. Far from proving that obesity is harmless, these findings suggest that alternative methods might be required to better characterize individuals who truly have excess body fat and that additional studies with different methods are needed. Moreover, still unknown is the unique contribution of higher muscle-to-fat ratio, which may be merely a surrogate of increased physical fitness. Future research is needed to assess the link between high muscle mass, high body fat and clinical outcomes.

The Use of CYFRA 21-1 for the Detection of Breast Cancer Axillary Lymph Node Metastases in Needle Washouts of Fine-Needle Aspiration Biopsies.

BACKGROUND: In the preoperative setting of breast cancer, fine-needle aspiration biopsy (FNAB) guided by ultrasonography can be used to detect axillary lymph node metastases. The aim of the current study was to determine whether measurement in needle washouts of CYFRA 21-1, a soluble fragment of cytokeratin 19 (CK19), can improve the diagnosis of lymph node tumor deposits. MATERIALS AND METHODS: Our prospective study included 329 breast cancer patients eligible for a sentinel node procedure. Eighty-two patients had a ultrasonography-guided FNAB of an abnormal or suspicious axillary node and were included in the current analysis. Samples were processed with smears and cell-block histology; afterwards, needles were washed with saline solution, and the CYFRA 21-1 content in the washouts was measured. The cutoff value for positive samples that expressed CK19, as shown by their immunohistochemistry, was determined by a receiver operating characteristic curve. On the basis of this value, the specificity and the sensitivity, as well as the positive and negative predictive values, were then calculated using cytology results as a reference standard. RESULTS: Of the 82 axillary lymph nodes sampled, 61 were positive on cytology and were metastatic for breast cancer, as confirmed by surgery. The median CYFRA 21-1 concentration of positive samples was 88.94 ng/mL, whereas in the 21 negative nodes, its median concentration was 1.02 ng/mL (P<0.0001). A CYFRA 21-1 cutoff value of 1.98 ng/mL, obtained by the receiver operating characteristic curve, was able to clearly separate negative from positive samples and gave the test a sensitivity of 0.98 and a specificity of 1.00. Positive and negative predictive values were 1.00 and 0.95, respectively. CONCLUSIONS: The measurement of CYFRA 21-1 levels in needle washouts after axillary lymph node FNABs represents an accurate, sensitive, and highly predictive procedure in detecting metastatic deposits of breast cancer and is fit to complement cytology and CK19 immunohistochemistry as a diagnostic tool.

Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women.

OBJECTIVE: The impact of homocysteine on cardiovascular disease can be more detrimental in women than in men, but it is unknown whether this applies to high-risk women. We therefore investigated the association of hyperhomocysteinemia with coronary artery disease (CAD) and cardiovascular mortality in high-risk women referred for CAD, both in the total population and in the hypertensive and normotensive cohorts. DESIGN: A prospective study cohort. SETTING: A tertiary centre. INCLUSION CRITERIA: 262 consecutive Caucasian postmenopausal women referred for coronary angiography. EXCLUSION CRITERIA: acute myocardial infarction and vitamin supplementation. MAIN OUTCOME MEASURE(S): We assessed total plasma homocysteine (tHcy), folate levels, and the MTHFR677C-->T polymorphism. CAD was defined as a modified Duke Index score greater than 0; hyperhomocysteinemia as tHcy levels of 15 micromol/l or greater. The primary study outcome was cardiovascular mortality at follow-up. RESULTS: Mild/moderate and severe hyperhomocysteinemia was found in 15.1 and 1.6% of women, respectively, without differences between CAD and non-CAD women. By the ATPIII criteria, 92.2% of the women were in the highest risk class and 55% had CAD; however, no association of tHcy with the CAD score was found. After a median follow-up of 3.6 years, 23 women (9.1%) had died, 15 (6%) of cardiovascular causes. Women with high tHcy levels showed the worst all-cause and cardiovascular death-free survival at Kaplan-Meier and Cox regression analysis. Moreover, in the hypertensive cohort only women with hyperhomocysteinemia showed increased cardiovascular mortality. CONCLUSION: Hyperhomocysteinemia is common in high-risk women and adversely affects their prognosis, although it is unrelated to the CAD atherosclerotic burden.

Hyperhomocysteinemia is inversely related with left ventricular ejection fraction and predicts cardiovascular mortality in high-risk coronary artery disease hypertensives.

OBJECTIVE: The purpose of this study was to investigate the relationship of plasma homocysteine (tHcy) levels with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) in high-risk patients undergoing coronary angiography for suspected CAD. METHODS AND RESULTS: In 936 consecutive patients, we measured LVEF, tHcy, folate levels, and quantified CAD with a modified Duke Index score. We also genotyped patients at the methylen-tetrahydrofolate-reductase 677C-->T polymorphism. Hyperhomocysteinemia (HHcy) was defined as tHcy levels > or =15.46 micromol/L; total and cardiovascular mortality was assessed at follow-up that lasted 43 months (median). CAD was confirmed in 75% of patients and ruled out in the rest (non-CAD group). No relationship of HHcy with either arterial hypertension or the CAD score was found. In contrast, there was a significant inverse relationship of tHcy with LVEF in arterial hypertensive but not in normotensive patients, regardless of previous myocardial infarction. At logistic regression, HHcy was the strongest predictor (P=0.001) of a low (<40%) LVEF, followed by type 2 diabetes mellitus and cigarette smoking. At follow-up, HHcy significantly predicted cardiovascular mortality but only in the arterial hypertension subgroup. CONCLUSIONS: In arterial hypertensive but not in normotensive patients, HHcy predicts cardiovascular mortality and a low LVEF, independent of CAD and history of myocardial infarction.

[Why cardiovascular rehabilitation services should include patients with intermittent claudication?]. / Perche i pazienti con claudicatio intermittens devono essere trattati nelle strutture di cardiologia riabilitativa?

Chronic peripheral arterial disease represents a frequent and underestimated localization of atherosclerosis and its management often appears to be inadequate. The association with ischemic heart disease, the weighty prevalence of coronary disease risk factors, the high cardiovascular rate of morbidity and mortality, the sharp reduction in the tenor of life and the well-being supervised physical training efficacy constitute the main reasons that transform Cardiac Rehabilitation into an ideal setting for the treatment of patients suffering from intermittent claudication. Thanks to the cultural patrimony of cardiologists, together with other professionals, such as psychologists, dietitians, physiotherapists and nurses, it is possible to initiate an multi-comprehensive treatment program. Besides, this type of management may decrease both morbidity and mortality as well as reduce symptoms and improve the patients' quality of life.

Antibodies to oxidized low-density lipoproteins and angiographically assessed coronary artery disease in white patients.

BACKGROUND: Low-density lipoprotein (LDL) can be oxidatively modified by reactive oxygen species, thus generating oxLDL. The latter induce formation of specific antibodies (oxLDLAb), which are detectable in patients with atherosclerosis, in which they might play a pathogenic or a protective role. Thus, we aimed to investigate the association of antibodies with oxidized LDLs (oxLDL) (oxLDLAbs) with coronary artery disease (CAD) and acute coronary syndromes. METHODS AND RESULTS: In a cross-sectional study of 529 consecutive patients undergoing quantitative coronary angiography for suspected CAD, we measured the titer of IgG oxLDLAbs by ELISA. With regression analysis techniques, we also investigated the determinants of oxLDLAb titer and the association of oxLDLAbs with CAD severity. We found no significant differences of oxLDLAb titer between groups of patients without and with different CAD severity. The oxLDLAb titer was 18.6 enzyme units (EU) (11.5 to 25.7 EU/mL) (mean, 95% CI) in patients without CAD; 16.8 EU (9.6 to 24.2 EU) in patients with stenosis <50%; and 19.9 EU (15 to 24.8 EU), 17.2 (13.8 to 20.6 EU), and 14.7 EU (12.1 to 17.3 EU) in those with in 1-, 2-, or 3-vessel > or =50% stenosis, respectively. Similarly, no differences of oxLDLAb titer between patients without and with acute coronary syndrome were found. The oxLDLAb titer correlated weakly with aging and with serum total, LDL, and HDL cholesterol and plasma homocysteine levels; however, only age and HDL cholesterol remained significant predictors of the oxLDLAb titer at a stepwise regression analysis. CONCLUSIONS: The results of this study, which was adequately powered from the statistical standpoint, provided no evidence for an association of IgG oxLDLAb titer with angiographically assessed CAD in whites.

Intracardiac echocardiography-guided transcatheter closure of secundum atrial septal defect: a new efficient device selection method.

OBJECTIVES: We assessed the use of intracardiac echocardiography (ICE) as the primary means for both selection of the Amplatzer Septal Occluder (ASO) and the guidance of transcatheter closure of secundum atrial septal defects (ASDs). BACKGROUND: The standard method for transcatheter closure of ASDs requires balloon-sizing maneuver and transesophageal echocardiographic (TEE) monitoring. The role of ICE during transcatheter closure of ASDs has not yet been established. METHODS: In 91 patients with ASDs, two standardized orthogonal sections were used to obtain ICE-derived measurements of the fossa ovalis and to assess optimal device deployment: the transverse section on the aortic valve plane, and the longitudinal section on the four-chamber plane. RESULTS: In all patients, ICE planes were identified with excellent resolution, providing proper measurements of the fossa ovalis, from which to derive geometric assumptions for the selection of an appropriately sized device. The ASO waist diameter was chosen on the basis of the r value (r = [square root c(2) + p(2)], where r is the radius of an ideal circle that intersects the elliptical fossa ovalis in its semi-latus rectum, c is the foci half-distance of the fossa ovalis, and p is its semi-latus rectum). During the procedure, the four-chamber plane allowed us to obtain easily interpretable images of all stages of device deployment. Midterm complete occlusion rate was 97.8%. No ICE-related complications occurred. CONCLUSIONS: The ICE evaluation of ASDs allows quantitative and qualitative information for both proper ASO selection and optimal device placement, thus eliminating the cumbersome balloon-sizing maneuver and the need for general anesthesia during TEE monitoring.

The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study.

OBJECTIVES: We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD). BACKGROUND: Endothelial dysfunction foretells cardiovascular events and can be genetically determined. METHODS: We genotyped for the promoter (T(-786)C) and exon 7 (Glu298Asp, G(894)T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5'- and 3'-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T(-786)C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD. RESULTS: The overall genotype distribution of T(-786)C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T(-786)C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T(-786)C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041). CONCLUSIONS: The C allele at the T(-786)C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.

A mystery featuring right-to-left shunting despite normal intracardiac pressure.

The cause of right-to-left atrial shunting despite normal intracardiac pressures and normal or near-normal pulmonary function through a patent foramen ovale has still not been completely clarified. It is probably responsible for several linked diseases, such as paradoxical embolism, platypnea-orthodeoxia syndrome, migraine with aura, transient global amnesia, and decompression sickness in sport divers. Despite modern diagnostic methods, the underlying anatomophysiologic and pathogenic mechanisms of right-to-left atrial shunting without abnormal intracardiac pressures remain a matter of debate and controversy. Holistically speaking, a return to a direct study of embryology, gross anatomy, and physiology may help us elucidate the real mechanism of this paradoxical shunting.

Catheter closure of perforated secundum atrial septal defect under intracardiac echocardiographic guidance using a single amplatzer device: feasibility of a new method.

OBJECTIVES: Little is known about the feasibility and effectiveness of perforated secundum atrial septal defects (ASDs) transcatheter closure. This study tested whether this type of fenestration can be percutaneously closed using a single Amplatzer PFO or Cribriform Occluder device in a patch-like fashion under intracardiac echocardiographic (ICE) guidance and monitoring. METHODS: Twenty-four adult patients with perforated ASDs underwent transcatheter single Amplatzer PFO or Cribriform Occluder device closure by using ICE as the primary imaging tool, both for crossing the flap valve and monitoring each stage of the procedure. The entire atrial septum and fossa ovalis end diastolic dimensions on 2 orthogonal ICE planes, as well as the distance between the eccentric guidewire passage and the more adjacent rim of the fossa ovalis on the longitudinal ICE plane, have been measured. RESULTS: On the basis of the ICE fossa ovalis size and its geometric evaluation, in order to completely cover the fossa ovalis with a single device, 2 Amplatzer PFO Occluders 25 mm, 9 Amplatzer PFO Occluders 35 mm, and 13 Amplatzer Cribriform Occluders (four 25 mm and nine 35 mm) have been implanted successfully. During follow-up (31.4, 7.2 months), complete closure by contrast echo color Doppler occurred in 16/24 (67%) patients after 24 hours, 19/24 (79%) after 1 mouth, 20/24 (83%) after 3 months, 22/24 (92%) after 1 year, and 23/24 (96%) after 2 years. CONCLUSIONS: Transcatheter closure of perforated ASDs using a single Amplatzer Occluder device under ICE guidance appears to be a suitable procedure, providing a low rate of residual shunting.