Echocardiographic predictors of reoperation for subaortic stenosis in children and adults.

OBJECTIVES: Subaortic stenosis (SAS) can present as various types of obstruction of the left ventricular outflow tract (LVOT) below the level of the aortic valve. Even though corrective surgery has been identified as the most effective treatment, SAS more frequently reoccurs requiring reoperation in a significant proportion of the patients. Previous studies have focused on predictors of recurrence in various subgroups of patients with SAS, but rarely in the overall population of patients with SAS. The aim of this study was to determine the predictors of recurrence of SAS after initial corrective surgery. METHODS: Patients from the database of the Congenital Cardiology Department of the University Hospital of Southampton with significant SAS requiring corrective surgery were included in the study. Data retrieved were obtained and used to determine the predictors of SAS recurrence after the initial corrective surgery. RESULTS: Eighty-two patients (paediatric, n = 72 and adult, n = 10) who underwent initial successful resection were included in the analysis. Thirty patients required reoperation for recurrent SAS. These were significantly younger (median age 3.0 vs 6.7 years, P = 0.002). The recurrence of SAS was more common in patients with an interrupted aortic arch (23.3% vs 3.8%, P = 0.010) and unfavourable left ventricle geometry (43.3% vs 7.6%, P < 0.001), with steeper aortoseptal angle (131.0° ± 8.7° vs 136.1° ± 8.6°, P = 0.030), shorter distance between the point of obstruction of the LVOT and the aortic valve annulus in systole and diastole (median 4.30 vs 5.90 mm, P = 0.003 and 3.65 vs 4.95 mm, P = 0.006, respectively) and in those who had higher residual peak and mean LVOT gradients postoperatively (29.3 ± 16.0 vs 19.8 ± 10.7 mmHg, P = 0.006 and 15.9 ± 8.3 vs 10.1 ± 5.8 mmHg, P = 0.002, respectively). Overall, the presence of an interrupted aortic arch [odds ratio (OR) 10.34, 95% confidence interval (CI) 1.46-73.25; P < 0.019] and unfavourable left ventricle geometry (OR 10.42, 95% CI 1.86-58.39; P < 0.008) could independently predict reoperation for SAS after initial successful resection. CONCLUSIONS: Patients who have initial corrective surgery for SAS at a younger age, unfavourable left ventricle geometry, an interrupted aortic arch and higher early postoperative LVOT gradients are more likely to have recurrent SAS requiring reoperation.

Comparison of ESC and NICE guidelines for patients with suspected coronary artery disease: evaluation of the pre-test probability risk scores in clinical practice.

The European Society of Cardiology (ESC) and UK National Institute for Health and Care Excellence (NICE) have recently published guidelines for investigating patients with suspected coronary artery disease (CAD). Both provide a risk score (RS) to assess the pre-test probability for CAD to guide clinicians to undertake the most effective investigation. The aim of the study was to establish whether there is a difference between the two RS models. We retrospectively reviewed records of 479 patients who presented to a UK district general hospital with chest pain between August 2011 and April 2013. The RS was calculated using ESC and NICE guidelines and compared. From the 479 patients, 277 (58%) were male and the mean age was 60 years. The mean RS was greater using NICE guidelines compared with ESC (66.3 vs 47.9%, 18.4% difference; p<0.0001). The difference in mean RS was smaller in patients with typical chest pain (13.0%). When we divided the cohort based on NICE criteria into 'high'- and 'low'-risk groups, the difference in the mean RS was 24.3% in the 'high'-risk group (p<0.001) compared with 2.8% in the 'low'-risk group. The UK NICE risk score model overestimates risk compared with the ESC model.

Reversible de novo left ventricular trabeculations in pregnant women: implications for the diagnosis of left ventricular noncompaction in low-risk populations.

BACKGROUND: Patients with heart failure and chronic anemia frequently demonstrate left ventricular (LV) trabeculations, which may be compatible with the diagnosis of LV noncompaction. We used the pregnancy model, which is characterized by a reversible increase in cardiac preload and other changes in cardiac function, to assess the development of de novo LV trabeculations in women with morphologically normal hearts. METHODS AND RESULTS: One hundred two primigravida pregnant women were evaluated longitudinally with a series of echocardiograms in the first trimester, in the third trimester, and postpartum. Echocardiograms were analyzed according to established guidelines. Increased LV trabeculations and the presence of LV noncompaction were based on established criteria. Pregnancy was associated with an increased heart rate, stroke volume, and cardiac output, as well as increased LV volume and mass. During pregnancy, 26 women (25.4%) developed increased trabeculations. Eight women showed sufficient trabeculations to fulfill criteria for LV noncompaction. During the postpartum follow-up period of 24±3 months, 19 women (73%) demonstrated complete resolution of trabeculations, and 5 showed a marked reduction in the trabeculated layer. CONCLUSIONS: Pregnancy induces de novo LV trabeculations in a significant proportion of women. The results suggest that LV trabeculations occur in response to increased LV loading conditions or other physiological responses to pregnancy and are not specific for LV noncompaction. These factors should be considered in the assessment of individuals with LV trabeculations outside the context of symptoms of heart failure or familial cardiomyopathy.

Paradoxical protective effect of central obesity in patients with suspected stable coronary artery disease.

OBJECTIVE: Increased body mass index (BMI) has been paradoxically inversely associated with the presence of angiographic coronary artery disease (CAD). Central obesity measures, considered to be more appropriate for assessing obesity-related cardiovascular risk, have been little studied in relation to the presence of CAD. The aim was to investigate the association of central obesity with the presence of angiographic CAD as well as the prognostic significance of obesity measures in CAD prediction when added to other cardiovascular risk factors. DESIGN AND METHODS: Patients with suspected stable CAD (n = 403, age 61 ± 10 years, 302 males) referred for diagnostic coronary angiography with documented anthropometric data were enrolled. RESULTS: Significant angiographic CAD was found in 51% of patients. Both BMI (OR = 0.64 per 1 SD increase, P = 0.001) and waist circumference (WC) (OR = 0.54 per 1 SD increase, P < 0.001) were inversely associated with the presence of CAD even after adjustment for cardiovascular risk factors. In subgroup analysis, BMI and WC were significantly inversely associated with the presence of CAD in males, non diabetics, patients >60 years old and patients with Framingham risk score (FRS) >20% (P < 0.01 for all). The addition of BMI or WC in FRS-based regression models improved prediction of CAD (P = 0.03 and P < 0.001 for BMI and WC respectively) without a significant difference between the two models (P = 0.08). CONCLUSIONS: Central and overall obesity were independently associated with a reduced prevalence of angiographic CAD, lending further credence to the existence of the 'obesity paradox'. Obesity measures may further improve risk discrimination for the presence of CAD when added in an established risk score such as FRS.

Increased aortic pulse wave velocity is associated with the presence of angiographic coronary artery disease in overweight and obese patients.

BACKGROUND: Increased arterial stiffness assessed by carotid-femoral pulse wave velocity (CFPWV) and central augmentation index (AIx), has been associated with a worse cardiovascular prognosis and increased prevalence of angiographic coronary artery disease (CAD). Obesity, a well-recognized cardiovascular risk factor, has been related to increased arterial stiffness, although not consistently. The aim of this work was to investigate the association of arterial stiffness indices with obesity measures in patients undergoing coronary angiography and to study any potential association of arterial stiffness with angiographic CAD in relation to obesity. METHODS: Three hundred ninety-three patients with suspected stable CAD (aged 61±10 years; n = 303 men) referred for diagnostic coronary angiography were included. Body mass index (BMI), waist circumference (WC), and traditional cardiovascular risk factors were measured. Arterial stiffness was assessed by CFPWV and AIx using applanation tonometry in all patients. RESULTS: CFPWV was not associated with obesity measures in multiple-adjusted logistic regression analysis (P > 0.05), whereas AIx was inversely associated with BMI and WC (P < 0.05 for both). Increased CFPWV was associated with CAD in overweight and obese patients (BMI ≥25kg/m(2); WC ≥94cm in men and ≥80cm in women; P < 0.05). No association of AIx with CAD was found (P > 0.05). CONCLUSIONS: Arterial stiffness indices were not consistently associated with obesity, opposite to what might have been expected. The association of increased CFPWV with the presence of angiographic CAD in patients with increased BMI or WC values warrants further research.

Determinants of pulmonary hypertension in patients with Beta-thalassemia major and normal ventricular function.

BACKGROUND/AIMS: We sought to define the incidence and predictive factors of pulmonary hypertension in ß-thalassemia major. METHODS: We studied 27 consecutive patients (19 male, 38 ± 9 years of age) with ß-thalassemia major. All the patients had normal (left and right) ventricular (systolic and diastolic) function and underwent echocardiographic assessment of pulmonary artery systolic pressure. Univariate regression and discriminant function analyses were used to identify predictive factors of pulmonary hypertension. RESULTS: Pulmonary hypertension was observed in 18.5% of the patients, but clinically significant disease was detected in only 3.7%. A total of 14 (51.8%) patients had been receiving a combined administration of deferoxamine and deferiprone for 7.0 ± 1.3 years. Amidst a large number of variables examined, ferritin levels and delayed onset of chelation therapy were the only predictors of pulmonary hypertension. CONCLUSION: Pulmonary hypertension in ß-thalassemia major is relatively infrequent and generally mild due to improved chelation therapy. The role of hemochromatosis in pulmonary hypertension development merits further study.

Changes in vascular function and structure in juvenile idiopathic arthritis.

OBJECTIVE: Chronic inflammatory diseases in adults have been associated with increased cardiovascular risk and impaired vascular function. We aimed to assess the presence of early vascular dysfunction in patients with juvenile idiopathic arthritis (JIA) and investigate the role of inherent inflammatory process of JIA in vascular health. METHODS: Thirty patients with JIA (age range 7-18 years) were compared to 33 age- and sex-matched controls. Endothelial function (brachial artery flow-mediated dilation [FMD]), carotid intima-media thickness (IMT), and arterial stiffness were examined. Endothelial inflammation was assessed by intercellular adhesion molecule 1 (ICAM-1) and P-selectin measurements. RESULTS: Patients with JIA showed decreased FMD compared to controls (P = 0.001), independent of age (P = 0.9 among age subgroups). Baseline differences in erythrocyte sedimentation rate, ICAM-1, and glucose between the 2 groups accounted for the difference in FMD. The presence of systemic JIA was associated with greater IMT compared to patients with oligoarticular disease, polyarticular disease, or controls (P = 0.014, P = 0.069, and P = 0.046, respectively). The difference in IMT between systemic versus oligoarticular/polyarticular JIA was attributed to the following risk factors: age, body mass index, blood pressure, disease activity, and corticosteroids use. There were no differences in arterial stiffness indices between JIA patients and controls or between patients with systemic versus nonsystemic disease. CONCLUSION: Endothelial function is impaired in patients with JIA at a very young age, while IMT is increased only in the presence of systemic JIA. Vascular dysfunction may be partly attributed to the effects of disease-related characteristics (inflammation, disease activity, and medications).

A highly constrained cyclic (S,S)-CDC- peptide is a potent inhibitor of carotid artery thrombosis in rabbits.

Inhibition of platelet aggregation is indispensable for the treatment of acute arterial thrombotic episodes. We have previously reported the synthesis of a highly constrained cyclic peptide, that incorporates the -CDC- sequence, (S,S) PSRCDCR-NH(2), which potently inhibits aggregation and fibrinogen binding to human platelets in vitro. We have tested the safety and efficacy of the peptide on the electrically induced carotid artery thrombosis experimental rabbit model. The peptide's effects on carotid blood flow, thrombus weight, in vitro and ex vivo platelet aggregation, and bleeding and hemostatic parameters were evaluated. The peptide was administered via the femoral vein. Carotid blood flow was continuously monitored for 90 min after electrical thrombus formation. The peptide, at 12 mg/kg, prevented total artery occlusion and significantly preserved carotid artery's patency compared with placebo and eptifibatide. Furthermore, (S,S) PSRCDCR-NH(2) administration at 12 mg/kg reduced thrombus weight, whereas it inhibited ex vivo ADP, arachidonic acid (AA) and collagen-induced platelet aggregation. Moreover (S,S) PSRCDCR-NH(2) at 12 mg/kg presented significantly higher inhibitory effects on AA and collagen-induced ex vivo platelet aggregation compared to eptifibatide. The peptide at any dose did not affect the coagulation cascade, the bleeding times or the hemostatic response of the animals. Thus highly constrained cyclic peptides like (S,S) PSRCDCR-NH(2) that incorporate the -CDC- motif and fulfil certain conformational criteria represent novel compounds that potently inhibit thrombus formation, ex vivo platelet aggregation and carotid artery occlusion superiorly to other non-RGD peptides, such as YMESRADR, without causing hemorrhagic complications in a rabbit model of arterial thrombosis.

Lack of effects of pioglitazone on cardiac function in patients with type 2 diabetes and evidence of left ventricular diastolic dysfunction: a tissue doppler imaging study.

BACKGROUND: Thiazolidinediones, used for the treatment of patients with type 2 diabetes mellitus (DM2), are associated with an increased incidence of heart failure. We sought to investigate the effects of pioglitazone on novel echocardiographic indices of left ventricular (LV) diastolic function in DM2 patients with LV diastolic dysfunction (LVDD). METHODS: Eighty-eight asymptomatic DM2 patients on metformin and/or sulfonylureas, aged 64.5 ± 7.7 years, without known cardiovascular disease, with normal LV systolic function and evidence of LVDD were randomly assigned to pioglitazone 30 mg/day (n = 42) or an increase in dose of other oral agents (n = 39) for 6 months. All patients underwent transthoracic conventional and Tissue Doppler Imaging echocardiography at baseline and follow-up. The primary end-point was change in early diastolic velocity of the mitral annulus (E'). RESULTS: Improvement of glycaemic control was similar in the 2 groups. A significant difference (p < 0.05) between the 2 groups was found in the treatment-induced changes in fasting insulin, the insulin resistance index HOMA, HDL cholesterol, triglycerides, diastolic blood pressure (all in favor of pioglitazone) and in body weight (increase with pioglitazone). No significant changes were observed in any echocardiographic parameter in either group and did not differ between groups (p = NS for all). E' increased non-significantly and to a similar extent in both groups (p = NS). CONCLUSIONS: In asymptomatic DM2 patients with LVDD, the addition of pioglitazone to oral conventional treatment for 6 months does not induce any adverse or favorable changes in LV diastolic or systolic function despite improvements in glycaemic control, insulin sensitivity, lipid profile, and blood pressure.

Effect of a synthetic peptide corresponding to residues 313 to 320 of the alphaIIb subunit of the human platelet integrin alphaIIbbeta3 on carotid artery thrombosis in rabbits.

The platelet integrin receptor alpha(IIb)beta(3) plays a critical role in thrombosis. We have shown previously that the octapeptide YMESRADR, corresponding to sequences 313 to 320 of the human alpha(IIb) subunit, inhibits human platelet activation and fibrinogen binding to alpha(IIb)beta(3), possibly interacting with the ligand. We investigated the effect of YMESRADR on electrically induced carotid artery thrombosis in New Zealand white rabbits. Peptide was administered via the femoral vein, starting 60 min before and continuing for 90 min after the electrical stimulation. Carotid blood flow was monitored for 90 min after the electrical stimulation. The peptide effects on platelet aggregation, in vitro and ex vivo, and on various coagulation, bleeding, and hemostatic parameters were evaluated. YMESRADR significantly inhibited rabbit platelet aggregation in vitro in a dose-dependent manner. It is important that peptide administration in vivo, at doses ranging from 3 to 15 mg/kg, prolonged the duration of the patency of the carotid artery, and no artery occlusion was observed until the end of the study (90 min after electrical stimulation). Furthermore, YMESRADR administration reduced platelet aggregation ex vivo and thrombus weight; however, these reductions reached statistical significance, compared with the control group, at the peptide doses of 12 and 15 mg/kg. YMESRADR did not affect any coagulation parameter studied and the hemostatic response observed in control animals. Thus, YMESRADR represents a novel antiplatelet agent that can inhibit thrombus formation effectively and carotid artery occlusion without causing hemorrhagic complications in a rabbit model of arterial thrombosis.