The APEX trial: Effects of allopurinol on exercise capacity, coronary and peripheral endothelial function, and natriuretic peptides in patients with cardiac syndrome X.

The role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has recently been recognized. Allopurinol has previously been shown to improve endothelial dysfunction, reduce oxidative stress burden, and improve myocardial efficiency. In this "proof of concept" study, we investigated the effect of allopurinol on exercise capacity, coronary and peripheral endothelial function, and serum B-type natriuretic peptide (BNP: a marker of cardiac function and myocardial ischemia) in patients with cardiac syndrome X. METHODS AND RESULTS: This study was a randomized, double-blind, placebo-control crossover trial. Nineteen patients (mean age 59 ± 10 years, 11 women and 8 men) with cardiac syndrome X were randomized to a 6-week treatment with either allopurinol (600 mg/day) or placebo. After 4 weeks of washout period, they were crossed over to the other arm. Outcomes measured at baseline and after treatment were maximum exercise time (ET) derived from Bruce protocol exercise treadmill test, serum BNP measurement, coronary flow reserve (CFR) as assessed by measuring the response of flow velocity in the left anterior descending artery to adenosine, and flow-mediated vasodilatation of the brachial artery (FMD). Allopurinol significantly reduced serum uric acid levels when compared with placebo (-48 ± 24% vs 1.9 ± 11%, P < .001). There was no significant difference in maximum ET, CFR, and FMD between allopurinol and placebo. However, there was a trend that allopurinol reduced serum BNP when compared to placebo (-8% [interquartile range -22% to 65%] vs 44% [interquartile range -18% to 140%]; P = .07). CONCLUSION: In patients with cardiac syndrome X, high-dose allopurinol did not improve exercise capacity, and coronary or peripheral endothelial function.

Impact of paravalvular leakage on outcome in patients after transcatheter aortic valve implantation.

OBJECTIVES: The aim of this study was to evaluate the performance of the aortic regurgitation (AR) index as a new hemodynamic parameter in an independent transcatheter aortic valve implantation (TAVI) cohort and validate its application. BACKGROUND: Increasing evidence associates more-than-mild periprosthetic aortic regurgitation (periAR) with increased mortality and morbidity; therefore precise evaluation of periAR after TAVI is essential. The AR index has been proposed recently as a simple and reproducible indicator for the severity of periAR and predictor of associated mortality. METHODS: The severity of periAR was evaluated by echocardiography, angiography, and periprocedural measurement of the dimensionless AR index = ([diastolic blood pressure - left ventricular end-diastolic pressure]/systolic blood pressure) × 100. A cutoff value of 25 was used to identify patients at risk. RESULTS: One hundred twenty-two patients underwent TAVI by use of either the Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) (79.5%) or the Edwards-SAPIEN bioprosthesis (Edwards Lifesciences, Irvine, California) (20.5%). The AR index decreased stepwise from 29.4 ± 6.3 in patients without periAR (n = 26) to 28.0 ± 8.5 with mild periAR (n = 76), 19.6 ± 7.6 with moderate periAR (n = 18), and 7.6 ± 2.6 with severe periAR (n = 2) (p < 0.001). Patients with AR index <25 had a significantly increased 1-year mortality rate compared with patients with AR index ≥ 25 (42.3% vs. 14.3%; p < 0.001). Even in patients with none/mild periAR, the 1-year mortality risk could be further stratified by an AR index <25 (31.3% vs. 14.3%; p = 0.04). CONCLUSIONS: The validity of the AR index could be confirmed in this independent TAVI cohort and provided prognostic information that was complementary to the severity of AR.

Independent value of echocardiography and N-terminal pro-natriuretic Peptide for the prediction of major outcomes in patients with suspected heart failure.

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and echocardiography have been shown to have diagnostic and prognostic value for the assessment of heart failure (HF) in the community. This study evaluated whether echocardiography and serum NT-pro-BNP estimation have independent value for the prediction of major outcome in patients with suspected HF from the community. Accordingly, 137 patients with suspected HF referred from the community were followed up after undergoing clinical assessment, electrocardiography, NT-pro-BNP estimation, and echocardiography. Abnormal echocardiogram was defined as visual left ventricular ejection fraction 26 ml/m(2) or presence of left ventricular hypertrophy or significant valvular heart disease. Data were obtained in 132 patients (96%) over a mean follow-up period of 26 +/- 7 months during which 19 (14%) developed major cardiac events (14 deaths and 5 HF admissions). Univariate predictors for major cardiac event were age (p = 0.05), male gender (p = 0.007), presence of clinical signs of HF (p = 0.02), NT-pro-BNP level >/=50 pmol/L (p <0.001), abnormal electrocardiogram (p = 0.02), and abnormal echocardiogram (p = 0.004). However, the only independent predictors were male gender (odds ratio 3.09, 95% confidence interval 1.01 to 9.46, p = 0.05), NT-pro-BNP level >/=50 pmol/L (odds ratio 5.78, 95% confidence interval 1.63 to 20.5, p = 0.007), and abnormal echocardiogram (odds ratio 11.1, 95% confidence interval 1.43 to 85.6, p = 0.02). In conclusion, NT-pro-BNP and abnormal echocardiogram provided independent information for predicting adverse outcome in patients with suspected HF referred from the community.

Cost effectiveness of the B type natriuretic peptide, electrocardiography, and portable echocardiography for the assessment of patients from the community with suspected heart failure.

To analyze the cost efficiency of guidelines proposed by the European Society of Cardiology for investigation of patients in the community with suspected heart failure (HF). The guidelines recommend electrocardiography (ECG) and/or measurement of N-terminal pro B type natriuretic peptide (NTproBNP) prior to referral for echocardiography. Portable echocardiography is a new but validated technique for the evaluation of HF. Accordingly, 137 suspected HF patients (mean age 71+/-13 years) from the community underwent ECG and NTproBNP estimation prior to portable echocardiography. Cost effective analysis for ECG, NTproBNP, portable echocardiography and a combination of these; to define valvular heart disease, right ventricular dysfunction and left ventricular systolic and diastolic dysfunction were compared. The cost of abnormal NTproBNP followed by portable echocardiography, abnormal ECG followed by portable echocardiography and portable echocardiography alone for the detection per case of left ventricular systolic dysfunction were 313 euro, 310 euro, and 296 euro respectively and that for detection per case of any of the aforementioned cardiac abnormalities were 198 euro, 223 euro, and 170 euro respectively. Portable echocardiography alone for the assessment of suspected HF patients resulted in a cost reduction of up to 1083 euro for the detection per case of cardiac abnormality. While a strategy where initial NTproBNP estimation is cost effective in detecting any causes of heart failure, portable echocardiography remains the most costeffective strategy to assess patients from the community with suspected heart failure.

Value of primary care electrocardiography for the prediction of left ventricular systolic dysfunction in patients with suspected heart failure.

To compare electrocardiogram (ECG) with measurement of N-terminal pro-B-type natriuretic peptides (NTproBNP) as the General Practitioner's (GP) initial test for suspected heart failure patients from the community. We prospectively studied 137 suspected heart failure patients who underwent ECG and NTproBNP estimation; were referred from primary care to a specialist unit for echocardiography. We demonstrated that sensitivity of ECG interpreted by GP was significantly lower than both by ECG interpreted by Hospital Physician (HP) and NTproBNP estimation for the detection of left ventricular systolic dysfunction (LVSD). Therefore, measurement of NTproBNP is a better investigation in primary care than ECG for the detection of significant LVSD.

Contrast echocardiography versus gated single photon emission computed tomography for the assessment of parameters of left ventricular remodeling after acute myocardial infarction.

BACKGROUND: Assessment of parameters of left ventricular (LV) remodeling after acute myocardial infarction (AMI) has both therapeutic and prognostic implication. Contrast echocardiography (CE) has the advantage of simultaneously assessing myocardial perfusion and LV remodeling. We aimed to evaluate the accuracy of CE to assess LV remodeling after AMI compared with technetium-99m sestamibi gated single photon emission computed tomography (SPECT). METHODS: Accordingly, 36 consecutive patients underwent gated SPECT, CE, and cardiovascular magnetic resonance imaging (CMR) 7 to 10 days after AMI. LV ejection fraction (LVEF), and LV end-systolic and end-diastolic volumes were assessed. RESULTS: Absolute differences for LVEF and LV end-diastolic volume between CMR and CE were significantly smaller than that between CMR and SPECT. CE estimate of LVEF more accurately classified patients into LVEF less than 35%, 35% to 45%, and greater than 45% (agreement = 83%, kappa = 0.66 with CMR) compared with SPECT (agreement = 61%, kappa = 0.36 with CMR). CONCLUSION: CE is more accurate than gated SPECT for the estimation of LV remodeling after AMI.

Clinical benefits of contrast-enhanced echocardiography during rest and stress examinations.

Despite the recent introduction of tissue harmonic imaging in echocardiography, 10-15% of patients have poor endocardial border definition. This may lead to erroneous assessment of regional and global left ventricular (LV) function or to further diagnostic imaging with another modality thus increasing the costs for the healthcare system. The recent development of second generation contrast echocardiography agents such as SonoVue has resulted in several studies showing the value of these agents to outline endocardium clearly, thereby improving assessment of LV function. The use of these contrast agents has also opened the possibility of automated and quantitative LV function assessment, making it more accurate and reproducible. Other major clinical uses of these contrast agents are evaluation of LV masses such as thrombus and tumors, and better definition of LV structure such as delineating LV aneurysm, pseudoaneurysm; and non-compaction of LV and apical cardiomyopathy. Furthermore, the use of these contrast agents during stress not only improved the assessment of wall motion but also made possible the evaluation of myocardial perfusion, thereby increasing diagnostic accuracy for the detection of coronary artery disease.

Improved accuracy of low-power contrast echocardiography for the assessment of left ventricular remodeling compared with unenhanced harmonic echocardiography after acute myocardial infarction: comparison with cardiovascular magnetic resonance imaging.

BACKGROUND: Assessment of left ventricular (LV) remodeling after acute myocardial infarction (AMI) has both therapeutic and prognostic implications. Low-power contrast echocardiography (CE) has the advantage of simultaneously assessing myocardial perfusion and LV remodeling. OBJECTIVE: This study aimed to evaluate the accuracy of low-power CE to assess LV remodeling after AMI compared with unenhanced harmonic echocardiography (HE). METHODS: A total of 36 consecutive patients underwent HE, CE (SonoVue), and cardiovascular magnetic resonance (CMR) imaging 7 to 10 days after AMI. Left ventricular ejection fraction (LVEF), end-systolic volume (LVESV), and end-diastolic volume (LVEDV) were assessed. RESULTS: Absolute differences for LVESV and LVEDV between CMR and CE were significantly smaller than those between CMR and HE. CE estimate of LVEF more accurately classified patients into LVEF < 35%, 35% to 45%, and > 45% (agreement, 83%; kappa = 0.66 with CMR) compared with HE (agreement, 69%; kappa = 0.33 with CMR). CONCLUSIONS: Low-power CE is more accurate than HE for estimating LV remodeling after AMI.