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Objective Current stroke risk schemes need improvement of predictive value in patients with atrial fibrillation. Transoesophageal echocardiography (TEE) may facilitate stroke risk assessment in such patients and guide antithrombotic treatment. Methods We randomised 238 patients with nonvalvular atrial fibrillation and a moderate stroke risk to aspirin or adjusted vitamin K antagonist therapy after TEE had ruled out thrombogenic features in the atria and aorta. The primary outcome was a composite of stroke, major bleeding, peripheral embolism and all-cause mortality. Results Mean CHA2DS2-VASc score was 2.1±1.1. The incidences of the composite primary outcome at a mean follow-up of 1.6 years were 3.2% (2.02% per year) in the aspirin group compared to 6.1% (3.84% per year) in the vitamin K antagonists group with an absolute advantage of 2.9 percentage points. Aspirin was noninferior to vitamin K antagonists (p<0.0001) because the upper limit of the 90% CI did not exceed the 7% absolute difference in event rate between the two treatment arms. Conclusions This hypothesis-generating pilot trial has found that TEE may be used for refinement of stroke risk in paroxysmal atrial fibrillation patients. A larger trial is needed to confirm these data. (ClinicalTrials.gov number NTC00224757). [ABSTRACT FROM AUTHOR]

Background and Objectives: Left ventricular mass (LVM) is known to be related to overall and cardiovascular mortality in end stage kidney disease (ESKD) patients. The aims of the present study are 1) to determine whether LVM is associated with mortality and various cardiovascular events and 2) to identify determinants of LVM including biomarkers of inflammation and fibrosis. Design, Setting, Participants, & Measurements: Analysis was performed with data of 327 ESKD patients, a subset from the CONvective TRAnsport STudy (CONTRAST). Echocardiography was performed at baseline. Cox regression analysis was used to assess the relation of LVM tertiles with clinical events. Multivariable linear regression models were used to identify factors associated with LVM. Results: Median age was 65 (IQR: 54–73) years, 203 (61%) were male and median LVM was 227 (IQR: 183–279) grams. The risk of all-cause mortality (hazard ratio (HR) = 1.73, 95% CI: 1.11–2.99), cardiovascular death (HR = 3.66, 95% CI: 1.35–10.05) and sudden death (HR = 13.06; 95% CI: 6.60–107) was increased in the highest tertile (>260grams) of LVM. In the multivariable analysis positive relations with LVM were found for male gender (B = 38.8±10.3), residual renal function (B = 17.9±8.0), phosphate binder therapy (B = 16.9±8.5), and an inverse relation for a previous kidney transplantation (B = −41.1±7.6) and albumin (B = −2.9±1.1). Interleukin-6 (Il-6), high-sensitivity C-reactive protein (hsCRP), hepcidin-25 and connective tissue growth factor (CTGF) were not related to LVM. Conclusion: We confirm the relation between a high LVM and outcome and expand the evidence for increased risk of sudden death. No relationship was found between LVM and markers of inflammation and fibrosis. Trial Registration: Controlled-Trials.com ISRCTN38365125 [ABSTRACT FROM AUTHOR]

Aims Although the accuracy of three-dimensional speckle tracking echocardiography (STE) to quantify left ventricular (LV) volumes and function has been demonstrated, its reliability has not been studied in great detail. The aim of the study was to determine inter-observer, intra-observer, and test–retest reliability of echocardiographic measurements of LV volumes and function using three-dimensional STE. Methods and results A total of 140 consecutive patients presenting for routine echocardiographic examination underwent three-dimensional STE. Twenty-three of the 140 patients (16%) were excluded from the analysis due to atrial fibrillation or insufficient image quality. In the remaining 117 patients [69 males, age 59 ± 16 years, ejection fraction (EF) 51 ± 13%], intra-observer and inter-observer reliability of LV volumes, EF, and global and segmental strain measurements was determined, whereas test–retest reliability was assessed in a subgroup of 50 patients. LV volumes and EF measurements demonstrated good reliability [intraclass correlation coefficient (ICC): 0.85–0.99; standard error of measurement (SEM): 3.1–9.2 mL and 1.7–4.0%, respectively]. Reliability of global circumferential strain measurements (ICC: 0.85–0.97; SEM: 1.4–2.6%) was superior to longitudinal (ICC: 0.66–0.92; SEM: 1.0–2.1%) and radial strain measurements (ICC: 0.52–0.88; SEM: 4.4–8.1%), with similar results found for segmental strain measurements (P < 0.001 for all). Reliability was not significantly affected by the image quality or temporal resolution of 3D data sets for any parameter. Conclusion Good intra-observer, inter-observer, and test–retest reliability support the use of three-dimensional STE for routine evaluation of LV volumes and EF. Global and segmental circumferential strain measurements also demonstrate high reliability, whereas analysis by a single observer is currently recommended for longitudinal and radial strain due to limited inter-observer and test–retest reliability. [ABSTRACT FROM PUBLISHER]

Background: Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarctarea is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA). Methods: Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded. Results: The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18- 0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051). Conclusion: We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability. [ABSTRACT FROM AUTHOR]

Nebivolol is a third-generation β-adrenergic receptor antagonist (β-blocker) with high selectivity for b1-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional β-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available β-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with β-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional β-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardio protective activity and a good tolerability profile. [ABSTRACT FROM AUTHOR]

Background: Isolated left bundle branch block (LBBB) may be an expression of idiopathic cardiomyopathy affecting both ventricles. The present study was conducted to evaluate right ventricular (RV) dimensions and function in asymptomatic LBBB patients with mildly depressed left ventricular (LV) function. Methods: Fifteen patients with asymptomatic LBBB in whom coronary artery disease, hypertension, and valvular pathology was excluded were studied. Fifteen healthy volunteers and 15 idiopathic dilated cardiomyopathy LBBB patients served as controls. RV long axis and tricuspid annulus diameter were obtained, as were tricuspid annular plane systolic excursion (TAPSE) and peak systolic velocity (Sm) of the RV free wall annulus. Tricuspid regurgitation (TR) jets (peak TR jets) were used for RV pressure assessment. Results: RV dimensions were comparable between the asymptomatic LBBB patients and controls. RV functions of healthy volunteers and asymptomatic LBBB patients were similar (TAPSE: 24 ± 3 and 24 ± 4 mm, Sm: 13 ± 2 and 13 ± 3 cm/s, respectively), whereas functional parameters in idiopathic dilated cardiomyopathy patients were significantly reduced (TAPSE: 19 ± 5 mm, Sm: 9 ± 2 cm/s, both P < 0.01 by analysis of variance [ANOVA]). For the three groups combined, a significant inverse correlation between RV pressure (peak TR jets) and RV function (Sm) was observed (r =–0.52, P = 0.017). Conclusions: In patients with an asymptomatic LBBB, RV dimensions and function are within normal range. The present study suggests that screening of RV functional parameters in asymptomatic LBBB patients is not useful for identification of an early-stage cardiomyopathy, and RV dysfunction is merely a consequence of increased RV loading conditions caused by left-sided heart failure and does not indicate a generalized cardiomyopathy affecting both ventricles. [ABSTRACT FROM AUTHOR]

Rationale and Objective: Shape analysis of endocardial contour sequences from echocardiograms can provide classification of wall motion abnormalities (WMA). Materials and Methods: We previously reported on active appearance motion models (AAMM) for automated detection of endocardial contours in sequences of echocardiograms. The shape analysis of AAMM renders eigenvariations of shape/motion, including typical normal and pathologic endocardial contraction patterns. A set of stress echocardiograms (single-beat four-chamber and two-chamber sequences with expert-verified endocardial contours) of 129 infarct patients was split randomly into training (n = 65) and testing (n = 64) sets. AAMMs were generated from the training set and AAMM shape coefficients (ASCs) were extracted for all sequences and statistically related to regional/global visual wall motion scoring (VWMS) and volumetric parameters. Results: Linear regression showed clear correlations between ASCs and VWMS. Discriminant analysis showed good prediction by ASCs of both segmental (74% correctness) and global WMA (90% correctness). Volumetric parameters correlated poorly to regional VWMS. Conclusion: 1) ASCs show promising accuracy for automated WMA classification. 2) VWMS and endocardial border motion are closely related; with accurate automated border detection, automated WMA classification should be feasible. 3) ASC shape analysis allows contour set evaluation by direct comparison to clinical parameters. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate left ventricular function and atrial and ventricular diameters in patients with persistent atrial fibrillation (AF) treated with rate or rhythm control.Background: Restoration of sinus rhythm in patients with persistent AF may improve left ventricular function and reduce atrial dimensions. Adequate rate control in AF may preserve ventricular function.Methods: In 335 patients included in the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study, echocardiography was performed at baseline and 1- and 2-year follow-up. Echocardiography was compared between patients randomized to rate control (n = 160) and rhythm control (n = 175). In the rhythm control group, echocardiography was compared between patients with AF versus sinus rhythm at study end. Multivariate analysis was performed to determine parameters related to improvement of left ventricular function and increase of atrial diameters.Results: Fractional shortening improved significantly under rate and rhythm control (31 +/- 10% at baseline to 33 +/- 9% at 2 years, and from 30 +/- 10% to 34 +/- 9%; both P < .05, respectively). Under rate control, left and right atrial size increased significantly compared to baseline. Under rhythm control, only left atrial size increased. Multivariate analysis revealed that only sinus rhythm at study end was associated with an increase of fractional shortening. AF at study end, hypertension, and no use of angiotensin-converting enzyme inhibitors were independently associated with increase in atrial size.Conclusions: Routine rate control prevents deterioration of left ventricular function. Maintenance of sinus rhythm is associated with improvement of left ventricular function and reduction of atrial sizes. [ABSTRACT FROM AUTHOR]

Reliable atrial sensing is the prerequisite for restoration of atrioventricular synchrony in patients with single-lead VDD pacing systems. To determine echocardiographic variables associated with inappropriate atrial sensing, 21 consecutive patients with symptomatic second- or third-degree AV block and normal sinus node function were studied. Prior to implantation echocardiographic measurements of end-systolic and end-diastolic dimensions and volumes of the right atrium and right ventricle were performed. All patients underwent implantation of a Medtronic Thera VDD(d) pacemaker with a bipolar Medtronic Capsure electrode. A minimal amplitude of the unfiltered atrial electrocardiogram of > 0.5 mV was required for permanent lead position and the atrial sensitivity was programmed below the lowest recorded value. Appropriate atrial sensing (atrial triggered ventricular paced complexes/total number of ventricular paced complexes) was assessed during 24-hour Holter monitoring and treadmill exercise testing 3 to 6 weeks after implantation. Inappropriate atrial sensing (< 95% correct atrial synchronization during Holter registration and/or < 97.5% during exercise testing) was present in nine patients. Right atrial volumes and the right ventricular end-diastolic volume was significantly higher, as compared to patients without inappropriate sensing (12 patients). The right atrial and diastolic volumes had the highest correlation with correct atrial sensing r = 0.83, P < 0.0001). Using a postdefined cut-off value of > 80 mL for the end-diastolic right atrial volume, sensitivity and specificity for inappropriate sensing was 100% and 92%, respectively. These findings show that preimplant echocardiography can identify patients with inappropriate sensing during VDD pacing, in whom DDD pacing should be considered. [ABSTRACT FROM AUTHOR]

Background: Women with hypertensive disorders in pregnancy, in particular early-onset preeclampsia, are at increased risk of developing cardiovascular disease later in life. These women have a more than 2-fold increased risk of dying from cardiovascular diseases. Most studies have focused on identification of risk factors shortly after pregnancy. Less is known on the prevalence of risk factors or actual signs of cardiovascular disease 5-20 years later. The presence of hypertension or metabolic syndrome can be seen as an opportunity for preventive interventions to reduce the development of severe cardiovascular diseases like myocardial infarction and stroke.Objective: To assess cardiovascular risk factors and established cardiovascular disease in women after early-onset preeclampsia, in the fifth decade of life. As a consequence, we can assess whether there is still a window of opportunity for preventive measures and to establish in what proportion of women cardiovascular disease already has developed.Study Design: In a prospective observational study, cardiovascular risk assessment was performed in women with early-onset preeclampsia (<34 weeks' gestation) and normotensive controls (≥37 weeks' gestation) 9-16 years after their index pregnancy. Medical records of 2 tertiary hospitals in Amsterdam, The Netherlands, were screened consecutively, and all eligible women were invited. Cardiovascular risk assessment consisted of a questionnaire, blood pressure measurement, anthropometrics, and blood and urine for fasting lipids, lipoproteins, glucose levels, glycated hemoglobin, renal function, N-terminal brain natriuretic peptide, and albuminuria. History of cardiovascular diseases (ie, myocardial infarction and stroke) was determined. Prevalence of women presenting in an optimal window of opportunity for preventive measures was defined by the presence of cardiovascular risk factors (ie, hypertension and metabolic syndrome) but in the absence of established cardiovascular diseases (ie, myocardial infarction and stroke).Results: Women with a history of early-onset preeclampsia (n = 131) had significantly greater systolic and diastolic blood pressure, greater body mass index, more often had an abnormal lipid profile (lower high-density lipoprotein levels, higher triglycerides), greater glycated hemoglobin, and greater levels of albuminuria compared to controls (n = 56). None of the women with a history of early-onset preeclampsia was diagnosed with cardiovascular disease; 38.2% were diagnosed with hypertension; and 18.2% were diagnosed with metabolic syndrome. A total of 42% met the criteria for the window of opportunity for preventive measures. In women with a history of an uncomplicated pregnancy, no women were diagnosed with cardiovascular disease; 14.3% were diagnosed with hypertension; 1.8% with metabolic syndrome. In this cohort, 14.3% met the criteria for the window of opportunity for preventive measures.Conclusion: A large proportion of women who experienced early-onset preeclampsia had major cardiovascular risk factors in the fifth decade of life, compared with healthy controls. These women are currently outside the scope of most preventive programs due to their relatively young age, but have important modifiable risk factors for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Objectives This double blinded, placebo controlled randomized clinical trial studies the effect of exenatide on myocardial infarct size. The glucagon-like peptide-1 receptor agonist exenatide has possible cardioprotective properties during reperfusion after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods 191 patients were randomly assigned to intravenous exenatide or placebo initiated prior to percutaneous coronary intervention using 10 μg/h for 30 min followed by 0.84 μg/h for 72 h. Patients with a previous myocardial infarction, Trombolysis in Myocardial Infarction flow 2 or 3, multi-vessel disease, or diabetes were excluded. Magnetic resonance imaging (MRI) was performed to determine infarct size, area at risk (AAR) (using T2-weighted hyperintensity (T2W) and late enhancement endocardial surface area (ESA)). The primary endpoint was of 4-month final infarct size, corrected for the AAR measured in the acute phase using MRI. Results After exclusion, 91 patients (age 57.4 ± 10.1 years, 76% male) completed the protocol. There were no baseline differences between groups. No difference was found in infarct size corrected for the AAR in the exenatide group compared to the placebo group (37.1 ± 18.8 vs. 39.3 ± 20.1%, p = 0.662). There was also no difference in infarct size (18.8 ± 13.2 vs. 18.8 ± 11.3% of left ventricular mass, p = 0.965). No major adverse cardiac events occurred during the in-hospital phase. Conclusion Exenatide did not reduce myocardial infarct size expressed as a percentage of AAR in ST elevated myocardial infarction patients successfully treated with percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Background: Rate control is often the therapy of choice for atrial fibrillation. Guidelines recommend strict rate control, but this is not based on clinical evidence. We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation. Methods: We randomly assigned 614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy (resting heart rate <110 beats per minute) or a strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute). The primary outcome was a composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events. The duration of follow-up was at least 2 years, with a maximum of 3 years. Results: The estimated cumulative incidence of the primary outcome at 3 years was 12.9% in the lenient-control group and 14.9% in the strict-control group, with an absolute difference with respect to the lenient-control group of −2.0 percentage points (90% confidence interval, −7.6 to 3.5; P<0.001 for the prespecified noninferiority margin). The frequencies of the components of the primary outcome were similar in the two groups. More patients in the lenient-control group met the heart-rate target or targets (304 [97.7%], vs. 203 [67.0%] in the strict-control group; P<0.001) with fewer total visits (75 [median, 0], vs. 684 [median, 2]; P<0.001). The frequencies of symptoms and adverse events were similar in the two groups. Conclusions: In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. (ClinicalTrials.gov number, NCT00392613.) N Engl J Med 2010;362:1363-73. [ABSTRACT FROM AUTHOR]

Heart rate (HR) at rest is an important marker of prognosis in heart failure, but has not been addressed in pulmonary arterial hypertension (PAH). To determine the prognostic value of HR at rest in patients with PAH, we retrospectively analyzed 140 consecutive patients with idiopathic PAH. Electrocardiogram (ECG)-derived HR at rest was evaluated as a potential predictor of adverse prognosis (death or lung transplantation), in addition to World Health Organization functional class, 6-minute walk distance, and hemodynamics before and approximately 1 year and 2 years after initiation of PAH treatment. During follow-up, 49 patients (35%) died, and 5 patients (4%) underwent lung transplantation. Before treatment initiation and after 1 year and 2 years of treatment, respectively, a higher HR at rest was an independent predictor of adverse prognosis (hazard ratios per 10-beats/min increase 1.76, 95% confidence interval 1.42 to 2.18, 2.31, 95% confidence interval 1.58 to 3.38, 2.1, 95% confidence interval 1.39 to 3.19, respectively, p <0.001 for all). Change in HR between the first and last ECG also independently predicted prognosis (hazard ratio per 1-beat/min increase 1.03, 95% confidence interval 1.01 to 1.06). In conclusion, a higher HR at rest and an important increase in HR at rest during follow-up signify a considerable risk of death in patients with PAH. ECG-derived HR at rest is an important marker of prognosis and should be assessed before and at frequent intervals after initiation of treatment for PAH. [Copyright &y& Elsevier]