Screening for Fabry Disease by Urinary Globotriaosylceramide Isoforms Measurement in Patients with Left Ventricular Hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is a frequent echocardiographic feature in Fabry disease (FD) and in severe cases may be confused with hypertrophic cardiomyopathy (HCM) of other origin. The prevalence of FD in patients primarily diagnosed with HCM varies considerably in screening and case finding studies, respectively. In a significant proportion of patients, presenting with only mild or moderate LVH and unspecific clinical signs FD may remain undiagnosed. Urinary Gb3 isoforms have been shown to detect FD in both, women and men. We examined whether this non-invasive method would help to identify new FD cases in a non-selected cohort of patients with various degree of LVH. METHODS AND RESULTS: Consecutive patients older than 18 years with a diastolic interventricular septal wall thickness of ≥12mm determined by echocardiography were included. Referral diagnosis was documented and spot urine was collected. Gb3 was measured by mass spectroscopy. Subjects with an elevated Gb3-24:18 ratio were clinically examined for signs of FD, α-galactosidase-A activity in leukocytes was determined and GLA-mutation-analysis was performed. We examined 2596 patients. In 99 subjects urinary Gb3 isoforms excretion were elevated. In these patients no new cases of FD were identified by extended FD assessment. In two of three patients formerly diagnosed with FD Gb3-24:18 ratio was elevated and would have led to further diagnostic evaluation. CONCLUSION: Measurement of urinary Gb3 isoforms in a non-selected cohort with LVH was unable to identify new cases of FD. False positive results may be prevented by more restricted inclusion criteria and may improve diagnostic accuracy of this method.

Natural history of very severe aortic stenosis.

BACKGROUND: We sought to assess the outcome of asymptomatic patients with very severe aortic stenosis. METHODS AND RESULTS: We prospectively followed 116 consecutive asymptomatic patients (57 women; age, 67 + or - 16 years) with very severe isolated aortic stenosis defined by a peak aortic jet velocity (AV-Vel) > or = 5.0 m/s (average AV-Vel, 5.37 + or - 0.35 m/s; valve area, 0.63 + or - 0.12 cm(2)). During a median follow-up of 41 months (interquartile range, 26 to 63 months), 96 events occurred (indication for aortic valve replacement, 90; cardiac deaths, 6). Event-free survival was 64%, 36%, 25%, 12%, and 3% at 1, 2, 3, 4, and 6 years, respectively. AV-Vel but not aortic valve area was shown to independently affect event-free survival. Patients with an AV-Vel > or = 5.5 m/s had an event-free survival of 44%, 25%, 11%, and 4% at 1, 2, 3, and 4 years, respectively, compared with 76%, 43%, 33%, and 17% for patients with an AV-Vel between 5.0 and 5.5 m/s (P<0.0001). Six cardiac deaths occurred in previously asymptomatic patients (sudden death, 1; congestive heart failure, 4; myocardial infarction, 1). Patients with an initial AV-Vel > or = 5.5 m/s had a higher likelihood (52%) of severe symptom onset (New York Heart Association or Canadian Cardiovascular Society class >II) than those with an AV-Vel between 5.0 and 5.5 m/s (27%; P=0.03). CONCLUSIONS: Despite being asymptomatic, patients with very severe aortic stenosis have a poor prognosis with a high event rate and a risk of rapid functional deterioration. Early elective valve replacement surgery should therefore be considered in these patients.

The endocardial binary appearance ('binary sign') is an unreliable marker for echocardiographic detection of Fabry disease in patients with left ventricular hypertrophy.

AIMS: The binary sign, a binary appearance of the left ventricular endocardial border, was suggested to be an echocardiographic hallmark in diagnosing Fabry disease, a hereditary, lysosomal storage disorder. The aim of the present study was to examine the reliability of the binary sign as a screening tool to identify patients with Fabry disease. METHODS AND RESULTS: In total 309 subjects with an interventricular septum (IVS) thickness of ≥12 mm were investigated, of which 14 had a confirmed diagnosis of Fabry disease. Urinary globotriaosylceramide testing was used to rule out Fabry disease in the control group. From all patients echocardiographic images of the apical four-chamber view were analysed offline by a blinded observer. A binary sign was seen in 63 patients (20%), 4 had Fabry disease and 59 belonged to the control group. Although the proportion of binary signs in patients with Fabry disease was higher (29%) compared with the control group (20%) this difference was not statistically significant. The sensitivity and specificity were 28% (95% confidence interval (CI): 12-65%) and 80% (95% CI: 76-85%), respectively. In a logistic regression model adjusted for age, sex and presence of Fabry disease, the occurrence of a binary sign was highly dependent on the IVS thickness (odds ratio: 1.21; 95% CI: 1.1-1.35; P<0.001). CONCLUSION: The endocardial binary appearance is associated with the degree of septal hypertrophy but cannot adequately distinguish between patients with Fabry disease and patients with other causes of left ventricular hypertrophy.

Re-estimation improved the performance of two Framingham cardiovascular risk equations and the Pooled Cohort equations: A nationwide registry analysis.

Equations predicting the risk of occurrence of cardiovascular disease (CVD) are used in primary care to identify high-risk individuals among the general population. To improve the predictive performance of such equations, we updated the Framingham general CVD 1991 and 2008 equations and the Pooled Cohort equations for atherosclerotic CVD within five years in a contemporary cohort of individuals who participated in the Austrian health-screening program from 2009-2014. The cohort comprised 1.7 M individuals aged 30-79 without documented CVD history. CVD was defined by hospitalization or death from cardiovascular cause. Using baseline and follow-up data, we recalibrated and re-estimated the equations. We evaluated the gain in discrimination and calibration and assessed explained variation. A five-year general CVD risk of 4.61% was observed. As expected, discrimination c-statistics increased only slightly and ranged from 0.73-0.79. The two original Framingham equations overestimated the CVD risk, whereas the original Pooled Cohort equations underestimated it. Re-estimation improved calibration of all equations adequately, especially for high-risk individuals. Half of the individuals were reclassified into another risk category using the re-estimated equations. Predictors in the re-estimated Framingham equations explained 7.37% of the variation, whereas the Pooled Cohort equations explained 5.81%. Age was the most important predictor.

Publisher Correction: Re-estimation improved the performance of two Framingham cardiovascular risk equations and the Pooled Cohort equations: A nationwide registry analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Comparison of Early Surgical or Transcatheter Aortic Valve Replacement Versus Conservative Management in Low-Flow, Low-Gradient Aortic Stenosis Using Inverse Probability of Treatment Weighting: Results From the TOPAS Prospective Observational Cohort Study.

Background No randomized comparison of early (ie, ≤3 months) aortic valve replacement (AVR) versus conservative management or of transcatheter AVR (TAVR) versus surgical AVR has been conducted in patients with low-flow, low-gradient (LFLG) aortic stenosis (AS). Methods and Results A total of 481 consecutive patients (75±10 years; 71% men) with LFLG AS (aortic valve area ≤0.6 cm2/m2 and mean gradient <40 mm Hg), 72% with classic LFLG and 28% with paradoxical LFLG, were prospectively recruited in the multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) study. True-severe AS or pseudo-severe AS was adjudicated by flow-independent criteria. During follow-up (median [IQR] 36 [11-60] months), 220 patients died. Using inverse probability of treatment weighting to address the bias of nonrandom treatment assignment, early AVR (n=272) was associated with a major overall survival benefit (hazard ratio [HR], 0.34 [95% CI, 0.24-0.50]; P<0.001). This benefit was observed in patients with true-severe AS but also with pseudo-severe AS (HR, 0.38 [95% CI, 0.18-0.81]; P=0.01), and in classic (HR, 0.33 [95% CI, 0.22-0.49]; P<0.001) and paradoxical LFLG AS (HR, 0.42 [95% CI, 0.20-0.92]; P=0.03). Compared with conservative management in the conventional multivariate model, trans femoral TAVR was associated with the best survival (HR, 0.23 [95% CI, 0.12-0.43]; P<0.001), followed by surgical AVR (HR, 0.36 [95% CI, 0.23-0.56]; P<0.001) and alternative-access TAVR (HR, 0.51 [95% CI, 0.31-0.82]; P=0.007). In the inverse probability of treatment weighting model, trans femoral TAVR appeared to be superior to surgical AVR (HR [95% CI] 0.28 [0.11-0.72]; P=0.008) with regard to survival. Conclusions In this large prospective observational study of LFLG AS, early AVR appeared to confer a major survival benefit in both classic and paradoxical LFLG AS. This benefit seems to extend to the subgroup with pseudo-severe AS. Our findings suggest that TAVR using femoral access might be the best strategy in these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01835028.

Predictors of outcomes in low-flow, low-gradient aortic stenosis: results of the multicenter TOPAS Study.

BACKGROUND: Patients with low-flow, low-gradient aortic stenosis have a poor prognosis with conservative therapy but a high operative mortality if treated surgically. Recently, we proposed a new index of aortic stenosis severity derived from dobutamine stress echocardiography, the projected aortic valve area at a normal transvalvular flow rate, as superior to other conventional indices to differentiate true-severe from pseudosevere aortic stenosis. The objective of this study was to identify the determinants of survival, functional status, and change in left ventricular ejection fraction during follow-up of patients with low-flow, low-gradient aortic stenosis. METHODS AND RESULTS: One hundred one patients with low-flow, low-gradient aortic stenosis (aortic valve area

External validation of two Framingham cardiovascular risk equations and the Pooled Cohort equations: A nationwide registry analysis.

BACKGROUND: Cardiovascular prevention guidelines advocate the use of statistical risk equations to predict individual cardiovascular risk. However, predictive accuracy and clinical value of existing equations may differ in populations other than the one used for their development. Using baseline and follow-up data of the Austrian health-screening program, we assessed discrimination, calibration, and clinical utility of three widely recommended equations-the Framingham 1991 and 2008 general cardiovascular disease (CVD) equations, and the Pooled Cohort equations predicting atherosclerotic CVD. METHODS: The validation cohort comprised 1.7 M individuals aged 30-79, without documented CVD history who participated in the program from 2009 to 2014. CVD events were defined by a cardiovascular cause of hospitalization or death. RESULTS: The observed five-year general CVD risk was 4.66%. Discrimination c-indices (0.72-0.78) were slightly lower than those reported for the development cohorts. C-indices for women were always higher than for men. CVD risk was overestimated by the Framingham 2008 equation, but underestimated by the Pooled Cohort equations. The Framingham 1991 equation was well-calibrated, especially for individuals up to 64 years. If applied to recommend health interventions at a predicted five-year risk between 5 and 10%, the equations were clinically useful with their net benefits, weighting true positives against false positives, ranging from 0.13 to 3.43%. CONCLUSION: The equations can discriminate high-risk from low-risk individuals, but predictive accuracy (especially for high-risk individuals) might be improved by recalibration. The Framingham 1991 equation yielded the most accurate predictions.

B-type natriuretic peptide in low-flow, low-gradient aortic stenosis: relationship to hemodynamics and clinical outcome: results from the Multicenter Truly or Pseudo-Severe Aortic Stenosis (TOPAS) study.

BACKGROUND: The prognostic value of B-type natriuretic peptide (BNP) is unknown in low-flow, low-gradient aortic stenosis (AS). We sought to evaluate the relationship between AS and rest, stress hemodynamics, and clinical outcome. METHODS AND RESULTS: BNP was measured in 69 patients with low-flow AS (indexed effective orifice area < 0.6 cm2/m2, mean gradient < or = 40 mm Hg, left ventricular ejection fraction < or = 40%). All patients underwent dobutamine stress echocardiography and were classified as truly severe or pseudosevere AS by their projected effective orifice area at normal flow rate of 250 mL/s (effective orifice area < or = 1.0 cm2 or > 1.0 cm2). BNP was inversely related to ejection fraction at rest (Spearman correlation coefficient r(s)=-0.59, P<0.0001) and at peak stress (r(s)=-0.51, P<0.0001), effective orifice area at rest (r(s)=-0.50, P<0.0001) and at peak stress (r(s)=-0.46, P=0.0002), and mean transvalvular flow (r(s)=-0.31, P=0.01). BNP was directly related to valvular resistance (r(s)=0.42, P=0.0006) and wall motion score index (r(s)=0.36, P=0.004). BNP was higher in 29 patients with truly severe AS versus 40 with pseudosevere AS (median, 743 pg/mL [Q1, 471; Q3, 1356] versus 394 pg/mL [Q1, 191 to Q3, 906], P=0.012). BNP was a strong predictor of outcome. In the total cohort, cumulative 1-year survival of patients with BNP > or = 550 pg/mL was only 47+/-9% versus 97+/-3% with BNP < 550 (P<0.0001). In 29 patients who underwent valve replacement, postoperative 1-year survival was also markedly lower in patients with BNP > or = 550 pg/mL (53+/-13% versus 92+/-7%). CONCLUSIONS: BNP is significantly higher in truly severe than pseudosevere low-gradient AS and predicts survival of the whole cohort and in patients undergoing valve replacement.

Heterogeneity of traumatic injury of the tricuspid valve: a report of four cases.

Tricuspid valve injury causing severe tricuspid regurgitation is the most common cardiac complication following blunt chest trauma. We present four cases with different clinical presentations that included pleural effusion, arrhythmias, cyanosis, peripheral edema and dyspnea, with varying onset of symptoms. Echocardiographic evaluation and intraoperative findings in these patients revealed a broad spectrum of injury to the tricuspid valve including papillary muscle and chordal rupture, chordal elongation and leaflet perforation. Because surgical treatment is required in most patients and since the diagnosis is often delayed, we believe that early echocardiographic evaluation is required in all patients with blunt chest trauma, in particular if clinical symptoms of right heart failure are present.

The impact of cardiopulmonary resuscitation (CPR) manikin chest stiffness on motivation and CPR performance measures in children undergoing CPR training-A prospective, randomized, single-blind, controlled trial.

BACKGROUND: Cardio-pulmonary-resuscitation (CPR) training starting at the age of 12 years is recommended internationally. Training younger children is not recommended because young children lack the physical ability to perform adequate CPR and discouragement to perform CPR later is apprehended. The aim of this study was to answer the following questions: Are younger children discouraged after CPR training? Is discouragement caused by their lack in physical ability to perform adequate chest compressions on a standard manikin and would the use of manikins with a reduced resistance affect their motivation or performance? METHODS: We investigated the motivation and CPR performance of children aged 8-13 years after CPR training on manikins of different chest stiffness in a prospective, randomized, single-blind, controlled trial. 322 children underwent randomization and received 30 minutes CPR training in small groups at school. We used two optically identical resuscitation manikins with different compression resistances of 45kg and 30kg. Motivation was assessed with a self-administered questionnaire. Performance was measured with the Resusci®Anne SkillReporter™. FINDINGS: Motivation after the training was generally high and there was no difference between the two groups in any of the questionnaire items on motivation: Children had fun (98 vs. 99%; P = 0.32), were interested in the training (99 vs. 98%; P = 0.65), and were glad to train resuscitation again in the future (89 vs. 91%; P = 0.89). CPR performance was generally poor (median compression score (8, IQR 1-45 and 29, IQR 11-54; P<0.001) and the mean compression depth was lower in the 45kg-resistance than in the 30kg-resistance group (33±10mm vs. 41±9; P<0.001). CONCLUSIONS: Compression resistances of manikins, though influencing CPR performance, did not discourage 8 to 13 year old children after CPR training. The findings refute the view that young children are discouraged when receiving CPR training even though they are physically not able to perform adequate CPR.

Dobutamine Stress Echocardiography for Management of Low-Flow, Low-Gradient Aortic Stenosis.

BACKGROUND: In the American College of Cardiology/American Heart Association guidelines, patients are considered to have true-severe stenosis when the mean gradient (MG) is ≥40 mm Hg with an aortic valve area (AVA) ≤1 cm2 during dobutamine stress echocardiography (DSE). However, these criteria have not been previously validated. OBJECTIVES: The aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with low-flow, low-gradient aortic stenosis (LF-LG AS). METHODS: One hundred eighty-six patients with low left ventricular ejection fraction (LVEF) LF-LG AS were prospectively recruited and underwent DSE, with measurement of the MG, AVA, and the projected AVA (AVAProj), which is an estimate of the AVA at a standardized normal flow rate. Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients, by measurement of the aortic valve calcium by computed tomography in 25 patients, and by both methods in 8 patients. According to these assessments, 50 of 87 (57%) patients in the study cohort had true-severe stenosis. RESULTS: Peak stress MG ≥40 mm Hg, peak stress AVA ≤1 cm2, and the combination of peak stress MG ≥40 mm Hg and peak stress AVA ≤1 cm2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVAProj ≤1 cm2 was better than all the previous markers (p < 0.007), with 70% correct classification. Among the subset of 88 patients managed conservatively (47% of the cohort), 52 died during a follow-up of 2.8 ± 2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure, and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVAProj ≤1 cm2 was a strong predictor of mortality under medical management (hazard ratio: 3.65; p = 0.0003). CONCLUSIONS: In patients with low LVEF LF-LG AS, the DSE criteria of a peak stress MG ≥40 mm Hg, or the composite of a peak stress MG ≥40 mm Hg and a peak stress AVA ≤1 cm2 proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVAProj better distinguishes true-severe AS from pseudo-severe AS and is strongly associated with mortality in patients under conservative management. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028).

Projected valve area at normal flow rate improves the assessment of stenosis severity in patients with low-flow, low-gradient aortic stenosis: the multicenter TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study.

BACKGROUND: We sought to investigate the use of a new parameter, the projected effective orifice area (EOAproj) at normal transvalvular flow rate (250 mL/s), to better differentiate between truly severe (TS) and pseudo-severe (PS) aortic stenosis (AS) during dobutamine stress echocardiography (DSE). Changes in various parameters of stenosis severity have been used to differentiate between TS and PS AS during DSE. However, the magnitude of these changes lacks standardization because they are dependent on the variable magnitude of the transvalvular flow change occurring during DSE. METHODS AND RESULTS: The use of EOAproj to differentiate TS from PS AS was investigated in an in vitro model and in 23 patients with low-flow AS (indexed EOA <0.6 cm2/m2, left ventricular ejection fraction < or =40%) undergoing DSE and subsequent aortic valve replacement. For an individual valve, EOA was plotted against transvalvular flow (Q) at each dobutamine stage, and valve compliance (VC) was derived as the slope of the regression line fitted to the EOA versus Q plot; EOAproj was calculated as EOAproj=EOArest+VCx(250-Q(rest)), where EOArest and Q(rest) are the EOA and Q at rest. Classification between TS and PS was based on either response to flow increase (in vitro) or visual inspection at surgery (in vivo). EOAproj was the most accurate parameter in differentiating between TS and PS both in vitro and in vivo. In vivo, 15 of 23 patients (65%) had TS and 8 of 23 (35%) had PS. The percentage of correct classification was 83% for EOAproj and 91% for indexed EOAproj compared with percentages of 61% to 74% for the other echocardiographic parameters usually used for this purpose. CONCLUSIONS: EOAproj provides a standardized evaluation of AS severity with DSE and improves the diagnostic accuracy for distinguishing TS and PS AS in patients with low-flow, low-gradient AS.

Tako-tsubo cardiomyopathy complicating left atrial radiofrequency ablation.

Two female patients undergoing left atrial radiofrequency catheter ablation developed Tako-tsubo cardiomyopathy. This reversible form of left ventricular dysfunction is known to occur under conditions associated with marked sympathetic nervous activation. Radiofrequency catheter ablation in the left atrium can damage autonomic ganglionated plexi, leading to vagal withdrawal, thus resulting in enhanced sympathetic tone. Tako-tsubo cardiomyopathy has not been previously described following radiofrequency catheter ablation.

NOGA-guided analysis of regional myocardial perfusion abnormalities treated with intramyocardial injections of plasmid encoding vascular endothelial growth factor A-165 in patients with chronic myocardial ischemia: subanalysis of the EUROINJECT-ONE multicenter double-blind randomized study.

BACKGROUND: The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A(165) using an elaborated transformation algorithm. METHODS AND RESULTS: After randomization, 80 no-option patients received either active, phVEGF-A165 (n=40), or placebo plasmid (n=40) percutaneously via NOGA-Myostar injections. The injected area (region of interest, ROI) was delineated as a best polygon by connecting of the injection points marked on NOGA polar maps. The ROI was projected onto the baseline and follow-up rest and stress polar maps of the 99m-Tc-sestamibi/tetrofosmin single-photon emission computed tomography scintigraphy calculating the extent and severity (expressed as the mean normalized tracer uptake) of the ROI automatically. The extents of the ROI were similar in the VEGF and placebo groups (19.4+/-4.2% versus 21.5+/-5.4% of entire myocardium). No differences were found between VEGF and placebo groups at baseline with regard to the perfusion defect severity (rest: 69+/-11.7% versus 68.7+/-13.3%; stress: 63+/-13.3% versus 62.6+/-13.6%; and reversibility: 6.0+/-7.7% versus 6.7+/-9.0%). At follow-up, a trend toward improvement in perfusion defect severity at stress was observed in VEGF group as compared with placebo (68.5+/-11.9% versus 62.5+/-13.5%, P=0.072) without reaching normal values. The reversibility of the ROI decreased significantly at follow-up in VEGF group as compared with the placebo group (1.2+/-9.0% versus 7.1+/-9.0%, P=0.016). Twenty-one patients in VEGF and 8 patients in placebo group (P<0.01) exhibited an improvement in tracer uptake during stress, defined as a >or =5% increase in the normalized tracer uptake of the ROI. CONCLUSIONS: Projection of the NOGA-guided injection area onto the single-photon emission computed tomography polar maps permits quantitative evaluation of myocardial perfusion in regions treated with angiogenic substances. Injections of phVEGF A165 plasmid improve, but do not normalize, the stress-induced perfusion abnormalities.

Right ventricular longitudinal strain for risk stratification in low-flow, low-gradient aortic stenosis with low ejection fraction.

BACKGROUND: Left ventricular global longitudinal strain (LVLS) is a powerful predictor of outcome in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) and low LV ejection fraction (LVEF). However, the impact of right ventricular (RV) function on the outcome of these patients remains unknown. OBJECTIVES: The aim of this study was to examine the impact of RV function as evaluated by RV free wall longitudinal strain (RVLS) on mortality in patients with LF-LG AS and low LVEF. METHODS: 211 patients with LF-LG AS (mean gradient < 40 mm Hg and indexed aortic valve area (AVA) ≤ 0.6 cm²/m²) and low LVEF (≤ 40%)) were prospectively recruited in the True or Pseudo-severe Aortic Stenosis study. AS severity was assessed using the projected AVA (AVAproj) at normal flow rate. Among the 211 patients, 128 had RVLS measurement available at rest and were included in this analysis. RVLS measurement at dobutamine stress echocardiography (DSE) was available in 58 of the 128 patients. RESULTS: Two-year survival was lower in patients with RVLS < |13|% (53% ± 9%) compared with those with RVLS > |13|% (69% ± 5%) (p = 0.04). In multivariable Cox analysis stratified for the type of treatment (aortic valve replacement vs conservative) and adjusted for age, AS severity, previous myocardial infarction and LVLS, rest RVLS < |13|% (HR = 2.70; 95% CI 1.19 to 6.11; p = 0.018) was independently associated with all-cause mortality. RVLS had incremental prognostic value over baseline risk factors and LVLS (χ² = 20.13 vs 13.56; p = 0.01). Reduced stress RVLS was also associated with increased risk of mortality (stress RVLS <| 14|%: HR = 2.98; 95% CI 1.30 to 6.52; p = 0.01). In multivariable Cox analysis, stress RVLS < |14|% remained independently associated with mortality (HR = 2.94; 95% CI 1.23 to 7.02; p = 0.015). After further adjustment for rest RVLS, stress RVLS < |14|% remained independently associated with mortality (HR = 3.29; 95% CI 1.17 to 9.25; p = 0.024), whereas rest RVLS was not (p > 0.05). CONCLUSIONS: In this series of patients with LF-LG AS and low LVEF, reduced RVLS was independently associated with increased risk of mortality. Furthermore, stress RVLS provided incremental prognostic value beyond that obtained from rest RVLS. Thus, RVLS measurement at rest and at DSE may be helpful to enhance risk stratification in this high-risk population. TRIAL REGISTRATION NUMBER: NCT01835028; Results.

Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis.

BACKGROUND: The prognostic value of natriuretic peptides in aortic stenosis (AS) remains unknown. METHODS AND RESULTS: B-type natriuretic peptide (BNP), N-terminal BNP (NtBNP), and N-terminal atrial natriuretic peptide (NtANP) were determined in 130 patients with severe AS (mean age, 70+/-12 years; mean gradient, 64+/-21 mm Hg; valve area, 0.64+/-0.15 cm2) who were followed up for 377+/-150 days. Natriuretic peptides increased with NYHA class and with decreasing ejection fraction (EF). Even asymptomatic patients frequently had elevated neurohormones. Asymptomatic patients who developed symptoms during follow-up had higher BNP and NtBNP levels at entry compared with those remaining asymptomatic (median for NtBNP, 131 pmol/L [interquartile range, 50 to 202 pmol/L] versus 31 pmol/L [range, 19 to 56 pmol/L]; P<0.001). Symptom-free survival at 3, 6, 9, and 12 months for patients with NtBNP <80 versus > or =80 pmol/L was 100%, 88+/-7%, 88+/-7%, and 69+/-13% compared with 92+/-8%, 58+/-14%, 35+/-15%, and 18+/-15%, respectively (P<0.001). Seventy-nine patients eventually underwent surgery because of symptoms. Considering preoperative neurohormone levels, age, NYHA class, aortic valve area, EF, and presence of coronary artery disease, we found that neurohormones, EF, and NYHA class predicted survival; neurohormones predicted postoperative symptomatic status; and neurohormones and preoperative EF predicted postoperative EF. However, by multivariate analysis, NtBNP was the only independent predictor of outcome. CONCLUSIONS: In severe AS, natriuretic peptides provide important prognostic information beyond clinical and echocardiographic evaluation. NtBNP independently predicts symptom-free survival, and preoperative NtBNP independently predicts postoperative outcome with regard to survival, symptomatic status, and left ventricular function. Thus, neurohormones may gain particular importance for timing of surgery in asymptomatic severe AS.

Long-term outcome of patients with ventricular septal defect considered not to require surgical closure during childhood.

OBJECTIVES: The purpose of the study was to assess the long-term outcome of patients with small ventricular septal defects (VSDs) considered not to require surgical closure during childhood. BACKGROUND: Although patients with small VSDs have generally been considered not to require surgery, more recent data suggest that a significant percentage of these patients develop serious problems during adult life. METHODS: A total of 229 consecutive patients (115 females) with a VSD considered too small to require surgery during childhood as defined by normal pulmonary artery pressure, less than 50% shunt, pulmonary vascular resistance < or =200 dynes x s cm(-5), no VSD-related aortic regurgitation (AR), and no symptoms and who had no additional hemodynamically relevant heart defect were followed in an adult congenital heart disease program. Physical examination, electrocardiography, and echocardiography were performed in all patients in one- to three-year intervals; exercise tests and Holter monitoring were performed in 140 and 127 patients, respectively. RESULTS: Follow-up was completed in 222 patients (97%). Mean age at last visit was 30 +/- 10 years. Spontaneous VSD closure was observed in 14 patients (6%). No patients died, four patients (1.8%) had an episode of endocarditis, of whom two required aortic valve replacement, and one additional patient (0.4%) had surgical closure for hemodynamic reasons. For 118 patients who entered the study between 1993 and 1996 and were prospectively followed for 7.4 +/- 1.2 years, event-free survival with end points defined as death, endocarditis or heart surgery was 99.1 +/- 0.8% at three years, 96.5 +/- 1.7% at six years and 95.5 +/- 1.9% at eight years. At last visit, 94.6% of all patients studied were symptom free. Left ventricular (LV) size by echocardiography was normal in 198 (89%) patients, borderline in 23 patients and definitely enlarged in only one patient. None had systolic LV dysfunction, and pulmonary artery pressure (PAP) was normal in all patients. Mean exercise capacity was 92 +/- 21% of expected, and 87% of patients had no arrhythmias on Holter monitoring, with the remainder showing benign rhythm disorders. CONCLUSIONS: Outcome in well-selected patients with a small VSD is good. Surgical closure does not appear to be required during childhood as long as left-to-right shunt is <50% and signs of LV volume overload are absent, when PAP is not elevated, and no VSD-related AR or symptoms are present.

Stress-echocardiography is underused in clinical practice: a nationwide survey in Austria.

BACKGROUND: The wide area of application, including coronary artery disease, valvular heart disease, or pulmonary hypertension makes stress echocardiography (SE) a powerful, cost-effective imaging modality in cardiology. The role of this technique in clinical practice in Austria is unknown. METHODS: A nationwide survey included all departments for cardiology and/or internal medicine in the years 2008 and 2013. By electronic questionnaire demographics, indication for the test, the numbers of examined cases per year, operators, and various applied techniques of SE were interrogated and completed by telephone interviews. RESULTS: Data could be obtained from all 117 departments. In the year 2007 in 58 (50%) and in 2012 57 (49%) departments SE was available in Austrian hospitals. More than 100 SEs per year were performed by only four (7%) units in the year 2007 and by five (8%) in 2012. Physical exercise, dobutamine, and dipyridamole SE were available in 27 (46%), 52 (90%), and six (10%) units in 2007, and in 15 (27%), 52 (91%), and five (9%) units in 2012, respectively. In 2007 41 (71%) and in 2012 26 (46%) echo-labs administered contrast agents during SE. Transesophageal SE and 3D-echo was performed in one (2%) and three (5%) units in 2007, and in six (10%) and four (7%) echo-labs in 2012. CONCLUSIONS: This representative survey demonstrates the underuse of SE in clinical practice in Austria. Even in established application fields performance is low, examination frequencies as recommended by the cardiology societies are fulfilled only by a minority of institutions.