The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Chronotropic incompetence demonstrated with cardiopulmonary exercise test.

In his case report, a 74-year-old physically fit man was evaluated repeatedly for several years in the cardiology department due to dyspnoea on exertion (DOE). Several standard cardiac and pulmonary tests were performed but did not provide sufficient cause for the DOE. Lastly, the patient was evaluated with a cardiopulmonary exercise test (CPET) with simultaneous in- and expiratory gas sampling. The test revealed a low aerobic capacity due to chronotropic incompetence (CI), thus explaining the DOE. Subsequently, the patient was treated with a rate-responsive pacemaker. CPET-is an ideal test for diagnosing CI.

Atrial fibrillation in aortic stenosis--echocardiographic assessment and prognostic importance.

BACKGROUND: Atrial fibrillation (AFib) exists more frequently in patients with aortic stenosis (AS) than in patients without, and AFib may be a sign of progressive deterioration of AS. Echocardiographic assessment of AS in sinus rhythm is well documented, however, little is known about AFib in AS since such patients often are excluded from clinical echocardiographic trials. AIM: The purpose of this study was to assess the prognostic importance of AFib in AS. METHODS: The study was designed as a single-center case-control study. Patients with AS and AFib were enrolled as cases (n = 103) and subsequently matched to controls (103 patients with AS but sinus rhythm). Cases and controls were matched according to age, gender and severity of AS. Primary outcome was all cause mortality and follow-up was 100% complete. RESULTS: Compared to controls the group with AFib had lower mean ejection fraction (42% vs. 49%; p < 0.001) and stroke volume (47 mL vs. 55 mL; p = 0.004), but higher heart rate (81 bpm vs. 68 bpm; p < 0.001) and no significant difference with regard to cardiac output (3.8 L vs. 4.0 L; p = 0.29). Accordingly, aortic jet velocity and gradients were significantly lower in AFib compared to controls but there were no differences (p = 0.38) in aortic valve area calculated by the continuity equation. During a median follow-up of 2.3 years (IQR: 1.2-3.6), 70 (34%) patients with AS died: 42 patients with AFib and 28 patients with sinus rhythm (p < 0.02). After adjusting for echocardiographic significant differences, AFib remained an independent predictor of mortality (HR 2.72 (95% CI: 1.12-6.61), p < 0.03). There was no significant interaction (p = 0.62) between AFib and AS on the risk of mortality, indicating that AFib predicted bad outcome regardless of the severity of AS. CONCLUSIONS: AFib is an independent risk factor in patients with AS and the prognostic impact of AFib seems to be the same despite the severity of AS.

Prognostic implications of left ventricular asymmetry in patients with asymptomatic aortic valve stenosis.

Aims: Left ventricular (LV) regional hypertrophy in the form of LV asymmetry is a common finding in patients with aortic valve stenosis. The aim of this study was to test the hypothesis that LV asymmetry predicts future symptomatic status and indication for aortic valve replacement (AVR) in patients with asymptomatic aortic valve stenosis. Methods and results: In total, 114 patients with asymptomatic aortic valve stenosis (peak velocity > 2.5 m/s assessed by echocardiographic screening and LV ejection fraction > 50%) were enrolled in the study. LV asymmetry and LV geometry was assessed by multi-detector computed tomography according to previous definitions. Follow-up was conducted using electronic health records. Event-free survival was assessed using Cox proportional hazards models. Patients were followed for a median of 2.2 years (interquartile range 1.6-3.6). Indication for AVR occurred in 46 patients (40%). Patients with LV asymmetry had more than 3 times the risk of AVR (hazard ratio: 3.16; 95% CI: 1.77-5.66; P < 0.001) compared with patients with no LV asymmetry. Multivariate Cox analysis revealed that LV asymmetry was a predictor of future need of AVR (hazard ratio: 3.10; 95% CI: 1.44-6.65; P = 0.004), independent of LV geometry, jet velocity, valvular calcification, and pro-BNP. Conclusions: LV asymmetry is an independent predictor of future need for AVR in patients with asymptomatic aortic valve stenosis. It has incremental prognostic value to LV geometry and may provide a useful method of risk stratification.

Six-minute walking test and long term prognosis in patients with asymptomatic aortic valve stenosis.

BACKGROUND: Management of asymptomatic patients with aortic valve stenosis is challenging due to the elusive relationship between symptomatic status and hemodynamic parameters in addition to the occurrence of cardiovascular death. The 6-minute walking test (6MWT) reflects overall hemodynamic function and could contribute to risk assessment in such patients. METHODS AND RESULTS: One hundred sixteen asymptomatic patients (peak velocity>2.5m/s and left ventricular ejection fraction >50% assessed by echocardiographic screening; 85 males; aged 72±8years) underwent clinical workup, transthoracic echocardiography and a 6MWT. The mean distance covered by patients able to perform the 6MWT (n=107) was 422±90m. Patients were grouped in tertiles according to distance covered in the 6MWT: Short, intermediate and long distance patients. During a median follow-up of 5.5years (IQR 4.5-6.3), 29 (25%) patients died, 10 (9%) from cardiovascular causes. Multivariate analysis revealed that short distance patients (≤390m) were at higher risk of all-cause mortality (HR: 2.44; 95% CI: 1.05-5.67; p=0.04) and cardiovascular mortality (HR: 6.12; 95% CI: 1.18-31.83; p=0.03). For every 100m covered, the risk of all-cause mortality decreased by 35% (HR: 0.65; 95% CI: 0.43-0.99; p=0.04). Long distance patients (>465m) did not experience cardiovascular deaths during follow-up. CONCLUSIONS: In asymptomatic patients with aortic valve stenosis, the 6MWT is an independent predictor of all-cause and cardiovascular mortality. It is of incremental value to the echocardiographic evaluation, suggesting that the 6MWT might be useful to guide clinical follow-up intervals and treatment strategy.

Basal longitudinal strain predicts future aortic valve replacement in asymptomatic patients with aortic stenosis.

AIMS: To evaluate the prognostic value of global longitudinal strain (GLS) and basal longitudinal strain (BLS) with the knowledge of coexisting coronary pathology evaluated by multi-detector computed tomography (MDCT) coronary angiography. BACKGROUND: GLS and BLS are both sensitive markers of myocardial dysfunction and predictors of outcome in asymptomatic aortic stenosis. Aortic stenosis and ischaemic heart disease share risk factors and longitudinal function can be severely reduced in both conditions, why some of the previous findings of impaired regional longitudinal function in asymptomatic aortic stenosis could in fact be explained by silent ischaemic heart disease. METHODS AND RESULTS: Prospective follow-up of 104 asymptomatic patients with moderate-severe aortic stenosis defined as an aortic valve area <1.5 cm(2). Patients underwent a thorough clinical work-up, advanced echocardiographic analysis and coronary angiography by MDCT. The combined endpoint was indication for aortic valve replacement (AVR) and sudden cardiac death. During a median follow-up of 2.3 years (interquartile range 1.7-3.6) 43 patients (41%) met the endpoint of indication for AVR. The basal (13.4 ± 3.1% vs. 15.7 ± 3.1%) and mid-ventricular segments (14.9 ± 2.7% vs. 16.2 ± 2.9%) were significantly reduced, but with sparing of the apical segments, in patients who later underwent AVR. In various multivariable Cox regression models, including only BLS, but not GLS, remained an independent predictor of AVR. CONCLUSION: In contrast to GLS, reduced BLS is a significant predictor of future AVR in asymptomatic patients with aortic stenosis, independently of clinical characteristics, conventional echocardiographic measures, and coronary pathology.

Prognostic value of multi-detector computed tomography in asymptomatic aortic valve stenosis.

BACKGROUND: Multi-Detector Computed Tomography (MDCT) is a high-resolution imaging technique with potential additive value in the evaluation of patients with aortic valve stenosis (AS). We aimed to assess the prognostic value of MDCT in asymptomatic patients with AS compared to conventional transthoracic echocardiography (TTE). METHODS: 116 patients with asymptomatic AS (Vmax>2.5m/s assessed by clinical screening TTE, LVEF>50%) were examined with TTE (Vivid e9) and MDCT (Aquilion 320) on the same day. The treating physician was blinded for research protocol defined imaging results. Outcome was defined as indication for aortic valve replacement (AVR) determined by the treating physician or sudden cardiac death. RESULTS: The mean age was 72 (8) years, 27% were women, mean AVA by TTE was 1.01 (0.30) cm(2). Median follow up time was 27 (IQR 19-44) months. Forty seven patients (41%) developed indication for AVR. No patients suffered a sudden cardiac death. AVA and aortic valve calcification were significant univariable predictors of AVR when measured by both TTE and MDCT, whereas left ventricular mass was only significant measured by MDCT. Significant coronary artery disease by MDCT tended to predict future indication for AVR, but this did not reach statistical significance (HR: 1.79 (95% CI 0.96-3.44), p=0.08). CONCLUSION: MDCT derived AVA can be of use as an alternative to TTE derived AVA in patients with asymptomatic AS to predict future clinical indication for AVR.

Association of ischemic heart disease to global and regional longitudinal strain in asymptomatic aortic stenosis.

Longitudinal deformation has been shown to deteriorate with progressive aortic stenosis as well as ischemic heart disease. Despite that both conditions share risk factors and are often coexisting, studies have not assessed the influence on longitudinal deformation for both conditions simultaneously. Thus the purpose of this study was to evaluate the association between subclinical ischemic heart disease and global and regional longitudinal strain in asymptomatic patients with significant aortic stenosis. Prevalent patients with a diagnosis of aortic stenosis at six hospitals in the Greater Copenhagen area were screened for inclusion. A total of 104 asymptomatic patients with moderate-severe aortic stenosis (aortic valve area ≤1.5 cm(2)) fulfilled study criteria and underwent advanced echocardiographic analysis and coronary angiography by multi-detector computed tomography. Angiography revealed coronary stenosis >50% in 31% (n = 32). All regional longitudinal strain measures (apical, mid and basal longitudinal strain) were significant predictors of significant coronary stenosis (>70% stenosis), but only apical and mid longitudinal strain were significant predictors in multivariable analyses independent of aortic valve area, stroke volume index, pro-BNP, valvulo-arterial impedance, body mass index and heart rate. In linear regression models with both aortic valve area and significant coronary stenosis, apical (p < 0.001) and mid (p < 0.01) longitudinal strain were associated to significant coronary stenosis but not aortic valve area. Conversely, basal longitudinal strain was significantly associated to aortic valve area (p = 0.001), but not to significant coronary stenosis. Subclinical coronary artery disease is frequent in moderate and severe aortic stenosis, and should be suspected when regional longitudinal dysfunction is predominant in the apical and mid ventricular segments.

Tissue Velocities and Myocardial Deformation in Asymptomatic and Symptomatic Aortic Stenosis.

BACKGROUND: Assessment of myocardial longitudinal function has proved to be a sensitive marker of deteriorating myocardial function in aortic stenosis, demonstrated by both color Doppler tissue imaging and recently by two-dimensional speckle-tracking echocardiography. The aim of this study was to compare velocity (color Doppler tissue imaging) and deformation (two-dimensional speckle-tracking echocardiography) in relation to global and regional longitudinal function in asymptomatic and severe symptomatic aortic stenosis. METHODS: In a cross-sectional design, 231 patients with aortic stenosis were divided into four groups: asymptomatic moderate aortic stenosis (aortic valve area, 1.0-1.5 cm(2); n = 38), asymptomatic severe aortic stenosis (aortic valve area < 1.0 cm(2); n = 66), and symptomatic severe aortic stenosis with preserved (n = 68) and reduced (<50%) left ventricular ejection fraction (n = 59). RESULTS: Among all global (peak systolic s', diastolic e' and a', longitudinal displacement, and global longitudinal strain and strain rate) and regional longitudinal (basal, middle, and apical longitudinal strain and strain rate) parameters, only diastolic e', longitudinal displacement, and basal longitudinal strain (BLS) remained significantly associated with symptomatic status, independent of age, gender, heart rate, aortic valve area, stroke volume index, left ventricular mass index, left atrial volume index, and tricuspid annular systolic plane excursion. Furthermore, in a model with the aforementioned parameters, including e', longitudinal displacement, and BLS, only BLS remained significantly associated with symptomatic status in the entire study population (BLS per one-unit decrease: odds ratio, 1.23; 95% CI, 1.04-1.46; P = .017). Furthermore, patients with BLS < 13% were more likely to be symptomatic (odds ratio, 4.97; 95% CI, 2.6-9.4; P < .001), and no patients with asymptomatic severe aortic stenosis with BLS ≥ 13% were admitted with myocardial infarction or heart failure during follow-up of 1,462 days. CONCLUSIONS: Among the many echocardiographic measures of longitudinal velocity and deformation, BLS has the strongest association with symptomatic status in aortic stenosis, and BLS < 13% is related to adverse outcomes in severe asymptomatic aortic stenosis.

Aortic valve area assessed with 320-detector computed tomography: comparison with transthoracic echocardiography.

To evaluate the diagnostic accuracy of aortic valve area (AVA) assessment with 320-detector Computed Tomography (MDCT) compared to transthoracic echocardiography (TTE) in a population with mild to severe aortic valve stenosis. AVA was estimated in 169 patients by planimetry on MDCT images (AVA(MDCT)) and by the continuity equation with TTE (AVA(TTE)). To generate a reference AVA (AVA(REF)) we used the stroke volume from MDCT divided by the velocity time integral from CW Doppler by TTE (according to the continuity equation: stroke volume in LVOT = stroke volume passing the aortic valve). AVA(REF) was used as the reference to compare both measures against, since it bypasses the assumption of LVOT being circular in the continuity equation and the potential placement error of PW Doppler in the LVOT. The mean (±SD) age of the patients was 71 (±9) years, 113 (67%) were males. Mean AVA(TTE) was 0.93 (±0.33) cm(2), mean AVA(MDCT) was 0.99 (±0.36) cm(2) and mean AVA(REF) was 1.00 (±0.39) cm(2). The mean difference between AVA(TTE) and AVA(MDCT) was -0.06 cm(2), p = 0.001, mean difference between AVA(TTE) and AVA(REF) was -0.06 cm(2), p < 0.001, and mean difference between AVA(MDCT) and AVA(REF) was -0.01 cm(2), p = 0.60. Calcification of the aortic valve quantified by Agatston score, significantly decreased the correlation between AVA(MDCT) and AVA(REF), (r low Agatston = 0.90, r high Agatston = 0.57). MDCT measured AVA is slightly larger than AVA measured by TTE (0.06 cm(2)). The accuracy and precision errors on AVA measurements are comparable for MDCT and TTE. Valvular calcification may primarily affect the accuracy of AVA(MDCT).