Myocardial analysis from routine 4D cardiac-CT to predict reverse remodeling and clinical outcomes after transcatheter aortic valve implantation.

PURPOSE: Our study aimed to determine whether 4D cardiac computed tomography (4DCCT) based quantitative myocardial analysis may improve risk stratification and can predict reverse remodeling (RRM) and mortality after transcatheter aortic valve implantation (TAVI). METHODS: Consecutive patients undergoing clinically indicated 4DCCT prior to TAVI were prospectively enrolled. 4DCCT-derived left- (LV) and right ventricular (RV), and left atrial (LA) dimensions, mass, ejection fraction (EF) and myocardial strain were evaluated to predict RRM and survival. RRM was defined by either relative increase in LVEF by 5% or relative decline in LV end diastolic diameter (LVEDD) by 5% assessed by transthoracic echocardiography prior TAVI, at discharge, and at 12-month follow-up compared to baseline prior to TAVI. RESULTS: Among 608 patients included in this study (55 % males, age 81 ± 6.6 years), RRM was observed in 279 (54 %) of 519 patients at discharge and in 218 (48 %) of 453 patients at 12-month echocardiography. While no CCT based measurements predicted RRM at discharge, CCT based LV mass index and LVEF independently predicted RRM at 12-month (ORadj = 1.012; 95 %CI:1.001-1.024; p = 0.046 and ORadj = 0.969; 95 %CI:0.943-0.996; p = 0.024, respectively). The most pronounced changes in LVEF and LVEDD were observed in patients with impaired LV function at baseline. In multivariable analysis age (HRadj = 1.037; 95 %CI:1.005-1.070; p = 0.022) and CCT-based LVEF (HRadj = 0.972; 95 %CI:0.945-0.999; p = 0.048) and LAEF (HRadj = 0.982; 95 %CI:0.968-0.996; p = 0.011) independently predicted survival. CONCLUSION: Comprehensive myocardial functional information derived from routine 4DCCT in patients with severe aortic stenosis undergoing TAVI could predict reverse remodeling and clinical outcomes at 12-month following TAVI.

Aortic Valve Planimetry in Aortic Stenosis Quantification: Reliability of Three-Dimensional-Multiplane Reconstruction and Comparison With Established Methods.

We aim to evaluate the reliability and consistency of measuring the aortic valve area (AVA) using 3-dimensional (3D) transesophageal echocardiography and compare it with invasive and noninvasive methods using a continuity equation (CE). Measurements were taken from 119 patients with different severity of aortic stenosis and with normal aortic valve who underwent elective transesophageal echocardiography encompassing the whole spectrum of aortic opening. Three methods were compared to determine AVA. First, the effective AVA was calculated with the standard CE, where the left ventricular outflow tract area was calculated from its 2-dimensional diameter (AVA-CEstd). Second, a modified CE method (AVA-CEmod) was used, in which the left ventricular outflow tract area was measured using 3D-multiplane reconstruction. Third, the geometric AVA was directly measured using 3D-multiplane reconstruction planimetry (AVA-3D). Interobserver and intraobserver variability were analyzed using intraclass correlation coefficients (ICCs). The values were measured by two blinded readers for interobserver variability and by one observer on the same dataset. AVA-3D was significantly larger than AVA-CEmod and AVA-CEstd (1.87 ± 1.00 cm2 vs 1.81 ± 0.92 cm2 p = 0.03 and 1.87 ± 1.00 cm2 vs 1.71 ± 0.85 cm2 p <0.001). However, in the subset of patients with AVA-3D <1.5 cm2, there was no significant difference between AVA-3D and AVA-CEmod (1.06 ± 0.24 vs 1.08 ± 0.26 cm2, paired t test: t = 0.77, degree of freedom = 58, p = 0.44). The ICC between the measurements of AVA-3D and AVA-CEmod (ICC 0.979), and AVA-3D and AVA- CEstd (ICC 0.940), were excellent. AVA-3D delivers very similar results as compared with more established echocardiographic parameters. The difference between effective and geometric AVA did not appear to be clinically relevant in patients with a higher degree of stenosis.

Imaging of Bioprosthetic Valve Dysfunction after Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) has become the standard of care in elderly high-risk patients with symptomatic severe aortic stenosis. Recently, TAVI has been increasingly performed in younger-, intermediate- and lower-risk populations, which underlines the need to investigate the long-term durability of bioprosthetic aortic valves. However, diagnosing bioprosthetic valve dysfunction after TAVI is challenging and only limited evidence-based criteria exist to guide therapy. Bioprosthetic valve dysfunction encompasses structural valve deterioration (SVD) resulting from degenerative changes in the valve structure and function, non-SVD resulting from intrinsic paravalvular regurgitation or patient-prosthesis mismatch, valve thrombosis, and infective endocarditis. Overlapping phenotypes, confluent pathologies, and their shared end-stage bioprosthetic valve failure complicate the differentiation of these entities. In this review, we focus on the contemporary and future roles, advantages, and limitations of imaging modalities such as echocardiography, cardiac computed tomography angiography, cardiac magnetic resonance imaging, and positron emission tomography to monitor the integrity of transcatheter heart valves.

Evidence for a sigmoidal flow-to-valve opening relation in low-flow low-gradient aortic stenosis.

We analyzed the relationship between flow (Q) and aortic valve opening area (AVA) using a sequence of echocardiographic stress tests of increasing strength. Low-dose dobutamine stress echocardiography (DSE) has been used to differentiate pseudo-severe from true severe aortic stenoses. Because the Q-response to DSE is so variable between individuals, AVA has been projected to a standardized flow (AVAproj) using linear interpolation. A linear Q-to-AVA relation implies that AVA shows an unconstrained increase. We applied three stress maneuvers of increasing strength to investigate whether AVA shows signs of saturation. We performed an echocardiographic examination at rest, during the passive leg raise maneuver ("PLR"), maximal dobutamine infusion ("Dmax"), and their combination ("Dmax + PLR") in 45 patients with severe low-flow, low-gradient aortic stenosis. We analyzed the effect of the stress maneuver on Q, AVA, valve compliance (VC), and AVAproj. We also compared the proportion of patients with nonconclusive test (ΔQ < 20%) between stress maneuvers. We computed the Akaike information criterion (AIC) to compare a linear with a saturating function for the Q-AVA relation. Q gradually increased from "PLR" to "Dmax" to "Dmax + PLR" (P < 0.0001), whereas the number of nonconclusive tests concomitantly diminished from n = 35 to n = 3. The stress sequence increased AVA (P < 0.001) but decreased AVAproj (P = 0.006) and VC (P = 0.005). In the pooled Q-AVA data, the AIC value was lower for the saturating (sigmoidal) model compared with the linear model fitting (-1,593 vs. -1,504). "Dmax + PLR" is capable of reducing the number of nonconclusive DSE tests. With increasing stress strength, the Q-AVA relation progressively flattens, indicating saturation.NEW & NOTEWORTHY The relation between transaortic flow (Q) and aortic valve opening area (AVA) shows a saturation when three different stress maneuvers are used to increase Q as much as possible. This has implications for the assessment of aortic stenosis severity.

Predicting progression of aortic stenosis by measuring serum calcification propensity.

BACKGROUND: The aim of this prospective, double-blinded study in patients with aortic sclerosis was to determine whether a new calcification propensity measure in the serum could predict disease progression. METHODS: We included 129 consecutive patients with aortic sclerosis as assessed during a routine clinical echocardiographic exam. Clinical, echocardiographic, and serum laboratory parameters were collected, including a new blood test providing an overall measure of calcification propensity by monitoring the maturation time of calciprotein particles (T50 test). The echocardiographic exam was repeated after 1 year. Multiple regression analysis was performed to identify independent predictors of the annual increase of peak transvalvular Doppler velocity (∆vmax). Furthermore, the accuracy of the T50 test to detect patients with the most marked stenosis progression was assessed by receiver operating characteristic (ROC)-analysis. RESULTS: Mean age was 75 ± 9 years, 79% were men. The T50 was 271 ± 58 min. Overall, there was no significant stenosis progression between baseline and follow-up (∆vmax 3.8 ± 29.8 cm/s, p = ns). The T50 test was not found to be an independent linear predictor in multivariate testing. By ROC-analysis, however, a T50-value ≤ 242 min was able to significantly detect a ∆vmax above the 90th percentile (∆vmax ≥ 43 cm/s, AUC = 0.67, p = .04, Sensitivity = 69%, Specificity = 70%). CONCLUSIONS: The T50 test showed a modest but significant ability to identify a pronounced aortic stenosis progression in patients with aortic sclerosis. The test could not be established as an independent linear predictor of disease progression, possibly due to the low valvular disease burden and short follow-up interval.

Sigmoid isostiffness-lines: An in-vitro model for the assessment of aortic stenosis severity.

Introduction: The aortic valve opening area (AVA), used to quantify aortic stenosis severity, depends on the transvalvular flow rate (Q). The currently accepted clinical echocardiographic method assumes a linear relation between AVA and Q. We studied whether a sigmoid model better describes this relation and determined "isostiffness-lines" across a wide flow spectrum, thus allowing building a nomogram for the non-invasive estimation of valve stiffness. Methods: Both AVA and instantaneous Q (Qinst) were measured at 10 different mean cardiac outputs of porcine aortic valves mounted in a pulsatile flow loop. The valves' cusps were chemically stiffened to obtain three stiffness grades and the procedure was repeated for each grade. The relative stiffness was defined as the ratio between LV work at grade with the added stiffness and at native stiffness grade. AVA peak ¯ corresponding to the selected Q peak ¯ of the highest 3 and 5 cardiac output values was predicted in K-fold cross-validation using sequentially a linear and a sigmoid model. The accuracy of each model was assessed with the Akaike information criterion (AIC). Results: The sigmoid model predicted more accurately AVA peak ¯ (AIC for prediction of AVA with Q peak ¯ of the 3 highest cardiac output values: -1,743 vs. -1,048; 5 highest cardiac output values: -1,471 vs. -878) than the linear model. Conclusion: This study suggests that the relation between AVA and Q can be better described by a sigmoid than a linear model. This construction of "isostiffness-lines" may be a useful method for the assessment of aortic stenosis in clinical echocardiography.

Passive Leg Raise Stress Echocardiography in Severe Paradoxical Low-Flow, Low-Gradient Aortic Stenosis.

BACKGROUND: Dobutamine stress echocardiography is used to increase transvalvular flow in patients with low-flow, low-gradient aortic stenosis (AS). Dobutamine fails to increase the stroke volume index (SVI) in one third of patients. The aim of this study was to test whether passive leg raise (PLR) added to dobutamine could increase SVI and transvalvular flow in patients with severe paradoxical low-flow, low-gradient AS. METHODS: Forty-five patients with apparent severe low-flow, low-gradient AS on the basis of traditional measurements were included. Twenty-five were categorized as belonging to the paradox group (left ventricular ejection fraction [EF] ≥ 50%) and 20 to the low EF group (left ventricular EF < 50% or "classical" low-flow, low-gradient AS) for comparison. A four-step stress echocardiographic examination was performed: resting conditions (rest), PLR alone (PLR), maximal dobutamine infusion rate (Dmax), and a combination of Dmax and PLR (Dmax+PLR). Aortic valve area, SVI, and mean transvalvular flow were calculated using both the velocity-time integral (VTI) of left ventricular outflow tract and the Simpson method. Changes compared with rest and between the stress maneuvers were analyzed. RESULTS: In the paradox group, compared with rest, left ventricular end-diastolic volume was significantly decreased with Dmax but was completely restored with Dmax+PLR (rest vs Dmax vs Dmax+PLR: 61 ± 15 vs 49 ± 18 mL [P < .001] vs 61 ± 18 mL [P = NS]). The smallest increase in SVI in the paradox group was observed during Dmax (PLR vs Dmax vs Dmax+PLR: VTI, 38 ± 4 mL/m2 [P < .001] vs 36 ± 7 mL/m2 [P = .019] vs 41 ± 7 mL/m2 [P < .001]; Simpson, 28 ± 6 mL/m2 [P < .001], 21 ± 7 mL/m2 [P = NS], 27 ± 7 mL/m2 [P = NS]). Compared with Dmax, Dmax+PLR was able to achieve a higher SVI (VTI, 36 ± 7 vs 41 ± 7 mL/m2 [P < .001]; Simpson, 21 ± 7 vs 27 ± 7 mL/m2 [P < .001]) and transvalvular flow with the Simpson method only (179 ± 56 vs 219 ± 56 mL/sec, P < .001), as well as a higher mean gradient (34 ± 10 vs 39 ± 12 mm Hg, P = .003) and AVA with the Simpson method (0.64 ± 0.21 vs 0.73 ± 0.21 cm2, P = .026). In the low EF group, only SVI VTI (31 ± 8 vs 35 ± 7 mL/m2, P = .034) and mean gradient (29 ± 12 vs 34 ± 14 mm Hg, P = .003) were higher with Dmax+PLR. The proportion of patients with SVI VTI ≥ 35 mL/m2 and increases of SVI VTI of >20% compared with rest was highest with Dmax+PLR in both groups. CONCLUSIONS: Dobutamine decreases preload in paradoxical low-flow, low-gradient AS. Adding PLR counteracts this effect, resulting in increased SVI and flow (in one method). The combined stress maneuver allowed reclassification of some patients from severe to moderate AS and may therefore be useful in selected cases in this population in which severity is uncertain.

Short- and Long-Term Effects of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Left Ventricular Remodeling in Patients Early After ST-Segment Elevation Myocardial Infarction-The HIIT-EARLY Randomized Controlled Trial.

Aim: Due to insufficient evidence on the safety and effectiveness of high-intensity interval training (HIIT) in patients early after ST-segment elevation myocardial infarction (STEMI), we aimed to compare short- and long-term effects of randomized HIIT or moderate-intensity continuous training (MICT) on markers of left ventricular (LV) remodeling in STEMI patients receiving optimal guideline-directed medical therapy (GDMT). Materials and Methods: Patients after STEMI (<4 weeks) enrolled in a 12-week cardiac rehabilitation (CR) program were recruited for this randomized controlled trial (NCT02627586). During a 3-week run-in period with three weekly MICT sessions, GDMT was up-titrated. Then, the patients were randomized to HIIT or isocaloric MICT for 9 weeks. Echocardiography and cardiopulmonary exercise tests were performed after run-in (3 weeks), end of CR (12 weeks), and at 1-year follow-up. The primary outcome was LV end-diastolic volume index (LVEDVi) at the end of CR. Secondary outcomes were LV global longitudinal strain (GLS) and cardiopulmonary fitness. Results: Seventy-three male patients were included, with the time between STEMI and start of CR and randomization being 12.5 ± 6.3 and 45.8 ± 10.8 days, respectively. Mixed models revealed no significant group × time interaction for LVEDVi at the end of CR (p = 0.557). However, there was a significantly smaller improvement in GLS at 1-year follow-up in the HIIT compared to the MICT group (p = 0.031 for group × time interaction). Cardiorespiratory fitness improved significantly from a median value of 26.5 (1st quartile 24.4; 3rd quartile 1.1) ml/kg/min at randomization in the HIIT and 27.7 (23.9; 31.6) ml/kg/min in the MICT group to 29.6 (25.3; 32.2) and 29.9 (26.1; 34.9) ml/kg/min at the end of CR and to 29.0 (26.6; 33.3) and 30.6 (26.0; 33.8) ml/kg/min at 1 year follow-up in HIIT and MICT patients, respectively, with no significant group × time interactions (p = 0.138 and 0.317). Conclusion: In optimally treated patients early after STEMI, HIIT was not different from isocaloric MICT with regard to short-term effects on LVEDVi and cardiorespiratory fitness. The worsening in GLS at 1 year in the HIIT group deserves further investigation, as early HIIT may offset the beneficial effects of GDMT on LV remodeling in the long term.

The effects of positive end-expiratory pressure on cardiac function: a comparative echocardiography-conductance catheter study.

BACKGROUND: Echocardiographic parameters of diastolic function depend on cardiac loading conditions, which are altered by positive pressure ventilation. The direct effects of positive end-expiratory pressure (PEEP) on cardiac diastolic function are unknown. METHODS: Twenty-five patients without apparent diastolic dysfunction undergoing coronary angiography were ventilated noninvasively at PEEPs of 0, 5, and 10 cmH2O (in randomized order). Echocardiographic diastolic assessment and pressure-volume-loop analysis from conductance catheters were compared. The time constant for pressure decay (τ) was modeled with exponential decay. End-diastolic and end-systolic pressure volume relationships (EDPVRs and ESPVRs, respectively) from temporary caval occlusion were analyzed with generalized linear mixed-effects and linear mixed models. Transmural pressures were calculated using esophageal balloons. RESULTS: τ values for intracavitary cardiac pressure increased with the PEEP (n = 25; no PEEP, 44 ± 5 ms; 5 cmH2O PEEP, 46 ± 6 ms; 10 cmH2O PEEP, 45 ± 6 ms; p < 0.001). This increase disappeared when corrected for transmural pressure and diastole length. The transmural EDPVR was unaffected by PEEP. The ESPVR increased slightly with PEEP. Echocardiographic mitral inflow parameters and tissue Doppler values decreased with PEEP [peak E wave (n = 25): no PEEP, 0.76 ± 0.13 m/s; 5 cmH2O PEEP, 0.74 ± 0.14 m/s; 10 cmH2O PEEP, 0.68 ± 0.13 m/s; p = 0.016; peak A wave (n = 24): no PEEP, 0.74 ± 0.12 m/s; 5 cmH2O PEEP, 0.7 ± 0.11 m/s; 10 cmH2O PEEP, 0.67 ± 0.15 m/s; p = 0.014; E' septal (n = 24): no PEEP, 0.085 ± 0.016 m/s; 5 cmH2O PEEP, 0.08 ± 0.013 m/s; 10 cmH2O PEEP, 0.075 ± 0.012 m/s; p = 0.002]. CONCLUSIONS: PEEP does not affect active diastolic relaxation or passive ventricular filling properties. Dynamic echocardiographic filling parameters may reflect changing loading conditions rather than intrinsic diastolic function. PEEP may have slight positive inotropic effects. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02267291 , registered 17. October 2014.

Differences in Atrial Remodeling in Hypertrophic Cardiomyopathy Compared to Hypertensive Heart Disease and Athletes' Hearts.

Background: Hypertrophic cardiomyopathy (HCM), hypertensive heart disease (HHD) and athletes' heart share an increased prevalence of atrial fibrillation. Atrial cardiomyopathy in these patients may have different characteristics and help to distinguish these conditions. Methods: In this single-center study, we prospectively collected and analyzed electrocardiographic (12-lead ECG, signal-averaged ECG (SAECG), 24 h Holter ECG) and echocardiographic data in patients with HCM and HHD and in endurance athletes. Patients with atrial fibrillation were excluded. Results: We compared data of 27 patients with HCM (70% males, mean age 50 ± 14 years), 324 patients with HHD (52% males, mean age 75 ± 5.5 years), and 215 endurance athletes (72% males, mean age 42 ± 7.5 years). HCM patients had significantly longer filtered P-wave duration (153 ± 26 ms) and PR interval (191 ± 48 ms) compared to HHD patients (144 ± 16 ms, p = 0.012 and 178 ± 31, p = 0.034, respectively) and athletes (134 ± 14 ms, p = 0.001 and 165 ± 26 ms, both p < 0.001, respectively). HCM patients had a mean of 4.9 ± 16 premature atrial complexes per hour. Premature atrial complexes per hour were significantly more frequent in HHD patients (27 ± 86, p < 0.001), but not in athletes (2.7 ± 23, p = 0.639). Left atrial volume index (LAVI) was 43 ± 14 mL/m2 in HCM patients and significantly larger than age- and sex-corrected LAVI in HHD patients 30 ± 10 mL/m2; p < 0.001) and athletes (31 ± 9.5 mL/m2; p < 0.001). A borderline interventricular septum thickness ≥13 mm and ≤15 mm was found in 114 (35%) HHD patients, 12 (6%) athletes and 3 (11%) HCM patients. Conclusions: Structural and electrical atrial remodeling is more advanced in HCM patients compared to HHD patients and athletes.

Reproducibility of 4D cardiac computed tomography feature tracking myocardial strain and comparison against speckle-tracking echocardiography in patients with severe aortic stenosis.

BACKGROUND: Myocardial strain is an established parameter for the assessment of cardiac function and routinely derived from speckle tracking echocardiography (STE). Novel post-processing tools allow deformation imaging also by 4D cardiac computed tomography angiography (CCT). This retrospective study aims to analyze the reproducibility of CCT strain and compare it to that of STE. METHODS: Left (LV) and right ventricular (RV), and left atrial (LA) ejection fraction (EF), dimensions, global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) were determined by STE and CCT feature tracking in consecutive patients with severe aortic stenosis evaluated for transcatheter aortic valve implantation. RESULTS: 106 patients (mean age 79.9 â€‹± â€‹7.8, 44.3% females) underwent CCT at a median of 3 days (IQR 0-28 days) after STE. In CCT, strain measures showed good to excellent reproducibility (intra- and inter-reader intraclass correlation coefficient ≥0.75) consistently in the LV, RV and LA. In STE, only LV GLS and LA GLS yielded good reproducibility, whereas LV GCS and LV GRS showed moderate, and RV GLS and free wall longitudinal strain (FWLS) poor reproducibility. Agreement between CCT and STE was strong for LV GLS only, while other strain features displayed moderate (LV GCS, LA GLS) or weak (LV GRS, RV GLS and FWLS) inter-modality correlation. CONCLUSION: LV, RV and LA CCT strain assessments were highly reproducible. While a strong agreement to STE was found for LV GLS, inter-modality correlation was moderate or weak for LV GCS, LV GRS, and RV and LA longitudinal strain, possibly related to poor reproducibility of STE measurements.

Age and Sex Specific Prevalence of Clinical and Screen-Detected Atrial Fibrillation in Hospitalized Patients.

BACKGROUND: The prevalence of atrial fibrillation (AF) is high in older patients. The present study aimed to estimate the age and sex specific prevalence of clinical and screen-detected atrial fibrillation (AF) in hospitalized patients. METHODS: The STAR-FIB cohort study was a prospective cohort study recruiting participants from a large source population of hospitalized patients aged 65-84 years. The estimated size of the source population was 26,035 (95% CI 25,918-26,152), and 795 consenting patients without clinical AF were included in the cohort study after stratification by sex and age (49.2% females; mean age 74.7 years). Patients in the cohort study underwent three seven-day Holter ECGs in intervals of two months to screen for AF. RESULTS: In the source population, the estimated prevalence of clinical AF was 22.2% (95% CI 18.4-26.1), 23.8% for males (95% CI 20.9-26.6) and 19.8% for females (95% CI 17.3-22.4; p for difference between sexes, 0.004). There was a linear trend for an increase in the prevalence of clinical AF with increasing age, overall and in both sexes. In the cohort study, AF was newly diagnosed in 38 patients, for an estimated prevalence of screen-detected AF of 4.9% overall (95% CI 3.3-6.6), 5.5% in males (95% CI 3.2-7.8) and 4.0% in females (95% CI 2.0-6.0; p for difference between sexes, 0.041). The estimated prevalence of screen-detected AF in the source population was 3.8% overall, 4.2% in males and 3.2% in females. CONCLUSION: In a large hospital-based patient population aged 65-84 years, the prevalence of clinical AF and of screen-detected AF was 22.2% and 3.8%, respectively, and significantly higher in males than females.

The SilenT AtRial FIBrillation (STAR-FIB) study programme - design and rationale.

AIMS OF THE STUDY: Anticoagulation of patients with screen-detected atrial fibrillation may prevent ischaemic strokes. The STAR-FIB study programme aims to determine the age- and sex-specific prevalence of silent atrial fibrillation and to develop a clinical prediction model to identify patients at risk of undiagnosed atrial fibrillation in a hospitalised patient population. METHODS: The STAR-FIB study programme includes a prospective cohort study and a case-control study of hospitalised patients aged 65–84 years, evenly distributed for both age and sex. We recruited 795 patients without atrial fibrillation for the cohort study (49.2% females; median age 74.8 years). All patients had three serial 7-day Holter ECGs to screen for silent atrial fibrillation. The primary endpoint will be any episode of atrial fibrillation or atrial flutter of ≥30 seconds duration. The age- and sex-specific prevalence of newly diagnosed atrial fibrillation will be estimated. For the case-control study, 120 patients with paroxysmal atrial fibrillation were recruited as cases (41.7% females; median age 74.6 years); controls will be randomly selected from the cohort study in a 2:1 ratio. All participants in the cohort study and all cases were prospectively evaluated including clinical, laboratory, echocardiographic and electrical parameters. A clinical prediction model for undiagnosed atrial fibrillation will be derived in the case-control study and externally validated in the cohort study. CONCLUSIONS: The STAR-FIB study programme will estimate the age- and sex-specific prevalence of silent atrial fibrillation in a hospitalised patient population, and develop and validate a clinical prediction model to identify patients at risk of silent atrial fibrillation.

Left atrial appendage closure versus medical therapy in patients with atrial fibrillation: the APPLY study.

AIMS: Left atrial appendage closure (LAAC) with AMPLATZER occluders is used for stroke prevention in atrial fibrillation (AF). Net clinical benefit compared to medical therapy has not been tested. The aim of this study was to test whether long-term clinical outcome after LAAC with AMPLATZER occluders may be similar to medical therapy. METHODS AND RESULTS: Five hundred consecutive patients who underwent LAAC with AMPLATZER occluders were compared to 500 patients with medical therapy by propensity score matching. The primary efficacy endpoint was a composite of stroke, systemic embolism and cardiovascular/unexplained death. The primary safety endpoint consisted of major procedural adverse events and major bleedings. For assessment of net clinical benefit, all of the above-mentioned hazards were combined. After 2,645 patient-years at a mean follow-up of 2.7±1.5 years, the primary efficacy endpoint was reached by 75/1,342, 5.6% in the LAAC group versus 102/1,303, 7.8% per 100 patient-years (hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.53-0.95, p=0.026). The primary safety endpoint occurred in 48/1,342, 3.6% versus 60/1,303, 4.6% per 100 patient-years (HR 0.80, 95% CI: 0.55-1.18, p=0.21), and the combined hazard endpoint in 109/1,342, 8.1% versus 142/1,303, 10.9% per 100 patient-years (HR 0.76, 95% CI: 0.60-0.97, p=0.018). Patients receiving LAAC demonstrated lower rates of both all-cause and cardiovascular mortality (111/1,342, 8.3% vs 151/1,303, 11.6% per 100 patient-years [HR 0.72, 95% CI: 0.56-0.92, p=0.005] and 54/1,342, 4.0% vs 84/1,303, 6.5% per 100 patient-years [HR 0.64, 95% CI: 0.46-0.89, p=0.007]). CONCLUSIONS: LAAC with AMPLATZER devices showed a net clinical benefit over medical therapy by superior efficacy, similar safety and a benefit in all-cause and cardiovascular mortality.

Clinical outcomes of Watchman vs. Amplatzer occluders for left atrial appendage closure (WATCH at LAAC).

AIMS: This study compares clinical outcomes of Watchman vs. Amplatzer devices for left atrial appendage closure (LAAC). METHODS AND RESULTS: Of two real-world registries, the Watchman registry Lichtenfels, Germany, and the Amplatzer registry Bern-Zurich, Switzerland, 303 and 333 consecutive patients, respectively, were included. After a 1:1 propensity score matching, 266 vs. 266 patients were compared by use of the predefined primary efficacy endpoint of stroke, systemic embolism and cardiovascular/unexplained death, the primary safety endpoint of major peri-procedural complications and major bleeding events at follow-up, and the combined hazard endpoint, a composite of all above-mentioned hazards. Mean age was 75.3 ± 7.8 (Watchman) vs. 75.1 ± 9.9 (Amplatzer) years, CHA2DS2-VASc score 4.5 ± 1.7 vs. 4.5 ± 1.5, and HAS-BLED score 3.2 ± 1.0 vs. 3.2 ± 1.0. At a mean follow-up of 2.4 ± 1.3 vs. 2.5 ± 1.5 years and 1.322 patient-years, the primary endpoints of efficacy [40/646, 6.2% [Watchman] vs. 43/676, 6.4% [Amplatzer]; hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.66-1.58; P = 0.92] and safety (33/646, 5.1% vs. 30/676, 4.4%; HR, 0.57; 95% CI, 0.29-1.11; P = 0.10), as well as the combined hazard endpoint (69/646, 10.7% vs. 66/676, 9.8%; HR, 0.80; 95% CI, 0.55-1.12; P = 0.26) were similar for both groups. CONCLUSION: This study suggests comparable efficacy and safety of the Watchman and Amplatzer devices.

Pulmonary Artery Pressure Ventricularization in a Patient With Carcinoid Heart Disease.

Ventricularization of the pulmonary artery pressure curve is shown, characterized by a steep diastolic pressure fall with mid-diastolic pressure equalization with the right ventricle, which was caused by severe pulmonary valvular regurgitation in a patient with carcinoid heart syndrome. (Level of Difficulty: Beginner.).

Transseptal puncture versus patent foramen ovale or atrial septal defect access for left atrial appendage closure.

AIMS: The aim of this study was to compare the periprocedural and late clinical outcomes of left atrial appendage closure (LAAC) with AMPLATZER devices by access through transseptal puncture (TSP) versus a patent foramen ovale (PFO) or an atrial septal defect (ASD). METHODS AND RESULTS: Between 2009 and 2018, 578 consecutive patients underwent LAAC via TSP or PFO/ASD access in three centres. After a 3:1 propensity score matching, 246 (TSP) versus 91 (PFO/ASD) patients were compared using the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death and the primary safety endpoint of major periprocedural complications and major bleedings at follow-up. Mean age was 75.2±8.7 (TSP) vs 74.4±10.9 (PFO/ASD) years, CHA2DS2-VASc score 4.5±1.6 vs 4.3±1.4 and HAS-BLED score 3.3±1.0 vs 3.3±0.9. Device success (97.6% vs 97.8%, p=0.90) was similar. After 2.5±1.4 vs 2.6±1.6 years, clinical efficacy (46/603, 7.6% [TSP] vs 21/233, 9.0% [PFO/ASD], hazard ratio [HR] 1.2; 95% confidence interval [CI]: 0.69-0.85, p=0.54) and safety (24/603, 4.0% vs 11/233, 4.7%; HR 1.4; 95% CI: 0.52-3.6, p=0.49) did not differ. CONCLUSIONS: Use of a PFO/ASD access for LAAC with AMPLATZER devices offers similar periprocedural and late clinical outcomes to TSP. Simultaneous PFO/ASD closure for an additional protective benefit does not increase risk.

Exercise-induced cardiac remodeling in non-elite endurance athletes: Comparison of 2-tiered and 4-tiered classification of left ventricular hypertrophy.

BACKGROUND: Long-term endurance sport practice leads to eccentric left ventricular hypertrophy (LVH). We aimed to compare the new 4-tiered classification (4TC) for LVH with the established 2-tiered classification (2TC) in a cohort of normotensive non-elite endurance athletes. METHODS: Male participants of a 10-mile race were recruited and included when blood pressure (BP) was normal (<140/90 mmHg). Phenotypic characterization of LVH was based on relative wall thickness (2TC), and on LV concentricity2/3 (LV mass/end-diastolic volume [LVM/EDV]2/3) plus LVEDV index (4TC). Parameters of LV geometry, BP, cumulative training hours, and race time were compared between 2TC and 4TC by analysis of variance, and post-hoc analysis. RESULTS: Of 198 athletes recruited, 174 were included. Mean age was 41.6±7.5 years. Forty-two (24%) athletes had LVH. Allocation in the 2TC was: 32 (76%) eccentric LVH and 10 (24%) concentric LVH. Using the 4TC 12 were reclassified to concentric LVH, and 2 to eccentric LVH, resulting in 22 (52%) eccentric LVH (7 non-dilated, 15 dilated), and 20 (48%) concentric LVH (all non-dilated). Based on the 2TC, markers of endurance training did not differ between eccentric and concentric LVH. Based on the 4TC, athletes with eccentric LVH had more cumulative training hours and faster race times, with highest values thereof in athletes with eccentric dilated LVH. CONCLUSIONS: In our cohort of normotensive endurance athletes, the new 4TC demonstrated a superior discrimination of exercise-induced LVH patterns, compared to the established 2TC, most likely because it takes three-dimensional information of the ventricular geometry into account.