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Background Fractional Flow Reserve (FFR) derived from coronary computed tomography angiography (CCTA) enables anatomical and hemodynamical assessment of coronary artery disease. CT-FFR, which can be acquired on-site workstation using fluid structure interaction during the multiple optimal diastolic phase, has an incremental diagnostic value over conventional CCTA. However, few studies are focused on investigating the appropriate measurement location of CT-FFR, considering the prognosis, using CCTA as a standalone modality. Purpose The aim of this study is to assess the clinical impact on CT-FFR with an appropriate measurement. Methods A total of 370 consecutive patients who underwent CCTA in a single-heartbeat scan with a phase window of 70% to 99% of the R-R interval, showing 50–90% stenosis of at least one major epicardial vessel measuring ≥1.8 mm in diameter on CCTA were retrospectively analyzed and followed during a median follow up 2.9 years. CT-FFR values were measured at three points: 1, 2 cm distal to a target lesion (CT-FFR1cm, 2cm) and the vessel terminus (CT-FFRlowest), and a CT-FFR value ≤0.80 was considered abnormal. The endpoint was MACE, a composite of cardiac death, non-fatal MI, and unplanned revascularization. Results The incidence of MACE occurred in 8.4% (31/370) of the whole patients, including four cardiac deaths, ten all cause deaths, two non-fatal MI, and twenty unplanned revascularization. The Kaplan-Meier survival analysis demonstrated a significantly higher cumulative MACE rate in patients with positive CT-FFR1cm and 2cm than those with negative CT-FFR1cm and 2cm, while there was no significant difference between negative and positive in CT-FFRlowest, among patients with negative CT-FFR1cm and 2cm (Figure 1). Among 221 patients, who did not perform early revascularization within 90 days from CCTA, there was no significant difference in CT-FFRlowest in the incidence of MACE. In contrast, the risk of MACE was significantly higher in both positive CT-FFR1cm and CT-FFR2cm (Figure 2). Conclusion From a view point of clinical outcome for patients with moderate to severe stenosis on CCTA, a CT-FFR value when measured at 1-to-2 cm distal to a target lesion could be feasible for the deferral of unnecessary invasive coronary angiography safely. Moreover, CT-FFR1–2cm showed better risk stratification measurement rather than CT-FFRlowest, based on future adverse cardiac event. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Canon Medical Systems Corporation Kaplan-Meier 1Kaplan-Meier 2

Funding Acknowledgements Type of funding sources: None. Background In left atrial appendage occlusion (LAAO), pre-procedural computed tomography (CT) is pivotal to describe the complex and highly variable LAA anatomy and to guide the operator in accurate planning of the intervention. Multiplanar reconstruction and 3D rendering are used for the navigation and analysis of the 3D datasets but they share some limitations that are due to the use of 2D screens; Mixed Reality (MxR) technology aims at overcoming such limitations by allowing for real-3D visualizations with holographic replicas of anatomical models while preserving a sense of presence within the true physical environment by the operator. Purpose To develop and test a MxR platform that provides a more intuitive and informative tool for the morphological analysis during the planning phase of LAAO. Methods Patients (n = 4) were randomly selected among those referred for a CT scan prior to transcatheter aortic valve replacement, each one characterized by a specific LAA morphology (cauliflower, bilobular, chicken wing, wind-sock). CT scans were performed in diastole at 75% of the R-R interval on a 64-slice scanner, with in-plane resolution 0.38-0.64 mm and slice thickness 0.62 mm. Firstly, the acquisition was cropped to contain the left atrium, the circumflex artery, the left upper pulmonary ridge. Subsequently, an isosurface with high coincidence between the blood cavity border and the endocardium was identified by the user and processed using a marching cube algorithm to obtain the 3D model. Finally, the 3D model was optimized for a MxR platform that allows for moving, zooming and cutting the model, measuring the main LAA linear dimensions and simulating the implant of a virtual replica of a transcatheter occluder. Results The workflow was successfully applied for all the patients independently from the morphology. All the models were successfully uploaded in the MxR platform (Fig 1.a) and for all the patients the morphological analysis was performed (Fig 1.b) in less than 10 minutes. The four different morphologies of the LAA were correctly identified allowing a very detailed holographic modeling of the structure, including the neck, the landing zone, the curvature and the position and size of lobes. For both the identified ostium and landing planes, using a dedicated measuring tool (Fig. 1.c), the operator measured the minimum and maximum diameters, which were later used to define the size of the occluder device to be used in the virtual implant simulation (Fig. 1.d). Conclusions The tested MxR platform suggested the potential to overcome the limits of the standard technologies in planning of LAAO thanks to the real-3D perception, potentially leading to a more accurate and faster planning phase. Furthermore, the use of MxR technology may enhance the ability to predict the optimal device size and position within the anatomy to obtain LAA complete sealing. Abstract Figure.

Introduction In order to improve knowledge of the tricuspid valve (TV) function and its coupling with the right atrio-ventricular junction (RAVJ) and right ventricle (RV), new four-dimensional high-definition imagery methods are mandatory (3D+t). Purpose Using an innovative reconstruction method based on multiphase cardiac computed tomography imaging (4D-MCCTI), we finely analyzed the morphological & dynamical features of tricuspid annulus (TA) and RAVJ components in order to assess new functional parameters of TV and RV functions. Methods Volume imaging data sets through time were obtained from 4D-MCCTI of 30 subjects (sex ratio 1, mean age 57±11y.) with no rhythm, valvular or ventricular abnormalities on echocardiography and implemented in a custom software for 3D semi-automated delineation of 18 points around TA perimeter. Coordinates of these points in each of the 10 time-phases within an RR interval were used to calculate specific geometrical features of TA such as 3D/2D areas, perimeters, 360°-diameters and vertical deformation. Subsequently, RV and Right Atrium (RA) inner contours were also delineated (Figure). Results TA shape was elliptical in horizontal projection with a mean eccentricity index (EcI) of 0.58±0.12; and saddle-shapped in vertical projection with a horn nearby the antero-septal commissure. This feature remained throughout the cardiac cycle but TA was more planar (minimal TA-height: 4.47±1.04 mm) and circular (minimal EcI=0.44±0.14) in mid-diastole when TA-3Darea and TA-3Dperimeter reached a maximum of 6.98±1.21 cm2/m2 and 7.41±0.91 cm, respectively. Correlation between TA-3Darea, TA-2Darea and latero-septal diameter (LSD) were R2=0.99 and R2=0.73, respectively. LSD was minimal in early-systole (18.83±3.04 mm/m2) and maximal in mid-diastole (20.04±3.05 mm/m2). Correlation of TA-3Darea with RV and RA cross-sectional areas were R2=0.82 and R2=0.71, respectively. Conversely, there was no significant correlation between TA, RV and RA concentric contractions. Conclusions Our method for 4D-MTCCI analysis has allowed confirming the shape and dynamics function of RAVJ throughout the cardiac cycle in healthy subjects, and giving new reference parameters for TV and RV evaluation. Software multiplanar view of TA Funding Acknowledgement Type of funding source: None

Background and aim The need for permanent pacemaker implantation (PPMI) is a burdensome complication of transcatheter aortic valve replacement (TAVR). Calcium distribution in the aortic-valvular complex (AVC) and, more recently, membranous septum (MS) length seem to be surrogate markers for conduction abnormalities after specific last generation balloon and self-expandable expandable valves. We sough to evaluate whether such pre-procedural association remains across the entire device spectrum. Methods Single-centre prospective study of 239 consecutive patients (140 women, median age of 84) with severe symptomatic aortic stenosis patients who underwent ECG-gated contrast-enhanced multi-detector computed tomography (MSCT) before TAVR since Jun/2017. Exclusion criteria were those with previous PPMI, previous bioprothesis, congenital bicuspid valve, and poor imaging quality. The J-score with an 850-Hounsfield unit threshold was used to detect areas of calcium in the region of interest. AVC was characterized by leaflet sector and region, using 3mensio Valves software 7.0 TM. An independent team retrospectively measured MS length blindly by determining the thinnest part of the interventricular septum in the coronal view in the better-defined systolic phase (usually at 40% of the R-R interval, Figure). Device selection (75.8% self-expandable devices, 20.1% balloon expandable, 3.1% other) and positioning were performed according to the operator criteria. Final implant depth was assessed based on the pre-release angiogram or final aortography. Results Mortality at 30-days was 1.3% and PPMI occurred in 43 patients (18%). Median MS length was 9.59mm (IQR: 3.11mm). After multivariable logistic regression analysis, MS length emerged as the single significant protective predictor for PPMI (OR: 0.14; 95% 95% CI: 0.05–0.42; p Conclusion In our experience, a short membranous septum was strongly and independently associated with new permanent pacemaker implantation, regardless of the device type. Our findings suggest that this simple measure should be routinely made to help device selection and implantation technique. Funding Acknowledgement Type of funding source: None

Background Atrial fibrillation (Afib) leads to beat-to-beat variability in cycle length; however, whether there is associated beat-to-beat variability in the tricuspid annulus (TA) dimensions or variability in the time in cardiac cycle when TA reaches maximal size is unknown. Purpose We aim to assess the beat-to-beat variability in the TA dimensions in Afib compared with sinus rhythm (SR). Methods Images were obtained from 58 patients (29 in Afib, 29 in SR) undergoing either 3D TTE or TEE examination. We measured TA in 3–6 cardiac cycles per patient using commercially available software (TomTec 4MV). Results Median absolute difference in maximal TA area over 3–6 cardiac cycles was 1.60 cm2 (range 0.35 cm2 to 4.08 cm2) in Afib vs. 1.17 cm2 (range 0.32 cm2 to 2.19 cm2) in SR, p=0.0063. Median absolute difference in the maximal circumference was 0.79 cm (range 0.09 cm to 2.2 cm) in Afib vs 0.54 cm (range 0.12 cm to 1.43 cm) in SR, p=0.0175. A total of 118 cardiac cycles were analyzed in patients in SR and 147 in Afib. Timing of maximal TA area was most commonly recorded at end-diastole (80–100% of the R-R interval) in 62% of cycles in SR; however, it was distributed over a broad range in Afib, p Conclusion Afib leads to significant beat-to-beat variability in the maximal TA area, minimal TA area, maximal TA circumference, and in the time of maximal TA area. These findings suggest that accurate assessment of TA dimensions should be based on continuous tracking of the TA over several cardiac cycles, especially in patients with Afib. These observations have significant implications for device sizing in percutaneous tricuspid valve interventions. Timing of Maximal TA Area Funding Acknowledgement Type of funding source: None

Background Forecasting atrial fibrillation (AF) a few minutes before its onset has been studied, mainly based on heart rate variability parameters, derived from 24-hour ECG Holter monitorings. However, these studies have shown conflicting, non-clinically applicable results. Nowadays, machine learning algorithms have proven their ability to anticipate events. Therefore, forecasting AF before its onset should be (re)assessed using machine learning techniques. A reliable forecasting could improve results of preventive pacing in patients with cardiac electronic implanted devices (CEID). Purpose To forecast an oncoming AF episode in individual patients using machine learning techniques. To evaluate the effect if the onset of an AF episode can be forecasted on longer time frames. Methods The totality of the raw data of a data set of 10484 ECG Holter monitorings was retrospectively analyzed and all AF episodes were annotated. Onset of each AF episode was determined with a precision of 5 msec. We only took AF events into consideration if they lasted longer than 30 seconds. Of all patients in the dataset, 140 presented paroxysmal AF (286 recorded AF episodes). We only used RR intervals to predict the presence of AF. We developed two different types of machine learning algorithms with different computational power requirements: a “dynamic” deep and recurrent neural net (RNN) and a “static” decision-tree with adaboost (boosting trees) more suitable for embedded devices. These algorithms were trained on one set of patients (around 90%) and tested on the remaining set of patients (around 10%). Results The performance figures are summarized in the table. Both algorithms can be tuned to increase their specificity (at a loss of sensitivity) or vice versa, depending on the objective. Performance of forecasting algorithms RR-distance Boosting trees AUC RNN AUC 30–1 RR-Interval(s) before an AF event 97.1% 98.77% 60–31 RR-Intervals before an AF event 97.5% 99.1% 90–61 RR-Intervals before an AF event 96.9% 99.1% 120–91 RR-Inervals before an AF event 98.2% 98.9% AUC for Area Under ROC Curves. Conclusion Based upon this retrospective study, we show that AF can be forecasted on an individual level with high predictive power using machine learning algorithm, with little drop-off of predictive value within the studied distances (1–120 RR intervals before a potential AF episode). We believe that the embedding of our new algorithm(s) in CEID's could open the way to innovative therapies that significantly decrease AF burden in selected implanted patients.

BACKGROUND The blood pressure-lowering mechanism of low-sodium diet is not fully understood. METHODS We assessed the effects of salt restriction on cardiac parasympathetic function as measured by heart-rate variability (HRV) in mild to moderate hypertensive patients. Eighty patients were randomized to a 6-month low- (N = 40) or normal (N = 40) sodium diet and a 24-h electrocardiogram (ECG) was carried out in the beginning of the study and at 6 months. Five time-domain and six frequency-domain HRV variables were analyzed: mean RR interval, standard deviation of normal RR intervals, mean of the standard deviations of all RR intervals for 5-min segments of the entire recording, percentage of differences between adjacent normal RR intervals exceeding 50 ms, square root of the mean of squared differences between adjacent normal RR intervals, total (0.01-0.40 Hz), high frequency (HF, 0.15-0.40 Hz), low frequency (LF, 0.04-0.15 Hz), very LF (0.01-0.04 Hz) and LF/HF ratio. RESULTS Although blood pressure diminished significantly (systolic blood pressure (SBP) from 149.9 +/- 14.7 mm Hg to 130.3 +/- 11.8 mm Hg, P < 0.001 and diastolic blood pressure (DBP) from 98.0 +/- 6.4 mm Hg to 87.1 +/- 6.2 mm Hg, P

Chagas disease patients often present premature ventricular complexes (PVCs), depression of left ventricular ejection fraction (LVEF) and autonomic dysfunction, which is generally evaluated by heart rate variability (HRV) analysis. As frequent PVCs may complicate HRV computation, we measured heart rate turbulence (HRT) and evaluated the correlation between ejection fraction and HRT or HRV in Chagas disease.We studied 30 patients (47+/-11 years, 20 men) with Chagas cardiomyopathy and left ventricular dilatation who underwent clinical evaluation, ejection fraction (EF: 45+/-14%) determination and 24-h Holter monitoring (median PVC=1781). In all patients, the standard deviation of normal RR intervals (SDNN), the square root of the mean square differences of successive RR intervals (RMSSD) and values of turbulence onset (TO) and turbulence slope (TS) were calculated.HRT indices were independent of mean RR interval and presented high correlation with EF: TO (-0.11+/-0.01%, r=-0.60, P0.001) and TS (5.8+/-3.7 ms/RR-interval, r=0.73, P0.001). Of HRV parameters, only SDNN, corrected for mean RR interval, showed a weak but not significant correlation with EF (r=0.41). The comparison of HRT/EF and HRV/EF correlation coefficients, indicated the presence of a significant difference (P=0.017).HRT indices appear to correlate better with EF than SDNN in Chagas disease. Thus, an analysis based on heart rate transient adaptation seems to perform better than HRV in detecting the autonomic alterations that parallel left ventricular dysfunction in Chagas disease patients. The high number of PVCs observed in these patients further support the use of HRT methodology.

Aim Changes in ventricular refractoriness and repolarization after successful electrical cardioversion to sinus rhythm in persistent atrial fibrillation (AF) patients were studied. Methods and results In 33 AF patients with controlled ventricular response, right ventricular ERP (VERP) at three basic cycle lengths (600, 500, 400 ms), as well as monophasic action potential duration (MAPd90) at a drive cycle length of 500 ms, were measured just before, 20 min and 24 h after cardioversion. VERP at 600 ms changed from 241 ± 19 ms to 249 ± 21 ms to 253 ± 24 ms ( P < 0.001), VERP at 500 ms changed from 234 ± 19 ms to 242 ± 22 ms to 246 ± 23 ms ( P < 0.001) and VERP at 400 ms changed from 224 ± 20 ms to 232 ± 23 ms to 236 ± 24 ms ( P < 0.001). MAPd90 changed from 247 ± 16 ms preconversion to 252 ± 17 ms 20 min postconversion to 253 ± 19 ms after 24 h ( P < 0.05). Change in refractoriness at 500 ms was well correlated with change of mean RR interval before and 20 min after conversion ( R = 0.616, P < 0.001). There was no correlation between RR variability and VERP before cardioversion. Conclusion Restoration of sinus rhythm in persistent AF patients is followed by significant effects on ventricular refractoriness and repolarization related to cycle length change. No AF related ventricular electrophysiological alterations were found.

Background Decreased heart rate variability (HRV) may predict cardiac death after myocardial infarction (MI). Coronary artery bypass grafting (CABG) strongly decreases HRV, but improves survival. The aim of the study was to determine the prognostic value of HRV decreased by coronary surgery. Design and methods Four-year follow-up was performed in 175 consecutive patients with HRV decreased by CABG (51) or MI (124). Mortality and secondary events rate were analysed. Decreased HRV, defined by the standard deviation of mean RR interval (SDNN) < 100 ms, was detected by a routine 24-h Holter ECG at admission to stationary rehabilitation 3 weeks to 3 months after acute MI or CABG. Two groups did not differ except by age ; CABG patients were younger (56 vs 64 years, P < 0.01), but this did not influence differences in survival (NS). Results HRV was lower among CABG patients than among MI patients (SDNN= 66 p ; ; 20ms vs 77p ; ; 14 ms ; P < 0.001), but cumulative survival and event-free survival were much better in the CABG group than in the MI group. During a 46 p ; ; 20 months follow-up, there were 10% new events in the CABG and 43% in the MI group (P < 0.001). Mortality was 8% in the CABG and 33% in the MI group (log-rank= 3.6 ; P

Aims: Predischarge identification of viable myocardium with a spontaneous recovery over time can be helpful in decision-making process following acute myocardial infarction (AMI). An intriguing hypothesis is that identification of viability in myocardial asynergic segments with or without spontaneous recovery over time may require an inotropic stimulus of a different intensity. To test this we used post-extrasystolic potentiation (PESP), which represents an inotropic stimulation of a different intensity as a function of coupling interval. Methods and results: Myocardial viability was assessed by PESP echocardiography in 86 patients with a first uncomplicated AMI. Spontenous changes in contractile function of viable but asynergic segments at predischarge were evaluated by a follow-up resting echocardiogram 1 month later. Viable myocardium of left ventricular asxynergic segments with spontaneous recovery or persistence of dysfunction showed its first significant improvement for different values of coupling interval during PESP (409±18 vs 336±23 ms (milliseconds), P

Objective: The interval from the peak to the end of the T wave (TpTe) has been proposed to reflect the heterogeneity of action potential durations within the ventricular wall. Several studies have previously described TpTe to be independent of heart rate, which contradicts the in vitro observation of marked changes in transmural repolarisation heterogeneity due to cycle length changes. Because of this inconsistency, we investigated heart rate related changes of TpTe interval. Methods: During 24-h recordings (SEER MC, Marquette GE) in healthy young women ( n = 25, 26±7 years) and men ( n = 25, 27±8 years), a 10-s 12-lead ECG was obtained every 30 s. Recordings were repeated after 1 day, 1 week, and 1 month and results in each subject were pooled together and grouped for women and men. The QT and QTpeak intervals were obtained automatically using QT Guard software (Marquette) and TpTe was computed as the difference between QT and QTpeak. In each subject TpTe values were averaged over 10-ms RR interval bands from 550 to 1150 ms. Results: In both sexes, TpTe interval showed marked rate dependence with prolongation at long RR intervals. TpTe intervals in men were significantly longer over the entire range of investigated RR intervals ( P = 1.4×10−25). However, whereas the difference between sexes was marked at short cycle length (RR interval bin 540–550 ms: women 87±5 vs. men 95±9, P = 5.1×10−4) it decreased at long cycle lengths (RR interval bin 1140–1150 ms: women 99±5 vs. men 106±6, P = 9.3×10−4). Conclusion: There is a marked rate dependence of TpTe interval, which differs between women and men. The finding is consistent with the TpTe interval being an approximate surrogate of the intraventricular repolarisation gradient. The rate dependent increase in transmural repolarisation heterogeneity might be one of the reasons for the increased propensity of torsades de pointes in women.

Aim to assess if the pattern of left ventricle (LV) volume curves variation using automatic border detection (ABD) can help in differentiation of desynchronized contraction. Methods patients (pts) with dilated cardiomyopathy were included (n = 41; 58.3±16.2 years). Currently accepted TDI and TM parameters were used to indicate LV desynchronization. On-line continuous LV volumes changing were recorded using ABD. Ejection time (ET ABD) was measured from ABD wave-forms as time interval between maximal and minimal volume variation during LV electromechanical systole. Ejection time index was derived as ratio ET ABD/RR interval (ETi ABD = ET/RR). Results 26 pts presented QRSd>120ms, 15 pts had QRSd 120ms, 8 pts QRSd

The aim of this study was to determine the validity of regression equations relating RR interval and heart rate to systolic time intervals in sheep. Regression equations were compiled employing the RR interval to correct systolic time intervals for heart rate in six Merino ewes. A range of heart rates was obtained by means of pharmacological intervention as well as electrical pacing. Heart rate did not affect the pre-ejection period, isovolumetric contraction time, the pre-ejection period to left ventricular ejection time ratio, the ratio QS2/QT, electrical delay (Q1), or the PR interval. Heart rate did, however, affect the duration of electromechanical systole (QS2), left ventricular ejection time and mechanical systole (S1S2). The study showed that it was preferable to correct the systolic time intervals using the RR interval rather than the heart rate. Bazett's equation to correct electrical systole (QT) for heart rate in humans was also validated in sheep.

The relation between the minimum RR interval during atrial fibrillation and the functional refractory period of the AV junctional tissues was studied in isolated perfused dog hearts. In each heart, the functional refractory period, the minimum ventricular interval obtained by regular pacing of the atria at increasing frequencies, and the minimum RR interval during atrial fibrillation were compared. It appears that the length of the minimum RR interval during atrial fibrillation is proportional to both the functional refractory period and the minimum RR interval obtained by atrial pacing. These values are nearly equal in preparations where the functional refractory period is short. However, in cases where the functional refractory period is long, the minimum RR interval during atrial fibrillation is appreciably longer than the two other parameters. It is suggested that this difference may be explained in terms of a decreased safety factor between the efficiency of the incoming atrial wavefront as a stimulus and the level of excitability of the atrioventricular junctional tissues. Alternatively, these results may also imply that the conduction velocity of a propagated impulse across the AV junction is prolonged in hearts with longer functional refractory periods.