Histopathological validation of semi-automated myocardial scar quantification techniques for dark-blood late gadolinium enhancement magnetic resonance imaging.

AIMS: To evaluate the performance of various semi-automated techniques for quantification of myocardial infarct size on both conventional bright-blood and novel dark-blood late gadolinium enhancement (LGE) images using histopathology as reference standard. METHODS AND RESULTS: In 13 Yorkshire pigs, reperfused myocardial infarction was experimentally induced. At 7 weeks post-infarction, both bright-blood and dark-blood LGE imaging were performed on a 1.5 T magnetic resonance scanner. Following magnetic resonance imaging (MRI), the animals were sacrificed, and histopathology was obtained. The percentage of infarcted myocardium was assessed per slice using various semi-automated scar quantification techniques, including the signal threshold vs. reference mean (STRM, using 3 to 8 SDs as threshold) and full-width at half-maximum (FWHM) methods, as well as manual contouring, for both LGE methods. Infarct size obtained by histopathology was used as reference. In total, 24 paired LGE MRI slices and histopathology samples were available for analysis. For both bright-blood and dark-blood LGE, the STRM method with a threshold of 5 SDs led to the best agreement to histopathology without significant bias (-0.23%, 95% CI [-2.99, 2.52%], P = 0.862 and -0.20%, 95% CI [-2.12, 1.72%], P = 0.831, respectively). Manual contouring significantly underestimated infarct size on bright-blood LGE (-1.57%, 95% CI [-2.96, -0.18%], P = 0.029), while manual contouring on dark-blood LGE outperformed semi-automated quantification and demonstrated the most accurate quantification in this study (-0.03%, 95% CI [-0.22, 0.16%], P = 0.760). CONCLUSION: The signal threshold vs. reference mean method with a threshold of 5 SDs demonstrated the most accurate semi-automated quantification of infarcted myocardium, without significant bias compared to histopathology, for both conventional bright-blood and novel dark-blood LGE.

Heart sound-derived systolic time intervals for atrioventricular delay optimization in cardiac resynchronization therapy.

BACKGROUND: Phonocardiography (PCG) can be used to determine systolic time intervals (STIs) from ventricular pacing spike to the first heart sound (VS1) and from the first to the second heart sound (S1S2). OBJECTIVE: The purpose of this study was to investigate the relations between STIs and hemodynamics during atrioventricular (AV) delay optimization of biventricular pacing (BiVP) in animals and patients. METHODS: Five pigs with AV block underwent BiVP, while PCG was collected from an epicardial accelerometer. In 21 patients undergoing cardiac resynchronization therapy device implantation, PCG was recorded with a pulse generator-embedded microphone. Optimal AV delays derived from shortest VS1 and longest S1S2 were compared with AV delays derived from highest left ventricular pressure (LVP), maximal rate of rise in LVP, and stroke work. RESULTS: In pigs, VS1 and S1S2 predicted the AV delays with optimal hemodynamics (highest LVP, maximal rate of rise in LVP, and stroke work) by a median error of 2-28 ms, resulting in a median loss of <2% of pump function. In patients, VS1 and S1S2 predicted the optimal AV delay by errors of 32.5 and 37.5 ms, respectively, resulting in 0.2%-0.9% lower LVP and stroke work, which were reduced to 21 and 24 ms in 8 patients with a full-capture AV delay of >180 ms. CONCLUSION: During BiVP with varying AV delays, close relations exist between PCG-derived STIs and hemodynamic parameters. AV delays advised by PCG-derived STIs cause only a minimal loss of pump function compared with those based on invasive hemodynamic measurements. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01832493.

Left bundle branch area pacing outcomes: the multicentre European MELOS study.

AIMS: Permanent transseptal left bundle branch area pacing (LBBAP) is a promising new pacing method for both bradyarrhythmia and heart failure indications. However, data regarding safety, feasibility and capture type are limited to relatively small, usually single centre studies. In this large multicentre international collaboration, outcomes of LBBAP were evaluated. METHODS AND RESULTS: This is a registry-based observational study that included patients in whom LBBAP device implantation was attempted at 14 European centres, for any indication. The study comprised 2533 patients (mean age 73.9 years, female 57.6%, heart failure 27.5%). LBBAP lead implantation success rate for bradyarrhythmia and heart failure indications was 92.4% and 82.2%, respectively. The learning curve was steepest for the initial 110 cases and plateaued after 250 cases. Independent predictors of LBBAP lead implantation failure were heart failure, broad baseline QRS and left ventricular end-diastolic diameter. The predominant LBBAP capture type was left bundle fascicular capture (69.5%), followed by left ventricular septal capture (21.5%) and proximal left bundle branch capture (9%). Capture threshold (0.77 V) and sensing (10.6 mV) were stable during mean follow-up of 6.4 months. The complication rate was 11.7%. Complications specific to the ventricular transseptal route of the pacing lead occurred in 209 patients (8.3%). CONCLUSIONS: LBBAP is feasible as a primary pacing technique for both bradyarrhythmia and heart failure indications. Success rate in heart failure patients and safety need to be improved. For wider use of LBBAP, randomized trials are necessary to assess clinical outcomes.

Left Ventricular Pressure Estimation Using Machine Learning-Based Heart Sound Classification.

Objective: A method to estimate absolute left ventricular (LV) pressure and its maximum rate of rise (LV dP/dtmax) from epicardial accelerometer data and machine learning is proposed. Methods: Five acute experiments were performed on pigs. Custom-made accelerometers were sutured epicardially onto the right ventricle, LV, and right atrium. Different pacing configurations and contractility modulations, using isoflurane and dobutamine infusions, were performed to create a wide variety of hemodynamic conditions. Automated beat-by-beat analysis was performed on the acceleration signals to evaluate amplitude, time, and energy-based features. For each sensing location, bootstrap aggregated classification tree ensembles were trained to estimate absolute maximum LV pressure (LVPmax) and LV dP/dtmax using amplitude, time, and energy-based features. After extraction of acceleration and pressure-based features, location specific, bootstrap aggregated classification ensembles were trained to estimate absolute values of LVPmax and its maximum rate of rise (LV dP/dtmax) from acceleration data. Results: With a dataset of over 6,000 beats, the algorithm narrowed the selection of 17 predefined features to the most suitable 3 for each sensor location. Validation tests showed the minimal estimation accuracies to be 93% and 86% for LVPmax at estimation intervals of 20 and 10 mmHg, respectively. Models estimating LV dP/dtmax achieved an accuracy of minimal 93 and 87% at estimation intervals of 100 and 200 mmHg/s, respectively. Accuracies were similar for all sensor locations used. Conclusion: Under pre-clinical conditions, the developed estimation method, employing epicardial accelerometers in conjunction with machine learning, can reliably estimate absolute LV pressure and its first derivative.

Physiology of Left Ventricular Septal Pacing and Left Bundle Branch Pacing.

Following the recognition of the adverse effects of right ventricular pacing, alternative permanent pacing strategies aiming to maintain a synchronous ventricular contraction have been sought. The quest for the optimal pacing site has recently led to several promising and rapidly emerging new pacing strategies, such as left ventricular septal pacing and left bundle branch pacing. In both animal and human studies, these pacing strategies seem to maintain electrical and mechanical activation of the left ventricle to a (near)physiologic level. However, more studies on the long-term effects of both strategies are needed.

Histopathological Validation of Dark-Blood Late Gadolinium Enhancement MRI Without Additional Magnetization Preparation.

BACKGROUND: Conventional bright-blood late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) often suffers from poor scar-to-blood contrast due to the bright blood pool adjacent to the enhanced scar tissue. Recently, a dark-blood LGE method was developed which increases scar-to-blood contrast without using additional magnetization preparation. PURPOSE: We aim to histopathologically validate this dark-blood LGE method in a porcine animal model with induced myocardial infarction (MI). STUDY TYPE: Prospective. ANIMAL MODEL: Thirteen female Yorkshire pigs. FIELD STRENGTH/SEQUENCE: 1.5 T, two-dimensional phase-sensitive inversion-recovery radiofrequency-spoiled turbo field-echo. ASSESSMENT: MI was experimentally induced by transient coronary artery occlusion. At 1-week and 7-week post-infarction, in-vivo cardiac MRI was performed including conventional bright-blood and novel dark-blood LGE. Following the second MRI examination, the animals were sacrificed, and histopathology was obtained. Matching LGE slices and histopathology samples were selected based on anatomical landmarks. Independent observers, while blinded to other data, manually delineated the endocardial, epicardial, and infarct borders on either LGE images or histopathology samples. The percentage of infarcted left-ventricular myocardium was calculated for both LGE methods on a per-slice basis, and compared with histopathology as reference standard. Contrast-to-noise ratios were calculated for both LGE methods at 1-week and 7-week post-infarction. STATISTICAL TESTS: Pearson's correlation coefficient and paired-sample t-tests were used. Significance was set at P < 0.05. RESULTS: A combined total of 24 matched LGE and histopathology slices were available for histopathological validation. Dark-blood LGE demonstrated a high level of agreement compared to histopathology with no significant bias (-0.03%, P = 0.75). In contrast, bright-blood LGE showed a significant bias of -1.57% (P = 0.03) with larger 95% limits of agreement than dark-blood LGE. Image analysis demonstrated significantly higher scar-to-blood contrast for dark-blood LGE compared to bright-blood LGE, at both 1-week and 7-weeks post-infarction. DATA CONCLUSION: Dark-blood LGE without additional magnetization preparation provides superior visualization and quantification of ischemic scar compared to the current in vivo reference standard. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Left Ventricular Myocardial Septal Pacing in Close Proximity to LBB Does Not Prolong the Duration of the Left Ventricular Lateral Wall Depolarization Compared to LBB Pacing.

Background: Three different ventricular capture types are observed during left bundle branch pacing (LBBp). They are selective LBB pacing (sLBBp), non-selective LBB pacing (nsLBBp), and myocardial left septal pacing transiting from nsLBBp while decreasing the pacing output (LVSP). Study aimed to compare differences in ventricular depolarization between these captures using ultra-high-frequency electrocardiography (UHF-ECG). Methods: Using decremental pacing voltage output, we identified and studied nsLBBp, sLBBp, and LVSP in patients with bradycardia. Timing of ventricular activations in precordial leads was displayed using UHF-ECGs, and electrical dyssynchrony (e-DYS) was calculated as the difference between the first and last activation. The durations of local depolarizations (Vd) were determined as the width of the UHF-QRS complex at 50% of its amplitude. Results: In 57 consecutive patients, data were collected during nsLBBp (n = 57), LVSP (n = 34), and sLBBp (n = 23). Interventricular dyssynchrony (e-DYS) was significantly lower during LVSP -16 ms (-21; -11), than nsLBBp -24 ms (-28; -20) and sLBBp -31 ms (-36; -25). LVSP had the same V1d-V8d as nsLBBp and sLBBp except for V3d, which during LVSP was shorter than sLBBp; the mean difference -9 ms (-16; -1), p = 0.01. LVSP caused less interventricular dyssynchrony and the same or better local depolarization durations than nsLBBp and sLBBp irrespective of QRS morphology during spontaneous rhythm or paced QRS axis. Conclusions: In patients with bradycardia, LVSP in close proximity to LBB resulted in better interventricular synchrony than nsLBBp and sLBBp and did not significantly prolong depolarization of the left ventricular lateral wall.

Physiology and Practicality of Left Ventricular Septal Pacing.

Left ventricular septal pacing (LVSP) and left bundle branch pacing (LBBP) have been introduced to maintain or correct interventricular and intraventricular (dys)synchrony. LVSP is hypothesised to produce a fairly physiological sequence of activation, since in the left ventricle (LV) the working myocardium is activated first at the LV endocardium in the low septal and anterior free-wall regions. Animal studies as well as patient studies have demonstrated that LV function is maintained during LVSP at levels comparable to sinus rhythm with normal conduction. Left ventricular activation is more synchronous during LBBP than LVSP, but LBBP produces a higher level of intraventricular dyssynchrony compared to LVSP. While LVSP is fairly straightforward to perform, targeting the left bundle branch area may be more challenging. Long-term effects of LVSP and LBBP are yet to be determined. This review focuses on the physiology and practicality of LVSP and provides a guide for permanent LVSP implantation.

Left bundle branch pacing compared to left ventricular septal myocardial pacing increases interventricular dyssynchrony but accelerates left ventricular lateral wall depolarization.

BACKGROUND: Nonselective His-bundle pacing (nsHBp), nonselective left bundle branch pacing (nsLBBp), and left ventricular septal myocardial pacing (LVSP) are recognized as physiological pacing techniques. OBJECTIVE: The purpose of this study was to compare differences in ventricular depolarization between these techniques using ultra-high-frequency electrocardiography (UHF-ECG). METHODS: In patients with bradycardia, nsHBp, nsLBBp (confirmed concomitant left bundle branch [LBB] and myocardial capture), and LVSP (pacing in left ventricular [LV] septal position without proven LBB capture) were performed. Timings of ventricular activations in precordial leads were displayed using UHF-ECG, and electrical dyssynchrony (e-DYS) was calculated as the difference between the first and last activation. Duration of local depolarization (Vd) was determined as width of the UHF-QRS complex at 50% of its amplitude. RESULTS: In 68 patients, data were collected during nsLBBp (35), LVSP (96), and nsHBp (55). nsLBBp resulted in larger e-DYS than did LVSP and nsHBp [- 24 ms (-28;-19) vs -12 ms (-16;-9) vs 10 ms (7;14), respectively; P <.001]. nsLBBp produced similar values of Vd in leads V5-V8 (36-43 ms vs 38-43 ms; P = NS in all leads) but longer Vd in leads V1-V4 (47-59 ms vs 41-44 ms; P <.05) as nsHBp. LVSP caused prolonged Vd in leads V1-V8 compared to nsHBp and longer Vd in leads V5-V8 compared to nsLBBp (44-51 ms vs 36-43 ms; P <.05) regardless of R-wave peak time in lead V5 or QRS morphology in lead V1 present during LVSP. CONCLUSION: nslbbp preserves physiological LV depolarization but increases interventricular electrical dyssynchrony. LV lateral wall depolarization during LVSP is prolonged, but interventricular synchrony is preserved.

Comparing Ventricular Synchrony in Left Bundle Branch and Left Ventricular Septal Pacing in Pacemaker Patients.

BACKGROUND: Left bundle branch area pacing (LBBAP) has recently been introduced as a novel physiological pacing strategy. Within LBBAP, distinction is made between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP, no left bundle capture). OBJECTIVE: To investigate acute electrophysiological effects of LBBP and LVSP as compared to intrinsic ventricular conduction. METHODS: Fifty patients with normal cardiac function and pacemaker indication for bradycardia underwent LBBAP. Electrocardiography (ECG) characteristics were evaluated during pacing at various depths within the septum: starting at the right ventricular (RV) side of the septum: the last position with QS morphology, the first position with r' morphology, LVSP and-in patients where left bundle branch (LBB) capture was achieved-LBBP. From the ECG's QRS duration and QRS morphology in lead V1, the stimulus- left ventricular activation time left ventricular activation time (LVAT) interval were measured. After conversion of the ECG into vectorcardiogram (VCG) (Kors conversion matrix), QRS area and QRS vector in transverse plane (Azimuth) were determined. RESULTS: QRS area significantly decreased from 82 ± 29 µVs during RV septal pacing (RVSP) to 46 ± 12 µVs during LVSP. In the subgroup where LBB capture was achieved (n = 31), QRS area significantly decreased from 46 ± 17 µVs during LVSP to 38 ± 15 µVs during LBBP, while LVAT was not significantly different between LVSP and LBBP. In patients with normal ventricular activation and narrow QRS, QRS area during LBBP was not significantly different from that during intrinsic activation (37 ± 16 vs. 35 ± 19 µVs, respectively). The Azimuth significantly changed from RVSP (-46 ± 33°) to LVSP (19 ± 16°) and LBBP (-22 ± 14°). The Azimuth during both LVSP and LBBP were not significantly different from normal ventricular activation. QRS area and LVAT correlated moderately (Spearman's R = 0.58). CONCLUSIONS: ECG and VCG indices demonstrate that both LVSP and LBBP improve ventricular dyssynchrony considerably as compared to RVSP, to values close to normal ventricular activation. LBBP seems to result in a small, but significant, improvement in ventricular synchrony as compared to LVSP.

Second heart sound splitting as an indicator of interventricular mechanical dyssynchrony using a novel splitting detection algorithm.

Second heart sound (S2) splitting results from nonsimultaneous closures between aortic (A2) and pulmonic valves (P2) and may be used to detect timing differences (dyssynchrony) in relaxation between right (RV) and left ventricle (LV). However, overlap of A2 and P2 and the change in heart sound morphologies have complicated detection of the S2 splitting interval. This study introduces a novel S-transform amplitude ridge tracking (START) algorithm for estimating S2 splitting interval and investigates the relationship between S2 splitting and interventricular relaxation dyssynchrony (IRD). First, the START algorithm was validated in a simulated model of heart sound. It showed small errors (<5 ms) in estimating splitting intervals from 10 to 70 ms, with A2/P2 amplitude ratios from 0.2 to 5, and signal-to-noise ratios from 10 to 30 dB. Subsequently, the START algorithm was evaluated in a porcine model employing a wide range of paced RV-LV delays. IRD was quantified by the time difference between invasively measured LV and RV pressure downslopes. Between LV pre-excitation to RV pre-excitation, mean S2 splitting interval decreased from 47 ms to 23 ms (p < .001), accompanied by a decrease in mean IRD from 8 ms to -18 ms (p < .001). S2 splitting interval was significantly correlated with IRD in each experiment (p < .001). In conclusion, the START algorithm can accurately assess S2 splitting and may serve as a useful tool to assess interventricular dyssynchrony.

Novel bradycardia pacing strategies.

The adverse effects of ventricular dyssynchrony induced by right ventricular (RV) pacing has led to alternative pacing strategies, such as biventricular, His bundle (HBP), LV septal (LVSP) and left bundle branch pacing (LBBP). Given the overlap, LVSP and LBBP are also collectively referred to as left bundle branch area pacing (LBBAP). Although among these alternative pacing sites HBP is theoretically the ideal strategy as it maintains a physiological ventricular activation, its application requires more skills and is associated with the most complications. LBBAP, where the ventricular pacing lead is advanced through the interventricular septum to its left side, creates ventricular activation that is only slightly more dyssynchronous. Preliminary studies have shown that LBBAP is feasible, safe and encounters less limitations than HBP. Further studies are needed to differentiate between LVSP and LBBP with regard to acute functional and long-term clinical outcome.

Sequential His bundle and left ventricular pacing for cardiac resynchronization.

INTRODUCTION: Fusion of left ventricular pacing with intrinsic conduction provides superior resynchronization compared to biventricular pacing. His bundle pacing (HBP) preserves intrinsic conduction and allows for constant fusion with left ventricular pacing. This study evaluated sequential His bundle and left ventricular pacing for cardiac resynchronization therapy (CRT). METHODS: In patients referred for CRT, sequential His bundle and left ventricular pacing was performed when HBP did not correct the QRS. At implant, QRS duration and area were compared between biventricular pacing and His bundle and left ventricular pacing. Devices were programmed for His and left ventricular pacing. Functional status and echocardiography were evaluated in follow up. RESULTS: Twenty-one patients, seven female, 70.7 ± 9.9 years, 57% with nonischemic cardiomyopathy were included. Baseline QRS duration was 170 ± 21 ms and was 157 ± 16 ms with HBP. Biventricular pacing resulted in a QRS duration of 141 ± 15 ms and decreased to 110 ± 14 ms with His bundle and left ventricular pacing (p < .0005). His bundle and left ventricular pacing resulted in a smaller paced QRS area (38.5 ± 22.6 µVs) compared to biventricular pacing (67.5 ± 24.0 µVs) and baseline (78.1 ± 28.1 µVs; p < .0005). Left ventricular ejection fraction increased from 27.6 ± 6.4% to 41.1 ± 12.5 (at 25 mean months, p = .001) and functional class improved from 3.1 ± 0.5 to 2.1 ± 0.8 (at mean 32 months, p < .001). CONCLUSIONS: Sequential His bundle and left ventricular pacing results in superior electrical synchrony in patients with indication for CRT when HBP does not correct the QRS and resulted in promising clinical and echocardiographic response rates.

Short-Term Hemodynamic and Electrophysiological Effects of Cardiac Resynchronization by Left Ventricular Septal Pacing.

BACKGROUND: Cardiac resynchronization therapy (CRT) is usually performed by biventricular (BiV) pacing. Previously, feasibility of transvenous implantation of a lead at the left ventricular (LV) endocardial side of the interventricular septum, referred to as LV septal (LVs) pacing, was demonstrated. OBJECTIVES: The authors sought to compare the acute electrophysiological and hemodynamic effects of LVs with BiV and His bundle (HB) pacing in CRT patients. METHODS: Temporary LVs pacing (transaortic approach) alone or in combination with right ventricular (RV) (LVs+RV), BiV, and HB pacing was performed in 27 patients undergoing CRT implantation. Electrophysiological changes were assessed using electrocardiography (QRS duration), vectorcardiography (QRS area), and multielectrode body surface mapping (standard deviation of activation times [SDAT]). Hemodynamic changes were assessed as the first derivative of LV pressure (LVdP/dtmax). RESULTS: As compared with baseline, LVs pacing resulted in a larger reduction in QRS area (to 73 ± 22 µVs) and SDAT (to 26 ± 7 ms) than BiV (to 93 ± 26 µVs and 31 ± 7 ms; both p < 0.05) and LVs+RV pacing (to 108 ± 37 µVs; p < 0.05; and 29 ± 8 ms; p = 0.05). The increase in LVdP/dtmax was similar during LVs and BiV pacing (17 ± 10% vs. 17 ± 9%, respectively) and larger than during LVs+RV pacing (11 ± 9%; p < 0.05). There were no significant differences between basal, mid-, or apical LVs levels in LVdP/dtmax and SDAT. In a subgroup of 16 patients, changes in QRS area, SDAT, and LVdP/dtmax were comparable between LVs and HB pacing. CONCLUSIONS: LVs pacing provides short-term hemodynamic improvement and electrical resynchronization that is at least as good as during BiV and possibly HB pacing. These results indicate that LVs pacing may serve as a valuable alternative for CRT.

Evaluating multisite pacing strategies in cardiac resynchronization therapy in the preclinical setting.

BACKGROUND: Multisite pacing strategies that improve response to cardiac resynchronization therapy (CRT) have been proposed. Current available options are pacing 2 electrodes in a multipolar lead in a single vein (multipoint pacing [MPP]) and pacing using 2 leads in separate veins (multizone pacing [MZP]). OBJECTIVE: The purpose of this study was to compare in a systematic manner the acute hemodynamic response (AHR) and electrophysiological effects of MPP and MZP and compare them with conventional biventricular pacing (BiVP). METHODS: Hemodynamic and electrophysiological effects were evaluated in a porcine model of acute left bundle branch block (LBBB) (n = 8). AHR was assessed as LVdP/dtmax. Activation times were measured using >100 electrodes around the epicardium, measuring total activation time (TAT) and left ventricular activation time (LVAT). RESULTS: Compared to LBBB, BiVP, MZP, and MPP reduced TAT by 26% ± 10%, 32% ± 13%, and 32% ± 14%, respectively (P = NS between modes) and LVAT by 4% ± 5%, 11% ± 5%, and 12% ± 5%, respectively (P <.05 BiVP vs MPP and MZP). On average, BiVP increased LVdP/dtmax by 8% ± 4%, and optimal BiVP increased LVdP/dtmax by 13% ± 4%. The additional improvement in LVdP/dtmax by MZP and MPP was significant only when its increase during BiVP and decrease in TAT were poor (lower 25% of all sites in 1 subject). The increase in LVdP/dtmax was larger when large interelectrode distances (>5 cm vs <2.2 cm) were used. CONCLUSION: In this animal model of acute LBBB, MPP and MZP create similar degrees of electrical resynchronization and hemodynamic effect, which are larger if interelectrode distance is large. MPP and MZP increase the benefit of CRT only if the left ventricular lead used for BiVP provides poor response.

Agatston score of the descending aorta is independently associated with coronary events in a low-risk population.

Objectives: A standard coronary artery calcium scan includes part of the aorta. This additional information is often not included in routine analyses. We aimed to determine the feasibility of assessing the Agatston score of the descending aorta calcification (DAC) on standard coronary calcium scans and the association of this score with coronary events in a low-risk study population. Methods: Between January 2008 and March 2011, 390 consecutive patients who were referred for cardiac CT as part of work-up for pulmonary vein isolation (n=115) or assessment of presence of coronary artery disease (n=275) were included. At baseline, all patients were free of a history of cardiovascular disease. Two independent observers determined the Agatston score of the ascending aorta and descending aorta. Results: A total of 16 patients (4.1%) developed coronary events (acute coronary syndrome (n=6) and symptomatic significant coronary artery disease requiring treatment (n=10)) during a follow-up of 67±12 months, with more events in patients with calcifications in the descending aorta than in those without (8.4% vs 3.7 %; p=0.08). Multivariable Cox regression, corrected for Framingham Risk Score (FRS) and coronary Agatston score (CAC), revealed that DAC was independently associated with coronary events (per 100 units; HR: 1.06, 95% CI 1.02 to 1.09; p=0.001). DAC furthermore increased the identification of patients that will experience a coronary event (area under the curve: 0.68 for FRS only, 0.75 for FRS+CAC and 0.78 for FRS+CAC+DAC). Conclusions: The Agatston score of the descending aorta could be included in the standard analysis of cardiac CT scans of low-risk patients since it holds valuable information for the prediction of coronary events.

Vitamin K Antagonists, Non-Vitamin K Antagonist Oral Anticoagulants, and Vascular Calcification in Patients with Atrial Fibrillation.

Background Vitamin K antagonists (VKAs) are associated with coronary artery calcification in low-risk populations, but their effect on calcification of large arteries remains uncertain. The effect of non-vitamin K antagonist oral anticoagulants (NOACs) on vascular calcification is unknown. We investigated the influence of use of VKA and NOAC on calcification of the aorta and aortic valve. Methods In patients with atrial fibrillation without a history of major adverse cardiac or cerebrovascular events who underwent computed tomographic angiography, the presence of ascending aorta calcification (AsAC), descending aorta calcification (DAC), and aortic valve calcification (AVC) was determined. Confounders for VKA/NOAC treatment were identified and propensity score adjusted logistic regression explored the association between treatment and calcification (Agatston score > 0). AsAC, DAC, and AVC differences were assessed in propensity score-matched groups. Results Of 236 patients (33% female, age: 58 ± 9 years), 71 (30%) used VKA (median duration: 122 weeks) and 79 (34%) used NOAC (median duration: 16 weeks). Propensity score-adjusted logistic regression revealed that use of VKA was significantly associated with AsAC (odds ratio [OR]: 2.31; 95% confidence interval [CI]: 1.16-4.59; p = 0.017) and DAC (OR: 2.38; 95% CI: 1.22-4.67; p = 0.012) and a trend in AVC (OR: 1.92; 95% CI: 0.98-3.80; p = 0.059) compared with non-anticoagulation. This association was absent in NOAC versus non-anticoagulant (AsAC OR: 0.51; 95% CI: 0.21-1.21; p = 0.127; DAC OR: 0.80; 95% CI: 0.36-1.76; p = 0.577; AVC OR: 0.62; 95% CI: 0.27-1.40; p = 0.248). A total of 178 patients were propensity score matched in three pairwise comparisons. Again, use of VKA was associated with DAC ( p = 0.043) and a trend toward more AsAC ( p = 0.059), while use of NOAC was not (AsAC p = 0.264; DAC p = 0.154; AVC p = 0.280). Conclusion This cross-sectional study shows that use of VKA seems to contribute to vascular calcification. The calcification effect was not observed in NOAC users.