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

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:

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 first heart sound (VS1) and from first to second heart sounds (S1S2). OBJECTIVE: 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 CRT implantation, PCG was measured 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 of left ventricular pressure (LV dP/dtmax) and stroke work. RESULTS: In the pigs, VS1 and S1S2 predicted the AV delays with optimal hemodynamics (highest LVP, LV dP/dtmax and stroke work) by a median error of 2 - 28 ms, resulting in a median loss of < 2% of pump function. In the patients, VS1 and S1S2 predicted the optimal AV delay by errors of 32.5 ms and 37.5 ms, respectively, resulting in 0.2% - 0.9% lower LVP and stroke work, which were reduced to 21 ms and 24 ms in the 8 patients with a full-capture AV delay longer than 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 in pump function compared with those based on invasive hemodynamic measurements

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

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 (P5NS between modes) and LVAT by 4% +/- 5%, 11% +/- 5%, and 12% +/- 5%, respectively (P &lt;.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 (&gt; 5 cm vs &lt; 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