Diagnostic Performance of Perfusion-Only SPECT/CT for Chronic Thromboembolic Pulmonary Hypertension in Comparison With Ventilation-Perfusion Planar, SPECT, and SPECT/CT Imaging.

PURPOSE: The aim of this study was to assess the diagnostic performance of perfusion-only SPECT/CT (Q SPECT/CT) in comparison with that of ventilation/perfusion planar scintigraphy (V/Q planar), perfusion SPECT with ventilation scan (V/Q SPECT), and perfusion SPECT/CT with ventilation scan (V/Q SPECT/CT) in chronic thromboembolic pulmonary hypertension (CTEPH). PATIENTS AND METHODS: Patients with pulmonary hypertension who underwent ventilation-perfusion planar and SPECT/CT were retrospectively recruited. Two nuclear medicine physicians interpreted V/Q planar, V/Q SPECT, V/Q SPECT/CT, and Q SPECT/CT according to the European Association of Nuclear Medicine criteria. The diagnostic accuracy of these modalities for CTEPH was compared using a composite reference standard of pulmonary angiography, imaging test, cardiorespiratory assessment, and follow-up. RESULTS: A total of 192 patients were enrolled, including 85 with CTEPH. The sensitivity of Q SPECT/CT was 98.8%, which similar to that of V/Q planar (97.6%), V/Q SPECT (96.5%), or V/Q SPECT/CT (100.0%). In contrast, Q SPECT/CT exhibited significantly lower specificity (73.8%) compared with V/Q planar (86.9%, P = 0.001), V/Q SPECT (87.9%, P < 0.001), and V/Q SPECT/CT (88.8%, P < 0.001). The significantly lower specificity of Q SPECT/CT, compared with the 3 others, was observed in the subgroup aged ≥50 years ( P < 0.001 for all), but not in those <50 years. CONCLUSIONS: Q SPECT/CT exhibited lower specificity compared with V/Q planar, V/Q SPECT, and V/Q SPECT/CT in diagnosing CTEPH. It might underscore the essential role of a ventilation scan in patients with PH, even with the introduction of SPECT/CT.

Comparisons of an automated oscillometric device with a hybrid manual auscultatory device for the Korea National Health and Nutrition Examination Survey.

This study evaluated an oscillometric device (OD), Microlife WatchBP Office AFIB, and a hybrid manual auscultatory device (AD), Greenlight 300TM, to determine a suitable blood pressure (BP) measurement device for the Korea National Health and Nutrition Examination Survey in a mercury-free context. Adhering to the 2018 Universal Standard's suggested consensus, the study involved 800 subjects (mean age 51.2 ± 17.5 years; 44.3% male), who underwent triplicate BP measurements following 5 min of rest in a randomized order (OD-first: 398 participants; AD-first: 402 participants). BP difference was calculated as OD value minus AD value, with results stratified by measurement sequence. The overall BP difference and tolerable error probability were -1.1 ± 6.5/-2.6 ± 4.9 mmHg and 89.2%/92.5% for systolic/diastolic BP (SBP/DBP), respectively. Lin's concordance correlation coefficient was 0.907/0.844 for SBP/DBP (OD-first/AD-first: 0.925/0.892 for SBP, 0.842/0.845 for DBP). The overall agreement for hypertension (BP ≥ 140 and/or 90 mmHg) was 0.71 (p < 0.0001), and the OD underestimated the overall hypertension prevalence by 5.1%. Analysis of the AD-first data revealed a lower level of agreement compared to the OD-first data; however, the observed blood pressure difference adhered to Criterion 1 of the 2018 Universal Standard. Microlife met the Criterion 1 of 2018 Universal Standard but underestimated the prevalence of hypertension. The BP discrepancy increased with higher BP levels, male sex, and smaller AC. With increasing age, the discrepancy decreased for SBP and increased for DBP.

Incidence and predictors of left atrial thrombus in patients with atrial fibrillation under anticoagulation therapy.

BACKGROUND: Left atrial thrombus (LAT) formation is associated with thromboembolic events. OBJECTIVE: To investigate the incidence and associated factors of LAT in patients with atrial fibrillation (AF) who had been receiving anticoagulation therapy for more than 4 weeks, and to develop a prediction model using clinical and echocardiographic features. METHODS: Medical records of 1,122 patients with AF (mean age, 59.4 ± 11.0 years, 58.3% male) who were on anticoagulation more than 4 weeks and underwent transesophageal echocardiography (TEE) were evaluated. The main outcome was the presence of LAT on TEE. RESULTS: Warfarin and non-vitamin K oral anticoagulants were used in 74.4% and 25.6% of the patients at the time of examination, respectively. LAT was present in 60 patients (5.3%). Presence of LAT on TEE was associated with age ≥ 75 years (odds ratio [OR] 2.13 [95% confidence interval, 0.94-4.58]), persistent/permanent AF (OR 2.61 [1.42-4.93]), CHA2DS2-VASc score ≥ 3 points (OR 1.91 [1.05-3.48]), left ventricular ejection fraction < 40% (OR 2.35 [1.07-4.81]), and severe left atrial enlargement (OR 3.52 [1.89-6.79]). The presence of moderate-to-severe mitral regurgitation was associated with a lower risk of LAT (OR 0.13 [0.04-0.34]). A scoring system composed of the aforementioned predictors showed excellent discrimination performance (area under the curve 0.791 [95% CI, 0.727-0.854]). CONCLUSIONS: LAT was present in a considerable number of patients who were already receiving anticoagulation therapy. A prediction model that combines clinical and echocardiographic predictors could be useful in distinguishing patients who require imaging evaluations before left atrial intervention.

Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Significant Tricuspid Regurgitation.

BACKGROUND: There are limited data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation with significant tricuspid regurgitation (TR), which can lead to hepatic dysfunction and intestinal malabsorption. We aimed to compare the efficacy and safety of DOACs and warfarin for patients with atrial fibrillation with significant (moderate to severe) TR. METHODS AND RESULTS: A total of 1215 patients with significant TR and atrial fibrillation who were treated with warfarin (N=491) or DOACs (N=724) were retrospectively analyzed. The primary outcomes were ischemic stroke, systemic embolic events, and hospitalization for major bleeding. The secondary outcomes were intracranial hemorrhage, hospitalization for gastrointestinal bleeding, all-cause mortality, and a composite outcome. The median follow-up duration was 2.4 years. In the inverse probability treatment weighting-adjusted cohort, DOACs and warfarin had a similar risk for ischemic stroke and systemic embolic events (adjusted hazard ratio [aHR], 0.95 [95% CI, 0.67-1.36]; P=0.79) and major bleeding (aHR, 0.78 [95% CI, 0.57-1.06]; P=0.11). For the secondary outcomes, relative to warfarin, DOACs had a lower risk of intracranial hemorrhage and the composite outcome, and a comparable risk for gastrointestinal bleeding and all-cause mortality. In the subgroup analysis, the effects of DOACs on ischemic stroke and systemic embolic events were comparable to the effects of warfarin, even in patients with inferior vena cava plethora (increased right atrial pressure) or severe TR. CONCLUSIONS: In this study, relative to warfarin, DOACs demonstrated comparable efficacy for ischemic stroke and systemic embolic events and major bleeding, with a lower intracranial hemorrhage risk in patients with significant TR and atrial fibrillation, indicating their effectiveness and safety.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Prognostic impact of the E/e' ratio in patients with chronic severe aortic regurgitation undergoing aortic valve replacement.

OBJECTIVES: The study objective was to evaluate the clinical implication of left ventricular diastolic dysfunction in patients with chronic severe aortic regurgitation undergoing aortic valve replacement. METHODS: We reviewed the medical records of 323 patients (age, 56.3 ± 14.1 years; 111 female) who underwent aortic valve replacement for chronic severe aortic regurgitation between 2005 and 2019. Left ventricular diastolic dysfunction was assessed by the ratio of peak left ventricular inflow velocity over mitral annular velocity (E/e'). The study end point was the composite of death and heart failure requiring hospital admission. RESULTS: The E/e' ratio was significantly correlated with age, left atrial dimension, left ventricular end-diastolic volume, mitral regurgitation grade, and tricuspid regurgitation grade (all P < .001). During follow-up (1748.3 patient-years), death and heart failure occurred in 36 patients (2.06/patient-year) and 9 patients (0.53/patient-year), respectively. In multivariable analysis, E/e' ratio (per 5 increment, hazard ratio, 1.32; 95% confidence interval, 1.02-1.71; P = .03), age (hazard ratio, 1.06; 95% confidence interval, 1.03-1.10; P < .001), and left ventricular ejection fraction (hazard ratio, 0.94; 95% confidence interval, 0.90-0.98; P = .002) were independent predictors of death and heart failure. The 5-year heart failure-free survival was 94.9% ± 1.7% in patients with E/e' less than 15% and 84.2% ± 4.2% in patients with E/e' 15 or greater (P < .001). CONCLUSIONS: The E/e' ratio was significantly associated with adverse outcomes in patients with chronic severe aortic regurgitation undergoing aortic valve replacement and may be useful as a prognostic marker in such patients.

Verification of a nationwide population-based myopia growth chart in a large longitudinal cohort of 1155 Korean children.

OBJECTIVE: To evaluate predictive value of the myopia growth chart based on population-based health survey data using longitudinal cohorts. METHODS: Patients aged from 5 to 18 years and underwent two or more cycloplegic refraction (CR) exams with at least one year of interval were included. Percentile deviation was calculated by subtracting percentile at final exam from the percentile at initial exam based on the chart. Spherical equivalent (SE) deviation was calculated by SE at final CR subtracted from predicted SE based on initial CR using the chart. RESULTS: 2310 eyes from 1155 subjects were included. There were 1344 eyes (58.2%) categorized as inliers, where both initial and final CR were within the 2nd to 99th percentile. Mean percentile and SE deviations were + 11.0 ± 22.9 percentiles and -0.60 ± 1.33 diopters, each. Outliers, those except the inliers, were 966 eyes (41.8%). Most outliers (709 eyes, 73.4%) were outside the chart for both initial and final exam. The rest of the outliers (257 eyes, 26.2%) were within the 2 to 99 percentile range on the chart at least once, either at initial or final exams; most of those (202 eyes, 78.6%) progressed toward myopia more than predicted. CONCLUSIONS: In our large cohorts, both inliers and outliers tended to progress toward more myopia than predicted from the chart. This suggests the chart predicts childhood myopia rather conservatively. The myopia growth chart may be useful as a screening tool in detecting children at high risk of developing high myopia.

Frequency, Predictors, and Clinical Impact of Valvular and Perivalvular Thrombus After Transcatheter Aortic Valve Replacement.

BACKGROUND: Subclinical aortic valve complex (valvular and perivalvular) thrombus is not rare after transcatheter aortic valve replacement (TAVR). The risk factors and clinical implications of these findings remain uncertain. OBJECTIVES: This study sought to evaluate the frequency, predictors, and clinical outcome of aortic valve complex thrombus after TAVR. METHODS: In the ADAPT-TAVR (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement) trial comparing edoxaban vs dual antiplatelet therapy in TAVR patients without an indication for chronic anticoagulation, the frequency of valvular (subclinical leaflet thrombus) and perivalvular (supravalvular, subvalvular, and sinus of Valsalva) thrombus was evaluated by 4-dimensional computed tomography at 6 months. The association of these phenomena with new cerebral thromboembolism on brain magnetic resonance imaging, neurologic and neurocognitive dysfunction, and clinical outcomes was assessed. RESULTS: Among 211 patients with 6-month computed tomography evaluations, 91 patients (43.1%) had thrombus at any aortic valve complex, 30 (14.2%) patients had leaflet thrombus, and 78 (37.0%) patients had perivalvular thrombus. A small maximum diameter of the stent at the valve level and low body surface area were independent predictors of aortic valve complex and perivalvular thrombus, and decreased renal function was an independent predictor of leaflet thrombus. No significant differences were observed in new cerebral lesions, neurologic or neurocognitive functions, or clinical outcomes among patients with or without valvular or perivalvular thrombus. CONCLUSIONS: Subclinical aortic valve complex (valvular and perivalvular) thrombus was common in patients who had undergone successful TAVR. However, these imaging phenomena were not associated with new cerebral thromboembolism, neurologic or neurocognitive dysfunction, or adverse clinical outcomes. (Anticoagulation Versus Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement [ADAPT-TAVR]; NCT03284827).

Bovine pericardial versus porcine bioprosthetic aortic valves: A nationwide population-based cohort study in Korea.

OBJECTIVE: To compare the clinical outcomes of aortic valve replacement (AVR) using bovine pericardial and porcine bioprostheses, utilizing a nationwide administrative claims database. METHODS: Adult patients (age ≥40 years) who underwent bioprosthetic AVR, without other valve replacements, between 2003 and 2018 were identified from the Korean National Health Insurance Service database. The outcomes of interest were all-cause mortality, cardiac mortality, and valve-related events, including the incidence of reoperation, endocarditis, systemic thromboembolism, and major bleeding. Baseline adjustment was performed using propensity score matching. Time-related outcomes were evaluated using a competing risk analysis, with death as a competing risk. RESULTS: Among the 7714 patients who underwent bioprosthetic AVR, 5621 (72.9%) received bovine pericardial prostheses and 2093 (27.1%) received porcine bioprostheses. After matching, 1937 pairs were included in the final analysis. During follow-up (median, 4.49 years; interquartile range, 2.83-8.20 years), the use of porcine bioprostheses was associated with a higher risk of aortic valve reoperation (adjusted hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.16 to 3.01); however, no significant differences were observed in cumulative incidences of all-cause mortality, cardiac mortality, thromboembolism, or major bleeding. Subgroup analyses revealed that the use of bovine valves was associated with improved survival in patients with diabetes mellitus, whereas in patients undergoing dialysis, porcine valves exhibited better survival than bovine valves. CONCLUSIONS: In this large nationwide cohort study of patients undergoing bioprosthetic aortic valve replacement, the use of porcine prostheses was significantly associated with an increased risk of reoperation compared with the use of bovine prostheses, supporting previous findings.

Standardized protocol of blood pressure measurement and quality control program for the Korea National Health and Nutrition Examination Survey.

Accurate blood pressure (BP) measurement is crucial for hypertension detection and management. The Korea National Health and Nutrition Examination Survey (KNHANES) assesses the health of Koreans using representative cross-sectional data. BP measurements were historically done with mercury sphygmomanometers for participants aged ≥10 years. However, KNHANES transitioned to Greenlight 300TM (mercury-free auscultatory device) in 2020 for participants aged ≥6 years and used dual devices (Microlife WatchBP Office AFIB and Greenlight) in 2021-2022. To ensure consistency, KNHANES will adopt Microlife as the unified BP device with Greenlight for device validation from 2023. Under the new protocol, participants aged ≥6 years will have their BP measured three times at 30-second intervals after a 5-minute rest under ambient temperature (20-25℃) and noise ≤65 dB. The average of the 2nd and 3rd readings will be used as the representative BP value. The quality control (QC) program involves four trained examiners passing the "quality control and assurance of BP measurement program" three times annually, and undergoing "video monitoring of weekly calibration process" once a year. Additionally, the QC team will conduct "on-site evaluations of BP measurement" at mobile examination centers three times a year. A Five-Step QC process for BP devices was also developed. This document outlines the standardized BP measurement protocol and rigorous QC program in KNHANES, aiming to ensure accurate and reliable BP data for epidemiological research and public health policymaking in South Korea.

Patterns of genetic mutations explored by systematic screening of patients with aortopathy and their family members.

Objective: Genetic aortopathy, if left untreated, leads to aortic catastrophe in most affected individuals. We sought to determine the genetic mutation patterns and detection rates in patients with aortopathy and their families with a systematic screening protocol. Methods: In 2016 to 2020, patients with aortic dissection or root aneurysm (Z score ≥2) and their first-degree relatives were enrolled in a prospective registry at a tertiary referral center. The individuals underwent systematic single- or multi-gene panel testing depending on clinical presentations. Results: Among 575 enrolled individuals (mean age, 46.6 ± 14.5 years; 203 women), 346 (60.2%) underwent genetic testing. Rates of relevant gene mutations identified were 39.4% (91/231), 27.1% (54/199) and 72.4% (n = 105) in aneurysm, dissection, and family screening groups, respectively (P < .001). Mutated genes frequently identified were FBN1 (n = 199; Marfan), TGFBR1/2 or SMAD3 (n = 14; Loeys-Dietz), COL3A1/COL5A2 (n = 15; Ehlers-Danlos), and ACTA2 (n = 10). After enrollment, 123 aortic surgeries were performed in 117 patients (20.3%) including 15 family members, with resultant operative mortality of 0.8% (n = 1). In logistic regression analysis, systemic score in Ghent nosology was the only significant factor associated with positive gene mutation (odds ratio, 14.81; 95% confidence interval, 6.87-31.96), and its 3.5 point cutoff showed the best predictive value with 78.2% sensitivity and 87.2% specificity. Conclusions: Genetic aortopathy was identified in a considerable proportion of patients with aortopathy and their family members by systematic genetic testing. This strategy is recommended for timely diagnosis and proactive management of genetic aortopathy.

Statement on chronotherapy for the treatment of hypertension: consensus document from the Korean society of hypertension.

Nocturnal blood pressure (BP) has been shown to have a significant predictive value for cardiovascular disease. In some cases, it has a superior predictive value for future cardiovascular outcomes than daytime BP. As efficacy of BP medications wanes during nighttime and early morning, control of nocturnal hypertension and morning hypertension can be difficult. As such, chronotherapy, the dosing of BP medication in the evening, has been an ongoing topic of interest in the field of hypertension. Some studies have shown that chronotherapy is effective in reducing nocturnal BP, improving non dipping and rising patterns to dipping patterns, and improving cardiovascular prognosis. However, criticism and concerns have been raised regarding the design of these studies, such as the Hygia study, and the implausible clinical benefits in cardiovascular outcomes considering the degree of BP lowering from bedtime dosing. Studies have shown that there is no consistent evidence to suggest that routine administration of antihypertensive medications at bedtime can improve nocturnal BP and early morning BP control. However, in some cases of uncontrolled nocturnal hypertension and morning hypertension, such as in those with diabetes mellitus, chronic kidney disease, and obstructive sleep apnea, bedtime dosing has shown efficacy in reducing evening and early morning BP. The recently published the Treatment in Morning versus Evening (TIME) study failed to demonstrate benefit of bedtime dosing in reducing cardiovascular outcomes in patients with hypertension. With issues of the Hygia study and negative results from the TIME study, it is unclear at this time whether routine bedtime dosing is beneficial for reducing cardiovascular outcomes.

Impact of leaflet thrombosis on valve haemodynamic status after transcatheter aortic valve replacement.

OBJECTIVES: The effect of subclinical leaflet thrombosis, characterised by hypoattenuated leaflet thickening (HALT), on the valve haemodynamic function and durability of the bioprosthetic valve, is not yet determined. We determined the impact of HALT on valve haemodynamics after transcatheter aortic valve replacement (TAVR) and the predictors of haemodynamic structural valve deterioration (SVD). METHODS: The Anticoagulation vs Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization after Transcatheter Aortic Valve Replacement(ADAPT-TAVR) trial is a multicenter, randomised trial that compared edoxaban and dual antiplatelet therapy in patients who had undergone successful TAVR. The presence of HALT was evaluated by four-dimensional CT at 6 months and serial echocardiography performed at baseline, immediately post-TAVR and after 6 months. SVD was defined as at least one of the following: (1) mean transprosthetic gradient ≥20 mm Hg, (2) change in the mean gradient ≥10 mm Hg from baseline, or (3) new or increase in intraprosthetic aortic regurgitation of at least ≥1 grade, resulting in moderate or greater regurgitation. RESULTS: At 6 months, HALT was found in 30 of 211 (14.2%) patients. The presence of HALT did not significantly affect aortic valve mean gradients (with vs without HALT; 14.0±4.8 mm Hg vs 13.7±5.5 mm Hg; p=0.74) at 6 months. SVD was reported in 30 of 206 patients (14.6%) at 6-month follow-up echocardiography. Older age (OR: 1.138; 95% CI: 1.019 to 1.293; p=0.033), use of aortic valve size ≤23 mm (OR: 6.254; 95% CI: 2.230 to 20.569; p=0.001) and mean post-TAVR pressure gradient (OR: 1.233; 95% CI: 1.123 to 1.371; p<0.001) were independent predictors of haemodynamic SVD; however, the presence of HALT was not identified as a predictor of SVD. CONCLUSIONS: In patients who had undergone successful TAVR, aortic valve haemodynamic status was not influenced by the presence of HALT. Although HALT was not a predictor of haemodynamic SVD at 6 months, it warrants further longer-term follow-up to evaluate the effect on long-term valve durability. TRIAL REGISTRATION NUMBER: NCT03284827 (https://www. CLINICALTRIALS: gov).

Impact of routine brain imaging on the prognosis of patients with left-sided valve infective endocarditis without neurological manifestations.

BACKGROUND: There are limited data on the impact of routine use of brain magnetic resonance imaging (MRI) on the prognosis of neurologically asymptomatic patients with left-sided infective endocarditis (IE). METHODS: Among patients diagnosed with possible or definite IE in two tertiary referral centers between January 2005 and March 2019, we identified 527 left-sided IE patients without neurological symptoms or signs at the time of diagnosis. Patients who underwent brain MRI within 1 week after the IE diagnosis were classified as the routine brain imaging group (n = 216), and the rest were categorized as the control group (n = 311). All-cause mortality at 3 months, attributable mortality (defined as death directly related to IE), and fatal neurological events compared after adjustment using inverse probability of treatment weighting (IPTW). RESULTS: During a median follow-up of 57 months, the routine brain imaging group had a similar risk of 3-month all-cause mortality to the control group in the multivariate analysis (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.14) and IPTW-adjusted cohort (HR, 0.59; 95% CI, 0.25-1.42). The risks of attributable mortality and fatal neurological events were also similar between the two groups in the multivariable analysis and IPTW-adjusted cohort. In the subgroup analysis, the routine brain imaging group showed more favorable outcomes in cases of large vegetation (> 10 mm) or acute-onset microorganisms. CONCLUSIONS: Routine use of brain MRI in left-sided IE patients without neurological manifestations is not associated with improved clinical outcomes. However, routine brain imaging in appropriate clinical settings could improve clinical outcomes.

Effect of Edoxaban Versus Antiplatelet Therapy on Leaflet Thrombosis and Cerebral Thromboembolism After TAVI According to Major Clinical and Anatomic Factors in Prespecified Subgroup Analysis from the ADAPT-TAVR Trial.

It is unknown whether edoxaban versus dual antiplatelet therapy (DAPT) has differential treatment effects on leaflet thrombosis, cerebral thromboembolism, and neurologic or neurocognitive dysfunction according to clinical and anatomic factors after transcatheter aortic valve implantation. To investigate the relative effects of edoxaban and DAPT on leaflet and cerebral thromboembolism in patients with major risk factors. The primary end point of this study was the incidence of leaflet thrombosis on computed tomography at 6 months. The secondary end points were new cerebral lesions on brain magnetic resonance imaging and neurologic and neurocognitive dysfunction between baseline and 6-month follow-up. Cox regression models assessed the consistency of the treatment effects in the prespecified subgroups. The favorable effect of edoxaban versus DAPT on the leaflet thrombosis was consistent across multiple clinical or anatomic subgroups, without significant interaction between the drug effect and each subgroup (p for interaction for age = 0.597, gender = 0.557, body mass index = 0.866, Society of Thoracic Surgeons score = 0.307, valve type = 0.702, edoxaban reduction criteria = 0.604, and valve morphology = 0.688). However, the incidence of new cerebral lesions on brain magnetic resonance imaging and worsening of neurologic and neurocognitive function were not significantly different between the groups among the various key subgroups. The relative effects of edoxaban and DAPT on the risk of leaflet thrombosis, cerebral thromboembolism, and neurologic dysfunction were consistent across a diverse spectrum of clinical or anatomical factors. Further studies are required to define tailored antithrombotic therapy for high-risk groups with specific clinical or anatomic characteristics.

Impact of new-onset arrhythmia on cardiac reverse remodeling following transcatheter aortic valve replacement: computed tomography-derived left ventricular and atrial strains.

OBJECTIVE: Patients who undergo transcatheter aortic valve replacement (TAVR) are at risk for new-onset arrhythmia (NOA) that may require permanent pacemaker (PPM) implantation, resulting in decreased cardiac function. We aimed to investigate the factors that are associated with NOA after TAVR and to compare pre- and post-TAVR cardiac functions between patients with and without NOA using CT-derived strain analyses. METHODS: We included consecutive patients who underwent pre- and post-TAVR cardiac CT scans six months after TAVR. New-onset left bundle branch block, atrioventricular block, and atrial fibrillation/flutter lasting over 30 days after the procedure and/or the need for PPM diagnosed within 1 year after TAVR were regarded as NOA. Implant depth and left heart function and strains were analyzed using multi-phase CT images and compared between patients with and without NOA. RESULTS: Of 211 patients (41.7% men; median 81 years), 52 (24.6%) presented with NOA after TAVR, and 24 (11.4%) implanted PPM. Implant depth was significantly deeper in the NOA group than in the non-NOA group (- 6.7 ± 2.4 vs. - 5.6 ± 2.6 mm; p = 0.009). Left ventricular global longitudinal strain (LV GLS) and left atrial (LA) reservoir strain were significantly improved only in the non-NOA group (LV GLS, - 15.5 ± 4.0 to - 17.3 ± 2.9%; p < 0.001; LA reservoir strain, 22.3 ± 8.9 to 26.5 ± 7.6%; p < 0.001). The mean percent change of the LV GLS and LA reservoir strains was evident in the non-NOA group (p = 0.019 and p = 0.035, respectively). CONCLUSIONS: A quarter of patients presented with NOA after TAVR. Deep implant depth on post-TAVR CT scans was associated with NOA. Patients with NOA after TAVR had impaired LV reserve remodeling assessed by CT-derived strains. CLINICAL RELEVANCE STATEMENT: New-onset arrhythmia (NOA) following transcatheter aortic valve replacement (TAVR) impairs cardiac reverse remodeling. CT-derived strain analysis reveals that patients with NOA do not show improvement in left heart function and strains, highlighting the importance of managing NOA for optimal outcomes. KEY POINTS: • New-onset arrhythmia following transcatheter aortic valve replacement (TAVR) is a concern that interferes with cardiac reverse remodeling. • Comparison of pre-and post-TAVR CT-derived left heart strain provides insight into the impaired cardiac reverse remodeling in patients with new-onset arrhythmia following TAVR. • The expected reverse remodeling was not observed in patients with new-onset arrhythmia following TAVR, given that CT-derived left heart function and strains did not improve.

Association of citrullination with the progression of aortic stenosis.

Despite its clinical importance, biomarkers of disease activity in aortic stenosis (AS) are lacking. We investigated the association between anti-cyclic citrullinated peptide (CCP) antibodies and AS. All 678 patients who underwent echocardiography and anti-CCP antibody testing were analysed. Anti-CCP antibody status was categorized as negative, low-positive, and high-positive. In addition, aortic valve (AV) tissues were obtained from the patients with and without AS to analyze the presence of citrullinated proteins. At baseline, 241 (35.5%) subjects with AV degeneration had a higher rate of anti-CCP antibody positivity (42.7% versus 34.6%, p = 0.035) than those without AV degeneration. Out of the 331 (48.8%) subjects who underwent echocardiographic follow-up, progression of AS was observed in 34 (10.3%) patients, with a higher incidence in the high-positive group compared to the low-positive or negative group (19.0% vs. 11.3% vs. 8.4%, respectively; p = 0.041). On multivariable analysis, high anti-CCP antibody positivity was independently associated with progression to AS (odds ratio: 2.312; 95% confidence interval: 1.006-5.310; p = 0.048). Furthermore, immunohistochemistry and Western blotting revealed increased citrullination in diseased AV compared to normal AV tissue. This study demonstrated that a high positive anti-CCP antibody result is associated with AV degeneration and may be an independent factor for AS progression.

Clinical outcomes after aortic valve replacement with severe stenosis of trileaflet aortic valve and low valve calcium score.

BACKGROUND: Some patients have severe aortic valve stenosis (AS) despite a lower degree of aortic valve calcification (AVC). This study compared the clinical features and prognosis of patients undergoing aortic valve replacement (AVR) for severe AS with a low AVC score compared with those with higher AVC scores. METHODS: This study included 1002 Korean patients with symptomatic severe degenerative AS who underwent AVR. We measured AVC score before AVR and defined low AVC as AVC score of <2000 units for male patients and <1300 units for female patients. Patients with bicuspid or rheumatic aortic valve disease were excluded. RESULTS: The mean age was 75.6±7.9 years and 487 patients (48.6%) were female. Mean left ventricular ejection fraction was 59.4%±10.4%, and concomitant coronary revascularisation was performed in 96 patients (9.6%). The median aortic valve calcium score was 3122 units (IQR 2249-4289 units) among male patients and 1756 units (IQR 1192-2572) among female patients. A total of 242 patients (24.2%) had low AVC; they were significantly younger (73.5±8.7 years vs 76.3±7.5 years, p<0.001) and were more likely to be female (59.5% vs 45.1%, p<0.001) and on haemodialysis (5.4% vs 1.8%, p=0.006) than those with high AVC. During a follow-up (median: 3.8 years), the patients with low AVC had significantly higher risk of death from any cause (adjusted HR 1.60, 95% CI 1.02 to 2.52, p=0.04), mostly non-cardiac cause. CONCLUSIONS: Patients with low AVC exhibit distinct clinical characteristics and a higher risk of long-term mortality compared with those with high AVC.

Effect of race on pressure recovery adjustment for prevention of aortic stenosis grading discordance.

OBJECTIVE: We sought to evaluate the potential impact of racial difference (Asians vs Caucasians) on the clinical usefulness of pressure recovery (PR) adjustment for preventing discordant aortic stenosis (AS) grading in patients with severe AS. METHODS: Data from 1450 patients (mean age, 70.2±10.6 years; 290 (20%) Caucasians; aortic valve area (AVA), 0.77±0.26 cm2) were retrospectively analysed. PR-adjusted AVA was calculated using a validated equation. Discordant grading of severe AS was defined as AVA of <1.0 cm2 and mean gradient of <40 mm Hg. The frequency of discordant grading was assessed in the overall cohort and the propensity score-matched cohort. RESULTS: Before PR adjustment, 1186 patients showed AVA values of <1.0 cm2; after PR adjustment, 170 (14.3%) were reclassified as having moderate AS. PR adjustment decreased the frequency of discordant grading from 31.4% to 14.1% in Caucasians and from 13.8% to 7.9% in Asians. Patients with reclassification to moderate AS after PR adjustment had a significantly lower risk of a composite of aortic valve replacement or all-cause death than did those with severe AS after PR adjustment (HR 0.38; 95% CI 0.31-0.46; p<0.001). In propensity score-matched cohorts (173 pairs), the frequency of discordant grading before PR adjustment was 42.2% and 43.9% in the Caucasian and Asian patients, respectively, which decreased to 21.4% and 20.2%, respectively, after PR adjustment. CONCLUSIONS: Clinically relevant PR occurred, regardless of race in patients with moderate to severe AS. Routine PR adjustment may be useful for reconciling discordant AS grading.