Comprehensive Myocardial Assessment by Computed Tomography: Impact on Short-Term Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: Quantification of myocardial changes in severe aortic stenosis (AS) is prognostically important. The potential for comprehensive myocardial assessment pre-transcatheter aortic valve replacement (TAVR) by computed tomography angiography (CTA) is unknown. OBJECTIVES: This study sought to evaluate whether quantification of left ventricular (LV) extracellular volume-a marker of myocardial fibrosis-and global longitudinal strain-a marker of myocardial deformation-at baseline CTA associate with post-TAVR outcomes. METHODS: Consecutive patients with symptomatic severe AS between January 2021 and June 2022 who underwent pre-TAVR CTA were included. Computed tomography extracellular volume (CT-ECV) was derived from septum tracing after generating the 3-dimensional CT-ECV map. Computed tomography global longitudinal strain (CT-GLS) used semi-automated feature tracking analysis. The clinical endpoint was the composite outcome of all-cause mortality and heart failure hospitalization. RESULTS: Among the 300 patients (80.0 ± 9.4 years of age, 45% female, median Society of Thoracic Surgeons Predicted Risk of Mortality score 2.80%), the left ventricular ejection fraction (LVEF) was 58% ± 12%, the median CT-ECV was 28.5% (IQR: 26.2%-32.1%), and the median CT-GLS was -20.1% (IQR: -23.8% to -16.3%). Over a median follow-up of 16 months (IQR: 12-22 months), 38 deaths and 70 composite outcomes occurred. Multivariable Cox proportional hazards model, accounting for clinical and echocardiographic variables, demonstrated that CT-ECV (HR: 1.09 [95% CI: 1.02-1.16]; P = 0.008) and CT-GLS (HR: 1.07 [95% CI: 1.01-1.13]; P = 0.017) associated with the composite outcome. In combination, elevated CT-ECV and CT-GLS (above median for each) showed a stronger association with the outcome (HR: 7.14 [95% CI: 2.63-19.36]; P < 0.001). CONCLUSIONS: Comprehensive myocardial quantification of CT-ECV and CT-GLS associated with post-TAVR outcomes in a contemporary low-risk cohort with mostly preserved LVEF. Whether these imaging biomarkers can be potentially used for the decision making including timing of AS intervention and post-TAVR follow-up will require integration into future clinical trials.

Feasibility of Redo-Transcatheter Aortic Valve Replacement in Sapien Valves Based on In Vivo Computed Tomography Assessment.

BACKGROUND: Our aim was to assess the feasibility of repeat transcatheter aortic valve (TAV) replacement for degenerated Sapien3 (S3) prostheses by simulating subsequent implantation of S3 or Evolut, using in vivo computed tomography-based sizing and the impact on coronary and patient-prosthesis mismatch risks. METHODS: Computed tomography scans from 356 patients with prior S3 TAV replacement implantation were analyzed. The in vivo sizing for second TAV based on averaged area of 3 levels of outflow, mid (narrowest) and inflow, was compared with in vitro recommendations, that is, same size as index S3 for second S3 and 1 size larger for Evolut. Risks of coronary obstruction and patient-prosthesis mismatch were determined by valve-to-aorta distance and estimated effective orifice area, respectively. RESULTS: Overall, the majority of patients (n=328; 92.1%) had underexpanded index S3 with an expansion area of 94% (91%-97%), leading to significant differences in size selection of the second TAV between in vivo and in vitro sizing strategies. Expansion area <89% served as a threshold, resulting in 1 size smaller than the in vitro recommendations were selected in 45 patients (13%) for S3-in-S3 and 13 (4%) for Evolut-in-S3, while the remaining patients followed in vitro recommendations (P<0.01, in vivo versus in vitro sizing). Overall, 57% of total patients for S3-in-S3 simulation and 60% for Evolut-in-S3 were considered low risk for coronary complications. Deep index S3 implantation (odds ratio, 0.76 [interquartile range, 0.67-0.87]; P<0.001) and selecting Evolut as the second TAV (11% risk reduction in intermediate- or high-risk patients) reduced coronary risk. Estimated moderate or severe patient-prosthesis mismatch risk was 21% for S3-in-S3 and 1% for Evolut-in-S3, assuming optimal expansion of the second TAV. CONCLUSIONS: Redo-TAV replacement with S3-in-S3 and Evolut-in-S3 could be feasible with low risk to coronaries in ≈60% of patients, while the remaining 40% will be at intermediate or high risk. The feasibility of redo-TAV replacement is influenced by sizing strategy, type of second TAV, native annular anatomy, and implant depth.

Importance of imaging-acquisition protocol and post-processing analysis for extracellular volume fraction assessment by computed tomography.

BACKGROUND: Computed tomography angiography (CTA) assessment of myocardial extracellular volume fraction (CT-ECV) is feasible, although the protocols for imaging acquisition and post-processing methodology have varied. We aimed to identify a pragmatic protocol for CT-ECV assessment encompassing both imaging acquisition and post-processing methodologies to facilitate its clinical implementation. METHODS: We evaluated consecutive patients with severe aortic stenosis undergoing evaluation for transcatheter aortic valve replacement (TAVR). Pre-contrast and 3-min-delayed CTA were obtained in systole using either helical prospective-ECG-triggered (high-pitch) or axial sequential-ECG-gated acquisition, adding to standard TAVR CTA protocol. Using a dedicated software for co-registration of CTA datasets, three methodologies for ECV measurement were evaluated: (1) mid-septum region of interest (Septal ECV), (2) averaged-global ECV (Global ECV) encompassing 16-AHA segments, and (3) average of septal and lateral segments (Averaged ECVsep and Averaged ECVlat). RESULTS: Among the 142 patients enrolled (median â€‹= â€‹81 years, 44% females), 8 were excluded due to significant imaging artifacts precluding Global ECV assessment. High-pitch scan mode was performed in 68 patients (48%). Suboptimal image quality for Global ECV assessment was associated with high-pitch scan mode (odds ratio: OR â€‹= â€‹2.26, p â€‹= â€‹0.036), along with the presence of intracardiac leads (OR â€‹= â€‹4.91, p â€‹= â€‹0.002), and BMI≥35 â€‹kg/m2 (OR â€‹= â€‹2.80, p â€‹= â€‹0.026). Septal ECV [median â€‹= â€‹29.4%] and Averaged ECVsep [29.0%] were similar (p â€‹= â€‹0.108), while Averaged ECVlat [27.5%] was lower than Averaged ECVsep (p â€‹< â€‹0.001), resulting in lower Global ECV [28.6%]. CONCLUSIONS: Myocardial CT-ECV assessment is feasible using a systolic sequential acquisition pre-contrast, and similar additional 3-min delayed scan. Septal ECV measurement provides similar values to Global ECV and is equally reproducible.

Clinical Predictors of Coronary Artery Plaque Progression by Quantitative Serial Assessment Using 320-Row Computed Tomography Coronary Angiography in Asymptomatic Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Natural history of coronary plaque progression (PP) in patients with diabetes mellitus (DM) remains unclear. This study aimed to investigate the clinical predictors of coronary PP in patients with DM. METHODS: In this prospective observational study, we analyzed 70 asymptomatic patients (age, 64.4 years; male, 67%) with type 2 DM without prior history of coronary artery disease who underwent serial 320-row computed tomography coronary angiography with an interscan interval of more than 24 months (median 37.7 months). Study endpoint was PP, which was defined if coronary plaque volumes (PVs) at follow-up minus PVs at baseline was >0. We evaluated plaque composition using the Hounsfield Unit thresholds and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Thirty-nine patients who showed PP had a higher increase in hemoglobin A1c (⊿HbA1c) from baseline to follow-up than those without PP (0.3% ± 0.8% vs -0.4% ± 1.1%; p = 0.01), although there was no statistical difference in HbA1c at baseline (7.1 ± 0.5% vs. 7.3 ± 1.4%; p = 0.24). In multivariable analysis, ⊿HbA1c [odds ratio (OR): 3.05; 95% confidence interval (CI): 1.39-6.67; p = 0.001] was an independent predictor for PP. Increase in low-density lipoprotein cholesterol (⊿LDL-C), not ⊿HbA1c, was significantly correlated to percent change in necrotic core (NC) volume (ß-coefficients: 0.04; 95% CI: 0.004 - 0.08; p = 0.03). Among 48 patients without insulin therapy, patients with PP (n = 28) had a higher increase in HOMA-IR than those without PP (n = 20) (0.95 ± 2.00 vs. -0.63 ± 1.31; p = 0.003). CONCLUSIONS: Increase in HbA1c and HOMA-IR was associated with PP in asymptomatic patients with type 2 DM, whereas increase in LDL-C was correlated to increase in NC.

Assessment of the bleeding risk of anticoagulant treatment in non-severe frail octogenarians with atrial fibrillation.

BACKGROUND: Physicians estimate the frailty in elderly patients with atrial fibrillation (AF) to aid in the decision making with respect to oral anticoagulant (OAC) therapy. There are limited data on the safety of OAC therapy in non-severe frail elderly patients. We evaluated the risk factors of bleeding among non-severe frail octogenarians with AF taking OACs. METHODS: Among 430 consecutive AF patients aged 80 years and over with non-severe frailty, we enrolled 346 patients [167 men, 83.7 (81.0-85.0) years] who were newly initiated on OACs: dabigatran, rivaroxaban, apixaban, edoxaban, or warfarin. To measure the frailty, the clinical frailty scale (CFS) was used. Non-severe frailty was defined as a CFS score of <7. The clinical factors were compared between the patients with and without bleeding during the OAC therapy. RESULTS: Out of the 346 patients enrolled, 266 (76.9%) received direct OACs (DOACs) and 80 (23.1%) warfarin. Of the 266 patients receiving DOACs, there were 204 (76.7%) prescribed appropriately adjusted-dose DOACs based on the approved Japanese recommendations. Of the 80 warfarin-treated patients, 52 (65.0%) were prescribed appropriately adjusted-dose warfarin. During a follow-up of 32.7 (14.0-51.0) months, bleeding events were detected in 59 patients (17.1%). Among the clinical factors, a multivariate analysis found that having a low body mass index (BMI) (<18.5kg/m2) was associated with the development of bleeding [hazard ratio (HR): 3.26, 95% confidence interval (CI): 1.65-6.50, p<0.01)]. Moreover, having a low BMI remained an independent risk factor for bleeding in the patients treated with appropriately adjusted-dose OACs (HR: 2.17, 95% CI: 1.01-4.70, p=0.048). CONCLUSIONS: In non-severe frail octogenarians with AF taking OACs, having a low BMI was the most significant factor associated with the development of bleeding.

Assessment of a novel transdermal selective ß1-blocker, the bisoprolol patch, for treating frequent premature ventricular contractions in patients without structural heart disease.

BACKGROUND: The autonomic nervous system involves the genesis of premature ventricular contractions (PVCs). Previous studies demonstrated that heart rate (HR) dependency of idiopathic PVCs has different autonomic mechanisms. Recently, the bisoprolol patch, a novel transdermal ß1-blocker formulation containing bisoprolol, became clinically available. We examined the efficacy of the bisoprolol patch for treating frequent PVCs in patients without structural heart disease (SHD) regarding the HR dependency of PVCs. METHODS: This prospective study included 44 consecutive patients without SHD (25 men, mean age, 63.6±12.3 years) with PVC counts≥3000 beats as measured by 24-hour Holter electrocardiograms (ECGs). PVCs were divided into positive HR-dependent PVCs (P-PVCs) and non-positive HR-dependent PVCs (NP-PVCs) based on the relationship between the hourly PVC density and hourly mean HR. A bisoprolol patch was administered once daily at a dose of 4mg. The 24-hour Holter ECGs were performed before and 1 month after the initiation of the therapy. RESULTS: In 44 patients, there were 24 P-PVCs and 20 NP-PVCs. The bisoprolol patch reduced the PVC count significantly (from 16,563±10,056 to 7892±8817 beats/24hours, p<0.001) in the P-PVC group, while the PVC count did not change significantly (from 16,409±9571 to 13,476±12,191beats/24hours, p=0.34) in the NP-PVC group. Moreover, in the P-PVC group, the patients with mean HRs ≥80 beats/minute had a significantly higher percent improvement in the PVC count than those with mean HRs <80 beats/minute (p=0.0080). The bisoprolol patch resulted in a significant reduction in the PVC count from baseline during each time period for the changes within a 24-hour period in the P-PVC group. CONCLUSIONS: The transdermal bisoprolol patch was effective for a PVC reduction in patients with P-PVCs, particularly in those with faster mean HRs. Furthermore, it demonstrated a stable PVC-reducing effect during the 24-hour period in the P-PVC group.

Assessment of drug-induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias.

BACKGROUND: Pilsicainide, a pure Na+ channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide. METHODS: This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management. We evaluated the relationship between DIPs and serum pilsicainide concentration, renal dysfunction (estimate glomerular filtration rate, eGFR), and electrocardiogram (ECG) parameters. RESULTS: Among the patients, 154 (17.6%) had renal dysfunction (eGFR<50 mL/min), including 12 (1.4%) on hemodialysis. DIPs were present in 10 patients (1.1%): all had renal dysfunction, and one was on hemodialysis. The eGFR in DIP patients was significantly lower than that in the non-DIP patients (32.2±15.1 vs. 68.4±22.1 mL/min, p<0.001). Among the clinical factors measured, only renal dysfunction (eGFR<50 mL/min) was significantly associated with DIPs (OR 44.6; 95% CI 5.61-335.0, p<0.001). Interestingly, among the ECG parameters, the corrected QT (QTc) intervals in DIP patients were longer than those in non-DIP patients (555.8±37.6 vs. 430.7±32.6 ms, p<0.001). As pilsicainide concentration increased, both QRS and QTc intervals prolonged. The latter were improved by discontinuing pilsicainide administration, and additional treatments. CONCLUSIONS: DIPs caused by pilsicainide administration were strongly associated with renal dysfunction. Hence, confirmation of renal function would be necessary prior to and/or during the pilsicainide administration.