Automatic 3D left atrial strain extraction framework on cardiac computed tomography.

BACKGROUND AND OBJECTIVE: Strain analysis provides insights into myocardial function and cardiac condition evaluation. However, the anatomical characteristics of left atrium (LA) inherently limit LA strain analysis when using echocardiography. Cardiac computed tomography (CT) with its superior spatial resolution, has become critical for in-depth evaluation of LA function. Recent studies have explored the feasibility of CT-derived strain; however, they relied on manually selected regions of interest (ROIs) and mainly focused on left ventricle (LV). This study aimed to propose a first-of-its-kind fully automatic deep learning (DL)-based framework for three-dimensional (3D) LA strain extraction on cardiac CT. METHODS: A total of 111 patients undergoing ECG-gated contrast-enhanced CT for evaluating subclinical atrial fibrillation (AF) were enrolled in this study. We developed a 3D strain extraction framework on cardiac CT images, containing a 2.5D GN-U-Net network for LA segmentation, axis-oriented 3D view extraction, and LA strain measure. The segmentation accuracy was evaluated using Dice similarity coefficient (DSC). The model-extracted LA volumes and emptying fraction (EF) were compared with ground-truth measurements using intraclass correlation coefficient (ICC), correlation coefficient (r), and Bland-Altman plot (B-A). The automatically extracted LA strains were evaluated against the LA strains measured from 2D echocardiograms. We utilized this framework to gauge the effect of AF burden on LA strain, employing the atrial high rate episode (AHRE) burden as the measurement parameter. RESULTS: The GN-U-Net LA segmentation network achieved a DSC score of 0.9603 on the test set. The framework-extracted LA estimates demonstrated excellent ICCs of 0.949 (95 % CI: 0.93-0.97) for minimal LA volume, 0.904 (95 % CI: 0.86-0.93) for maximal LA volume, and 0.902 (95 % CI: 0.86-0.93) for EF, compared with expert measurements. The framework-extracted LA strains demonstrated moderate agreement with the LA strains based on 2D echocardiography (ICCs >0.703). Patients with AHRE > 6 min had significantly lower global strain and LAEF, as extracted by the framework than those with AHRE ≤ 6 min. CONCLUSION: The promising results highlighted the feasibility and clinical usefulness of automatically extracting 3D LA strain from CT images using a DL-based framework. This tool could provide a 3D-based alternative to echocardiography for assessing LA function.

Exercise capacity-hemodynamics mismatch in elderly patients with pulmonary hypertension: A nationwide multicenter study from Taiwan Society of Cardiology Pulmonary Hypertension Registry (TAIPANS).

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45-65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45-65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45-65: 14.5, >65: 31.6 %; p < 0.0001) than young patients. Elderly patients had shorter 6-min walking distance (6 MWD) (≤45 vs. >65, mean difference, 77.8 m [95% confidence interval (CI), 2.1-153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37-15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45-65, mean difference, -2.1 mmHg [95% CI, -3.9 to -0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45-65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

Deep learning-based automatic left atrial appendage filling defects assessment on cardiac computed tomography for clinical and subclinical atrial fibrillation patients.

Rationale and objectives: Selecting region of interest (ROI) for left atrial appendage (LAA) filling defects assessment can be time consuming and prone to subjectivity. This study aimed to develop and validate a novel artificial intelligence (AI), deep learning (DL) based framework for automatic filling defects assessment on CT images for clinical and subclinical atrial fibrillation (AF) patients. Materials and methods: A total of 443,053 CT images were used for DL model development and testing. Images were analyzed by the AI framework and expert cardiologists/radiologists. The LAA segmentation performance was evaluated using Dice coefficient. The agreement between manual and automatic LAA ROI selections was evaluated using intraclass correlation coefficient (ICC) analysis. Receiver operating characteristic (ROC) curve analysis was used to assess filling defects based on the computed LAA to ascending aorta Hounsfield unit (HU) ratios. Results: A total of 210 patients (Group 1: subclinical AF, n = 105; Group 2: clinical AF with stroke, n = 35; Group 3: AF for catheter ablation, n = 70) were enrolled. The LAA volume segmentation achieved 0.931-0.945 Dice scores. The LAA ROI selection demonstrated excellent agreement (ICC ≥0.895, p < 0.001) with manual selection on the test sets. The automatic framework achieved an excellent AUC score of 0.979 in filling defects assessment. The ROC-derived optimal HU ratio threshold for filling defects detection was 0.561. Conclusion: The novel AI-based framework could accurately segment the LAA region and select ROIs while effectively avoiding trabeculae for filling defects assessment, achieving close-to-expert performance. This technique may help preemptively detect the potential thromboembolic risk for AF patients.

Multimodality imaging assessment of the Biatrial remodeling of the burden of atrial high-rate episodes in patients with cardiac implanted electronic devices.

AIMS: The underlying mechanisms of atrial remodeling in cardiac implanted electronic device(CIED)-detected atrial high-rate episodes(AHRE) remains to be elucidated. METHODS: A cardiac computed tomography and a strain echocardiography were performed to delineate the structural and functional characteristics of both atria. Biatrial volumes, emptying fraction(EF) and peak atrial longitudinal/contractile strain(PALS/PACS) were evaluated. All AHRE were analyzed. RESULTS: A total of 80 CIED patients with AHRE were categorized by AHRE duration into 3 groups: Group 1: <6 min(n = 42), Group 2: 6 min âˆ¼ 6 h(n = 23), and Group 3: >6 h(n = 15). Left atrial(LA) maximal volume(Vmax), atrial precontraction volume(Vapc), minimal volume(Vmin), LAEF, and PALS/PACS were all increasingly worsened among the patients in the 3 groups (p value for trend <0.05). Compared to Group 1, Group 2 had decreased LA PALS/PACS. There was no significant difference in LA volume or EF between Group 1 and 2. Group 3 had enlarged biatrial volumes (LAVmax: 57.1(SD 16.0) vs. 45.4(SD 9.2) mL/m2, p = 0.002; LAVmin: 42.6(SD 18.2) vs. 28.2(SD 7.2) mL/m2, p < 0.001), impaired total LAEF (28.0(SD 13.7) vs. 38.2(SD 7.7)%, p = 0.004) and reduced PALS/PACS compared to Group 1. Atrial remodeling in those with AHRE >6 h had increased LA volumes, impaired LAEF and reduced PALS/PACS compared to those with AHRE <6 h. CONCLUSION: Functional remodeling of the atria manifested after AHRE >6 min. Increased biatrial volumes and decreased LA reservoir and pump function occurred when AHRE were > 6 h. These LA structural and functional may be considered surrogate imaging markers for stroke risk assessment in patients with CHA2DS2-VASc ≥2 and AHRE.

Distinct atrial remodeling in patients with subclinical atrial fibrillation: Lessons from computed tomographic images.

AIMS: Cardiac implanted electronic devices (CIEDs) can detect atrial high-rate episodes (AHREs) and challenge current management of subclinical atrial fibrillation (AF). METHODS: To characterize the anatomic and functional remodeling of cardiac structures between patients with subclinical AF (SCAF) and clinical AF. The predictors for AHREs ≥6 min were also investigated. RESULTS: We compared the atrial volume, dynamic function, and peri-atrial fat between 104 CIEDs (AHREs = 0, n = 12; SCAF, n = 66; CIEDs with AF, n = 26) and 40 paroxysmal AF patients who were planning for catheter ablation (AF for ablation) using 256-slice multidetector computed tomography for the duration of the AHREs. The maximal volume of the left atrium (LA) and LA appendage (LAA) were significantly smaller; the total emptying fraction (EF) and active EF of the LA and LAA were significantly better in the patients with SCAF than in those with clinical AF. Less peri-atrial fat (p < 0.001) and a greater LAA/ascending aorta (AA) Hounsfield unit (HU) ratio (p < 0.05) were noted in the patients with SCAF. Significantly increased volume reduced the total EF of LA and LAA and a reduced LAA/AA HU ratio (0.91 ± 0.18 vs 0.98 ± 0.03 vs 0.97 ± 0.05, p < 0.05) were demonstrated in patients with AHREs ≥6 min compared to those with AHREs <6 min and without AHRE. Multivariate analysis showed the reduced LAA/AA HU ratio is an independent predictor for the development of AHREs ≥6 min. CONCLUSION: As compared to clinical AF, patients with SCAF show a more favorable LA remodeling process. Among the patients with device-detected AHREs, worse LA remodeling and a reduced LAA/AA HU ratio were associated with the occurrence of AHREs ≥6 min. These findings may provide an incremental value for understanding SCAF.

Prediction of Recurrent Atrial Tachyarrhythmia After Receiving Atrial Flutter Ablation in Patients With Prior Cardiac Surgery for Valvular Heart Disease.

Background: Surgical scars cause an intra-atrial conduction delay and anatomical obstacles that facilitate the perpetuation of atrial flutter (AFL). This study aimed to investigate the outcome and predictor of recurrent atrial tachyarrhythmia after catheter ablation in patients with prior cardiac surgery for valvular heart disease (VHD) who presented with AFL. Methods: Seventy-two patients with prior cardiac surgery for VHD who underwent AFL ablation were included. The patients were categorized into a typical AFL group (n = 45) and an atypical AFL group (n = 27). The endpoint was the recurrence of atrial tachyarrhythmia during follow-up. A multivariate analysis was performed to determine the predictor of recurrence. Results: No significant difference was found in the recurrence rate of atrial tachyarrhythmia between the two groups. Patients with concomitant atrial fibrillation (AF) had a higher recurrence of typical AFL compared with those without AF (13 vs. 0%, P = 0.012). In subgroup analysis, typical AFL patients with concomitant AF had a higher incidence of recurrent atrial tachyarrhythmia than those without it (53 vs. 14%, P = 0.006). Regarding patients without AF, the typical AFL group had a lower recurrence rate of atrial tachyarrhythmia than the atypical AFL group (14 vs. 40%, P = 0.043). Multivariate analysis showed that chronic kidney disease (CKD) and left atrial diameter (LAD) were independent predictors of recurrence. Conclusions: In our study cohort, concomitant AF was associated with recurrence of atrial tachyarrhythmia. CKD and LAD independently predicted recurrence after AFL ablation in patients who have undergone cardiac surgery for VHD.

Identification of critical isthmus using coherent mapping in patients with scar-related atrial tachycardia.

INTRODUCTION: Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs. METHODS: Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval < 20 ms), CV < 0.3 m/s and local fractionated electrograms were evaluated. RESULTS: Twenty-six complex ATs were mapped (mean: 1.3 ± 0.7 maps/pt; 4 focal, 22 isthmus-dependent). Coherent mapping was better in identifying CI/breakout sites where ablation terminated the tachycardia (96.2% vs 69.2%; P = .010) and identified significantly more CI (mean/chamber 2.0 ± 1.1 vs 1.0 ± 0.7; P < .001) with narrower width (19.8 ± 10.5 vs 43.0 ± 23.9 mm; P < .001) than conventional mapping. Ablation at origin and CI sites was successful in 25 (96.2%) with long-term recurrence in 25%. CONCLUSIONS: Coherent mapping with conduction velocity vectors derived from adjacent mapping sites significantly improved the identification of CI sites in scar-related ATs with isthmus-dependent re-entry better than conventional mapping. It may be used in conjunction with conventional mapping strategies to facilitate recognition of slow conduction areas and critical sites that are important targets of ablation.

The presence of ectopic atrial rhythm predicts adverse cardiovascular outcomes in a large hospital-based population.

BACKGROUND: Whether ectopic atrial rhythm (EAR) is a high-risk cardiovascular phenotype (eg, the manifestation of a diseased sinoatrial node) or just a benign accelerated ectopic pacemaker remains unclear. OBJECTIVE: We aimed to analyze the cardiovascular outcomes and underlying mechanisms in patients with EAR. METHODS: From a 12-lead electrocardiogram hospital-based electrocardiogram database, a total of 2896 adults with EAR were propensity score matched at 1:5 with 14,480 patients with sinus rhythm (SR). Patients were retrospectively followed up for cardiovascular mortality (the primary outcome) and permanent pacemaker implantation (the secondary outcome). Heart rate variability was analyzed to compare autonomic function between patients with EAR and those with SR. RESULTS: The prevalence of EAR was 1.13%, which increased with age. Compared with the matched patients, those with EAR had a higher risk of cardiovascular mortality (adjusted hazard ratio 1.93; 95% confidence interval 1.52-2.44; P < .0001) and permanent pacemaker implantation (adjusted hazard ratio 5.94; 95% confidence interval 3.89-9.09; P < .0001) according to the Cox proportional hazards regression model. The risk of cardiovascular mortality was similar across the subgroups on the basis of age, sex, hypertension, type 2 diabetes mellitus, congestive heart failure, myocardial infarction, stroke, and chronic kidney diseases. In patients with EAR, the low frequency/high frequency and standard deviation of the mean normal-to-normal intervals/root mean square of successive RR interval differences ratios for heart rate variability were both lower than those in patients with SR. This implied autonomic imbalance in patients with EAR. CONCLUSION: Patients with EAR have a higher risk of cardiovascular mortality and permanent pacemaker implantation, which was associated with autonomic imbalance.

Protein-bounded uremic toxin p-cresylsulfate induces vascular permeability alternations.

The goal of the present studies is to investigate that the impact of p-cresylsulfate (PCS) on the endothelial barrier integrity via in situ exposure and systemic exposure. Vascular permeability changes induced by local injection of PCS were evaluated by the techniques of both Evans blue (EB) and India ink tracer. Rats were intravenously injected with EB or India ink followed by intradermal injections of various doses of PCS (0, 0.4, 2, 10 and 50 µmol/site) on rat back skins. At different time points, skin EB was extracted and quantified. The administration of India ink was used to demonstrate leaky microvessels. Skin PCS levels were also determined by liquid chromatography-mass spectrometry. We also investigated whether the increased endothelial leakage occurred in the aortic endothelium in rats treated with 5/6 nephrectomy and intraperitoneal injection of PCS 50 mg/kg/day for 4 weeks. The aortic endothelial integrity was evaluated by increased immunoglobulin G (IgG) leakage. High doses of PCS, but not lower doses, significantly induced vascular leakage as compared to saline injection and EB leakage exhibited in time-dependent manner. A time-correlated increase in leaky microvessels was detected in the tissues examined. The injected PCS declined with time and displayed an inverse relationship with vascular leakage. Chronic kidney disease (CKD) rats administered with PCS, compared to control rats, had significantly higher serum levels of PCS and apparent IgG deposition in the aortic intima. Increased endothelial leakage induced by PCS in skin microvessels and the aorta of CKD rats suggests that the PCS-induced endothelial barrier dysfunction.

Concurrence of UGT1A polymorphism and end-stage renal disease leads to severe toxicities of irinotecan in a patient with metastatic colon cancer.

AIMS AND BACKGROUND: Colorectal cancer is one of the most common malignancies in the world, and irinotecan (CPT-11) is useful in its treatment. However, the safety and pharmacokinetics of irinotecan in dialysis patients with metastatic colorectal cancer are unclear. CASE REPORT: We report the case of a 74-year-old man receiving chronic hemodialysis who had metastatic colorectal cancer. Palliative chemotherapy with irinotecan (80 mg/m2 weekly) was administered after hemodialysis. Blood samples were collected before and 1.5, 3, 6, 9, and 15 hours after administration of irinotecan. The peak serum concentrations (Cmax) of irinotecan and SN-38 in this patient were 1,480 and 17.8 ng/mL, respectively, which were similar to the reported values in patients with normal renal function after a similar dose of irinotecan (75 mg/m2). The area under the serum concentration-time curve (AUC0-∞) was 8,240 ng×h/mL for irinotecan and 619 ng×h/mL for SN-38. The AUC0-∞ for SN-38 was markedly higher than that for patients with normal renal function. Sequencing analysis of the UGT1A genes found that the patient had variant alleles of UGT1A1*28, UGT1A1*60 and UGT1A9*22, which may lead to decreased glucuronidation and excretion of SN-38, and may account for increased irinotecan-related toxicity. The patient developed febrile grade 4 neutropenia on day 7 after chemotherapy and died of septic shock on day 14. CONCLUSIONS: UGT1A polymorphisms and renal failure may lead to accumulation of SN-38, which may have played a role in the death of this patient. Irinotecan should be used cautiously in dialysis patients with metastatic colorectal cancer and screening for UGT1A polymorphisms may help in identifying patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan-induced toxicity.

Impact of circulating monocyte CD36 level on atrial fibrillation and subsequent catheter ablation.

BACKGROUND: Inflammation, an important mechanism in the pathogenesis of atrial fibrillation (AF), can be regulated by CD36 in monocytes. OBJECTIVE: The purpose of this study was to test the hypothesis that CD36 in monocytes contributes to the pathogenesis of AF. METHODS: A prospective study that enrolled 87 patients with AF and 70 without AF was conducted. RESULTS: Compared to patients without AF, patients with AF had monocytes with a lower level of CD36 protein, which correlated with left atrial diameter, left atrial emptying fraction, and left atrial mean voltage. In AF patients after catheter ablation, Kaplan-Meier analysis showed that the sinus rhythm maintenance rate was higher in patients with high CD36 levels. Low CD36 level was an independent predictor of recurrence. After successful ablation, the CD36 level increased by 57%, reaching that of control patients. CD36 level was not correlated with the level of high-sensitivity C-reactive protein. Analysis of mRNA levels from a buffy coat revealed that AF patients had lower CD36 and interleukin-10 levels and higher peroxisome proliferator-activated receptor-γ and tumor necrosis factor-α levels, with CD36 level positively correlated with interleukin-10 level but inversely correlated with peroxisome proliferator-activated receptor-γ and tumor necrosis factor-α levels. CONCLUSION: Low CD36 levels in circulating monocytes were associated with AF occurrence and predicted recurrence after catheter ablation. The link between CD36 and AF identified a novel AF-related inflammatory pathway.

The impact of diastolic dysfunction on the atrial substrate properties and outcome of catheter ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: The presence of diastolic dysfunction increases the risk of atrial fibrillation (AF), and might be associated with the left atrial (LA) substrate. The aim of the present study was to investigate the relationships between the diastolic dysfunction, atrial substrate and outcome of the catheter ablation. METHODS AND RESULTS: Eighty-three patients with paroxysmal AF were enrolled. Diastolic dysfunction was defined as a left ventricular ejection fraction (LVEF) of ≥ 50%, and one of the following criteria: (1) a mitral inflow early filling velocity to atrial filling velocity ratio (E/A) of ≤ 0.75; or (2) an E/A ratio of >0.75 and a ratio of the mitral inflow early filling velocity to the velocity of the early medial mitral annular ascent of >10. Patients with diastolic dysfunction were older than those with normal cardiac function. There were no differences in the other baseline characteristics, LA diameter, or LVEF. A decreased LA voltage, and higher recurrence rate were noted in patients with diastolic dysfunction. In the univariate analysis, the patients with recurrence had a lower LA voltage and greater diastolic dysfunction. The multivariate analysis also indicated diastolic dysfunction and LA voltage as independent predictors of recurrence. CONCLUSIONS: The patients with diastolic dysfunction developed a different atrial substrate and had a worse outcome of catheter ablation for atrial fibrillation.

Acute left ventricular rupture following posterior wall myocardial infarction.

Free wall rupture, the most fearful complication of myocardial infarction, mostly attacks anterior walls. Acute rupture is characterized by rapid development of mechanical arrest accompanied with bradyarrhythmia or electromechanical dissociation. The majority of patients succumb to death as the result of cardiac tamponade. Risk factors are advanced age, female gender, the first-time myocardial infarction, hypertension, and ST-segment elevation. We report a rare case of posterior wall myocardial infarction complicated with left ventricular rupture initially presenting with junctional escape rhythm.

Acute effect of circumferential pulmonary vein isolation on left atrial substrate.

INTRODUCTION: The left atrial (LA) substrate plays an important role in the maintenance of atrial fibrillation (AF). However, little is known about the acute effect of circumferential pulmonary vein isolation (CPVI). This study was to investigate the acute change of LA activation, voltage and P wave in surface electrocardiogram (ECG) after CPVI. METHODS AND RESULTS: Electroanatomic mapping (NavX) was performed in 50 patients with AF (mean age = 54 +/- 10 years, 36 males) who underwent only CPVI. The mean peak-to-peak bipolar voltage and total activation time of LA were obtained during sinus rhythm before and immediately after CPVI. The average duration and amplitude of P waves in 12-lead ECG were also analyzed before and after CPVI. Change in the earliest LA breakthrough sites could cause decreased LA total activation time. Downward shift in the breakthrough site was inversely proportional to the proximity of the breakthrough site to the radiofrequency lesions. A shortening of P-wave duration and decrease in voltage after CPVI were observed after CPVI. Patients with recurrent AF had less voltage reduction in the atrial wall 1 cm from the circumferential PV lesions compared with those without recurrent AF (60.1 +/- 11.7% vs 74.1 +/- 6.6%, P = 0.002). Reduction of voltage < or = 64.4% in this area after CPVI is related with recurrent AF. CONCLUSION: CPVI could result in acute change of LA substrate, involving LA activation and voltage. Less reduction of voltage in the atrial wall adjacent to the circumferential PV lesions after CPVI may be associated to the recurrence of AF.