Interaction of left ventricular size with the outcome of cardiac resynchronization therapy in Japanese patients.

BACKGROUND: We analyzed the influence of the QRS duration (QRSd) to LV end-diastolic volume (LVEDV) ratio on cardiac resynchronization therapy (CRT) outcomes in heart failure patients classified as III/IV per the New York Heart Association (NYHA) and with small body size. HYPOTHESIS: We proposed the hypothesis that the QRSd/LV size ratio is a better index of the CRT substrate. METHODS: We enrolled 114 patients with advanced heart failure (NYHA class III/IV, and LV ejection fraction >35%) who received a CRT device, including those with left bundle branch block (LBBB) and QRSd ≥120 milliseconds (n = 60), non-LBBB and QRSd ≥150 milliseconds (n = 30) and non-LBBB and QRSd of 120-149 milliseconds (n = 24). RESULTS: Over a mean follow-up period of 65 ± 58 months, the incidence of the primary endpoint, a composite of all-cause death and hospitalization for heart failure, showed no significant intergroup difference (43.3% vs. 50.0% vs. 37.5%, respectively, p = .72). Similarly, among 104 patients with QRSd/LVEDV ≥ 0.67 (n = 54) and QRSd/LVEDV < 0.67 (n = 52), no significant differences were observed in the incidence of the primary endpoint (35.1% vs. 51.9%, p = .49). Nevertheless, patients with QRSd/LVEDV ≥ 0.67 showed better survival than those with QRSd/LVEDV < 0.67 (14.8% vs. 34.6%, p = .0024). CONCLUSION: Advanced HF patients with a higher QRSd/LVEDV ratio showed better survival in this small-body-size population. Thus, the risk is concentrated among those with a larger QRSd, and patients with a relatively smaller left ventricular size appeared to benefit from CRT.

Paced QRS morphology mimicking complete left bundle branch block induced by right ventricular pacing is associated with pacing-induced cardiomyopathy.

INTRODUCTION: Right ventricular (RV) pacing sometimes causes left ventricular (LV) systolic dysfunction, also known as pacing-induced cardiomyopathy (PICM). However, the association between specifically paced QRS morphology and PICM development has not been elucidated. This study aimed to investigate the association between paced QRS mimicking a complete left bundle branch block (CLBBB) and PICM development. METHODS: We retrospectively screened 2009 patients who underwent pacemaker implantation from 2010 to 2020 in seven institutions. Patients who received pacemakers for an advanced atrioventricular block or bradycardia with atrial fibrillation, baseline LV ejection fraction (LVEF) ≥ 50%, and echocardiogram recorded at least 6 months postimplantation were included. The paced QRS recorded immediately after implantation was analyzed. A CLBBB-like paced QRS was defined as meeting the CLBBB criteria of the American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society in 2009. PICM was defined as a ≥10% LVEF decrease, resulting in an LVEF of <50%. RESULTS: Among the 270 patients analyzed, PICM was observed in 38. Baseline LVEF was lower in patients with PICM, and CLBBB-like paced QRS was frequently observed in PICM. Multivariate analysis revealed that low baseline LVEF (odds ratio [OR]: 0.93 per 1% increase, 95% confidence interval [CI]: 0.89-0.98, p = 0.006) and CLBBB-like paced QRS (OR: 2.69, 95% CI: 1.25-5.76, p = 0.011) were significantly associated with PICM development. CONCLUSION: CLBBB-like paced QRS may be a novel risk factor for PICM. RV pacing, which causes CLBBB-like QRS morphology, may need to be avoided, and patients with CLBBB-like paced QRS should be followed-up carefully.

Pulsed Field Ablation Index-Guided Ablation for Lesion Formation: Impact of Contact Force and Number of Applications in the Ventricular Model.

BACKGROUND: The effect of contact force (CF) on lesion formation is not clear during pulsed field ablation (PFA). The aim of this study was to evaluate the impact of CF, PFA, and their interplay through the PFA index (PF index) formula on the ventricular lesion size in swine. METHODS: PFA was delivered through the CF-sensing OMNYPULSE catheter. Predefined PFA applications (×3, ×6, ×9, and ×12) were delivered maintaining low (5-25 g), high (26-50 g), and very high (51-80 g) CFs. First, PFA lesions were evaluated on necropsy in 11 swine to investigate the impact of CF/PFA-and their integration in the PF index equation-on lesion size (study characterization). Then, 3 different PF index thresholds-300, 450, and 600-were tested in 6 swine to appraise the PF index accuracy to predict the ventricular lesion depth (study validation). RESULTS: In the study characterization data set, 111 PFA lesions were analyzed. CF was 32±17 g. The average lesion depth and width were 3.5±1.2 and 12.0±3.5 mm, respectively. More than CF and PFA dose alone, it was their combined effect to impact lesion depth through an asymptotically increasing relationship. Likewise, not only was the PF index related to lesion depth in the study validation data set (r2=0.66; P<0.001) but it also provided a prediction accuracy of the observed depth of ±2 mm in 69/73 lesions (95%). CONCLUSIONS: CF and PFA applications play a key role in lesion formation during PFA. Further studies are required to evaluate the best PFA ablation settings to achieve transmural lesions.

Long-term prognosis and prognostic factors after primary prophylactic implantable cardioverter-defibrillator therapy.

BACKGROUND: Little is known regarding which patients with ischemic cardiomyopathy (ICM) should be considered for prophylactic therapies, such as an implantable cardioverter-defibrillator (ICD), in the primary percutaneous intervention era. The aim of this study was to investigate the influence of non-sustained ventricular tachycardia (NSVT) on major adverse cardiac events (MACE) in heart failure with reduced ejection fraction (HFrEF) patients. METHODS: We retrospectively analyzed patients of ICM and non-ICM who underwent ICD implantation at our institute from October 2006 to August 2020. MACE were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. RESULTS: A total of 167 patients were enrolled [male, 138 (83 %); age, 62.1 ±â€¯11.7 years; left ventricular ejection fraction, 23.5 ±â€¯6.1 %; left ventricular diastolic diameter, 67.4 ±â€¯9.0 mm; atrial fibrillation, 47 (28 %); NSVT, 124 (74 %); use of class III antiarrhythmic drugs, 55 (33 %); ischemic cardiomyopathy, 56 (34 %); cardiac resynchronization therapy, 73 (44 %)]. The median follow-up duration was 61 months. MACE occurred with 71 patients (43 %). When comparing baseline characteristics of the patients, left ventricular ejection fraction (p = 0.02) and atrial fibrillation (p = 0.04) were significantly associated with MACE. The multivariable Cox analysis for the target variable MACE identified atrial fibrillation (hazard ratio 2.00; 95 % confidence index 1.18-3.37; p = 0.01) as an independent predictor for MACE. CONCLUSIONS: Prior NSVT before ICD implantation was not an independent predictor of future MACE in patients with HFrEF with primary prophylactic ICD. In contrast, atrial fibrillation was associated with worse prognosis. To predict the prognosis of patients with primary prophylactic ICD, these factors should be assessed as comprehensive risk stratification factors for MACE.

Effects of Contact Force on Lesion Size During Pulsed Field Catheter Ablation: Histochemical Characterization of Ventricular Lesion Boundaries.

BACKGROUND: Effects of contact force (CF) on lesion formation during pulsed field ablation (PFA) have not been well validated. The purpose of this study was to determine the relationship between average CF and lesion size during PFA using a swine-beating heart model. METHODS: A 7F catheter with a 3.5-mm ablation electrode and CF sensor (TactiCath SE, Abbott) was connected to a PFA system (CENTAURI, Galvanize Therapeutics). In 5 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and a skin patch at 40 separate sites in right ventricle (28 Amp) and 55 separate sites in left ventricle (35 Amp) with 4 different levels of CF: (1) low (CF range of 4-13 g; median, 9.5 g); (2) moderate (15-30 g; median, 21.5 g); (3) high (34-55 g; median, 40 g); and (4) no electrode contact, 2 mm away from the endocardium. Swine were sacrificed at 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. In 1 additional swine, COX (cytochrome c oxidase) staining was performed to examine mitochondrial activity to delineate reversible and irreversible lesion boundaries. Histological examination was performed with hematoxylin and eosin and Masson trichrome staining. RESULTS: Ablation lesions were well demarcated with triphenyl tetrazolium chloride staining, showing (1) a dark central zone (contraction band necrosis and hemorrhage); (2) a pale zone (no mitochondrial activity and nuclear pyknosis, indicating apoptosis zone); and a hyperstained zone by triphenyl tetrazolium chloride and COX staining (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). At constant PFA current intensity, lesion depth increased significantly with increasing CF. There were no detectable lesions resulting from ablation without electrode contact. CONCLUSIONS: Acute PFA ventricular lesions show irreversible and reversible lesion boundaries by triphenyl tetrazolium chloride staining. Electrode-tissue contact is required for effective lesion formation during PFA. At the same PFA dose, lesion depth increases significantly with increasing CF.

Right ventricular systolic function as a predictor of appropriate ICD therapy.

BACKGROUND: Recent studies have shown that right ventricular dysfunction is associated with a significantly increased risk of sudden cardiac death. The purpose of this study was to evaluate the association of the right ventricular fractional area change (RVFAC) and appropriate implantable cardioverter-defibrillator (ICD) therapy to determine the cutoff value of the RVFAC. METHODS: Consecutive patients who underwent initial ICD implantations except those with hypertrophic cardiomyopathy, Brugada syndrome, and long QT syndrome were retrospectively enrolled. The primary endpoint was defined as any appropriate ICD therapy. The right ventricular dimensions and function on transthoracic echocardiography were measured for analysis. RESULTS: In total, 172 patients (60.3 ± 13.6 years, 131 males) were enrolled. Ninety patients received an ICD as a secondary prophylaxis. The mean LV ejection fraction and RVFAC were 38.3 ± 14.3% and 35.8 ± 8.8%, respectively. Regarding appropriate ICD therapy events, the best cutoff value of the RVFAC was 34.8%, while 74 patients had an RVFAC < 34.8%. Regarding the primary endpoint, the hazard ratio of a low RVFAC was 2.73 (95% CI 1.46-5.12, P < 0.01). In the multivariate analysis, a low RVFAC was an independent predictor of appropriate ICD therapy (HR: 3.40, 95% CI 1.74-6.64, P < 0.01). The secondary prophylactic cohort with a low RVFAC had the highest incidence of appropriate ICD therapy. Among the patients with RV dysfunction, the RVFAC normalized in 39% of patients during follow-up. This recovered RVFAC group had a significantly lower incidence of appropriate ICD therapy than the unrecovered RVFAC group (P = 0.043). CONCLUSION: A low RVFAC might be associated with increased appropriate ICD therapy.

Deep learning-based coronary computed tomography analysis to predict functionally significant coronary artery stenosis.

Fractional flow reserve derived from coronary CT (FFR-CT) is a noninvasive physiological technique that has shown a good correlation with invasive FFR. However, the use of FFR-CT is restricted by strict application standards, and the diagnostic accuracy of FFR-CT analysis may potentially be decreased by severely calcified coronary arteries because of blooming and beam hardening artifacts. The aim of this study was to evaluate the utility of deep learning (DL)-based coronary computed tomography (CT) data analysis in predicting invasive fractional flow reserve (FFR), especially in cases with severely calcified coronary arteries. We analyzed 184 consecutive cases (241 coronary arteries) which underwent coronary CT and invasive coronary angiography, including invasive FFR, within a three-month period. Mean coronary artery calcium scores were 963 ± 1226. We evaluated and compared the vessel-based diagnostic accuracy of our proposed DL model and a visual assessment to evaluate functionally significant coronary artery stenosis (invasive FFR < 0.80). A deep neural network was trained with consecutive short axial images of coronary arteries on coronary CT. Ninety-one coronary arteries of 89 cases (48%) had FFR-positive functionally significant stenosis. On receiver operating characteristics (ROC) analysis to predict FFR-positive stenosis using the trained DL model, average area under the curve (AUC) of the ROC curve was 0.756, which was superior to the AUC of visual assessment of significant (≥ 70%) coronary artery stenosis on CT (0.574, P = 0.011). The sensitivity, specificity, positive and negative predictive value (PPV and NPV), and accuracy of the DL model and visual assessment for detecting FFR-positive stenosis were 82 and 36%, 68 and 78%, 59 and 48%, 87 and 69%, and 73 and 63%, respectively. Sensitivity and NPV for the prediction of FFR-positive stenosis were significantly higher with our DL model than visual assessment (P = 0.0004, and P = 0.024). DL-based coronary CT data analysis has a higher diagnostic accuracy for functionally significant coronary artery stenosis than visual assessment.

Antithrombotic Regimen After Percutaneous Left Atrial Appendage Closure　- A Real-World Study.

BACKGROUND: Antithrombotic therapy after left atrial appendage closure (LAAC) in patients at high risk of bleeding remains controversial. We present real-world clinical outcomes of LAAC.Methods and Results: Data from 74 consecutive patients who received LAAC therapy between January 2020 and June 2022 were analyzed. Patients received 1 of 3 antithrombotic therapies according to the bleeding risk category or clinical event. Regimen 1 was based on a prior study, regimen 2 comprised a lower antiplatelet drug dose without dual antiplatelet therapy, and regimen 3 was antiplatelet drug administration for as long as possible to patients with uncontrollable bleeding who were required to stop anticoagulant drugs. Overall, 73 (98.6%) procedures were successful. Of them, 16 (21.9%) patients were selected for regimen 1, 46 (63.0%) for regimen 2, and 11 (15.1%) for regimen 3. Device-related thrombosis (13% vs. 0% vs. 0%, P=0.0257) only occurred with regimen 1. There was no difference in major bleeding event rates (6% vs. 2% vs. 9%, P=0.53). CONCLUSIONS: The post-LAAC antithrombotic regimen was modified without major concerns.

Junctional rhythm during cryoablation for typical atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Cryoablation is being used as an alternative to radiofrequency (RF) ablation for atrioventricular nodal reentrant tachycardia (AVNRT) owing to the lower risk of atrioventricular block (AVB) compared to RF ablation. Junctional rhythm often occurs during successful application of RF ablation for AVNRT. In contrast, junctional rhythm has rarely been reported to occur during cryoablation. This retrospective study evaluated the characteristics of junctional rhythm during cryoablation for typical AVNRT. METHODS AND RESULTS: This retrospective study included 127 patients in whom successful cryoablation of typical AVNRT was performed. Patients diagnosed with atypical AVNRT were excluded. Junctional rhythm appeared during cryofreezing in 22 patients (17.3%). These junctional rhythms appeared due to cryofreezing at the successful site in the early phase within 15 s of commencement of cooling. Transient complete AVB was observed in 10 of 127 patients (7.9%), and it was noted that atrioventricular conduction improved immediately after cooling was stopped in these 10 patients. No junctional rhythm was observed before the appearance of AVB. No recurrence of tachycardia was confirmed in patients in whom junctional rhythm occurred by cryofreezing at the successful site. CONCLUSION: Occurrence of junctional rhythms during cryoablation is not so rare and can be considered a criterion for successful cryofreezing. Furthermore, junctional rhythm may be associated with low risk of recurrent tachycardia.

Anagrelide-associated Cardiomyopathy and Heart Failure in a Patient with Essential Thrombocythemia: A Case Report and Literature Review.

Anagrelide is used worldwide to treat essential thrombocythemia (ET) by reducing platelet counts. Cardiomyopathy and heart failure (HF) are rare but serious complications associated with anagrelide use, although no cases were reported during Japanese Phase I to III studies. A 46-year-old, otherwise healthy, Japanese ET patient developed HF with reduced ejection fraction after 18 months of treatment with 1.0-3.5 mg of anagrelide daily. HF was stabilized with anagrelide withdrawal and guideline-directed HF therapy. The cardiac function returned to normal after six months. This case suggests that anagrelide can cause cardiomyopathy and HF in ET patients, regardless of nationality, comorbid cardiovascular conditions, or therapy duration.

Pathophysiological background and prognosis of common atrial flutter in non-elderly patients: Comparison to Atrial Fibrillation.

BACKGROUND: It is unclear whether there is any difference in the background and prognosis between non-elderly patients who undergo catheter ablation of atrial fibrillation (AF) and common atrial flutter (CAFL). PURPOSE: To investigate the difference between the patient background of both CAFL and AF in the non-elderly. METHODS: In 526 consecutive patients who underwent catheter ablation of clinical paroxysmal/persistent CAFL or AF in our hospital, we enrolled only patients under 60 years old. Cases harboring both AFL and AF were excluded. We analyzed the patient characteristics, echocardiographic findings, electrocardiographic (ECG) abnormalities during sinus rhythm, and clinical course after ablation. RESULTS: In total, 196 patients (Cohort 1: 142 males, 156 AF cases) were analyzed. AFL patients were younger than AF patients (47.4 ± 10.6 vs. 50.2 ± 6.4years, p = 0.031) and organic heart disease (OHD) was significantly more common in AFL patients than AF patients (42.5% vs. 11.5%, p<0.001). In 161 patients excluding OHD (Cohort 2), ECG abnormalities were more frequent in AFL than in AF patients (78.3% vs. 39.1%, p = 0.001). There were no significant differences in all-cause death, onset of heart failure, and cerebral strokes. On the other hand, the number of cases that required a pacemaker was significantly higher in the CAFL group than AF group (0.0% vs. 26.1%, p-value <0.001). These results suggested that CAFL may reflect occurrence of any atrial myocardial damage, even if it does not lead to heart failure. CONCLUSIONS: Our present study suggested that CAFL may be associated with a broader atrial myocardial disorder in non-elderly patients.