Evaluation and comparison of impedance and amplitude changes in lesion index-guided pulmonary vein isolation.

Background: The lesion index (LSI) has been used to estimate lesion formation after radiofrequency catheter ablation. However, the impedance drop and decrease in bipolar amplitude of intracardiac electrograms, which are parameters that are traditionally used to predict effective ablation lesions, are not used to calculate LSI. Therefore, we aimed to investigate the association between LSI and traditional parameters. Methods: We retrospectively investigated 1355 ablation points from 31 patients who underwent LSI-guided pulmonary vein isolation (PVI) using TactiCath. All points were classified into 3 groups based on the impedance drop: (i) <10 Ω (n = 67), (ii) 10-20 Ω (n = 909), and (iii) >20 Ω (n = 379). The LSI targets were 4.5 for the posterior left atrium and 5.2 for the anterior left atrium. After excluding 583 points at which it was difficult to measure the amplitude, 772 ablation points during sinus rhythm were included in the analysis of bipolar amplitude. Results: The target LSI was achieved at 1177 points (86.9%). The median total impedance drop and amplitude just after ablation were 16.0 [13.0-20.0] Ω and 0.21 [0.14-0.30] mV, respectively. There were significant differences among the 3 groups in the impedance and amplitude before ablation, power, target LSI, final LSI, contact force, and interlesion distance. An impedance drop of >10 Ω or an amplitude reduction of >50% was achieved at 95% and 82% of the study points, respectively. There were no major complications at any of the ablation points. Conclusion: LSI-guided PVI seemed to be useful for making sufficient ablation lesions, as assessed by the conventional parameters of impedance and amplitude change.

Rate-dependent elevation of the capture threshold after implantation of a leadless pacemaker.

The procedural success in the implantation of cardiac electric devices depends on both the implanted position and the electric performance. The capture threshold and the pacing output affect the estimated battery longevity. In a case with a high capture threshold, recapture and reimplantation of a leadless pacemaker are commonly recommended. We experienced a case with the rate-dependent elevation of the capture threshold following the implantation of a leadless pacemaker. The recognition of the rate-dependency of the capture threshold and the acceptable programming could avoid the unnecessary recapture and reimplantation of that, avoiding the increase of procedural risks.

Feasibility of energy-guided short duration protocol of laser balloon based pulmonary vein isolation for atrial fibrillation (EG-Laser Study).

BACKGROUND: Laser balloon-based pulmonary vein isolation (LB-PVI) is available for atrial fibrillation (AF) ablation. The lesion size depends on laser energy; however, the default protocol is not an energy-based setting. We hypothesized that an energy-guided (EG) short-duration protocol may be an alternative to shorten the procedure time without affecting efficacy and safety. METHODS: We evaluated the efficacy and safety of the EG short-duration protocol (EG group) (target energy 120 J/site [12W/10s; 10W/12s; 8.5W/14s; 5.5W/22s]) compared with the default protocol (control group) (12W/20s; 10W/20s; 8.5W/20s; 5.5W/30s). RESULTS: A total of 52 consecutive patients (EG: n = 27 [103veins] and control: n = 25 [91veins]) undergoing LB-PVI (64 ± 10 years, 81% male, 77% paroxysmal) were enrolled. The EG group had a shorter total time in the pulmonary vein (PV) (43.0 ± 13.9 min vs. 61.1 ± 16.0 min, p < .0001), a shorter total laser application time (1348 ± 254 sec vs. 2032 ± 424 sec, p < .0001), and lower total laser energy (12455 ± 2284J vs. 18084 ± 3746J, p < .0001). There was no difference in the total number of laser applications (p = 0269) or first-pass isolation (p = .725). Acute reconduction was identified only in one vein in the EG. No significant differences were observed in the incidence of pinhole rupture (7.4% vs. 4%, p = 1.000) or phrenic nerve palsy (3.7% vs. 12%, p = .341). During a mean follow-up of 13.5 ± 6.1 months, Kaplan-Meier analysis revealed no significant difference in atrial tachyarrhythmia recurrence (p = .227). CONCLUSION: LB-PVI with the EG short-duration protocol may be achieved in a shorter procedure time to avoid deterioration of efficacy and safety. The EG protocol is feasible as a novel point-by-point manual laser-application approach.

Actual conditions of atrial septal lead implantation and the factors related to successful implantation.

BACKGROUND: Pacemaker leads were originally implanted into the right atrial appendage (RAA) and right ventricular apex, but septal pacing, which is more physiological, is becoming increasingly popular. The usefulness of atrial lead implantation in the RAA or atrial septum is inconclusive, and whether or not atrial septum implantation is accurate has not yet been verified. METHODS: Patients who underwent pacemaker implantation between January 2016 and December 2020 were included. The success rate of atrial septal implantation was validated using thoracic computed tomography performed for any reason postoperatively. We examined factors related to the successful implantation of the atrial lead in the atrial septum. RESULTS: Forty-eight people were included in this study. Lead placement was performed with a delivery catheter system (SelectSecure MRI SureScan; Medtronic Japan Co., Ltd., Tokyo, Japan) in 29 cases and a conventional stylet in 19 cases. The mean age was 74 ±â€¯12 years old, and 28 (58%) were male. Successful atrial septal implantation was performed in 26 patients (54%), with only 4 (21%) successful implantations in the stylet group. There were no significant differences in the age, gender, body mass index (BMI), pacing P wave axis, duration, or amplitude between the atrial septal implantation group and non-septal groups. The only significant difference was for delivery catheter use [22 (85%) vs. 7 (32%), p < 0.001]. In multivariate logistic analysis, the use of a delivery catheter was independently associated with successful septal implantation [odds ratio (OR): 16.9, 95% confidence interval 3.0-90.9] after adjusting for the age, gender, and BMI. CONCLUSION: The success rate of atrial septal implantation was very low at 54%, and only the use of a delivery catheter was associated with successful septal implantation. However, even with a delivery catheter, the success rate was 76%, so further investigations are warranted.

Prevalence and Characteristics of Inspiration-Induced Negative Left Atrial Pressure during Pulmonary Vein Isolation.

BACKGROUND: Atrial fibrillation (AF) ablation is performed under deep sedation, which may cause inspiration-induced negative left atrial pressure (INLAP) associated with deep inspiration. INLAP could be the cause of periprocedural complications. METHODS: We retrospectively enrolled 381 patients with AF (mean age, 63.9 ± 10.8 years; 76 women; 216 cases of paroxysmal AF) who underwent CA under deep sedation using an adaptive servo ventilator (ASV). Patients whose LAP was not obtained were excluded. INLAP was defined as <0 mmHg of mean LAP during inspiration immediately after the transseptal puncture. The primary and secondary endpoints were the presence of INLAP and the incidence of periprocedural complications. RESULTS: Among 381 patients, INLAP was observed in 133 (34.9%). Patients with INLAP had higher CHA2DS2-Vasc scores (2.3 ± 1.5 vs. 2.1 ± 1.6) and 3% oxygen desaturation indexes (median 18.6 (interquartile range 11.2-31.1) vs. 15.7 (8.1-25.3)), and higher prevalence of diabetes mellitus (23.3 vs. 13.3%) than patients without INLAP. Air embolism occurred in four patients with INLAP (3.0 vs. 0.0%). CONCLUSION: INLAP is not rare in patients undergoing CA for AF under deep sedation with ASV. Much attention should be paid to the possibility of air embolism in patients with INLAP.

Association of an Increased Abnormal Mitochondria Ratio in Cardiomyocytes with a Prolonged Oxygen Uptake Time Constant during Cardiopulmonary Exercise Testing of Patients with Non-ischemic Cardiomyopathy.

Objective The cardiac function, blood distribution, and oxygen extraction in the muscles as well as the pulmonary function determine the oxygen uptake (VO2) kinetics at the onset of exercise. This factor is called the VO2 time constant, and its prolongation is associated with an unfavorable prognosis for heart failure (HF). The mitochondrial function of skeletal muscle is known to reflect exercise tolerance. Morphological changes and dysfunction in cardiac mitochondria are closely related to HF severity and its prognosis. Although mitochondria play an important role in generating energy in cardiomyocytes, the relationship between cardiac mitochondria and the VO2 time constant has not been elucidated. Methods We calculated the ratio of abnormal cardiac mitochondria in human myocardial biopsy samples using an electron microscope and measured the VO2 time constant during cardiopulmonary exercise testing. The VO2 time constant was normalized by the fat-free mass index (FFMI). Patients Fifteen patients with non-ischemic cardiomyopathy (NICM) were included. Patients were divided into two groups according to their median VO2 time constant/FFMI value. Results Patients with a low VO2 time constant/FFMI value had a lower abnormal mitochondria ratio than those with a high VO2 time constant/FFMI value. A multiple linear regression analysis revealed that the ratio of abnormal cardiac mitochondria was independently associated with a high VO2 time constant/FFMI. Conclusion An increased abnormal cardiac mitochondria ratio might be associated with a high VO2 time constant/FFMI value in patients with NICM.

Individualised left anterior oblique projection for lead implantation into interventricular septum.

OBJECTIVE: We sought to investigate whether it is possible to obtain individualised left anterior oblique (LAO) by preprocedural electrocardiographic parameters and, if so, whether these parameters can help to improve the success rate of right ventricular (RV) lead implantation into the interventricular septum. METHODS: In this observational study, we assessed the relationship between preoperative electrocardiographic parameters and the angle of the interventricular septum obtained using thoracic CT. The participants were divided into two groups: a retrospective derivation cohort to derive the optimal formula for the individual septum axis, and a prospective internal validation cohort to which we applied the optimal formula and implanted using the new method. RESULTS: In the retrospective derivation cohort (n=39), the mean angle of individualised LAO assessed by thoracic CT was 53.1°±8.9°, and the preoperative ECG QRS axis was strongly correlated with the interventricular septum axis (R2=0.490). LAO projection derived from the preoperative ECG QRS axis confirmed that the RV lead was placed in the interventricular septum during the pacemaker procedure in the prospective internal validation group (n=30). The success rate for placing the RV lead into the interventricular septum was significantly improved in the internal validation cohort (93% vs 64%, p<0.05). In addition, the N-terminal pro-brain natriuretic peptide level decreased significantly after surgery in the interventricular septal indwelling group. CONCLUSIONS: Individualised LAO angle derived from the preoperative ECG QRS axis is a new useful and simple method for RV lead implantation into the interventricular septum. TRIAL REGISTRATION NUMBER: UMIN000045741.

Distribution of evoked delayed potential and delayed potential in a patient with subendocardial inferior infarction and transmural postero-lateral infarction: A case report.

A 47-year-old man with transmural posterolateral myocardial infarction (MI) and subendocardial inferior MI underwent catheter ablation for monomorphic ventricular tachycardia (VT). Right ventricular extra stimulation could unmask evoked delayed potentials in the subendocardial infarction area without delayed potentials in the sinus rhythm. Extra stimulation mapping for VT is useful for hidden VT substrates, particularly in the subendocardial infarction area.

Safety of a Cardiac Resynchronization Therapy Device Implantation in a Patient with Unstable Heart Failure Who Require Impella-Device Assistance.

Implantation of a cardiac resynchronization therapy (CRT) device is usually scheduled in the compensated phase of heart failure; however, procedural safety may be sometimes disturbed in the decompensated phase. We report a case of a successful semi-urgent implantation of a CRT device temporary assisted with Impella in a patient with the decompensated phase of severe heart failure dependent on inotropic agents and who cannot maintain the supine position. Impella assistance with left ventricular (LV) unloading and maintenance of end-organ perfusion contributed to early recovery from acute heart failure. Furthermore, an acute effect of mechanical resynchronization by biventricular pacing plays an important role in weaning from the mechanical support or inotropic dependence. These mutual effects of mechanical support and CRT might contribute to a decrease in LV end-diastolic pressure and to a remarkable early recovery from a severely decompensated condition.

Pre-procedural predictors of left atrial low-voltage zones in patients undergoing catheter ablation of atrial fibrillation.

Pulmonary vein isolation has become a cornerstone treatment for catheter ablation of atrial fibrillation (AF). Recent reports show that additional ablation targeting low-voltage zones reduces AF recurrence. However, the pre-procedural predictors of low-voltage zones remain elusive. We retrospectively enrolled 359 patients (mean age 63.7 ± 10.8 years; 73 females; and 149 had persistent atrial fibrillation) who underwent catheter ablation for AF and left atrial (LA) voltage mapping during sinus rhythm or atrial pacing. Low-voltage zones were defined as area of > 5 cm2 with a bipolar electrogram amplitude of < 0.50 mV. Overall, 51 (14.2%) patients had low-voltage zones. Patients with low-voltage zones were older (67.9 ± 9.9 vs. 63.0 ± 10.8 years; P = 0.003), predominantly female (33.3% vs. 18.2%; P = 0.013), had higher prevalence of dilated cardiomyopathy (DCM) (11.8% vs. 1.6%; P = 0.002) and hypertrophic cardiomyopathy (HCM) (9.8% vs. 2.6%; P = 0.025), and had larger LA volumes (153.6 ± 46.4 vs. 117.7 ± 67.8 mL; P < 0.001) than those without low-voltage zones. Multivariate logistic regression analysis revealed that age (OR 1.060; 95% CI 1.022-1.101, P = 0.002), female sex (OR 2.978; 95% CI 1.340-6.615, P = 0.007), DCM (OR 8.341; 95% CI 1.381-50.372, P = 0.021), HCM (OR 5.044; 95% CI 1.314-19.363, P = 0.018), persistent AF (OR 4.188; 95% CI 1.928-9.100, P < 0.001), and larger LA volume (OR 3.215; 95% CI 1.378-7.502, P = 0.007) were independently associated with the presence of low-voltage zones. Patient age, female sex, DCM, HCM, persistent AF and larger LA volume may predict the presence of low-voltage zones and could be useful in selecting the appropriate ablation strategy for AF.

Targeting MicroRNA-192-5p, a Downstream Effector of NOXs (NADPH Oxidases), Reverses Endothelial DHFR (Dihydrofolate Reductase) Deficiency to Attenuate Abdominal Aortic Aneurysm Formation.

[Figure: see text].

Pseudothrombotic appearance on pulmonary valve by intracardiac echocardiography during atrial fibrillation ablation.

We report a case with a thrombus-like image on pulmonary valve detected by intracardiac echocardiography before transseptal puncture for atrial fibrillation (AF) ablation. The multimodality assessment provided diagnosis of the imaging artifact and exclusion from the harmful mass. This finding could be useful for a safety management of AF ablation and avoidance of an unnecessary interruption of the procedure.

The association between microRNA-21 and hypertension-induced cardiac remodeling.

Hypertension is a major public health problem among the aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its contribution to cardiac remodeling in hypertension is poorly understood. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-ß1 (TGF-ß1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-ß1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic stimulation-induced cardiac remodeling by regulating PDCD4, AP-1, and TGF-ß1 signaling pathway.

Therapeutic inhibition of microRNA-34a ameliorates aortic valve calcification via modulation of Notch1-Runx2 signalling.

AIMS: Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease and is increased with elderly population. However, effective drug therapy has not been established yet. This study aimed to investigate the role of microRNAs (miRs) in the development of CAVS. METHODS AND RESULTS: We measured the expression of 10 miRs, which were reportedly involved in calcification by using human aortic valve tissue from patients who underwent aortic valve replacement with CAVS or aortic regurgitation (AR) and porcine aortic valve interstitial cells (AVICs) after treatment with osteogenic induction medium. We investigated whether a specific miR-inhibitor can suppress aortic valve calcification in wire injury CAVS mice model. Expression of miR-23a, miR-34a, miR-34c, miR-133a, miR-146a, and miR-155 was increased, and expression of miR-27a and miR-204 was decreased in valve tissues from CAVS compared with those from AR. Expression of Notch1 was decreased, and expression of Runt-related transcription factor 2 (Runx2) was increased in patients with CAVS compared with those with AR. We selected miR-34a among increased miRs in porcine AVICs after osteogenic treatment, which was consistent with results from patients with CAVS. MiR-34a increased calcium deposition in AVICs compared with miR-control. Notch1 expression was decreased, and Runx2 expression was increased in miR-34a transfected AVICs compared with that in miR-control. Conversely, inhibition of miR-34a significantly attenuated these calcification signals in AVICs compared with miR-control. RNA pull-down assay revealed that miR-34a directly targeted Notch1 expression by binding to Notch1 mRNA 3' untranslated region. In wire injury CAVS mice, locked nucleic acid miR-34a inhibitor suppressed aortic velocity, calcium deposition of aortic valves, and cardiac hypertrophy, which were involved in decreased Runx2 and increased Notch1 expressions. CONCLUSION: miR-34a plays an important role in the development of CAVS via Notch1-Runx2 signalling pathway. Inhibition of miR-34a may be the therapeutic target for CAVS.

Cardiac Nuclear High-Mobility Group Box 1 Ameliorates Pathological Cardiac Hypertrophy by Inhibiting DNA Damage Response.

High-mobility group box 1 (HMGB1) is a deoxyribonucleic acid (DNA)-binding protein associated with DNA repair. Decreased nuclear HMGB1 expression and increased DNA damage response (DDR) were observed in human failing hearts. DNA damage and DDR as well as cardiac remodeling were suppressed in cardiac-specific HMGB1 overexpression transgenic mice after angiotensin II stimulation as compared with wild-type mice. In vitro, inhibition of HMGB1 increased phosphorylation of extracellular signal-related kinase 1/2 and nuclear factor kappa B, which was rescued by DDR inhibitor treatment. DDR inhibitor treatment provided a cardioprotective effect on angiotensin II-induced cardiac remodeling in mice.

Novel Treatment of Hypertension by Specifically Targeting E2F for Restoration of Endothelial Dihydrofolate Reductase and eNOS Function Under Oxidative Stress.

We have shown that hydrogen peroxide (H2O2) downregulates tetrahydrobiopterin salvage enzyme DHFR (dihydrofolate reductase) to result in eNOS (endothelial NO synthase) uncoupling and elevated blood pressure. Here, we aimed to delineate molecular mechanisms underlying H2O2 downregulation of endothelial DHFR by examining transcriptional pathways hypothesized to modulate DHFR expression and effects on blood pressure regulation of targeting these novel mechanisms. H2O2 dose and time dependently attenuated DHFR mRNA and protein expression and enzymatic activity in endothelial cells. Deletion of E2F-binding sites, but not those of Sp1 (specificity protein 1), abolished H2O2 attenuation of DHFR promoter activity. Overexpression of E2F1/2/3a activated DHFR promoter at baseline and alleviated the inhibitory effect of H2O2 on DHFR promoter activity. H2O2 treatment diminished mRNA and protein expression of E2F1/2/3a, whereas overexpression of E2F isoforms increased DHFR protein levels. Chromatin immunoprecipitation assay indicated direct binding of E2F1/2/3a to the DHFR promoter, which was weakened by H2O2. E2F1 RNA interference attenuated DHFR protein levels, whereas its overexpression elevated tetrahydrobiopterin levels and tetrahydrobiopterin/dihydrobiopterin ratios in vitro and in vivo. In Ang II (angiotensin II)-infused mice, adenovirus-mediated overexpression of E2F1 markedly abrogated blood pressure to control levels, by restoring endothelial DHFR function to improve NO bioavailability and vasorelaxation. Bioinformatic analyses confirmed a positive correlation between E2F1 and DHFR in human endothelial cells and arteries, and downregulation of both by oxidized phospholipids. In summary, endothelial DHFR is downregulated by H2O2 transcriptionally via an E2F-dependent mechanism, and that specifically targeting E2F1/2/3a to restore DHFR and eNOS function may serve as a novel therapeutic option for the treatment of hypertension.

Impact of Impaired Pancreatic ß-Cell Function on Cardiovascular Prognosis in Heart Failure Patients Without Diabetes Mellitus.

Background: Insulin resistance as assessed using homeostasis model assessment ratio (HOMA-R) is associated with latent myocardial damage in apparently healthy subjects in health check. Meanwhile, diabetes mellitus (DM) is an unfavorable prognostic risk factor in patients with heart failure (HF). We examined the impact of pancreatic ß-cell dysfunction on clinical outcomes in HF patients without DM. Methods and Results: This study enrolled 312 HF patients without DM. Pancreatic ß-cell dysfunction was defined as HOMA-ß <30%. A total of 108 patients (35%) had ß-cell dysfunction. Plasma brain natriuretic peptide was higher in patients with pancreatic ß-cell dysfunction compared with those without (625.2 vs. 399.0 pg/mL, P<0.001). On Kaplan-Meier analysis, a significantly higher cardiovascular events rate was observed in patients with pancreatic ß-cell dysfunction (log-rank test, P=0.001), but there was no significant difference between patients with and without insulin resistance. On Cox hazard analysis, pancreatic ß-cell dysfunction was independently associated with cardiovascular events after adjustment for confounding factors (HR, 1.58; 95% CI: 1.02-2.45), whereas insulin resistance was not associated with cardiovascular events. Conclusions: Pancreatic ß-cell dysfunction, but not insulin resistance, was associated with unfavorable outcome in HF patients without DM.

Combined assessment of myocardial damage and electrical disturbance in chronic heart failure.

AIM: To investigate feasibility of combined assessment of biochemical and electrophysiological myocardial impairment markers risk-stratifying patients with chronic heart failure (CHF). METHODS: Serum levels of heart-type fatty acid binding protein (H-FABP) as a marker of ongoing myocardial damage and QRS duration on electrocardiogram were measured at admission in 322 consecutive patients with CHF. A prolonged QRS duration was defined as 120 ms or longer. The cut-off value for H-FABP level (4.5 ng/mL) was determined from a previous study. Patients were prospectively followed during a median follow up period of 534 d. The primary endpoint was cardiac deaths and rehospitalization for worsening CHF. RESULTS: There were 117 primary events, including 27 cardiac deaths and 90 rehospitalizations. Patients were stratified into four groups according to H-FABP level and QRS duration (≥ 120 ms). Multivariate analysis demonstrated that high H-FABP levels [hazard ratio (HR) = 1.745, P = 0.021] and QRS prolongation (HR 1.612, P = 0.0258) were independent predictors of cardiac events. Kaplan-Meier analysis demonstrated that the combination of high H-FABP levels and QRS prolongation could be used to reliably stratify patients at high risk for cardiac events (log rank test P < 0.0001). CONCLUSION: Combined assessment of myocardial damage and electrical disturbance can be used to risk-stratify patients with CHF.