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.

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.

The Neutrophil-to-Lymphocyte Ratio Predicts All-Cause Mortality in Patients with Implantable Cardioverter Defibrillators.

BACKGROUND: The relationship between the neutrophil-to-lymphocyte ratio (NLR) and outcome in patients with implantable cardioverter-defibrillators (ICDs) is unclear. METHODS AND RESULTS: Consecutive patients with cardiomyopathy who had received an ICD (n = 120, mean age 64 ± 11 years) were prospectively enrolled. Blood samples were obtained on the morning of the day of implantation. Patients were followed for a median period of 61.2 months, to an endpoint of all-cause mortality or appropriate ICD shock, which occurred in 35 (29%) and 28 (23%) patients, respectively. Multivariate Cox analysis revealed that secondary prevention was only associated with appropriate ICD shocks. The NLR, brain natriuretic peptide level, and estimated glomerular filtration rate were independent predictors of all-cause mortality but not of appropriate ICD shocks. Subgroup analysis revealed that a high NLR (≥2.1) was valuable for anticipating all-cause mortality among patients who had received ICDs for primary or secondary prevention. A high NLR was also associated with death prior to appropriate ICD shock. CONCLUSION: Evaluating the NLR may be useful for predicting outcomes in patients with cardiomyopathy who have received ICDs.

Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome.

The importance of the central nervous system in cardiovascular events has been recognized. Recently, brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is involved in depression mechanisms and also in stress and anxiety. Because BDNF is reported about cardioprotective role, we elucidated whether BDNF is associated with cardiovascular events in patients with chronic heart failure (CHF). We examined serum BDNF levels in 134 patients with CHF and 23 control subjects. The patients were followed to register cardiac events for a median of 426 days. BDNF was significantly lower in CHF patients than in control subjects (25.8 ± 8.4 vs 14.7 ± 8.4, P < 0.0001). Serum BDNF was also lower in patients with cardiac events than in event-free patients (16.1 ± 8.0 vs 12.5 ± 8.5, P < 0.0001). The cutoff value of BDNF was determined by performing receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that patients with low levels of BDNF experienced higher rates of cardiac events than those with high levels of BDNF. Multivariate Cox hazard analysis demonstrated that low BDNF levels (≤12.4 ng/mL) were an independent prognostic factor for cardiac events (hazard ratio 2.932, 95 % confidence interval 1.622-5.301; P = 0.0004). Adding levels of BDNF to the model with BNP levels, age, and eGFR for the prediction of cardiac events yielded significant net reclassification improvement of 0.429 (P < 0.001) and an integrated discrimination improvement of 0.101 (P < 0.001). Low serum BDNF levels were found in patients with CHF, and these levels were found to be independently associated with an increased risk of cardiac events.

Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion.

Early myocardial reperfusion is an effective therapy but ischemia/reperfusion (I/R) causes lethal myocardial injury. The aging heart was reported to show greater cardiac damage after I/R injury than that observed in young hearts. Senescence marker protein 30 (SMP30), whose expression decreases with age, plays a role in reducing oxidative stress and apoptosis. However, the impact of SMP30 on myocardial I/R injury remains to be determined. In this study, the left anterior descending coronary artery was occluded for 30 min, followed by reperfusion in wild-type (WT) and SMP30 knockout (KO) mice. After I/R, cardiomyocyte apoptosis and the ratio of infarct area/area at risk were higher, left ventricular fractional shortening was lower, and reactive oxygen species (ROS) generation was enhanced in SMP30 KO mice. Moreover, the previously increased phosphorylation of GSK-3ß and Akt was lower in SMP30 KO mice than in WT mice. In cardiomyocytes, silencing of SMP30 expression attenuated Akt and GSK-3ß phosphorylation, and increased Bax to Bcl-2 ratio and cardiomyocyte apoptosis induced by hydrogen peroxide. These results suggested that SMP30 deficiency augments myocardial I/R injury through ROS generation and attenuation of Akt activation.

High-mobility group box 1-mediated heat shock protein beta 1 expression attenuates mitochondrial dysfunction and apoptosis.

AIMS: Apoptosis of cardiomyocytes is thought to account for doxorubicin cardiotoxicity as it contributes to loss of myocardial tissue and contractile dysfunction. Given that high-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein capable of inhibiting apoptosis, we aimed to clarify the role of HMGB1 in heat shock protein beta 1 (HSPB1) expression during doxorubicin-induced cardiomyopathy. METHODS AND RESULTS: Mitochondrial damage, cardiomyocyte apoptosis, and cardiac dysfunction after doxorubicin administration were significantly attenuated in mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) compared with wild type (WT) -mice. HSPB1 levels after doxorubicin administration were significantly higher in HMGB1-Tg mice than in WT mice. Transfection with HMGB1 increased the expression of HSPB1 at both the protein and mRNA levels, and HMGB1 inhibited mitochondrial dysfunction and apoptosis after exposure of cardiomyocytes to doxorubicin. HSPB1 silencing abrogated the inhibitory effect of HMGB1 on cardiomyocyte apoptosis. Doxorubicin increased the binding of HMGB1 to heat shock factor 2 and enhanced heat shock element promoter activity. Moreover, HMGB1 overexpression greatly enhanced heat shock element promoter activity. Silencing of heat shock factor 2 attenuated HMGB1-dependent HSPB1 expression and abrogated the ability of HMGB1 to suppress cleaved caspase-3 accumulation after doxorubicin stimulation. CONCLUSIONS: We report the first in vivo and in vitro evidence that cardiac HMGB1 increases HSPB1 expression and attenuates cardiomyocyte apoptosis associated with doxorubicin-induced cardiomyopathy. Cardiac HMGB1 increases HSPB1 expression in cardiomyocytes in a heat shock factor 2-dependent manner.

A novel mouse model of aortic valve stenosis induced by direct wire injury.

OBJECTIVE: The response-to-tissue-injury theory is currently the favorite paradigm to investigate valve pathology. To the best of our knowledge, there are currently no in vivo valve injury models. There are few calcific aortic valve stenosis (AVS) models that develop hemodynamically significant stenosis. Here, we investigated the effect of direct mechanical injury on aortic valves in vivo and developed a novel mouse model of calcific AVS. APPROACH AND RESULTS: Aortic valve injury was created by inserting and moving a spring guidewire under echocardiographic guidance into the left ventricle of male C57/BL6 mice via right common carotid artery. Serial echocardiographic measurements revealed that aortic velocity was increased 1 week after injury and persistently increased until 16 weeks after injury. AVS mice showed a higher heart weight/body weight ratio and decreased left ventricular fractioning shortening 4 weeks after injury, compared with sham mice. We found remarkable proliferation of valve leaflets 4 weeks after injury. Proliferative valves showed increased production of reactive oxygen species and expression of inflammatory cytokines and osteochondrogenic factors. Alizarin red staining showed valvular calcification 12 weeks after injury. CONCLUSIONS: We report a novel calcific AVS model to support the response-to-tissue-injury theory. This model may be a valuable tool for analyzing the mechanism of AVS and assessing therapeutic options.

Midkine exacerbates pressure overload-induced cardiac remodeling.

Midkine is a multifunctional growth factor, and its serum levels are increased with the functional severity of heart failure. This study aimed to examine the role of midkine in heart failure pathogenesis. Midkine expression levels were increased in the kidney and lung after transverse aortic constriction (TAC) surgery, but not sufficiently increased in the heart. After TAC, phosphorylation of extracellular signal-regulated kinase1/2 and AKT, and the expression levels of foetal genes in the heart were considerably increased in transgenic mice with cardiac-specific overexpression of midkine (MK-Tg) compared with wild-type (WT) mice. MK-Tg mice showed more severe cardiac hypertrophy and dysfunction, and showed lower survival rate after TAC than WT mice. We conclude that midkine plays a critical role in cardiac hypertrophy and remodelling.

Impact of serum omentin-1 levels on cardiac prognosis in patients with heart failure.

BACKGROUND: Various adipokines are reported to be associated with the development of heart failure (HF) through insulin resistance and chronic inflammation. Omentin-1 is a novel adipokine and is associated with incident coronary artery disease. However, it remains unclear whether serum omentin-1 levels are associated with cardiac prognosis in patients with HF. METHODS: We measured serum omentin-1 levels at admission in 136 consecutive patients with HF, and 20 control subjects without signs of significant heart disease. We prospectively followed patients with HF to endpoints of cardiac death or re-hospitalization for worsening HF. RESULTS: Serum omentin-1 levels were markedly lower in HF patients with cardiac events compared with to without. The patients who were in New York Heart Association (NYHA) functional class IV showed significantly lower serum omentin-1 levels compared to those in class II and III, whereas serum omentin-1 levels did not correlate with serum brain natriuretic peptide levels (r = 0.217, P = 0.011). We divided the HF patients into three groups based on the tertiles of serum omentin-1 level (low T1, middle T2, and high T3). Multivariate Cox hazard analysis showed that the lowest serum omentin-1 level (T1) was independently associated with cardiac events after adjustment for confounding factors (hazard ratio 5.78, 95% confidence interval 1.20-12.79). We divided the HF patients into two groups according to the median serum omentin-1 levels. Kaplan-Meier analysis revealed that the patients with low serum omentin-1 levels had a higher risk of cardiac events compared with those with high serum omentin-1 levels (log-rank test p < 0.001). CONCLUSION: Decreased serum omentin-1 levels were associated with a poor cardiac outcome in patients with HF.

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.

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.

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.