Mapping of Purkinje-related ventricular arrhythmias by a multispline catheter with small and close-paired electrodes: Comparison with conventional catheters.

BACKGROUND: Precise mapping of the Purkinje fiber network is essential in catheter ablation of Purkinje-related ventricular arrhythmias (PrVAs). We sought to evaluate the mapping ability of a multi-spline duodecapolar catheter (PentaRay) for PrVAs. METHODS: Mappings of Purkinje fibers by PentaRay catheters were compared with those by conventional mapping catheters in consecutive patients undergoing catheter ablation of PrVAs from 2015 to 2022. RESULTS: Sixteen PrVAs (7 premature ventricular contractions or non-reentrant fascicular tachycardias [PVCs/NRFTs] and 9 fascicular ventricular tachycardias [FVTs]) were retrospectively studied. In PVCs/NRFTs, earliest preceding Purkinje potentials (PPs) could be recorded by the PentaRay catheters but not by the mapping and ablation catheters in 5 cases. At the earliest PP sites, the precedence from the QRS onset was greater, and the amplitude of the preceding potentials was higher in the PentaRay catheter compared with those in the mapping and ablation catheter (-62.0 ± 42.8 vs. -29.4 ± 34.2 ms, P = 0.02; 0.45 ± 0.43 vs. 0.09 ± 0.08 mV, P = 0.02). In FVTs, late diastolic potentials (P1) were recorded by the PentaRay catheters but not by the mapping and ablation catheters or the linear duodecapolar catheter in 2 cases. The amplitude of P1 was higher in the PentaRay catheter compared with that in the linear duodecapolar catheter and the mapping and ablation catheters (0.72 ± 0.49 vs. 0.17 ± 0.18 vs. 0.27 ± 0.21 mV, P = 0.0006, P = 0.002). The localized critical PPs, defined as the earliest preceding potentials in PVCs/NRFTs and P1 in FVTs, could be recorded in all the patients by the PentaRay catheter. The mapping ability of critical PPs of PrVAs was better with the PentaRay catheter than with the conventional mapping catheters (16/16 vs. 9/16, P = 0.004 by McNemar exact test). CONCLUSIONS: The PentaRay catheter has clinical advantages in mapping of the Purkinje fiber network to reveal critical PPs as ablation targets of PrVAs.

A scoring evaluation for the practical introduction of guideline-directed medical therapy in heart failure patients.

AIMS: The guideline-directed medical therapy (GDMT) has been recommended for heart failure (HF) with reduced ejection fraction (HFrEF) based on the accumulating clinical evidence. However, it is difficult to implement all the trial-proven medications for every patient in the real world. METHODS AND RESULTS: A simple GDMT score was created, according to the combination of GDMT drugs (renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose transporter 2 inhibitors) administration and their dosage (0-9 points). Its impact on the prognosis of HF patients was investigated. Admitted HF patients [HFrEF and HF with mildly reduced ejection fraction (HFmrEF), n = 1054] were retrospectively analysed (excluding those with in-hospital death and dialysis). A simple GDMT score ≥5, but not the number of medications, was significantly associated with a reduction of all-cause death, HF readmission, and composite outcome (HF readmission and all-cause death) (P < 0.001). Subgroup analysis showed that almost all groups with a simple GDMT score of 5 or higher had a better prognosis. CONCLUSIONS: The developed simple GDMT score was associated with prognosis in HFrEF and HFmrEF patients. Even if all four drugs cannot be introduced for some reason, a regimen with a simple GDMT score ≥5 may lead to a prognosis in HF patients.

Electrophysiological features of repetitive focal Purkinje ventricular arrhythmias originating from the proximal cardiac conduction system.

Background: Focal Purkinje ventricular arrhythmias (VAs) might originate from the vicinity of the proximal portion of the cardiac conducting system. This study aimed to clarify the features associated with focal Purkinje VAs originating from the proximal conduction system. Methods: A total of 18 patients with focal Purkinje VAs undergoing radiofrequency catheter ablation (RFCA) were retrospectively examined and divided into the proximal type or the non-proximal type. The proximal type was defined as having the origin at the proximal half of the interventricular septum, or the proximal half and the septal side of the anterior wall. The 12-lead electrocardiogram and electrophysiological findings were investigated. Results: Seven patients met criteria for proximal type of focal Purkinje VA. Out of the 7, 4 patients with proximal VAs had multiple QRS morphologies of VAs clinically, whereas out of 11 patients with non-proximal VAs, only 1 had multiple morphologies (p = .047). VA QRS duration was shorter in the proximal type than in the non-proximal type (111.2 ± 19.8 ms vs. 135.7 ± 17.7 ms; p = .003). The absolute axis difference between sinus rhythm and VA was smaller in the proximal type (80.4 ± 46.1°vs. 138.8 ± 59.6°; p = .014). The absolute axis difference ≤134° was useful in distinguishing the two types. Recurrence of VA was recorded in 3 proximal type patients and 3 non-proximal type patients. No procedure-related conduction block was observed. Conclusion: A VA of absolute axis difference ≤134°, and multiple QRS morphologies of clinical VAs indicate a proximal origin. Focal Purkinje VAs from proximal origins can be suppressed by RFCA without severe conduction disturbance.

Successful recovery of tachycardia-induced cardiomyopathy with severely depressed left ventricular systolic function by catheter ablation with mechanical hemodynamic support: a case report.

We describe the case that persistent atrial fibrillation refractory to rhythm control by pharmacotherapy and electrical cardioversions caused tachycardia-induced cardiomyopathy with low ejection fraction and hemodynamic instability. Mechanical hemodynamic support using an intra-aortic balloon pump is one of the choices of hemodynamic support during catheter ablation by pulmonary vein isolation.

Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure.

BACKGROUND: Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure. METHODOLOGY/PRINCIPAL FINDINGS: MI-induced heart failure model rats were created by ligation of left coronary artery. The expression level of TLR4 in brainstem was significantly higher in MI-induced heart failure treated with intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in brainstem was significantly lower in MI-induced heart failure treated with ICV injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA. Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were significantly lower and LV dimension was significantly smaller in MI-induced heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for 2 weeks. CONCLUSIONS: Partially silencing brain TLR4 by ICV injection of TLR4-SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of the treatment for MI-induced heart failure.

Inhibition of oxidative stress in rostral ventrolateral medulla improves impaired baroreflex sensitivity in stroke-prone spontaneously hypertensive rats.

Reactive oxygen species (ROS) in rostral ventrolateral medulla (RVLM) of brainstem contribute to sympathoexcitation and are critically involved in the pathogenesis of hypertension. Baroreflex sensitivity (BRS) is a valuable prognostic parameter of the autonomic nervous system, and is impaired in hypertension. The aim of the present study was to determine whether or not a chronic reduction of ROS in the RVLM improves impaired BRS in hypertensive rats. We transfected adenovirus vectors encoding either manganese superoxide dismutase (AdMnSOD) or ß-galactosidase (AdLacZ) into the RVLM of stroke-prone spontaneously hypertensive rats (SHRSP). We measured BRS using the spontaneous sequence method. BRS was significantly lower in SHRSPs than in Wistar-Kyoto rats. In the AdMnSOD-transfected SHRSP, blood pressure, heart rate, and sympathetic nervous system activation were significantly decreased from day 5 after the gene transfer. BRS in the AdMnSOD-transfected SHRSP was significantly increased from day 4 after the gene transfer with the reduction of ROS in the RVLM. Furthermore, in the AdMnSOD-transfected SHRSP, intravenous infusion of atropine dramatically decreased BRS. In contrast, in the AdLacZ-transfected SHRSP, atropine did not decrease BRS. These results suggest that chronic reduction of ROS in the local RVLM improves the impaired BRS in SHRSP through inhibition of the sympathetic component.

Exercise training causes sympathoinhibition through antioxidant effect in the rostral ventrolateral medulla of hypertensive rats.

Exercise training normalizes sympathetic outflow in hypertension and chronic heart failure. The aim of this study was to determine whether the exercise training inhibits sympathetic nerve activity (SNA) via reduction of oxidative stress through blocked angiotensin II type 1 receptor (AT(1)R) in rostral ventrolateral medulla (RVLM). We divided stroke-prone spontaneously hypertensive rats (SHRSP) into SHRSP with exercised training (SHRSP-EX) and control (SHRSP-C). SNA and oxidative stress in the RVLM were significantly lower in SHRSP-EX than in SHRSP-C. These results suggest that exercise training inhibits SNA via reduction of oxidative stress through blocked AT(1)R in the RVLM of hypertension.

Combination therapy of olmesartan and azelnidipine inhibits sympathetic activity associated with reducing oxidative stress in the brain of hypertensive rats.

It has been demonstrated that the antihypertensive drugs with the antioxidant action on the brainstem inhibit the sympathetic activity and consequently decrease blood pressure and heart rate (HR) in hypertensive rats. Combination drugs of the angiotensin receptor blocker and calcium channel blocker, such as olmesartan (OLM)/azelnidipine (AZ) and candesartan (CAN)/amlodipine (AM), are widely used for treating hypertension in Japan. In this study, it was investigated whether there are differences in the antioxidant effect in the brain and the sympathoinhibitory effect between OLM/AZ and CAN/AM combination therapies in stroke-prone spontaneously hypertensive rats (SHRSP). OLM/AZ (10/8 mg kg(-1) day(-1)), CAN/AM (4/2.5 mg kg(-1) day(-1)), or vehicle was orally administered for 30 days to SHRSP. OLM/AZ and CAN/AM markedly decreased systolic blood pressure to the same extent. OLM/AZ decreased HR to a greater extent than CAN/AM. Urinary norepinephrine excretion as a marker of sympathetic activity was unchanged in the CAN/AM group, but reduced in the OLM/AZ group. Oxidative stress in the whole brain assessed using the in vivo electron spin resonance method was similarly decreased in both OLM/AZ and CAN/AM groups. Importantly, thiobarbituric acid reactive substance levels in the brainstem were significantly lower in the OLM/AZ group, but not in the CAN/AM group, than in the vehicle group. These results suggest that combination therapy of either OLM/AZ or CAN/AM does not induce reflex-mediated sympathetic activation despite the marked blood pressure reduction, which is associated with an antioxidant effect in the brain regions affecting the sympathetic activity. Furthermore, the antioxidant effect in the brainstem and the sympathoinhibitory effect of OLM/AZ combination may be greater than those of CAN/AM combination treatment.

Brain AT1 receptor activates the sympathetic nervous system through toll-like receptor 4 in mice with heart failure.

The activation of angiotensin II type 1 receptor (AT1R) in the brain plays a pivotal role in enhanced sympathetic drive in heart failure (HF). Activation of the AT1R in the brain produces oxidative stress and inflammation. Toll-like receptor 4 (TLR4) signaling in the brain induces the inflammatory cascade. We hypothesized that sympathoexcitation is mediated by the AT1R-activated TLR4 in the brainstem in HF. As a model of HF, the left coronary artery was ligated to induce a large myocardial infarction and subsequent chronic heart failure (CHF) in Institute of Cancer Research mice. On day 10 after the surgery, we started intracerebroventricular infusion of losartan (CHF-Los) or vehicle (CHF-Veh) via osmotic minipumps for 14 days. Expression level of the TLR4 in the brainstem was significantly higher in HF mice than in sham mice and significantly lower in CHF-Los mice than in CHF-Veh mice. Urinary norepinephrine excretion was significantly higher in HF mice than in sham mice and was significantly lower in CHF-Los than in CHF-Veh. Chronic intracerebroventricular infusion of angiotensin II increased the expression level of the second messenger of the TLR4. These results suggest that activation of the TLR4 via AT1R in the brainstem contributes to the sympathoexcitation probably due to the inflammation in the brain of the myocardial infarction-induced HF.

Calorie restriction inhibits sympathetic nerve activity via anti-oxidant effect in the rostral ventrolateral medulla of obesity-induced hypertensive rats.

In the patients and animals with metabolic syndrome (MetS), sympathetic nerve activity (SNA) is increased. We have demonstrated that oxidative stress in the rostral ventrolateral medulla (RVLM), a vasomotor center in the brainstem, increases SNA. The aim of the present study was to determine whether calorie restriction inhibits SNA via anti-oxidant effect in the RVLM of obesity-induced obesity rats. Male Sprague-Dawley rats were fed on a high-fat diet and segregated into obesity-prone (OP) showing a MetS profile and obesity-resistant (OR) after 13 weeks. Obesity-prone was divided into OP treated with calorie restriction (CR-OP) for 8 weeks and control (CTR-OP). Systolic blood pressure (SBP), heart rate (HR), SNA, and thiobarbituric acid-reactive substances (TBARS) levels as a marker of oxidative stress in the RVLM were significantly higher and the depressor effects due to the microinjection of tempol, a superoxide dismutase mimetic into the RVLM, were significantly greater in OP than in OR. Body weight was significantly lower in CR-OP than in CTR-OP. SBP, HR, SNA, TBARS, and the depressor effects due to the microinjection of tempol into the RVLM were significantly lower in CR-OP than in CTR-OP. These results suggest that calorie restriction inhibits SNA via anti-oxidant effect in the RVLM of obesity-induced obesity rats.

Angiotensin II type 1 receptor-activated caspase-3 through ras/mitogen-activated protein kinase/extracellular signal-regulated kinase in the rostral ventrolateral medulla is involved in sympathoexcitation in stroke-prone spontaneously hypertensive rats.

In the rostral ventrolateral medulla (RVLM), angiotensin II-derived superoxide anions, which increase sympathetic nerve activity, induce a pressor response by activating the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK) pathway. The small G protein Ras mediates a caspase-3-dependent apoptotic pathway through p38 MAPK, ERK, and c-Jun N-terminal kinase. We hypothesized that angiotensin II type 1 receptors activate caspase-3 through the Ras/p38 MAPK/ERK/c-Jun N-terminal kinase pathway in the RVLM and that this pathway is involved in sympathoexcitation in stroke-prone spontaneously hypertensive rats (SHRSP), a model of human hypertension. The activities of Ras, p38 MAPK, ERK, and caspase-3 in the RVLM were significantly higher in SHRSP (14 to 16 weeks old) than in age-matched Wistar-Kyoto rats (WKY). The mitochondrial apoptotic proteins Bax and Bad in the RVLM were significantly increased in SHRSP compared with WKY. c-Jun N-terminal kinase activity did not differ between SHRSP and WKY. In SHRSP, intracerebroventricular infusion of a Ras inhibitor significantly reduced sympathetic nerve activity and improved baroreflex sensitivity, partially because of inhibition of the Ras/p38 MAPK/ERK, Bax, Bad, and caspase-3 pathway in the RVLM. Intracerebroventricular infusion of a caspase-3 inhibitor also inhibited sympathetic nerve activity and improved baroreflex sensitivity in SHRSP. Intracerebroventricular infusion of an angiotensin II type 1 receptor blocker in SHRSP partially inhibited the Ras/p38 MAPK/ERK, Bax, Bad, and caspase-3 pathway in the RVLM. These findings suggest that in SHRSP, angiotensin II type 1 receptor-activated caspase-3 acting through the Ras/p38 MAPK/ERK pathway in the RVLM might be involved in sympathoexcitation, which in turn plays a crucial role in the pathogenesis of hypertension.

Intracardiac echocardiography-guided cardiac tumor biopsy.

A 63-year-old woman was admitted to hospital with the chief complaint of new onset chest discomfort and pretibial pitting edema. Transthoracic echocardiography revealed a large invasive tumor on the heart protruding into the right atrium and right ventricle, which obstructed the outflow tract. She underwent transvenous 9Fr, 9-MHz ultra intracardiac echocardiography (ICE) (EP Technologies, Boston Scientific Corporation, San Jose, CA, USA) guided biopsy, and a diagnosis of malignant lymphoma was established from the specimen obtained. ICE-guided cardiac tumor biopsy may be one of the most useful strategies for diagnosis of cardiac tumors.