Hisanori Kanazawa

Heart rate on admission is an independent risk factor for poor cardiac function and in-hospital death after acute myocardial infarction

BACKGROUND Increased resting heart rate (HR) due to sympathetic hyperactivity is associated with coronary risk factors and increased cardiovascular events. Acute myocardial infarction (AMI) is accompanied by autonomic imbalance, which is characterized by sympathetic activation and parasympathetic inactivation. Although an increased HR in patients with acute coronary syndrome has been reported to be associated with 30-day and 6-month mortality before the coronary intervention era, it is unclear if an increased HR on admission is associated with the prognosis of AMI in the coronary intervention era. METHODS We enrolled 200 consecutive patients with AMI within 24 h of symptom onset. All patients underwent coronary angiography. They were divided into quartiles based on resting HR on admission. RESULTS There was no difference in coronary risk factors and previous medical treatment among the four groups. Anterior AMI was significantly lower in the lowest quartile compared with other quartiles. There was no difference in peak creatine kinase value among the four groups, however left ventricular ejection fraction (LVEF) before discharge evaluated by echocardiography in the highest quartile group was significantly reduced compared to other quartiles. An increased HR was significantly associated with in-hospital death. Patients in the highest quartile of HR were about nine times more likely to have a poor prognosis after AMI compared to those in the lowest quartile. Multiple logistic analysis revealed that HR ≥93 was an independent risk factor for in-hospital death. HR was significantly associated with Killip class and LVEF on admission. CONCLUSIONS These findings indicate that increased HR on admission predicts for poor cardiac function and in-hospital death after AMI.

Importance of pericardial fat in the formation of complex fractionated atrial electrogram region in atrial fibrillation

BACKGROUND/OBJECTIVES Pericardial fat (PF) and complex fractionated atrial electrogram (CFAE) are both associated with atrial fibrillation (AF). Therefore, we examined the relation between PF and CFAE area in AF. METHODS The study population included 120 control patients without AF and 120 patients with AF (80 paroxysmal AF and 40 persistent AF) who underwent catheter ablation. Total cardiac PF volume, representing all adipose tissue within the pericardial sac, was measured by contrast-enhanced computed tomography. The location and distribution of CFAE region were identified by left atrial endocardial mapping using a three-dimensional mapping system. We analyzed the significance of total cardiac PF volume and total area of CFAE region on AF, persistence of AF from paroxysmal to persistent form, and the relation between total cardiac PF volume and total CFAE area. We also evaluated the regional distribution of PF volume and CFAE area in five areas of the left atrium (LA). RESULTS Total cardiac PF volume correlated with AF (odds ratio [OR]: 1.024, p<0.001). Total cardiac PF volume and total CFAE area were both independently associated with persistence of AF (OR: 1.018, p=0.018, OR: 1.144, p=0.002, respectively). Multivariate linear regression analysis identified total cardiac PF volume as a significant and independent determinant of total CFAE area (r=0.488, p<0.001). Furthermore, regional PF volume correlated with local CFAE area in an each LA area. CONCLUSIONS PF volume correlated significantly with CFAE area in patients with AF. This finding suggests that PF is directly related to the progression of CFAE area and promotes the pathogenic process of AF.

Total Thrombus‐Formation Analysis System (T‐TAS) Can Predict Periprocedural Bleeding Events in Patients Undergoing Catheter Ablation for Atrial Fibrillation

Background Non–vitamin K antagonist oral anticoagulants are used to prevent thromboembolism in patients with atrial fibrillation. The T‐TAS “Total Thrombus‐formation Analysis System” (Fujimori Kogyo Co Ltd) was developed for quantitative analysis of thrombus formation using microchips with thrombogenic surfaces (collagen, platelet chip [PL] ; collagen plus tissue factor, atheroma chip [AR]). We evaluated the utility of T‐TAS in predicting periprocedural bleeding in atrial fibrillation patients undergoing catheter ablation (CA). Methods and Results After exclusion of 20 from 148 consecutive patients undergoing CA, the remaining 128 patients were divided into 2 treatment groups: the warfarin group (n=30) and the non–vitamin K antagonist oral anticoagulants group (n=98). Blood samples obtained on the day of CA (anticoagulant‐free point) and at 3 and 30 days after CA were used in T‐TAS to compute the thrombus formation area under the curve (AUC; AUC for the first 10 minutes for PL tested at flow rate of 24 μL/min [PL 24‐AUC 10]; AUC for the first 30 minutes for AR tested at flow rate of 10 μL/min [AR 10‐AUC 30]). AR 10‐AUC 30 and PL 24‐AUC 10 levels were similar in the 2 groups on the day of CA. Levels of AR 10‐AUC 30, but not PL 24‐AUC 10, were significantly lower in the 2 groups at days 3 and 30 after CA. Multiple logistic regression analyses identified the AR 10‐AUC 30 level on the day of CA as a significant predictor of periprocedural bleeding events (odds ratio 5.7; 95% CI 1.54–21.1; P=0.009). Receiver operating characteristic analysis showed that the AR 10‐AUC 30 level on the day of CA significantly predicted periprocedural bleeding events (AUC 0.859, 95% CI 0.766–0.951; P<0.001). The cutoff AR 10‐AUC 30 level was 1648 for identification of periprocedural bleeding events. Conclusions These results suggested that the AR 10‐AUC 30 level determined by T‐TAS is a potentially useful marker for prediction of bleeding events in atrial fibrillation patients undergoing CA.

Demonstration of anatomical reentrant tachycardia circuit in verapamil-sensitive atrial tachycardia originating from the vicinity of the atrioventricular node

BACKGROUND The anatomical location of the reentry circuit in verapamil-sensitive atrial tachycardia originating from the vicinity of atrioventricular node (V-AT) is not well clarified. OBJECTIVE To define the reentry circuit of V-AT. METHODS In 17 patients with V-AT, rapid atrial pacing at a rate 5 beats/min faster than the tachycardia rate was delivered from multiple sites of the right atrium (RA) during tachycardia to define the direction of the proximity of the slow conduction area of the reentry circuit. After identification of manifest entrainment and orthodromic capture of the earliest atrial activation site (EAAS), radiofrequency energy was delivered starting at a site 2 cm away from the EAAS in the direction of the pacing site. Radiofrequency energy application site was then gradually advanced toward EAAS until the termination of tachycardia to define the entrance of the slow conduction area. RESULTS The EAAS was orthodromically captured by pacing delivered from one of the high anterolateral RA (n = 6), high posteroseptal RA (n = 9), and RA appendage (n = 2). Radiofrequency energy delivery to the site, 10.1 ± 2.8 mm away from the EAAS, terminated V-AT immediately after the onset of delivery (2.9 ± 1.0 seconds). The successful ablation site located outside the Kochs triangle, being more distant from the His bundle site than the EAAS (12.4 ± 2.9 vs 6.4 ± 1.9 mm; P <.0001). CONCLUSION The reentry circuit of V-AT located outside the Kochs triangle. V-AT was eliminated by the radiofrequency energy delivered to the entrance of the reentry circuit, which was more distant from the His bundle site than the EAAS, under the navigation of entrainment.

Analysis of the mechanisms initiating random wave propagation at the onset of atrial fibrillation using noncontact mapping: Role of complex fractionated electrogram region

BACKGROUND The complex fractionated atrial electrogram (CFAE) region has been suggested to contribute to the maintenance of atrial fibrillation (AF), but its role for the initiation of AF has not been clarified. OBJECTIVE We analyzed the mechanisms of the initiation of random reentrant wave propagation at AF onset, especially in relation to CFAE region. METHODS Endocardial mapping of the left atrium using a 3-dimensional noncontact mapping system was performed in 19 patients. RESULTS Thirty-two spontaneous AF onset episodes, which were initiated by the focal repetitive discharges (9 ± 9 beats), deriving from the pulmonary veins (PV) (n = 17) and from non-PV CFAE regions (n = 15) were observed. The coupling intervals of the focal discharges that initiated AF (AF-D) were significantly shorter than those that did not initiate AF (non-AF-D) (179 ± 33 ms vs. 217 ± 45 ms, P = .0005). After the AF-D, localized conduction blocks occurred in the CFAE region. Subsequently, the waves propagated to the remainder of the atrium, accompanying the anchored activation around the localized conduction block lines in the CFAE regions. Left atrial activation times of AF-D were significantly longer than those of non-AF-D (151 ± 35 ms vs. 83 ± 17 ms, P < .0001). These longer activation times after AF-D enabled the waves to reenter the previously blocked CFAE region from the opposite direction, and thus the meandering reentrant wave propagation was initiated. CONCLUSION Unidirectional conduction block in the CFAE region and subsequent prolonged left atrial activation time following short coupled premature discharge were the underlying mechanisms of AF initiation, suggesting the importance of the CFAE region as the substrate for AF onset.

Prevalence and mechanism of rotor activation identified during atrial fibrillation by noncontact mapping: Lack of evidence for a role in the maintenance of atrial fibrillation

BACKGROUND It remains unclear whether atrial fibrillation (AF) is maintained by the rotor. OBJECTIVE We evaluated the role of the rotor and examined its mechanism. METHODS Among 75 patients with AF (60 paroxysmal, 15 persistent AF) who underwent 3-dimensional noncontact left atrial mapping during AF, we examined the prevalence and location of rotor activation and elucidated its mechanism. Catheter ablation was performed in a stepwise fashion (linear roof lesion and complex fractionated atrial electrogram ablation after pulmonary vein [PV) isolation) until AF termination. RESULTS Rotor activation was observed in 11 patients (14.7%; 10 paroxysmal and 1 persistent AF) (tachycardia cycle length 160.0 ± 19.8 ms). Rotors were observed transiently (duration 6128 ± 9094 ms) during AF at the roof (n = 5), septum (n = 3), and ostium of the left superior PV (n = 3). Five rotors circulated in clockwise and 6 in counterclockwise directions. The length of the block line at the center of the rotor was 15.2 ± 6.9 mm. The electrograms at the block line showed low-amplitude multiple deflections (n = 7) or double potentials (n = 4), and the amplitudes during rotor activation were significantly lower than those during sinus rhythm (0.27 ± 0.18 mV vs 1.22 ± 0.92 mV; P < .01). No conduction disturbances were found during sinus rhythm, suggesting that the central line of block was formed functionally. AF was terminated by PV isolation alone without additional lesions in patients with rotors. CONCLUSION Functionally formed rotor activation was observed during AF in a limited number of patients. These rotor activations may not be related to AF maintenance, but rather may reflect a transient organization of random propagation.

Difference in the maintenance mechanism of atrial fibrillation perpetuated after pulmonary vein isolation between paroxysmal and persistent atrial fibrillation: Effects of subsequent stepwise ablation.

BACKGROUND Neither the atrial fibrillation (AF) maintenance mechanism after pulmonary vein isolation (PVI) nor the mechanism of AF termination via stepwise ablation is clearly understood. METHODS Among 226 consecutive AF patients (154 paroxysmal (P-AF) and 72 persistent AF (Per-AF) patients), left atrial endocardial non-contact mapping was performed after PVI in the initial 10 P-AF and 16 Per-AF patients to define the AF maintenance mechanism. Subsequently, effect of stepwise catheter ablation (linear roof lesion and complex fractionated atrial electrogram (CFAE) following PVI) was evaluated in all patients. RESULTS After PVI, AF was maintained by the activation around isolated PV/mitral annulus, focal discharge and disorganized activations mostly observed over residual CFAE region (pivoting activation, wave break and fusion). CFAE region in P-AF was smaller than Per-AF after PVI (1.6 ± 2.1 vs. 7.7 ± 2.5 cm(2), p<0.0001). The frequency of pivoting activation, wave break and fusion in P-AF were lower than those in Per-AF (1.9 ± 2.0 vs. 11.8 ± 5.0 times/s; p<0.0001, 0.1 ± 0.3 vs. 3.6 ± 2.5 times/s; p<0.001, 5.8 ± 3.6 vs. 9.8 ± 3.2 times/s; p<0.01). AF termination was more frequent in P-AF than Per-AF (94.8% vs 81.9%, p=0.0019). AF termination by PVI alone was more frequent in P-AF than Per-AF (85.6% vs. 18.6%, p<0.0001). However, AF termination via roof line and/or CFAE ablation was less frequent in P-AF than Per-AF (14.4 vs. 81.4%, p<0.0001). CONCLUSIONS Disorganized activations after PVI, more prominent in Per-AF, were associated with residual CFAE region. Most P-AF was terminated by PVI alone, however additional roof line lesion and CFAE ablation were necessary to terminate Per-AF, consistent with mapping results.

Coronary blood flow volume change is negatively associated with platelet aggregability in patients with non-obstructive ischemic heart disease who have no anti-platelet agents

BACKGROUND Thrombus formation is one of the main pathogeneses of acute coronary syndrome with atherosclerotic rupture. Previous studies have reported that atherosclerosis increases platelet aggregability and that vascular endothelial dysfunction reflects early change of atherosclerosis. However, the relationship between coronary endothelial dysfunction and platelet reactivity remains unclear. Therefore, in this study, we investigated the relationship between them in non-obstructive ischemic heart disease (IHD) patients. METHODS Three hundred sixty-eight consecutive stable patients with suspected angina presenting non-obstructive coronary arteries (<50% diameter) in coronary angiography were investigated with the intracoronary acetylcholine provocation test and measured adenosine triphosphate-induced coronary flow reserve. Finally, 25 non-obstructive IHD patients who had no anti-platelet agents were assessed for the relationship between coronary blood flow volume (CBFV) change and platelet aggregability as P2Y12 reaction unit (PRU) by VerifyNow P2Y12 assay system. RESULTS CBFV change by intracoronary 20 μg/kg per minute acetylcholine provocation showed a significant negative correlation with platelet aggregability as PRU (r = 0.44, P = 0.03). Conversely, there was no significant correlation between PRU and endothelial function as coronary flow reserve. Furthermore, multivariable linear regression analysis indicated that an incremental CBFV change was independently associated with PRU (β = 0.63, P < 0.001) in non-obstructive IHD patients. CONCLUSIONS In patients with non-obstructive IHD, CBFV change was significantly associated with platelet aggregability, indicating that coronary endothelial dysfunction might mediate higher platelet aggregability.

Serum Potassium and Cardiovascular Events in Heart Failure With Preserved Left Ventricular Ejection Fraction Patients

BACKGROUND Although serum potassium (sK) levels are closely associated with the prognosis of chronic heart failure patients, the clinical significance of sK levels in cardiovascular outcomes of heart failure with preserved ejection fraction (HFpEF) patients is not fully understood. METHODS This study was a retrospective, single-center, observational study. We enrolled 506 consecutive HFpEF patients admitted to Kumamoto University Hospital and divided them into four groups according to the quartiles of the sK levels at discharge (Q1: sK < 4.1 mEq/l, Q2: 4.1 ≤ sK < 4.4 mEq/l, Q3: 4.4 ≤ sK < 4.7 mEq/l, and Q4: sK ≥ 4.7 mEq/l). RESULTS No significant differences were observed in the use of all drugs (loop diuretics, mineralocorticoid receptor antagonists, renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, β-blockers, and statins) among the four groups. Hemoglobin, the estimated glomerular filtration rate, and pulse wave velocity levels were lower, and the serum sodium levels were higher in the Q4 group compared with those in the Q2 group. Kaplan-Meier analysis revealed significantly higher probabilities of both cardiovascular and HF-related events in the Q1, Q3, and Q4 groups than those in the Q2 group. Multivariate Cox proportional hazard analysis revealed that the Q1, Q3, and Q4 groups had significantly and independently higher probabilities of cardiovascular events compared with those in the Q2 group, indicating a J-shaped association between sK levels and cardiovascular events. CONCLUSIONS sK levels at discharge could provide important prognostic information in regard to HFpEF. Further evaluation in a larger number of patients might be needed. Clinical Trials Registration UMIN-CTR (http://www.umin.ac.jp/ctr/). Identifier UMIN000029600. Public Access Information Opt-out materials are available at the website: http://www.kumadai-junnai.com/home/wp-content/uploads/houkatsu.pdf.

Usefulness of non-contact mapping for catheter ablation of ventricular tachycardias originating at the right ventricular outflow tract

Different QRS morphologies are often observed in idiopathic ventricular tachycardias or premature ventricular contractions originating from the right ventricular outflow tract (RVOT). However, the precise mechanism underlying multiple QRS morphologies has not been clarified adequately. The purpose of this study was to examine the mechanism underlying different QRS morphologies in RVOT arrhythmia. We also investigated the usefulness of non‐contact mapping guided radiofrequency catheter ablation for RVOT arrhythmia.