How Electrical Storms Recur Over Time in Patients With Implantable Cardioverter Defibrillators　- Subanalysis of the Nippon Storm Study.

BACKGROUND: Electrical storms (E-storms), defined as multiple fatal ventricular arrhythmias over a short period, negatively affect the prognosis of patients receiving an implantable cardioverter defibrillator or cardiac resynchronization therapy with a defibrillator (ICD/CRT-D). However, the prognostic impact of recurrent E-storms has not been well elucidated. METHODS AND RESULTS: We analyzed the association between E-storm recurrences and mortality using data from 1,274 participants in the Nippon Storm Study, a prospective observational study conducted at 48 ICD/CRT-D centers in Japan. Differences in E-storm recurrences by patient characteristics were evaluated using the mean cumulative function (MCF), which is the cumulative number of E-storm episodes per patient as a function of time. Patients with multiple E-storms had a 3.39-fold higher mortality risk than those without E-storms (95% confidence interval 1.82-6.28; P<0.01). However, there was no significant difference in mortality risk between patients with a single E-storm and those without E-storms. The MCF curve exhibited a slower ascent in patients who received primary prevention ICD/CRT-D than in those who received secondary prevention ICD/CRT-D. However, when analyzing only patients with E-storms, the MCF curves demonstrated comparable trajectories in both groups. CONCLUSIONS: E-storm recurrences may have a negative impact on prognosis. Once patients with primary prevention experience an E-storm episode, they face a similar risk of subsequent recurrent E-storms as patients with secondary prevention.

Is ischemic stimulus involved for J wave augmentation during coronary angiography and intracoronary administration of normal saline?

BACKGROUND: J waves may be augmented by coronary angiography (CAG) or intracoronary drug administration but the underlying mechanism is unknown. PURPOSE: The effect of intracoronary normal saline (NS) on J waves were investigated. PATIENTS AND METHODS: After the standard CAG using iopamidol (IopamiroR Inj), NS was injected into the right coronary artery in 10 patients with and eight patients without J waves at the baseline. The 12-lead ECG was monitored, stored on a computer and retrieved later for measurement of the J wave amplitude before or during the coronary interventions. RESULTS: J waves in leads II, III and aVF at baseline increased significantly in each lead during the right CAG and NS injection into the right coronary artery. The J wave changes were similar between the two interventions and distinct similar alterations were observed in the QRS complex. We postulated that the ischemic myocardium that was induced during CAG or intracoronary NS administration slowed the conduction velocity of depolarization in the perfusion territory and delayed the timing of J waves to appear. Then, the delayed appearance of J waves would be less opposed by electromotive force from other areas resulting in augmentation. CONCLUSION: J wave augmentation was observed during CAG and intracoronary NS administration. As a mechanism of augmentation, we postulated that contrast media and NS induce myocardial ischemia and delay the timing of J waves to a point of less opposition by electromotive force from other areas. HIGHLIGHTS: J wave augmentation has been reported during intracoronary injection of contrast media or drugs. The present study confirmed that normal saline alone was able to augment J waves. Mechanistically, coronary interventions using anoxic solutions can cause regional myocardial ischemia and reduce the conduction velocity of depolarization. Then, delayed J waves are less opposed by the electromotive force from remote areas which leads to augmentation. When a drug is diluted in normal saline and given intracoronarily, changes in J waves can be due to normal saline. The pathophysiological and clinical significance of J waves augmented during coronary interventions need to be established.

Atrial electrical remodeling and function after transcatheter aortic valve replacement in patients with aortic stenosis.

To examine reverse atrial electrical remodeling in patients with aortic stenosis (AS) after trans-catheter aortic valve replacement (TAVR). In 65 consecutive patients with severe AS (83 ± 4 years, 47 (72.3%) females), we analyzed ECG records for the P wave duration (PWD) in lead II and P-terminal force (PTFV1) in V1, and measured cardiac dimensions and function by echocardiography (ECHO) following TAVR. Biomarkers were measured to assess myocardial injury by TAVR. TAVR was successfully performed without major complications: the aortic valve area increased from 0.62 ± 0.14 cm2 to 1.52 ± 0.24cm2, and the trans-aortic pressure gradient decreased from 58.4 ± 15.9 mmHg to 15.0 ± 19.6 mmHg. PWD and PTFV increased immediately after TAVR and returned to the pre-TAVR levels on the next day. Then, the PWD declined toward 6 months after TAVR non-significantly in all patients, but significantly in 25 patients with baseline PWD ≥ 130 ms (P = 0.039). PTFV1 showed no long-term change. Improvement was observed in the ejection fraction, all thickness of the left ventricle and in the left atrial dimensions on ECHO. After recovery from transient aggravation by TAVR procedure, PWD reversed slowly, and the change was significant in those with baseline PWD ≥ 130 ms while change in PTFV1 was not significant at 6 months of follow-up. ECHO showed a reversal of remodeling in the left ventricle and in the left atrial dimension after TAVR.

J wave dynamicity during coronary angiography and intracoronary acetylcholine administration.

BACKGROUND: J-waves may be observed during coronary angiography (CAG) or intracoronary acetylcholine (ACh) administration, but their significance is unknown. METHODS: Forty-nine patients, 59.1 ± 11.5 years old and 59% male, were studied on suspicion of vasospastic angina, and J wave dynamicity was compared between CAG and Ach administration. RESULTS: Diagnostic (≥0.1 mV) or nondiagnostic (<0.1 mV) J waves in 9 and 3 patients, respectively, were augmented, and J waves were newly observed in 2 patients during CAG and Ach administration. Similar changes in the J-wave amplitude were observed: from 0.10 ± 0.09 mV to 0.20 ± 0.15 mV (p < .002) and from 0.10 ± 0.10 mV to 0.20 ± 0.16 mV (p < .001) during CAG and Ach administration, respectively. J waves were located in the inferior leads and changed only during the right coronary interventions. In the remaining 35 patients, J waves were absent before and during the coronary interventions. Augmentation of J waves was found when the RR interval was shortened in some patients. Injection of anoxic media into the coronary artery might induce a conduction delay from myocardial ischemia that manifests as augmentation or new occurrence of J waves. CONCLUSIONS: Both CAG and intracoronary Ach administration affected J waves similarly in the same individuals. A myocardial ischemia-induced conduction delay may be responsible for the changes in J waves, but further studies are needed.

Predictors and outcomes of ischemia-driven target lesion revascularization in deferred lesion based on fractional flow reserve: a multi-center retrospective cohort study.

Background: Fractional flow reserve (FFR) has become the gold standard for diagnosing ischemia in angiographically intermediate epicardial coronary artery stenosis. This study investigated the clinical outcomes and predictors of revascularization deferral based on FFR. Methods: In this retrospective cohort study, we assessed 474 lesions (440 patients) where revascularization was deferred based on the FFR value. Minimum lumen diameter and %-diameter stenosis were measured. Calcification was graded as none, mild, moderate, or heavy. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score I was also determined. The primary outcome was ischemia-driven target lesion revascularization (TLR) in deferred lesions within 3 years. Patients were also assigned into two groups based on FFR value. Results: The average age of the patients was 69.7±10.4 years. The average FFR value was 0.86±0.05. Stable angina pectoris was noted in 298 (67.7%) cases, and in-stent restenosis (ISR) was present in 28 (5.9%). The average SYNTAX score was 7.2±4.2. The 3-year ischemia-driven TLR was 18 lesions (3.8%). Cox proportional hazard model revealed that the SYNTAX score and ISR were independent predictors for TLR in deferred lesions [hazard ratio (HR) =1.10, 95% confidential interval (CI): 1.01-1.19, P=0.03; HR =6.33; 95% CI: 2.25-17.8, P<0.01, respectively]. The deferral group, with a low FFR value, tended to have higher TLR rates than other groups. Conclusions: Lesions with lower FFR values were associated with a higher incidence of ischemia-driven TLR than those with higher FFR values. SYNTAX score and ISR were predictors for ischemia-driven TLR at 3 years in the deferred lesions.

Effectiveness of Implantable Cardioverter Defibrillator in Patients With Non-Ischemic Heart Failure With Systolic Dysfunction　- Subanalysis of the Nippon Storm Study.

BACKGROUND: The prospective observational Nippon Storm Study aggregated clinical data from Japanese patients receiving implantable cardioverter-defibrillator (ICD) therapy. This study investigated the usefulness of prophylactic ICD therapy in patients with non-ischemic heart failure (NIHF) enrolled in the study.Methods and Results: We analyzed 540 NIHF patients with systolic dysfunction (left ventricular ejection fraction <50%). Propensity score matching was used to select patient subgroups for comparison; 126 patients were analyzed in each of the primary (PP) and secondary (SP) prophylaxis groups. The incidence of appropriate ICD therapy during follow-up in the PP and SP groups was 21.4% and 31.7%, respectively (P=0.044). The incidence of electrical storm (ES) was higher in SP than PP patients (P=0.024). Cox proportional hazard analysis revealed that increased serum creatinine in SP patients (hazard ratio [HR] 1.18; 95% confidence interval [CI] 1.02-1.33; P=0.013) and anemia in PP patients (HR 0.92; 95% CI 0.86-0.98; P=0.008) increased the likelihood of appropriate ICD therapy, whereas long-lasting atrial fibrillation in PP patients (HR, 0.64 [95% CI, 0.45-0.91], P=0.013) decreased that likelihood. CONCLUSIONS: In propensity score-matched Japanese NIHF patients, the incidence of appropriate ICD therapy and ES was significantly higher in SP than PP patients. Impaired renal function in SP patients and anemia in PP patients increased the likelihood of appropriate ICD therapy, whereas long-lasting atrial fibrillation reduced that likelihood in PP patients.

Predictors and outcomes of acute recoil after ultrathin bioresorbable polymer sirolimus-eluting stents implantation: an intravascular ultrasound in native coronary arteries.

BACKGROUND: Ultrathin bioresorbable polymer sirolimus-eluting stents (BP-SESs) may easily lead to acute recoil. This study investigated acute recoil after BP-SES implantation on the basis of intravascular ultrasound (IVUS). METHODS: We enrolled 40 consecutive stents. Absolute acute recoil by quantitative coronary angiography was defined as the difference between the mean diameter of the last inflated balloon (X) and mean lumen diameter of the BP-SES immediately after balloon deflation (Y). Percent (%) acute recoil was defined as (X-Y)×100/X. IVUS was performed within the culprit lesion. Plaque eccentricity, % plaque burden and calcification grade score were assessed using IVUS. Calcification grade was scored on the basis of quadrants. On the basis of the median acute recoil value of 5.0%, the stents were divided into two groups: low (LAR, n = 20) and high % acute recoil (HAR, n = 20). RESULTS: Mean % acute recoil was 5.8 ± 5.3%. Plaque eccentricity, % plaque burden and stent/artery ratio were significantly higher in the HAR group than in the LAR group. Significant differences in % acute recoil were not observed regarding the types of stent diameter. In multivariate logistic regression and multiple linear regression analysis, plaque eccentricity and % plaque burden in the culprit plaque were significant positive predictors for the occurrence of % acute recoil. No significant differences, including clinical outcomes, were found between both groups at follow-up. CONCLUSION: Acute recoil of BP-SESs may be influenced by an eccentric plaque with a large burden, which did not affect long-term outcomes. However, the present study might suggest the proper strategy (e.g. a more exhaustive plaque preparation) before BP-SES implantation in a case with these IVUS characteristics.

Incidence and Implications of J waves Observed During Coronary Angiography.

J waves may be observed during coronary angiography (CAG), but they have not been fully studied. We investigated the characteristics of J waves in 100 consecutive patients during CAG. The patients and their family members had no history of cardiac arrest. Approximately 60% of patients had ischemic heart disease, previous myocardial infarction, or angina pectoris, but at the time of this study, the right coronary artery was shown to be normal or patent after stenting. Electrocardiogram was serially recorded to monitor J waves and alteration of the QRS complex during CAG. In 12 patients (12%), J waves (0.249 ± 0.074 mV) newly appeared during right CAG, and in another 13 patients (13%), preexisting J waves increased from 0.155 ± 0.060 mV to 0.233 ± 0.133 mV during CAG. Left CAG induced no J waves or augmentation of J waves. Distinct alterations were observed in the QRS complex during CAG of both coronary arteries. Mechanistically, myocardial ischemia induced by contrast medium was considered to result in a local conduction delay, and when it occurred in the inferior wall, the site of the late activation of the ventricle, the conduction delay was manifested as J waves. In conclusion, J waves were confirmed to emerge or increase during angiography of the right but not the left coronary artery. Myocardial ischemia induced by contrast medium caused a local conduction delay that was manifested as J waves in the inferior wall, the site of the late activation of the ventricle.

Electrical Storm as an Independent Mortality Risk in Patients with Preserved or Moderately Reduced Left Ventricular Function.

Electrical storm (ES), defined by 3 or more occurrences of ventricular arrhythmias within 24 hours, has been shown to be associated with an increased risk of mortality; however, detailed information remains lacking. We aimed to examine the incidence and determinants of ES and its impact on mortality in patients enrolled in the nationwide implantable cardioverter-defibrillator (ICD) registry.We studied 1,256 patients (age 65 ± 12 years) who had structural heart disease with an ICD. The patients were classified into reduced ejection fraction (EF < 35%; 657 (52%) patients) and preserved or moderately reduced EF (EF ≥ 35%; 599 (48%) patients).ES occurred in 49 (7%) and 36 (6%) patients in the EF < 35% and EF ≥ 35% groups (log-rank P = 0.297) during the median follow-up of 2.3 years. ICD with resynchronization therapy was associated with a lower incidence of ES in patients with EF < 35%. Non-ischemic heart disease and diuretics were associated with ES in patients with EF ≥ 35%. During the follow-up, 10/49 (20%) patients with ES and 80/608 patients (13%) without ES died in patients with EF < 35%, while 7/36 (19%) patients with ES and 38/563 patients (7%) without ES died in those with EF ≥ 35%. We have created 4 Cox multivariate models. All models showed approximately 2-fold higher hazard ratios in patients with EF ≥ 35% compared to EF < 35%.Our study showed that the determinants of ES differed between EF < 35% and EF ≥ 35%. The impact of ES for mortality was numerically higher in EF ≥ 35% than in EF < 35%, although a significant interaction was not detected.

Anti-tachycardia pacing for non-fast and fast ventricular tachycardias in individual Japanese patients: From Nippon-storm study.

BACKGROUND: Anti-tachycardia pacing (ATP) delivered from an implantable device is a useful tool to terminate ventricular tachycardia (VT). But its real-world efficacy for those patients having multiple VTs with varying VT rates has not been fully studied. METHODS: Using the Nippon-storm study database, efficacy of patient-by-patient basis ATP programing for Japanese patients having both non-fast (120-187 bpm) and fast VT (≥188 bpm) was assessed. According to the useful criteria of ≥50% success termination by ATP, patients were divided into three subgroups; success ≥50% for both non-fast and fast VT (both useful), ≥50% only for non-fast VT (non-fast VT useful), or ≥50% for neither non-fast nor fast VT (neither useful). RESULTS: During a median follow-up of 28 months, ATP terminated 184 of the 203 non-fast VT episodes (91%) and 86 of the 113 fast VT episodes (76%) in all 41 patients. In the patient-by-patient analysis, efficacy of ATP was not different between non-fast and fast VT in most of the patients (36/41 = 88%); 32 patients were in the both useful and four other patients in the neither useful. Neither ischemic nor non-ischemic structural heart disease was associated with the ATP efficacy, whereas LVEF more than 37.0% and non-prescribed amiodarone were characteristics of the patients classified into the both useful. CONCLUSIONS: ATP well terminated both non-fast and fast VT occurring in individual Japanese patients with various structural heart diseases in the real-world device treatment and this finding further supports ATP programing for all device tachycardia detection zones in most patients with multiple VTs.

Comparison of 2-year outcomes between primary and secondary prophylactic use of defibrillators in patients with coronary artery disease: A prospective propensity score-matched analysis from the Nippon Storm Study.

BACKGROUND: The Nippon Storm Study was a prospective observational study designed to gather clinical data on implantable cardioverter-defibrillator (ICD) therapy in Japanese patients. OBJECTIVE: The purpose of this subanalysis was to compare the incidence of ICD therapy in patients with left ventricular dysfunction owing to coronary artery disease (CAD) for primary and secondary prophylaxis of sudden cardiac death. METHODS: We analyzed data of 493 patients with CAD and ICDs (men, 87%; age, 68 ± 10 years; left ventricular ejection fraction, 36% ± 13%; primary prophylaxis, 36%). All patients were followed up for at least 2 years. Propensity score matching was used to select patient subgroups for comparison: 133 patients with ICD for primary prophylaxis and 133 with ICD for secondary indications. RESULTS: There were no significant differences between primary and secondary prophylaxis groups with respect to the incidence of appropriate ICD therapy within 2 years (0.153 vs 0.239; hazard ratio, 1.565 [95% confidence interval (CI), 0.898-2.727]; P = .114). Two-year electrical storm risks were 3.3% and 9.6% with HR = 3.236 (95% CI, 1.058-9.896; P = .039) in patients with primary and secondary prophylaxis, respectively. CONCLUSION: The incidence of ICD therapy received by patients with CAD for primary and secondary prophylaxis was not significantly different based on our propensity score-matched analysis. However, secondary-prophylaxis ICD therapy seems to be associated with a significantly higher risk for electrical storm than primary-prophylaxis ICD therapy.

Risk factors for the first and second inappropriate implantable cardioverter-defibrillator therapy.

INTRODUCTION: Various risk factors for the first inappropriate implantable cardioverter-defibrillator (ICD) therapy event have been reported, including a history of atrial fibrillation/atrial flutter (AF/AFL), younger age, and multiple zones. Nonetheless, which factors are concordant with real-world data has not been clarified, and risk factors for the second inappropriate ICD therapy event have not been well examined. This study aimed to clarify the risk factors for the first and second inappropriate ICD therapy events. METHODS: We conducted a post-hoc secondary analysis of data from a multicenter, prospective observational study (the Nippon Storm Study) designed to clarify the risk factors for electrical storm. RESULTS: The analysis included data from 1549 patients who received ICD or cardiac resynchronization therapy with defibrillator (CRT-D). Over a median follow-up of 28 months, 293 inappropriate ICD therapy events occurred in 153 (10.0%) patients. On multivariate Cox regression analysis, the risk factors for the first inappropriate ICD therapy event were younger age (hazard ratio [HR], 0.986; p = 0.028), AF/AFL (HR, 2.324; p = 0.002), ICD without CRT implantation (HR, 2.377; p = 0.004), and multiple zones (HR, 1.852; p = 0.010). "No-intervention" after the first inappropriate ICD therapy event was the sole risk factor for the second inappropriate ICD therapy event. CONCLUSIONS: Risk factors for the first inappropriate ICD therapy event were similar to those previously reported. Immediate intervention after the first inappropriate ICD therapy event could reduce the risk of the second inappropriate event.

Impact of atrial fibrillation/flutter on outcomes of patients with implantable cardioverter defibrillators: A sub-analysis of the Nippon Storm study.

BACKGROUND: Implantable cardioverter-defibrillator and cardiac resynchronization therapy using a defibrillator (ICD/CRT-D) are established means of reducing mortality due to ventricular arrhythmia. Although atrial fibrillation/flutter (AF) is the most common cardiac arrhythmia in patients with heart disease, the impact of AF on the prognosis of patients with ICD/CRT-D remains controversial. METHODS AND RESULTS: We analyzed data from the Nippon Storm Study, a prospective observational study of 1570 patients that was conducted at 48 Japanese ICD centers. We allocated 1549 participants to AF and non-AF groups, compared their clinical data at the time of enrollment, and monitored the incidences of mortality, hospitalization, and appropriate and inappropriate ICD/CRT-D therapy during a median 28 months. When the AF (n = 257, 16.6%) and non-AF-(n = 1292, 83.4%) groups were compared, the AF group was older (67.7 vs. 61.4 years; p<0.0001), and had lower left ventricular ejection fraction (38.0 ± 17.0% vs. 43.5 ± 18.9%; p<0.0001). During follow up, mortality was significantly higher in the AF than the non-AF group (p<0.0001). In multivariate analysis, AF was significantly associated with all-cause mortality [p = 0.013; hazard ratio (HR)=1.62]. Inappropriate ICD/CRT-D therapy occurred in 40/257 patients (15.6%) and AF was associated with a higher prevalence of inappropriate ICD/CRT-D therapy (p<0.0001; HR=2.25). CONCLUSION: The presence of AF at ICD/CRT-D implantation carries subsequent independent risks of 1.62-fold for death and 2.25-fold for inappropriate therapy.

P-wave indices in Japanese patients with ischemic stroke: Implication of atrial myopathy in subtype of ischemic stroke.

BACKGROUND: P-wave indices have been not fully studied in subtypes of ischemic stroke. We compared P-wave indices among embolic stroke, lacunar stroke and the control. METHODS: P-wave duration, advanced interatrial block (aIAB) defined as P-wave duration ≥120 ms and biphasic (positive negative) morphology in inferior leads, and P-terminal force in lead V1 (PTFV1) were measured at the time of the first episode of cardioembolic stroke in 81 patients with paroxysmal atrial fibrillation (PAF), and in 64 patients with lacunar stroke, and compared with 100 control subjects. The latter two groups had no episode of PAF. RESULTS: The age of participants was 76 ± 11 years. Age, sex distribution, body mass index and CHADS2 score were comparable among three groups. Maximum P-wave duration, the longest across 12 leads, was significantly prolonged in cardioembolic and lacuna stroke compared to the control; 118 ± 12 ms and 118 ± 11 ms vs. 110 ± 11 ms, respectively (P < 0.0001). P-wave duration ≥120 ms and aIAB were more prevalent in ischemic stroke groups than the control, and associated with a higher Odds ratio for stroke, more so in cardioembolic stroke. However, PTFV1 value and the prevalence of PTFV1 ≥ 4.0 ms·mV were significantly not different among the three groups. Abnormal P-wave duration and aIAB indicating the presence of atrial myopathy were present in cardioembolic and lacuna stroke. CONCLUSION: Atrial myopathy was present in cardioembolic and lacunar stroke, but it can't be the direct cause of small vessel occlusion in lacunar stroke. Roles of atrial myopathy in each subtype of ischemic stroke should be studied.

Small lipid core burden index in patients with stable angina pectoris is also associated with microvascular dysfunction: Insights from intracoronary electrocardiogram.

Near-infrared spectroscopy with intravascular ultrasound (NIRS)-IVUS enables precise detection of lipid core burden. Intracoronary electrocardiography (ECG) can detect slight ischemia during percutaneous coronary intervention (PCI), indicating microvascular dysfunction (MD) by distal embolization, etc. Thus, this study aimed to investigate whether plaques with a low max-lipid core burden index (LCBI) at 4 mm (LCBI4mm) influence MD, using intracoronary ECG. We enrolled 40 consecutive patients who underwent PCI for stable angina pectoris (SAP) due to stenosis of the proximal segment of the left anterior descending artery in this study. Max-LCBI4mm was measured for each culprit lesion. Gray-scale IVUS data including plaque burden were measured. Intracoronary ECG was performed to measure the time from the initiation of ST-segment elevation from the isoelectric baseline after stent balloon inflation to the return of the ST-segment to the isoelectric baseline after the deflation of the stent balloon, which was defined as the severity of the MD. The patients were divided into two groups according to median max-LCBI4mm of 120 as follows: low- [n = 20] and high- [n = 20] LCBI groups. The overall mean Max-LCBI4mm was 120 ± 86. No differences in baseline characteristics, including prevalence of dyslipidemia, were found between both groups, as well as in the gray-scale IVUS parameters. The severity of the MD was greater in the high-LCBI group than in the low-LCBI group (16.6 ± 9.1 vs 4.7 ± 4.8 s, P < 0.01). The no-reflow and slow-flow phenomena were not observed. Even max-LCBI4mm value <400 on NIRS-IVUS was associated with MD during PCI in patients with SAP.