Left bundle branch area pacing for atrioventricular block and mild to moderately reduced left ventricular systolic function.

INTRODUCTION: The clinical efficacy of left bundle branch area pacing (LBBAP) has not been fully elucidated in patients with atrioventricular block and mild to moderately reduced left ventricular ejection fraction (LVEF). This study evaluated the impact of LBBAP on patients with an LVEF of ≤50% and dependent on ventricular pacing. METHODS AND RESULTS: Thirty-seven patients with atrioventricular block underwent successful LBBAP. All patients had a reduced LVEF of 36%-50% and underwent pacemaker implantation. Ventricular pacing was performed using the LBBAP alone throughout the follow-up period. Clinical outcomes, including death from any cause, fatal ventricular arrhythmias, hospitalization for heart failure, and echocardiographic improvements after 1 year, were assessed. Thirty-three (89%) patients were free from the composite endpoint during a median follow-up of 36 months, whereas four patients experienced noncardiovascular deaths or hospitalization for heart failure. No fatal ventricular arrhythmias occurred. LVEF was improved using LBBAP from 42.6 ± 4.7% to 52.1 ± 9.1% (p < .001). LVEF normalization (>50%) was achieved in 64.5% of patients, while in 11 patients LVEF remained stable demonstrating no deterioration (from 42.5 ± 4.7% to 42.4 ± 6.3%). Nonischemic cardiomyopathy (odds ratio, 21.52; 95% confidence interval, 1.96-236.45) and Pre-existing bundle branch block (odds ratio, 11.79; 95% confidence interval, 1.11-125.75) were independent preoperative predictors of LVEF normalization using LBBAP. CONCLUSION: LBBAP significantly improved cardiac systolic dysfunction without causing fatal ventricular arrhythmias. Moreover, LBBAP may provide a promising alternative to biventricular pacing in patients with atrioventricular block and a reduced LVEF of 36%-50%.

Early Invasive Strategy for Octogenarians and Nonagenarians With Acute Myocardial Infarction.

Background: Older adults with acute myocardial infarction (AMI) are currently a rapidly growing population. However, their clinical presentation and outcomes remain unresolved. Methods and Results: A total of 268 consecutive AMI patients were analyzed for clinical characteristics and outcomes with major adverse cardiovascular events (MACE) and all-cause mortality within 1 year. Patients aged ≥80 years (Over-80; n=100) were compared with those aged ≤79 years (Under-79; n=168). (1) Primary percutaneous coronary intervention (PCI) was frequently and similarly performed in both the Over-80 group and the Under-79 group (86% vs. 89%; P=0.52). (2) Killip class III-IV (P<0.01), in-hospital mortality (P<0.01), MACE (P=0.03) and all-cause mortality (P<0.01) were more prevalent in the Over-80 group than in the Under-79 group. (3) In the Over-80 group, frail patients showed a significantly worse clinical outcome compared with non-frail patients. (4) Multivariate analysis revealed Killip class III-IV was associated with MACE (odds ratio [OR]=3.51; P=0.02) and all-cause mortality (OR=9.49; P<0.01) in the Over-80 group. PCI was inversely associated with all-cause mortality (OR=0.13; P=0.02) in the Over-80 group. Conclusions: The rate of primary PCI did not decline with age. Although octogenarians/nonagenarians showed more severe clinical presentation and worse short-term outcomes compared with younger patients, particularly in those with frailty, the prognosis may be improved by early invasive strategy even in these very old patients.

Predictors of implantation failure in left bundle branch area pacing using a lumenless lead in patients with bradycardia.

Background: Left bundle branch area pacing (LBBAP) is a novel conduction system pacing technique. In this multicenter study, we aimed to evaluate the procedural success, safety, and preoperative predictors of procedural failure of LBBAP. Methods: LBBAP was attempted in 285 patients with pacemaker indications for bradyarrhythmia, which were mainly atrioventricular block (AVB) (68.1%) and sick sinus syndrome (26.7%). Procedural success and electrophysiological and echocardiographic parameters were evaluated. Results: LBBAP was successful in 247 (86.7%) patients. Left bundle branch (LBB) capture was confirmed in 54.7% of the population. The primary reasons for procedural failure were the inability of the pacemaker lead to penetrate deep into the septum (76.3%) and failure to achieve shortening of stimulus to left ventricular (LV) activation time in lead V6 (18.4%). Thickened interventricular septum (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.15-5.35), severe tricuspid regurgitation (OR, 8.84; 95% CI, 1.22-64.06), and intraventricular conduction delay (OR, 8.16; 95% CI, 2.32-28.75) were preoperative predictors of procedural failure. The capture threshold and ventricular amplitude remained stable, and no major complications occurred throughout the 2-year follow-up. In patients with ventricular pacing burden >40%, the LV ejection fraction remained high regardless of LBB capture. Conclusions: Successful LBBAP was affected by abnormal cardiac anatomy and intraventricular conduction. LBBAP is feasible and safe as a primary strategy for patients with AVB, depending on ventricular pacing.

Refractory electrical storm in a patient with hypertrophic cardiomyopathy and an implantable cardioverter-defibrillator.

A 63-year-old man with hypertrophic cardiomyopathy (HCM), mid-ventricular obstruction, and an apical aneurysm had an episode of cardiac arrest due to sustained ventricular tachycardia (VT). He was resuscitated and an implantable cardioverter-defibrillator (ICD) was implanted. In the following years, several episodes of VT and ventricular fibrillation were successfully terminated by antitachycardia pacing or ICD shocks. Three years after ICD implantation, he was re-admitted because of refractory electrical storm (ES). Since aggressive pharmacological treatments, direct current cardioversions, and deep sedation were not effective, he underwent epicardial catheter ablation which was successful to terminate ES. However, because of the recurrence of refractory ES after one year, he proceeded to surgical left ventricular myectomy with apical aneurysmectomy which provided him a relatively stable clinical course for six years. Although epicardial catheter ablation may be an acceptable option, surgical resection of apical aneurysm seems to be most efficacious for ES in patients with HCM and an apical aneurysm. Learning objectives: In patients with hypertrophic cardiomyopathy (HCM), implantable cardioverter-defibrillators (ICDs) are the gold standard of therapy for prophylaxis against sudden death. Electrical storm (ES) caused by recurrent episodes of ventricular tachycardia can cause sudden death even in patients with ICDs. Although epicardial catheter ablation may be an acceptable option, surgical resection of apical aneurysm is most efficacious for ES in patients with HCM, mid-ventricular obstruction, and an apical aneurysm.

Analysis of the anatomical features of pulmonary veins on pre-procedural cardiac CT images resulting in incomplete cryoballoon ablation for atrial fibrillation.

BACKGROUND: To investigate the anatomical features related to the failure of cryoballoon (CB) ablation for atrial fibrillation (AF) on pre-procedural CT images. METHODS: We retrospectively analyzed CT images of 100 patients with AF who had undergone a first CB ablation at our institution between June 2016 and April 2017. We measured the angle, short- and long axis length, and the area and ovality of 4 major pulmonary vein (PV) ostium on CT images. We performed logistic regression analysis to analyze the anatomical features related to the failure (incomplete CB ablation) of PV isolation. We also performed a receiver-operating characteristic (ROC) curve analysis to identify an appropriate cut-off value for anatomical features significantly associated with incomplete CB ablation. RESULTS: We analyzed 400 PVs in 100 patients [aged 64 (range, 27-82) years, 59% male]. The rate of incomplete CB ablation was significantly higher for right-than left-sided PVs (p < 0.001). The anatomical feature significantly associated with incomplete CB ablation was the angle at the right inferior PV (RIPV) (AOR: 1.17; 95% CI: 1.09-1.27, p < 0.001) and the right superior PV (RSPV) (AOR: 1.12; 95% CI: 1.01-1.23; p = 0.014). In the ROC analysis, the optimal cut-off value for RIPV and RSPV angle to discriminate an incomplete CB ablation were 40.1° and 79.7°, respectively. CONCLUSION: Our findings may help to select the appropriate ablation strategy to treat patients with AF. We show that the angle is an anatomical feature significantly related to failed CB ablation.

Ablation of the bach1 gene leads to the suppression of atherosclerosis in bach1 and apolipoprotein E double knockout mice.

This study was designed to determine whether Bach1 gene ablation leads to suppression of atherosclerosis in apolipoprotein E (Apo E)/Bach1 double knockout (DKO) mice. Apo E/Bach1 DKO mice were generated by intercrossing Apo E knockout (KO) and Bach1 KO mice. The animals were fed a high-fat diet for 8 weeks, and the atherosclerotic plaques in the thoracic and abdominal aorta were visualized by oil red O staining. In DKO mice, the total plaque area was reduced by 32% compared with that in Apo E KO mice. In DKO mice, heme oxygenase-1 (HO-1) was upregulated in the endothelium and, to a lesser extent, in vascular smooth muscles. In atherosclerotic plaques in Apo E KO mice and DKO mice, HO-1 was abundantly expressed in the endothelium and macrophages. Urine excretion of 8-iso-prostaglandin (PG) F2alpha, a marker for lipid peroxidation, was reduced in DKO mice compared with that in Apo E KO mice. The effects of Bach1 ablation on the plaque area and 8-iso-PG F2alpha excretion were almost completely abolished by treating DKO mice with Sn protoporphyrin, an inhibitor of HO activity. Disruption of the Bach1 gene in Apo E KO mice caused inhibition of atherosclerosis through upregulation of HO-1. Inhibition of Bach1, conversely, may be a novel therapeutic strategy to treat atherosclerotic diseases.

Role of osteoprotegerin in arterial calcification: development of new animal model.

OBJECTIVES: Enhanced osteoclastogenesis, increased bone resorption, and osteoporosis have been reported in osteoprotegerin-deficient (OPG (-/-)) mice. OPG (-/-) mice available in Japan usually do not show vascular calcification. We have found that arterial calcification can be quickly induced by a simple procedure in OPG (-/-) mice. METHODS AND RESULTS: Male OPG (-/-), OPG (+/-), and OPG (+/+) mice were fed a high phosphate diet from 6 to 10 weeks after birth, and then 1alpha,25-dihydroxyvitamin D3 (calcitriol) was injected for 3 days. We found that severe calcification developed in the media of the aorta in OPG (-/-) mice. Under electron microscopy, calcium deposits were observed in the cytoplasm and extracellular matrix of vascular smooth muscle cells (VSMCs). Neither apoptosis of VSMCs nor infiltration of macrophages was observed. Alkaline phosphatase (ALP) activity of aortic tissue correlated with the calcified lesion area. Mouse aorta and bone extracts revealed an identical pattern by ALP electrophoresis. CONCLUSIONS: Our results demonstrated that OPG had anticalcification activity in the aorta, probably through the downregulation of ALP activity. Because the time course of arterial calcification after the injection of calcitriol is accurate and reproducible, this mouse model will be useful for further investigation of vascular calcification.

Partial left superior pulmonary vein potential elimination by an inferior ganglionated plexus ablation.

Ganglionated plexus (GP) plays an important role in the initiation and maintenance of atrial fibrillation (AF). The GP ablation has been found to be effective for AF treatment. In this case, we reported an AF case in which the pulmonary vein (PV) potentials of the anterior region of the left superior PV were eliminated by an inferior right GP ablation.

Atrial electrical abnormality in patients with Brugada syndrome assessed by signal-averaged electrocardiography.

BACKGROUND: Ventricular fibrillation and atrial fibrillation are well-known arrhythmias in patients with Brugada syndrome. This study evaluated the characteristics of the atrial arrhythmogenic substrate using the signal-averaged electrogram (SAECG) in patients with Brugada syndrome. METHODS: SAECGs were performed during normal sinus rhythm in 23 normal volunteers (control group), 21 patients with paroxysmal atrial fibrillation (PAF; PAF group), and 21 with Brugada syndrome (Brugada group). RESULTS: The filtered P wave duration (fPd) in the control, Brugada, and PAF groups was 113.9±12.9ms, 125.3±15.0ms, and 137.1±16.3ms, respectively. The fPd in the PAF group was significantly longer compared to that in the control and Brugada groups (p<0.05). The fPd in the Brugada group was significantly longer than that in the control group (p<0.05) and significantly shorter than that in the PAF group (p<0.05). CONCLUSION: Patients with Brugada syndrome had abnormal P waves on the SAECG. The abnormal P waves on the SAECG in Brugada syndrome patients may have intermediate characteristics between control and PAF patients.

Validation of lactate level as a predictor of early mortality in acute decompensated heart failure patients who entered intensive care unit.

BACKGROUND: The significance of routine measurement of lactate level is unclear in patients with critical acute decompensated heart failure (ADHF). METHODS AND RESULTS: Consecutive 754 patients who were admitted to the intensive care unit (ICU) in our hospital from January 2007 to March 2012 and given a diagnosis of ADHF were eligible for retrospective entry into the registry. Lactate level was measured on admission from routine arterial blood sample and we investigated by comparing the lactate level and parameters of conventional in-hospital mortality predictors. Among the patients, 88 (12%) died during hospitalization. The lactate level had great power to predict in-hospital mortality, as suggested by the c-statistics of 0.71. The occurrence of in-hospital death was more pronounced in patients with high levels of lactate (>3.2mmol/l) and the tendency was observed in patients in both the acute coronary syndrome (ACS) group and non-ACS group. In multivariate analysis, elevated lactate levels remained an independent predictor of in-hospital death (odds ratio, 2.14; 95% confidence interval, 1.10-4.21; p=0.03). CONCLUSIONS: Elevated levels of arterial lactate on admission were related to worse in-hospital mortality in patients with ADHF either with or without ACS, suggesting that the presence of high lactate in patients who enter the ICU with ADHF could help stratify the initial risk of early mortality.

Long-term effects of quinapril with high affinity for tissue angiotensin-converting enzyme after coronary intervention in Japanese.

BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown experimentally to prevent restenosis after balloon injury. We previously reported that quinapril reduced the 6-month restenosis (percent diameter stenosis >or=50%) rate after percutaneous coronary intervention (PCI). However, it was not established whether this favorable outcome was maintained for longer periods. METHODS: This study was a prospective, randomized, open, and non-placebo controlled trial. Patients with coronary artery disease were enrolled after successful coronary balloon angioplasty or stenting. Two hundred and fifty-three patients were randomly assigned to the quinapril (10-20 mg per day) or control groups. The major clinical end points included death, myocardial infarction, cerebrovascular accident, or revascularization (either coronary artery bypass grafting or repeat PCI). These were tabulated according to the intention-to-treat principle. RESULTS: Long-term follow-up was available with a median of 4.8 (interquartile range 4.2-5.1) years after the procedure. The incidence of combined end points of mortality and morbidity (myocardial infarction and cerebrovascular accident) in the quinapril group was lower than that in the control group (6.1% vs 14.8%; relative risk [RR] 0.42, 95% CI 0.18-0.96, P =.033). The overall incidence of end-point events in patients with quinapril also occurred less frequently (29.8% vs 46.7%; RR 0.58, 95% CI 0.38-0.86, P =.007). CONCLUSIONS: These clinical outcomes show that the benefit of quinapril in patients following PCI is maintained for 4 years.

Effect of statin on the 5 years clinical outcomes in dialysis patients treated with sirolimus-eluting stent.

OBJECTIVE: The optimal medication therapies are recommended in patients with coronary artery disease even after the coronary revascularization. However, the information of optimal medical therapy in dialysis population is scant. We assessed the efficacy of statin on the clinical outcomes after Sirolimus-eluting stent (SES) implantation in patients with and without dialysis. METHODS AND RESULTS: We analyzed date from 843 consecutive patients who successfully treated with SES in our institution between August 2004 and November 2006. Among patients, 96 patients (11.4%) were undergoing dialysis. In non-dialysis patients, 405 patients (54%) were treated with statin at hospital discharge. In dialysis patients, only 16 patients (17%) were treated with statin. In non-dialysis patients, mortality rate was significantly lower in patients treated with statin than those without statin (4.4% vs. 13.9%, p<0.0001). While in dialysis patients, mortality rate was similar between patients treated with and without statin (56.3% vs. 57.6%, p=0.86). After adjusting for confounders, the hazard ratios for mortality were 0.39 (95% confidence interval (CI), 0.14-0.99; p=0.047) in non-dialysis patients and 1.79 (95% CI, 0.39-7.86; 0.45) for dialysis patients. The interaction probability between statin use and dialysis for mortality was 0.016. CONCLUSION: The use of statin may have beneficial effect on reducing mortality rate in patients after SES implantation in non-dialysis patients. However, such favorable effect was not observed in dialysis population.

Comparison of heart-type fatty acid binding protein and sensitive troponin for the diagnosis of early acute myocardial infarction.

BACKGROUND: The current development of serological biomarkers allows detection of smaller myocardial necrosis and early acute myocardial infarction (AMI). We evaluated the relevance of the heart-type fatty acid binding protein (H-FABP) assay, which has recently been approved in Japan, for early diagnosis of AMI as compared with the sensitive troponin assay. METHODS: This is an observational study in a single center. From 2010 July to 2011 January, 114 patients who presented with symptoms suggestive of AMI were enrolled. RESULTS: AMI was adjudicated in 45 patients (40%). The diagnostic accuracy of measurements obtained at presentation for AMI, as quantified by the area under the receiver-operating-characteristic curve (AUC), was significantly lower with H-FABP assay than the sensitive troponin assay [AUC for H-FABP, 0.59; 95% confidence interval (CI) 0.48-0.70; and for troponin I, 0.89; 95% CI, 0.83-0.94; P<.0001]. Among patients who presented within 2h after the onset of chest pain, the AUC for H-FABP was even low as compared with sensitive troponin (0.55; 0.39-0.72 vs. 0.89; 0.80-0.98, p<0.001). The clinical sensitivity for the diagnosis of AMI with the cutoff point of 99 th percentile was similar in both assays (81% and 81%, respectively), however, the specificity was extremely low in the H-FABP assay as compared with sensitive troponin assay (19% and 79%, respectively). CONCLUSION: The measurement of H-FABP in 114 consecutive patients with chest pain suggestive of AMI showed no improvement of diagnosis for early AMI as compared with the current sensitive troponin assay because of its extremely low specificity.

A case of adult patient ductus arteriosus with congestive heart failure and severe mitral regurgitation.

A 46-year-old woman presented herself at the hospital with progressive effort dyspnea and lower limbs edema which she had had for 3 months. She had a history of surgical ligation of patent ductus arteriosus (PDA) at the age of 25-year-old. A transthoracic cardiac ultrasonography showed left ventricular dilatation, severe functional mitral regurgitation, and a recurrent shunt of PDA. Percutaneous coil closure of PDA was performed and 6 months after the procedure, resolution of functional mitral regurgitation and normalization of left atrial and ventricular sizes were achieved.

Clinical usefulness of drug-eluting stents in the treatment of dialysis patients with coronary artery disease.

AIMS: To investigate the clinical outcomes of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) in patients on dialysis. METHODS AND RESULTS: Between May 2004 and December 2008, 95 patients on dialysis with 124 lesions were treated with PES alone, and were compared to 184 patients on dialysis with 244 lesions treated with SES alone, retrospectively. One-year major adverse cardiac event (MACE) including stent thrombosis, target lesion revascularisation (TLR), myocardial infarction (MI) and cardiac death were compared. Baseline characteristics were similar except for previous CABG (p = 0.02) and reference vessel diameter (p = 0.04). During hospitalisation, all cause death was more frequently observed in the PES group (p = 0.004). In-hospital MACE was not significantly different (p = 0.8). The incidence of 1-year MACE in the PES group was lower than that in the SES group (14.7%, 28.3%, p = 0.04), mainly due to the reduction of TLR (11.6%, 25.0%, p = 0.03). Rates of stent thrombosis (0%, 2.7%, p = 0.1), MI (1.1%, 3.8%, p = 0.2), and cardiac death (3.2%, 4.4%, p = 0.6) were not significantly different. CONCLUSIONS: PES appears to be more efficient in reducing angiographic and clinical restenosis in dialysis patients compared with SES.

A case of acute coronary syndrome caused by extrinsic compression of the left main coronary artery due to pulmonary hypertension.

Stenosis of the left main coronary artery (LMCA) due to extrinsic compression, producing symptoms of myocardial ischemia, is called left main compression syndrome. We report on a 43-year-old male with acute coronary syndrome who developed left main compression syndrome while waiting for a lung transplantation secondary to interstitial pneumonia, but underwent successful LMCA stenting as emergent treatment. Coronary angiography 3 months after the operation showed good stent patency in the LMCA, and the clinical course was favorable.

Intravenous administration of adenosine triphosphate disodium during primary percutaneous coronary intervention attenuates the transient rapid improvement of myocardial wall motion, not myocardial stunning, shortly after recanalization in acute anterior myocardial infarction.

BACKGROUND AND PURPOSE: Administration of adenosine attenuates myocardial stunning after reperfusion in a canine experimental ischemic model. However, it is unknown whether administration of adenosine triphosphate disodium (ATP) during reperfusion can attenuate myocardial stunning after coronary recanalization in patients with acute myocardial infarction (MI). Therefore, we sought to elucidate the effects of ATP administration on serial changes of left ventricular systolic function before and after coronary recanalization. METHODS: In 27 patients with first ST-elevation acute anterior MI, in whom primary percutaneous coronary intervention (PCI) was completed within 10 h after symptom onset, ATP at a mean rate of 103 microg/kg/min (n=16) or normal saline (n=11) was intravenously administered for 1 h during reperfusion. Left ventricular regional wall motion within the initially severely ischemic region was serially analyzed using the standard wall motion score index (WMSI) by transthoracic echocardiography. RESULTS: Means of WMSIs were similar shortly before primary PCI in both groups (2.79 in ATP group and 2.69 in controls). They changed to 2.56 and 2.22 shortly after PCI, 2.49 and 2.39 on day 2, 2.34 and 2.30 on day 3, 2.19 and 2.25 on day 10, and 1.85 and 2.02, 6 months later, respectively. Transient improved regional wall motion within the initially severely ischemic region was observed shortly after PCI in controls (10.3% of observed segments); however, it was significantly suppressed in the ATP group (2.55%). The percent recovery of WMSI on day 10, which was defined as WMSI on day 10 normalized by improvement of WMSI for 6 months, was 63.8% in ATP group and 65.7% in controls, implying ATP administration could not reduce myocardial stunning by day 10 after primary PCI. CONCLUSIONS: The high-dose administration of ATP during primary PCI prevented transient improved wall motion shortly after coronary recanalization rather than preventing left ventricular stunning. These results suggest that ATP can prevent reperfusion injury during primary PCI.

Myocardial protection against pressure overload in mice lacking Bach1, a transcriptional repressor of heme oxygenase-1.

Bach1 is a stress-responsive transcriptional factor that is thought to control the expression levels of cytoprotective factors, including heme-oxygenase (HO)-1. In the present study, we investigated the roles of Bach1 in the development of left ventricular (LV) hypertrophy and remodeling induced by transverse aortic constriction (TAC) in vivo using Bach1 gene-deficient (Bach1(-/-)) mice. TAC for 3 weeks in wild-type control (Bach1(+/+)) mice produced LV hypertrophy and remodeling manifested by increased heart weight, histological findings showing increased myocyte cross-sectional area (CSA) and interstitial fibrosis (picro Sirius red staining), reexpressions of ANP, BNP, and betaMHC genes, and echocardiographic findings showing wall thickening, LV dilatation, and reduced LV contraction. Deletion of Bach1 caused significant reductions in heart weight (by 16%), CSA (by 36%), tissue collagen content (by 38%), and gene expression levels of ANP (by 75%), BNP (by 45%), and betaMHC (by 74%). Echocardiography revealed reduced LV dimension and ameliorated LV contractile function. Deletion of Bach1 in the LV caused marked upregulation of HO-1 protein accompanied by elevated HO activity in both basal or TAC-stimulated conditions. Treatment of Bach1(-/-) mice with tin-protoporphyrin, an inhibitor of HO, abolished the antihypertrophic and antiremodeling effects of Bach1 gene ablation. These results suggest that deletion of Bach1 caused upregulation of cytoprotective HO-1, thereby inhibiting TAC-induced LV hypertrophy and remodeling, at least in part, through activation of HO. Bach1 repressively controls myocardial HO-1 expression both in basal and stressed conditions, inhibition of Bach1 may be a novel therapeutic strategy to protect the myocardium from pressure overload.