Search

Background: The fibrosis-5 (FIB-5) index is a noninvasive marker for assessing the progression of liver fibrosis and predictor in patients with heart failure (HF). This study investigated the association between the FIB-5 index and response to cardiac resynchronization therapy (CRT) and evaluated its predictive value for prognosis., Methods: In total, 203 patients who underwent CRT/CRT-defibrillator (CRT-D) implantation were retrospectively included. The FIB-5 index was calculated using blood samples obtained before and after CRT/CRT-D. Response to CRT was defined as a relative reduction in left ventricular end-systolic volume of ≥15% 6 months after CRT/CRT-D. We compared the prognosis after CRT/CRT-D between the groups according to the FIB-5 index., Results: One hundred and twenty-three patients (61%) responded to CRT. The responder group demonstrated a significantly higher FIB-5 index than the nonresponder group (-2.76 ± 3.85 vs. -4.67 ± 3.29, p < 0.001). Receiver-operating characteristic analysis demonstrated that the area under the curve of the FIB-5 index was 0.660 with a cutoff value of -4.00 for responders. In multivariate analysis, FIB-5 index ≥ -4.00 was an independent predictor for CRT response (odds ratio: 3.665, p = 0.003), in addition to QRS duration ≥ 150 ms and echocardiographic dysynchrony. The FIB-5 index increased significantly after 6 months in the responder group but not in the nonresponder group. The FIB-5 index ≥ -4.00 group showed a significantly better prognosis for cardiac death, HF hospitalization, and composite endpoint than the FIB-5 index < -4.00 group., Conclusion: The FIB-5 index in addition to classical predictors may be a useful marker for predicting response to CRT., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: The fibrosis-4 (FIB-4) index is a noninvasive scoring system that is used to assess the progression of liver fibrosis. This study aimed to assess whether the FIB-4 index is associated with recurrent atrial fibrillation (AF) after catheter ablation in patients with and without heart failure (HF)., Methods: We included 1,184 patients who underwent initial AF catheter ablation between 2016 and 2021. The patients were classified into low-risk (< 1.3), intermediate-risk (1.3-2.67), and high-risk (> 2.67) groups based on their FIB-4 indices at baseline. The patients were divided into HF (n = 552) and non-HF groups (n = 632); the HF group was further divided into paroxysmal AF (PAF) and non-PAF groups. AF recurrence after catheter ablation was then compared among the groups., Results: In the non-HF group, no significant differences in recurrence after ablation were observed between the low-(n = 219), intermediate-(n = 364), and high-risk (n = 49) groups. In contrast, in the HF group, the intermediate-(n = 341) and high-risk (n = 112) groups had significantly higher recurrence rates than the low-risk group (n = 99) (log-rank test, p = 0.005). This association remained significant after multivariate analysis (hazard ratio [HR]:1.374; p = 0.027). The FIB-4 index increased incrementally as the brain natriuretic peptide levels and severity of tricuspid regurgitation increased. The FIB-4 index was an independent predictor of recurrence in the non-PAF HF group (HR:1.498; p = 0.007) but not in the PAF group., Conclusions: The FIB-4 index may be a useful predictor of AF recurrence after catheter ablation in patients with HF, particularly in those with non-PAF., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The clinical outcomes and mechanisms of delayed responses to cardiac resynchronization therapy (CRT) remain unclear. We aimed to investigate the differences in outcomes and gain insight into the mechanisms of early and delayed responses to CRT., Methods: This retrospective study included 110 patients who underwent CRT implantation. Positive response to CRT was defined as ≥15% reduction of left ventricular (LV) end-systolic volume on echocardiography at 1 year (early phase) and 3 years (delayed phase) after implantation. The latest mechanical activation site (LMAS) of the LV was identified using two-dimensional speckle-tracking radial strain analysis., Results: Seventy-eight (71%) patients exhibited an early response 1 year after CRT implantation. Of 32 non-responders in the early phase, 12 (38%) demonstrated a delayed response, and 20 (62%) were classified as non-responders after 3 years. During the follow-up time of 10.3 ± 0.5 years, the delayed and early responders had a similar prognosis of mortality and heart failure (HF) hospitalization. In contrast, non-responders had a worse prognosis. Multivariate analysis revealed that a longer duration (months) between initial HF hospitalization and CRT (odds ratio [OR]: 1.126; 95% confidence interval [CI]: 1.036-1.222; p = .005), non-exact concordance of LV lead location with LMAS (OR: 32.744; 95% CI: 1.101-973.518; p = .044), and pre-QRS duration (OR: 0.901; 95% CI: 0.827-0.981; p = .016) were independent predictors of delayed response to CRT compared with early response., Conclusion: The prognoses were similar regardless of the response time after CRT. A longer history of HF, suboptimal LV lead position, and shorter pre-QRS duration were related to delayed response than early response., (© 2023 Wiley Periodicals LLC.)

Functional mitral regurgitation (FMR) often coexists with atrial fibrillation (AF) and may have a causal relation with AF persistence and exacerbation of heart failure (HF). The purpose of this study was to investigate the impact of FMR on AF catheter ablation (AFCA) outcomes and improvement in FMR after AFCA in patients with HF with preserved ejection fraction (HFpEF) and nonparoxysmal AF. Excluding patients with primary valve disease or post-mitral valve repair, 280 patients with HFpEF who underwent CA for nonparoxysmal AF were retrospectively included. All patients completed 1-year follow-up and were assessed for FMR, AF recurrence and HF parameters, including echocardiography. At baseline, FMR was present in 153 (54.6%) patients (mild, n = 112; moderate, n = 40; severe, n = 1), and these were decreased to 70 (25%) significantly 1 year after AFCA (mild, n = 64; moderate, n = 6), 119 patients (78%) had improvement in MR (a decrease of ≥1 level in the severity from baseline to 1 year on echocardiography). Overall, 274 patients (97.9%) had sinus rhythm at the 1-year examination, and recurrent AF-free survival did not differ in patients with and without MR improvement (83.2% vs 82.4%, p = 0.908). However, the MR improvement group had a significantly lower cardiothoracic ratio, left atrial diameter, E/e', and B-type natriuretic peptide levels after 1 year than those in the MR nonimprovement group. In conclusion, the majority of the HFpEF patients with nonparoxysmal AF had improvement of FMR after AFCA with the high maintenance of sinus rhythm, leading to a virtuous cycle of cardiac function., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Data are limited regarding outcomes of cryoballoon ablation for atrial fibrillation (AF) in patients with heart failure (HF). This large-scale multicenter study aimed to evaluate the prognosis of patients with HF after cryoballoon ablation for AF., Methods: Among 3655 patients undergoing cryoballoon ablation at 17 institutions, 549 patients (15%) (391 with paroxysmal AF and 158 with persistent AF) diagnosed with HF preoperatively were analyzed. Clinical endpoints were recurrence, mortality, and HF hospitalization after ablation., Results: Most patients had a preserved left ventricular ejection fraction (LVEF) ≥ 50%. During a mean follow-up period of 25.7 months, recurrence, all-cause death, and HF hospitalization occurred in 29%, 4.0%, and 4.8%, respectively. Cardiac function on echocardiography and B-type natriuretic peptide (BNP) levels significantly improved postoperatively, and the effect was more pronounced in the nonrecurrence group. Major complications occurred in 33 patients (6.0%), but most complications were phrenic nerve palsy (3.6%). Although death and HF hospitalization occurred more frequently in patients with LVEF ≤ 40% (n = 73) and New York Heart Association (NYHA) class III-IV (n = 19) than other subgroups, the BNP levels, and LVEF significantly improved after ablation in all LVEF and NYHA class subgroups. High BNP levels, NHYA class, CHADS 2 score, and structural heart disease, but not postablation recurrence, independently predicted death, and HF hospitalization on multivariate analysis. The patients with tachycardia-induced cardiomyopathy had better recovery of BNP levels and LVEF after ablation than those with structural heart disease., Conclusions: Cryoballoon ablation for AF in HF patients is feasible and leads to significantly improved cardiac function., (© 2022 Wiley Periodicals LLC.)

Background: The adaptive cardiac resynchronization therapy (aCRT) algorithm automatically produces synchronized left ventricular pacing (sLVP) with intrinsic atrioventricular conduction to improve clinical outcomes. However, relationship between sLVP percentage and risk for ventricular tachyarrhythmia (VT/VF) remains unclear. This study aimed to evaluate the clinical impact of sLVP rate on VT/VF occurrence., Methods: In total, 1,419 device interrogation data from 42 consecutive patients who underwent new aCRT device implantation were retrospectively analyzed. The primary endpoint was the first time VT/VF episode after aCRT device implantation., Results: During a median follow-up of 34 months, 15 patients had VT/VF episodes. Patients were divided into a high sLVP (the average sLVP percentage of ≥ 51.5%, n = 27) or low sLVP group (< 51.5%, n = 15). The high sLVP group had a significantly lower VT/VF incidence (22% vs. 60%; p = 0.014) and an independent predictor for VT/VF occurrence on multivariate analysis (hazard ratio 0.21; p = 0.007). LV ejection fraction improvements after 6 months (12.3 ± 8.7% vs. 2.8 ± 10.3%; p = 0.004) and 12 months (13.8 ± 9.3% vs. 6.2 ± 11.1%; p = 0.030) were significantly greater in the high sLVP group than in the low sLVP group. Age, PR interval, and left atrial diameter were significantly associated with the sLVP rate after aCRT., Conclusions: Patients with high sLVP percentage after aCRT had lower long-term risk of VT/VF incidence with a favorable response to CRT. A synchronized pacing algorithm using intrinsic conduction may prevent malignant arrhythmias, as well as recover cardiac functions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aimed to compare acute hemodynamic improvements and responses to His bundle pacing (HBP) and conventional biventricular pacing (BVP)., Background: HBP can correct left bundle branch block (LBBB) and may be an alternative cardiac resynchronization therapy (CRT) to BVP., Methods: Fourteen consecutive patients with heart failure (HF) and typical LBBB who required CRT were enrolled. The acute hemodynamic responses during HBP and BVP were compared using a micromanometer-tipped catheter inserted into the left ventricle (LV) before CRT. Each configuration was compared with AAI mode. A permanent HBP device was implanted when LBBB correction threshold was ≤1.5 V at 1.0 ms, and remaining patients were treated with BVP. Clinical and echocardiographic improvements were assessed during a 12-month follow-up period., Results: The LV contractile index (positive maximal rate of LV pressure rise [dP/dt max ]) increased similarly during HBP and BVP (18.8% ± 6.4% vs 18.0% ± 10.2%; P = 0.810). LV relaxation indices (negative dP/dt max and tau) were significantly improved during HBP compared with BVP (negative dP/dt max : 14.3% ± 5.5% vs 3.1% ± 8.1%; P < 0.001; tau: 7.2% ± 4.3% vs -0.8% ± 8.1%; P = 0.001). Nine (64%) patients received permanent HBP devices, while 5 patients were treated with BVP. The New York Heart Association functional class, LV ejection fraction, LV end-systolic volume, and B-type natriuretic peptide level improved in patients treated with HBP and BVP (all P < 0.05 vs baseline). Patients treated with HBP exhibited earlier and greater improvements of the LV ejection fraction and LV end-systolic volume than did those with BVP., Conclusions: HBP improves systolic function and LV relaxation in patients with HF and LBBB. CRT via HBP produced earlier and greater clinical responses than BVP., Competing Interests: Funding Support and Author Disclosures Dr. Yanagisawa is affiliated with a department sponsored by Medtronic Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Evaluations of His bundle pacing (HBP) lead location at autopsy examination have been rarely reported. We report an autopsy case of a 98-year-old man who underwent HBP implantation due to atrioventricular block and heart failure. Although selective HBP was achieved with an acceptable threshold, the stimulus-to-QRS interval was relatively longer without correction of the right bundle-branch block. A macroscopic examination revealed that the HBP lead was inserted on the ventricular side passing through the anteroseptal commissure of the tricuspid valve. Transthyretin cardiac amyloidosis may affect the distal conduction system resulting in a long stimulus-to-QRS interval during selective HBP., (© 2020 Wiley Periodicals LLC.)

Introduction: Patients with advanced heart failure and dyssynchrony can benefit from cardiac resynchronization therapy (CRT). To predict the response to CRT, myocardial viability and improved dyssynchrony are suggested to be important., Methods: We retrospectively investigated 93 patients who underwent CRT implantation in Nagoya University Hospital. We assessed QRS narrowing the day after implantation to measure the improvement in dyssynchrony and measured the left ventricular pacing threshold (LVPT) to determine the local myocardial viability in all patients. Responders to CRT were defined as those having a greater than or equal to 15% decrease in left ventricular end-systolic volume by echocardiography at their 6-month follow-up., Results: Sixty-two patients (67%) were classified as responders. The QRS width before CRT implantation, QRS narrowing after implantation, left atrial diameter, septal-to-posterior wall motion delay, left ventricular end-diastolic diameter, radial strain, and LVPT were significantly different between the responder and nonresponder groups. On multivariate analysis, QRS narrowing (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = 0.005) and LVPT (OR, 0.42; 95% CI, 0.22-0.82; P = 0.011) were independent predictors of a response to CRT. We calculated the cutoff values from the receiver operating characteristic curves as 22.5 milliseconds of QRS narrowing and 1.55 V of LVPT. The response rates in patients with both predictive factors (QRS narrowing ≥ 22.5 milliseconds and LVPT ≤ 1.55 V), one factor, and no factors were 91%, 61%, and 25%, respectively (P < 0.001)., Conclusion: Both myocardial viability and improved electrical dyssynchrony may be essential to predict a good response to CRT., (© 2018 Wiley Periodicals, Inc.)

Background: Little is known about the association between B-type natriuretic peptide (BNP) levels and catheter ablation of atrial fibrillation (AF) in patients with heart failure. This study aimed to examine the impact of elimination of AF by catheter ablation on BNP levels in patients with left ventricular systolic dysfunction., Methods: Fifty-four AF patients with left ventricular ejection fraction (LVEF) ≤ 50%, who underwent radiofrequency catheter ablation therapy of AF, were included. BNP sampling was performed at baseline, 3 days, and 1 month after ablation., Results: After a follow-up period of 6 months, the BNP levels decreased significantly in the nonrecurrence group (n = 35; median 126.3 [interquartile 57.2-206.5] pg/mL, 63.5 [23.9-180.2] pg/mL, and 45.9 [21.9-160.3] pg/mL, P < 0.001, respectively), but not in the recurrence group (n = 19; 144.7 [87.1-217.3] pg/mL, 88.8 [12.9-213.2] pg/mL, and 118.5 [51.6-298.2] pg/mL, P = 0.368, respectively). The patients in the nonrecurrence group had a higher percentage relative reduction in BNP levels from baseline to 1 month after ablation than those in the recurrence group (56.5 [-9.0-77.4]% vs -2.4 [-47.1-60.9]%, P = 0.027). Additionally, a relative reduction in BNP levels significantly correlated with an increase in LVEF after ablation (r = 0.486, P < 0.001)., Conclusions: Plasma BNP levels decreased significantly with successful catheter ablation of AF in patients with impaired LVEF. The decrease in BNP levels might be associated with early recovery of cardiac function and subsequent maintenance of sinus rhythm at follow-up., (©2015 Wiley Periodicals, Inc.)

Purpose: This study aimed to examine the association between body mass index (BMI) and prognosis in heart failure patients after cardiac resynchronization therapy-defibrillator (CRT-D) implantation., Methods: We retrospectively investigated 125 patients (33 overweight [BMI ≥25 kg/m(2)], 75 normal weight [BMI 18.5-24.9 kg/m(2)], and 17 underweight patients [BMI <18.5 kg/m(2)]) who underwent CRT-D implantation. The clinical outcome endpoints were all-cause death and appropriate shock therapy., Results: During the follow-up period (mean 3.1 ± 1.8 years), 23 patients died (1 [3.0 %] overweight, 17 [22.7 %] normal weight, and 5 [29.4 %] underweight patients), and appropriate shock events were observed in 14 patients (2 [6.1 %] overweight, 10 [13.3 %] normal weight, and 2 [11.8 %] underweight patients). All patients survived shock therapy. After adjusting for confounding factors, overweight patients had significantly fewer outcomes relating to all-cause death and appropriate shock events (hazard ratio 0.27, 95 % confidence interval 0.08-0.91, p = 0.034) than normal weight patients. However, the prognostic difference between overweight and normal weight patients could be diminished as a result of the successful shock therapies (p = 0.067). Additionally, prognosis did not differ between overweight and normal weight patients among the responders, but did differ among the non-responders. The underweight patients had a poorer prognosis after CRT-D implantation compared with the other groups., Conclusions: Although high BMI was associated with better outcomes among heart failure patients with CRT-D implantations, the difference in the prognosis between overweight and normal weight patients was reduced because of defibrillator therapy and the improvement in cardiac function provided by CRT-D implantation.

Background: Patients with greater improvement of cardiac function after cardiac resynchronization therapy (CRT) implantation are identified as "super-responders." However, it remains unclear which kind of preimplant assessments could accurately predict outcomes after CRT. Thus, we aimed to examine the essential predicting factors for super-response to CRT, and to construct an accurate predictable model., Methods: We retrospectively analyzed the CRT patients who underwent implantation at Nagoya University Hospital. Super-responders are defined as those who show a relative reduction in left ventricular end-systolic volume ≥30% after 6 months of CRT., Results: Eighty patients (mean age, 67.8 ± 10.2 years) were included. Twenty-two patients received upgrading procedure to CRT implantation. Six months after the implantation, 29 patients (36%) were super-responders. Multiple logistic regression analysis shows that consistent right ventricular pacing with a previous device (odds ratio [OR] 7.28, 95% confidence interval [CI] 1.52-34.9; P = 0.013), lack of prior history of ventricular arrhythmia (OR 5.32, 95% CI 1.52-18.6; P = 0.009), and smaller left atrial diameter (LAD) (OR 0.92, 95% CI 0.86-0.98; P = 0.014) are independent predictors for CRT super-responders. The use of a combination of these predictive factors could increase the certainty with which a greater response to CRT is predicted and the presence of such a combination could improve prognosis., Conclusion: Greater response to biventricular pacing occurs more frequently in patients with consistent right ventricular pacing, lack of prior history of ventricular arrhythmia, and smaller LAD. An association between patient background characteristics and a super-response to CRT was also identified., (©2014 Wiley Periodicals, Inc.)

Background: Cardiac resynchronization therapy (CRT) improves cardiac function, but CRT recipients with advanced heart failure (HF) do not always respond well. Because the best parameters for the prediction of CRT response are not established, we investigated whether improvement of invasive left ventricular (LV) hemodynamic diastolic parameters could identify CRT responders., Methods: A total of 34 consecutive patients (age, 69 ± 9 years; 70% men) who received CRT devices for HF were assessed as to whether acute invasive hemodynamic parameters with and without CRT function could predict LV volume responders., Results: These patients demonstrated an improvement in LV dP/dtmax (11.1 ± 11.7%), LV dP/dtmin (4.6 ± 12.1%), and tau (3.7 ± 11.6%) by biventricular pacing. Nineteen patients (55%) were classified as CRT responders, which was defined by a >15% decrease in LV end-systolic volume (ESV) at the 6-month follow-up evaluation. The area under the receiver operator characteristic curve to detect CRT volume response was 0.93 for the shortening of tau, which was superior to any other hemodynamic parameter. The multivariate analysis revealed that this improvement in tau was the strongest predictive factor for identifying CRT volume responders. Of note, the magnitude of tau shortening during biventricular pacing was significantly correlated with the reduction in LVESV at the 6-month follow-up evaluation., Conclusions: The extent of acute improvement in LV isovolumic relaxation time, as assessed by tau, was associated with favorable response to CRT. The assessment of invasive diastolic function could provide valuable information about CRT volume response., (©2014 Wiley Periodicals, Inc.)

Objective: A low level of serum albumin is common in chronic kidney disease (CKD) patients with heart failure (HF). Cardiac resynchronization therapy (CRT), a novel therapeutic option, improves cardiac performance in patients with severe HF. In addition, CKD has recently been found to be associated with outcomes after CRT; however, the associations of the serum albumin levels with adverse events and the long-term prognosis in CKD patients who have undergone CRT are unknown. In this study, we investigated whether the albumin levels can be used to the predict mortality rate and incidence of cardiovascular events in CKD patients treated with CRT., Methods: A retrospective chart review was conducted in 102 consecutive CKD patients receiving a CRT device for the treatment of advanced HF. The long-term outcomes following device implantation were assessed according to the albumin levels., Results: During a median follow-up of 2.6 years, 34 patients (33.3%) died and 66 patients (64.7%) experienced cardiovascular events. A Kaplan-Meier survival analysis revealed that the CKD patients with decreased albumin levels exhibited significantly higher rates of all-cause mortality and cardiovascular events, including hospitalization for progressive HF, than the CKD patients without hypoalbuminemia. Importantly, a multivariate Cox regression analysis of confounding factors showed a low serum albumin level to independently predict all-cause death and cardiovascular events., Conclusion: Hypoalbuminemia independently predicts cardiac morbidity and mortality in CKD patients receiving CRT. Assessing the albumin levels provides valuable information regarding the long-term prognosis in CKD patients who undergo CRT.

Background: Cardiac resynchronization therapy (CRT) has been reported to improve symptoms and cardiac performance in patients with severe heart failure (HF), but CRT recipients with advanced HF do not always experience improved mortality rates. Cystatin C has recently been involved in HF, but the association of serum cystatin C level with adverse events and long-term prognosis after CRT is unknown. This study investigated whether cystatin C level can predict mortality and cardiovascular events after CRT., Methods and Results: A total of 117 consecutive patients receiving a CRT device for the treatment of advanced HF were assessed according to cystatin C level and long-term outcome after implantation of the device. Over a median follow-up of 3.2 years, 34 patients (29.1%) died and 59 patients (50.4%) developed cardiovascular events. Kaplan-Meier survival analysis indicated that elevated cystatin C level was significantly associated with higher all-cause mortality and prevalence of cardiovascular events, including hospitalization for progressive HF. After multivariate Cox regression analysis, serum cystatin C level and QRS duration, but not conventional echocardiographic parameters, were found to independently predict all-cause death or cardiovascular events. Of importance, only cystatin C level was an independent predictor of all-cause mortality after CRT., Conclusions: Cystatin C level independently predicts cardiac mortality or morbidity in patients receiving CRT. The assessment of cystatin C level could provide valuable information about long-term prognosis after CRT.

Atrial fibrillation (AF) is associated with morbidity and mortality of heart failure. Eicosapentaenoic acid (EPA), which is contained in fish oil, was shown to reduce the risk of cardiovascular diseases. We investigated the effects of EPA on AF associated with heart failure in a rabbit model. Rabbits were subjected to ventricular tachypacing (VTP) for 4 wk with or without EPA treatment. Continuous VTP induced heart failure status in these rabbits. The duration of AF (DAF) induced by burst pacing was analyzed by electrophysiological studies. VTP resulted in increased DAF following burst pacing. EPA treatment attenuated increased DAF. Atrial fibrosis increased in response to VTP, accompanied by extracellular signal-regulated kinase (ERK) phosphorylation and transforming growth factor-β1 (TGF-β1) expression in the atrium. Treatment with EPA attenuated atrial fibrosis, ERK phosphorylation, and TGF-β1 expression in response to VTP. EPA treatment increased adiponectin as an anti-inflammatory adipokine and decreased tumor necrosis factor-α as a proinflammatory adipokine in the atrium and epicardial adipose tissues. EPA attenuated VTP-induced AF promotion and atrial remodeling, which was accompanied by modulating the profiles of adipokine production from epicardial adipose tissue. EPA may be useful for prevention and treatment of AF associated with heart failure.

Aims: MicroRNAs (miRNAs) are small non-coding RNAs discovered as potential new gene regulators. Their roles in the development of chronic heart failure (CHF), however, are largely unknown. Reduced catecholamine sensitivity is an early step of CHF. We examined whether altered expression of miRNAs was related to reduced catecholamine sensitivity in patients with CHF., Methods and Results: Maximum first derivative of left ventricular pressure (LV dP/dt(max)) at baseline and during infusion of dobutamine (10 μg kg(-1)min(-1)) were determined in 14 asymptomatic or mildly symptomatic (New York Heart Association class I or II) patients with idiopathic dilated cardiomyopathy (DCM). We performed microarray analysis for a total of 485 miRNAs using endomyocardial biopsy specimens from these 14 patients. Patients were classified into 2 groups based on a percent increase in LV dP/dt(max) by dobutamine infusion (ΔLV dP/dt(max)). These are Group I (n=7) with ΔLV dP/dt(max)>90%, and Group II (n=7) with ΔLV dP/dt(max)<90%. Out of 485 miRNAs, 32 were differentially expressed in the myocardium with reduced catecholamine sensitivity. Among those, four miRNAs were decreased and one miRNA was increased in the Group II compared to the Group I (p<0.01). LVEF measured by left ventriculography at baseline did not differ between the 2 groups. Also there were no differences in plasma norepinephrine levels between the 2 groups., Conclusions: Altered expression of several miRNAs was related to the reduced catecholamine sensitivity in mildly symptomatic patients with DCM. These findings shed light on the potential of miRNAs to provide possible etiologic insights as well as therapeutic targets for CHF., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF (n=18) and control (n=17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs)>1,000 ms but significantly shorter at BCLs<400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17-81%), and conduction velocity was significantly decreased in CHF (by 6-20%). In both groups, high-frequency stimulation (BCLs<150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs<150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

Background: Cardiac resynchronization therapy (CRT) has been reported to improve cardiac performance. However, CRT in patients with advanced heart failure is not always accompanied by an improvement in survival rates. We investigated the association between hemodynamic studies and long-term prognosis after CRT., Methods: A total of 68 consecutive patients receiving CRT devices due to advanced heart failure were assessed by hemodynamic study and long-term outcome after implantation of the device. Hemodynamic parameters were measured both with the CRT on and off., Results: Patients demonstrated significant improvement in the maximum first derivative of left ventricular (LV) pressure (LV dP/dt(max) ) and QRS duration after periods with the CRT on. During the follow-up period of 34.9 ± 17.6 months, basal LV dP/dt(max) and isovolemic LV pressure half-time (T½), but not percent change in LV dP/dt(max) , were independent predictors of cardiac mortality or hospitalization due to heart failure after multivariate Cox regression analysis. The Kaplan-Meier survival analysis revealed that patients in the lowest basal LV dP/dt(max) tertile or the longest basal T½ tertile exhibited a significantly higher cardiac-caused mortality or heart failure hospitalization., Conclusions: Lower LV dP/dt(max) or longer T½ independently predicts cardiac mortality or heart failure hospitalization in patients receiving CRT. The assessment of the basal LV dP/dt(max) and T½ could provide useful information in long-term prognosis after CRT., (Copyright © 2010 Wiley Periodicals, Inc.)

A 51-year-old man was referred to the Department of Cardiology in our hospital due to severe congestive heart failure and ventricular arrhythmias in March 2008. He had repeated ventricular tachycardia for years and the left ventricular ejection fraction (EF) was 11% on admission. A myocardial biopsy revealed that over 50% cardiomyocytes were replaced by fibrosis. Due to the typical acromegalic features, he was referred to the endocrinology department and diagnosed as acromegaly. He was treated with octreotide for 8 months followed by trans-sphenoidal surgery. The plasma levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) decreased by octreotide and normalised by surgery after which the cardiac function improved drastically. The current case demonstrates that cardiac dysfunction in acromegaly could be recovered by normalisation of GH and IGF-1 even in the presence of severe fibrosis in the myocardium.

Background: The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activator pioglitazone antagonizes angiotensin II actions and possesses anti-inflammatory and antioxidant properties in vitro. There is evidence that pioglitazone improves ventricular remodeling in some experimental models., Objective: The purpose of this study was to assess the effects of pioglitazone on arrhythmogenic atrial structural remodeling versus the effects of the angiotensin II type 1 receptor blocker candesartan in a rabbit model of congestive heart failure., Methods: Rabbits subjected to ventricular tachypacing at 380 to 400 bpm for 4 weeks in the absence and presence of treatment with pioglitazone, candesartan, and combined pioglitazone and candesartan were assessed by electrophysiologic study, atrial fibrosis measurements, and cytokine expression analyses., Results: Atrial fibrillation (AF) lasting longer than 2 seconds was induced in no nonpaced controls but in all ventricular tachypacing-only rabbits (mean duration of AF: 8.0 +/- 1.4 seconds). Pioglitazone reduced the duration of AF (3.5 +/- 0.2 seconds, P <.05) and attenuated atrial structural remodeling, with significant reductions in interatrial activation time (50 +/- 2 ms vs 41 +/- 2 ms, P <.05) and atrial fibrosis (16.8% +/- 0.8% vs 10.9% +/- 0.7%, P <.05; control 1.6% +/- 0.2%), effects comparable to those of candesartan (duration of AF: 3.0 +/- 0.2 seconds; activation time 44 +/- 2 ms; fibrosis: 9.4% +/- 0.6%). Both pioglitazone and candesartan reduced transforming growth factor-beta1, tumor necrosis factor-alpha, and activated extracellular signal-regulated kinase expression similarly, but neither affected p38-kinase or c-Jun N-terminal kinase activation. The effects of combined pioglitazone and candesartan therapy were not significantly different from the effects of pioglitazone or candesartan alone., Conclusion: Pioglitazone can attenuate congestive heart failure-induced atrial structural remodeling and AF promotion, with effects similar to those of candesartan. PPAR-gamma may be a potential therapeutic target for human AF.

Aims: We assessed the effects of cardiac re-synchronization therapy (CRT) in patients who developed otherwise unexplained heart failure (HF) during right ventricular apical (RVA)-pacing for acquired complete atrioventricular block (CAVB)., Methods and Results: Eighteen consecutive CAVB patients with HF during RVA-pacing were assessed with haemodynamic studies immediately and 12 months after CRT-upgrade. Ten patients had idiopathic CAVB and 13 showed normal left ventricular (LV) function at RVA-pacemaker implantation. HF developed after 81 +/- 10 months. RVA-pacing duration correlated (r = 0.49, P < 0.05) with LV ejection fraction (LVEF) deterioration. Biventricular- (BiV) and LV-pacing acutely improved the systolic function comparably, but only BiV improved diastolic function. One-year post-CRT-initiation, New York Heart Association classification improved 35 +/- 3% (P < 0.05) and the number of hospitalizations decreased 85 +/- 3% (P < 0.0001). CRT decreased LV end-diastolic diameter (LVEDd) 7 +/- 2% (P < 0.01) and increased LVEF by 23 +/- 7% (P < 0.01). The CRT-induced reduction in LVEDd tended to be greater in patients with RVA-pacing for < 5 years vs. > 5 years (7.7 +/- 2.5 vs. 3.6 +/- 1.0 mm, P = 0.08)., Conclusion: CRT-upgrade improves the cardiac function and symptoms in CAVB patients with HF progression related to RVA-pacing. Because adverse LV-remodelling may be partly irreversible, consideration should be given to BiV- and LV-pacing upgrade as soon as possible after the indications appear, and prospective studies of the optimal timing of CRT-upgrade may be useful.

Background and Objectives: The left ventricular (LV) stimulation site is currently recommended to position the lead at the lateral wall. However, little is known as to whether right ventricular (RV) lead positioning is also important for cardiac resynchronization therapy. This study compared the acute hemodynamic response to biventricular pacing (BiV) at two different RV stimulation sites: RV high septum (RVHS) and RV apex (RVA)., Methods and Results: Using micro-manometer-tipped catheter, LV pressure was measured during BiV pacing at RV (RVA or RVHS) and LV free wall in 33 patients. Changes in LV dP/dt(max) and dP/dt(min) from baseline were compared between RVA and RVHS. BiV pacing increased dP/dt(max) by 30.3 +/- 1.2% in RVHS and by 33.3 +/- 1.7% in RVA (P = n.s.), and decreased dP/dt(min) by 11.4 +/- 0.7% in RVHS and by 13.0 +/- 1.0% in RVA (P = n.s.). To explore the optimal combination of RV and LV stimulation sites, we assessed separately the role of RV positioning with LV pacing at anterolateral (AL), lateral (LAT), or posterolateral (PL) segment. When the LV was paced at AL or LAT, the increase in dP/dt(max) with RVHS pacing was smaller than that with RVA pacing (AL: 12.2 +/- 2.2% vs 19.3 +/- 2.1%, P < 0.05; LAT: 22.0 +/- 2.7% vs 28.5 +/- 2.2%, P < 0.05). There was no difference in dP/dt(min) between RVHS- and RVA pacing in individual LV segments., Conclusions: RVHS stimulation has no overall advantage as an alternative stimulation site for RVA during BiV pacing. RVHS was equivalent with RVA in combination with the PL LV site, while RVA was superior to RVHS in combination with AL or LAT LV site.

Background Guidelines recommend optimal medical therapy before cardiac resynchronization therapy (CRT) implantation. Herein, we report the potential effect of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in improving the QRS duration and volume reduction in a patient with complete left bundle branch block (CLBBB) and reduced cardiac function. Case summary A 68-year-old man with a history of ischaemic cardiomyopathy and decreased cardiac function had exacerbation of heart failure (HF) at an outpatient clinic. His QRS duration increased remarkably with a CLBBB of 143 ms on an electrocardiogram, and left ventricular desynchrony was assessed by echocardiography, suggesting an indication of CRT implantation. Administration of an SGLT2i and multimodal treatment for HF stabilized his HF condition and improved the QRS duration and volume reduction thereafter. The CLBBB recovered to incomplete LBBB with a QRS duration of 112 ms on electrocardiography after 6 months. The patient has been stably followed up with continuous medications, including SGLT2i, without requiring CRT implantation or worsening of HF for 12 months. Discussion This case presents a unique scenario wherein electrical and mechanical reverse remodelling occurred in a patient with systolic HF and CLBBB, highlighting the potential benefits of SGLT2i in HF management. It may be important to carefully consider CRT indications when seeking other options to treat HF conditions and recognize an unusual phenomenon of reverse LBBB in clinical cases. [ABSTRACT FROM AUTHOR]

A 69‐year‐old man presented bradycardia with a constant blocked atrial bigeminy and heart failure. Successful catheter ablation of blocked atrial bigeminy with bradycardia resulted in myocardial reverse remodeling and restoration of the normal sinus rhythm from the ectopic atrial rhythm. [ABSTRACT FROM AUTHOR]

Septal coronary artery fistula is a rare but concerning complication of left bundle branch area pacing (LBBAP). We report the case of an 82‐year‐old man who was indicated for cardiac resynchronization therapy and underwent LBBAP. The patient had no chest symptoms during or after implantation. Postoperative echocardiography demonstrated a new abnormal tunnel inside the interventricular septum (IVS) and shunt flow from the IVS toward the right ventricle. Coronary angiography confirmed a septal coronary artery fistula, which might have been formed by failed deep screw attempts. Since the shunt volume assessed by the Qp/Qs was small, the patient was treated conservatively. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) improves functional mitral regurgitation (MR); however, the mechanism and differences in acute and late improvement in MR are unclear. We aimed to evaluate the factors associated with the acute and late MR improvements and the prognosis of MR improvement after CRT. This retrospective study included 121 patients who underwent CRT implantation with full echocardiography assessment at baseline, 1 week, and 6 months after implantation. MR severity was classified into five grades (0: none to 4: severe). Two-dimensional speckle-tracking echocardiography with radial strain was used to assess dyssynchrony, and the time difference between the lateral and inferior segments at papillary muscle levels (TDlate-inf) was calculated. The MR improved 1 week and 6 months after CRT in 40 (33%) and 45 (37%) patients, respectively. On multivariate analyses, TDlate-inf (baseline–1 week) and SPWMD were independently associated with acute MR improvement. The %reduction in left ventricular end-systolic volume (LVESV) (baseline–6 months) and TDlate-inf (baseline–1 week) were independently correlated with late MR improvement. The patients with pre-MR grades 2–4 and improved MR after CRT showed significantly better prognosis in heart failure hospitalization. Cutoff values of ≥ 19.5 ms of the reduction of TDlate-inf and ≥ 30.8% of the %reduction of LVESV were significantly associated with the decrease in heart failure hospitalization. The improved interpapillary muscle activation time delay and volume reduction after CRT were associated with acute and late MR improvements. There may be different time course of recovery and distinct causes for late MR improvement. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) improves the morbidity and mortality rate in patients with left bundle‐branch block (LBBB); however, some LBBB patients are non‐responders for CRT. Previous studies have shown that a transmural functional line block alters the left ventricular (LV) activation sequence, and that the presence of a line block is predictive for responders. We investigated whether responders could be predicted in patients with LBBB by 2‐dimensional (2‐D) speckle tracking strain imaging. Methods: We enrolled 54 patients with LBBB, who underwent echocardiography before and 6 months after CRT implantation. A responder was defined by a decrease in the LV end‐systolic volume >15% at the 6‐month follow‐up. We calculated a difference in the time from QRS onset to maximum strain between adjacent segments and defined the Tmax‐diff as the maximum difference among six intersegments. We compared the Tmax‐diff between responders and non‐responders. Results: Among 54 patients, 37 patients were identified as responders. The Tmax‐diff of the responders was significantly longer than that of the non‐responders (309.6 ± 168.6 ms vs 181.5 ± 138.4 ms, P = .009). Furthermore, Tmax‐diff ≥ 195 ms was higher in the septal and the anterior area. And patients with a Tmax‐diff ≥ 195 ms tended to be responders (P = .02). Conclusion: The present study showed that discontinuous contraction of the LV could be detected in CRT responders by 2‐D speckle tracking strain imaging, which may be a useful tool to identify the contraction pattern of patients with LBBB and predict CRT responders. [ABSTRACT FROM AUTHOR]

Background: Mechanical dyssynchrony is an important factor in the response to cardiac resynchronization therapy (CRT). However, no echocardiographic measure can improve prediction of case selection for CRT. Objective: The purpose of this study was to assess the efficacy of a newly combined echocardiographic index for ventricular dyssynchrony and contractility using speckled tracking strain analysis to predict responders to CRT. Methods: Forty-seven patients with severe heart failure in New York Heart Association functional class III/IV, left ventricular ejection fraction ≤35%, and QRS duration ≥130 ms were included in the study. Echocardiography was performed, and a novel index (i-Index), the product of radial dyssynchrony and radial strain, was calculated. Responder to CRT was defined as a patient with a ≥15% decrease in left ventricular end-systolic volume at 6-month follow-up. Results: Thirty-two patients (68%) were classified as responders. The i-Index was significantly higher in responders than in nonresponders (3,450 ± 1180 vs 1,481 ± 841, P <.001). The area under receiver operator characteristic curve was 0.92 for the i-Index, which was better than the index of radial dyssynchrony only (0.74). A cutoff value of i-Index >2,000 predicted responders with 94% sensitivity and 80% specificity. The index using only radial dyssynchrony had 81% sensitivity and 53% specificity. Furthermore, i-Index decreased in responders (1,985 ± 1261, P <.001) but not in nonresponders (1,684 ± 866, P = .48). Conclusion: Our findings suggest that a novel combined index by radial strain echocardiography might be a predictor of response to CRT. The value of this novel echocardiographic index requires further assessment in larger studies. [Copyright &y& Elsevier]

Aims We assessed the effects of cardiac re-synchronization therapy (CRT) in patients who developed otherwise unexplained heart failure (HF) during right ventricular apical (RVA)-pacing for acquired complete atrioventricular block (CAVB). [ABSTRACT FROM PUBLISHER]

Objectives: The aim of this study was to investigate the prevalence and severity of left atrial (LA) edema after pulmonary vein (PV) ablation and its effect on the cardiac function. Background: Though extensive LA catheter ablation has been demonstrated to be more effective in curing paroxysmal atrial fibrillation (PAF) than segmental ostial pulmonary vein isolation (S-PVI), it might cause life-threatening complications, including congestive heart failure associated with LA edema. Methods: Fifty patients underwent S-PVI (Group S) and 27 underwent circumferential PV antrum ablation (Group C) for drug-refractory PAF. Enhanced electron beam tomography (EBT) was performed before, 1 or 2 days after, and 1 month after the PV ablation, and transthoracic ultrasound cardiography (UCG) was performed 1 month after the PV ablation in all patients. Results: The EBT assessment revealed LA edema immediately after the PV ablation in 47 Group S patients and all Group C patients. The severity of the LA edema, number of radiofrequency applications, and amount of radiofrequency energy delivered during the PV ablation was significantly greater in Group C than in Group S. One month after the PV ablation, in all patients, the EBT assessment revealed that those edematous changes had disappeared, and the UCG assessment showed no reduction in the cardiac function. Conclusions: Left atrial edema was observed in a large portion of the patients immediately after the PV ablation, and the severity of the LA edema depended on the extent and amount of the radiofrequency energy delivered in the PV ablation. The LA edema soon disappeared naturally and did not reduce the cardiac function. [Copyright &y& Elsevier]