Exercise capacity is lowered in patients with heart failure, which limits their daily activities and also reduces their quality of life. Furthermore, lowered exercise capacity has been well demonstrated to be closely related to the severity and prognosis of heart failure. Skeletal muscle abnormalities including abnormal energy metabolism, transition of myofibers from type I to type II, mitochondrial dysfunction, reduction in muscular strength, and muscle atrophy have been shown to play a central role in lowered exercise capacity. The skeletal muscle abnormalities can be classified into the following main types: 1) low endurance due to mitochondrial dysfunction; and 2) low muscle mass and muscle strength due to imbalance of protein synthesis and degradation. The molecular mechanisms of these skeletal muscle abnormalities have been studied mainly using animal models. The current review including our recent study will focus upon the skeletal muscle abnormalities in heart failure.

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Angiotensin II (AngII) type I receptor (AT1R) recognizes AngII, a cardiovascular peptide hormone that acts as a terminal effector of the renin-angiotensin system (RAS). AT1R belongs to the rhodopsin-like peptidergic family of G protein-coupled receptors (GPCRs) and serves as a therapeutic target for the treatment of cardiovascular diseases, such as hypertension, cardiac hypertrophy and heart failure. Classically, AT1R was considered to signal only through G proteins. However, recent studies have revealed that AT1R is capable of activating G protein-independent signaling that is mediated by β-arrestins. β-arrestin is a cytosolic scaffold that is recruited to the activated GPCRs. In vitro and ex vivo studies have demonstrated that the activation of the AT1R-β-arrestin pathway stimulates contractility and exerts prosurvival effects in cardiomyocytes. TRV027, a potent synthetic β-arrestin-biased ligand for AT1R, specifically activates AT1R-β-arrestin signaling without stimulating G proteins. In preclinical studies, TRV027 not only produced vasodilation by antagonizing the AT1R-Gαq pathway but also enhanced cardiac performance by activating AT1R-β-arrestin signaling. Because of this unique pharmacological profile, TRV027 is now being evaluated in a phase II clinical trial as a novel therapeutic for acute heart failure (AHF).

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The transradial approach has been used for coronary procedures, but this procedure carries a risk of injury to the endothelium of the radial artery. In this study, the vascular dysfunction caused by transradial catheterization was examined using reactive hyperemia peripheral arterial tonometry (RH-PAT), a recently developed technique for assessing endothelial function in digits, and the differences in injuries were compared according to the size of sheath.
Forty-three patients undergoing transradial catheterization with 6-Fr sheaths (n = 17) or 4-Fr/5-Fr (non-6-Fr; n = 26) sheaths underwent RH-PAT using an Endo-PAT2000 before, the day after, and 6 months after catheterization. RH-PAT was assessed in the arm of sheath placement and in the other arm as a control.
RH-PAT values decreased from 2.42 ± 0.67 before catheterization to 2.08 ± 0.41 the day after catheterization in the 6-Fr group (P = 0.031); this was more evident in patients with a longer procedure time (> 91 minutes). In contrast, the change in the non-6-Fr group was not significant. RH-PAT of the non-catheterized arm was unchanged in both groups. At 6 months after catheterization, RH-PAT values in the 6-Fr group had not completely returned to baseline.
In conclusion, the insertion of a 6-Fr catheter sheath into the radial artery, especially with a longer procedure time, impaired vascular endothelial function assessed by RH-PAT the day after the procedure and was sustained for 6 months. Thus, the use of smaller size sheaths (< 6-Fr) with a shorter procedure should be considered when performing transradial catheterization.

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Cardiac resynchronization therapy (CRT) reverses structural remodeling of the left ventricle. We investigated whether CRT reverses left-ventricular electrical remodeling.
Eighty patients were enrolled and implanted with CRT-devices. Echocardiography and electrocardiography data were obtained from each patient prior to implantation and two years after implantation. At two years after implantation, the patients were classified into a responder group and a non-responder group based on echocardiography.
Over the next 2 years, 75 patients completed follow-up, and 5 patients had died. Echocardiography results showed that 23 patients could be classified as non-responders and 52 as responders. Larger numbers of non-responders were diagnosed with either ischemic cardiomyopathy (ICM) or nonspecific intraventricular conduction delay (NICD). The intrinsic QRS duration was not changed in responders, patients with dilated cardiomyopathy, or in the patient categories of male and female. However, the intrinsic QRS duration was significantly prolonged in non-responders and patients with ischemic cardiomyopathy (P = 0.041). The mean left ventricular end-diastolic diameter in the responder group was significantly decreased by CRT (P < 0.05), while there was no significant change in intrinsic QRS duration.
While CRT does not reduce the intrinsic QRS duration, it can delay negative ventricular electrical remodeling. Continuous CRT is necessary.

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Autonomic dysfunction has been associated with paroxysmal atrial fibrillation (PAF). The head-up tilt test (HUTT) is an important diagnostic tool for autonomic dysfunction. The aim of this study was to examine atrial fibrillation recurrence after RFCA by performing HUTT. A total of 488 consecutive patients with PAF who underwent RFCA were prospectively enrolled. HUTT was positive in 154 (31.6%) patients after a mean follow-up of 22.7 ± 3.5 months, and 163 (33.4%) had a recurrence. HUTT positive was significantly higher in PAF patients with recurrence compared to those without (68 (41.7%) versus 86 (26.5%), P < 0.001). Multivariate Cox regression analysis revealed that HUTT positive (HR: 1.96; 95% CI: 1.49–2.48, P < 0.001), left atrial diameter (HR: 1.77; 95%CI: 1.15–2.11, P = 0.004), AF duration (HR: 1.27; 95%CI: 0.98–1.83, P = 0.014), and sleep apnea (HR: 1.02; 95%CI: 0.81–1.53, P = 0.032) were independent predictors of clinical recurrence after RFCA. The success rate of ablation was 70.4% in patients in the HUTT negative group compared with 58.4% in patients in the HUTT positive group (log-rank P = 0.006). Patients with a positive headup tilt test were at an increased risk of AF recurrence after catheter ablation. Our results suggest that HUTT was a significant predictor for AF recurrence after catheter ablation for PAF.

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The aim of this study was to provide a histopathological validation of cardiac late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) for the assessment of left atrial (LA) substrate remodeling (SRM) in patients with rheumatic mitral valve disease and persistent atrial fibrillation (AF).
Adult patients with rheumatic mitral valve disease and persistent AF undergoing open-heart surgery for mitral valve replacement were enrolled. Both two-dimensional (2D) sections and 3-dimensional (3D) full-volume LGE-MRI with different signal intensities were performed preoperatively to determine the extent of LA-SRM. Tissue samples were obtained intraoperatively from the LA roof and posterior lateral wall for pathological validation with Masson trichrome staining and immunostaining for collagen type I/III deposition. A linear regression model was used to determine the relationship between MRI-derived LA-SRM parameters and pathological results.
Between February 2013 and March 2014, we successfully acquired LA tissue samples from 22 patients (13 men), with a mean age of 47 ± 8 years. All patients had rheumatic mitral valve stenosis, with a mean effective orifice area of 0.9 ± 0.2 cm² on echocardiography and a mean LA volume of 235 ± 85 mL on 3D-MRI. Multiple moderate linear associations were noted between the pathological results and LGE-MRI–derived LA-SRM parameters, with correlation indices (r²) of 0.194–0.385.
LA-SRM measured by LGE-MRI showed moderate agreement with LA pathology in patients with rheumatic valve disease and persistent AF.

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To investigate the relationship between KCNN3 SNP (single-nucleotide polymorphism) rs13376333 and risk of atrial fibrillation (AF) and to provide evidence for prevention and treatment for AF.
The PubMed, Embase, OVID, Cochrane library, CNKI, and Wan Fang databases were searched to identify studies on the relationship between KCNN3 SNP rs13376333 polymorphism and atrial fibrillation. Two authors performed independent article reviews and study quality assessment using the Newcastle-Ottawa Scale (NOS) checklist.
Seven studies involving 24,339 individuals were included in the meta-analysis. The overall combined OR of rs13376333 polymorphism was observed for both lone AF (OR: 1.58 [95%CI: 1.37 to 1.82]; P < 0.001; I² = 47.0%) and total AF (OR: 1.33 [95%CI: 1.14 to 1.54]; P < 0.001; I² = 0). Further, when stratified by ethnicity, control sources, sample sizes, and genotyping method, similar results were observed in both subgroups. Sensitivity analysis revealed that the source of control was the source of the heterogeneity for lone AF. Omission of any single study had little effect on the combined risk estimate. No evidence of publication bias was found.
This meta-analysis suggests that KCNN3 SNP rs13376333 polymorphism significantly increases the risk of lone AF and total AF, which suggests the rs13376333 polymorphism of the KCNN3 gene may play an important role in the pathogenesis of AF.

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Worsening of mitral regurgitation (MR) is sometimes observed after closure of an atrial septal defect (ASD). However, since the mechanism of this deterioration remains unclear, the aim of our study was to investigate the effect of left (LV) and right ventricular (RV) geometry on MR after transcatheter closure of ASD.
We studied 27 patients with ASD who underwent transcatheter closure. Echocardiography was performed before and 6 ± 2 months after the procedure. In addition to conventional echocardiographic parameters, full volume data of the whole LV and RV heart was obtained with 3-dimensional echocardiography. MR was quantified by measuring the width of the vena contracta, and was graded as mild (< 3.0 mm), moderate (3.0 to 6.9 mm), or severe (≥ 7.0 mm).
Ten patients (37%) were classified as having worsening MR and the remaining 17 (63%) as not having worsening MR. The two groups showed similar baseline characteristics, except for patients with worsening MR being more likely to be older (P = 0.009) and having a larger left-to-right shunt of pulmonary and systemic blood flow ratio (P = 0.02). It is noteworthy that the horizontal-to-vertical ratio of basal-RV at end-systole for patients with worsening MR was significantly smaller than that for patients without worsening MR (1.0 ± 0.2 versus 1.4 ± 0.2, P < 0.0001). Furthermore, multivariate analysis showed that the horizontal-to-vertical ratio of basal-RV at end-systole was the independent predictor of worsening MR during follow-up (P < 0.001).
RV geometry may affect MR after closure of ASD. The pre-operative horizontal-to-vertical ratio of basal-RV is considered useful for predicting worsening of MR after closure of ASD.

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Due to similar manifestations of hypertensive ventricular walls and abnormal ventricular compliance, it is difficult to differentiate cardiac amyloidosis (CA) and nonobstructive hypertrophic cardiomyopathy (NOHCM) clinically. The purpose of the study was to investigate the value of electrocardiography (ECG) in the differentiation of the two diseases.
Methods: We enrolled 46 consecutive patients with CA and 64 patients with NOHCM and compared their ECG characteristics.
Compared with NOHCM patients, the ECG of CA patients showed more low voltage on limb leads (50% versus 1.6%), atrioventricular block (21.7% versus 4.7%), pseudo-infarct pattern (84.8% versus 39.1%), and longer QRS duration (104 ± 25 versus 98 ± 14 ms) (all P < 0.05). The QRS complex voltage of avR demonstrated the highest diagnostic performance (sensitivity 89%, specificity 94%, cut-off value 0.45mV) as assessed by ROC analysis. The combination of the R wave voltage of I and avR reached a sensitivity of 95% and a specificity of 87% for the diagnosis of amyloidosis.
Compared with NOHCM patients, CA patients showed more ECG characteristics of low voltage on limb leads, pseudo-infarct pattern, atrioventricular block, and longer QRS duration. The combination of the R wave voltage of I, avR, and QRS was of diagnostic value in the differentiation of CA from NOHCM.

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Adaptive servo-ventilation (ASV) has been attracting attention as a novel respiratory support therapy for heart failure (HF). However, the acute hemodynamic effects have not been compared between ASV and continuous positive airway pressure (CPAP) in HF patients.
We studied 12 consecutive patients with stable chronic HF. Hemodynamic measurement was performed by right heart catheterization before and after CPAP 5 cmH₂O, CPAP 10 cmH₂O, and ASV for 15 minutes each.
Heart rate, blood pressure, pulmonary capillary wedge pressure (PCWP), and stroke volume index (SVI) were not changed by any intervention. Right atrial pressure significantly increased after CPAP 10 cmH₂O (3.6 ± 3.3 to 6.7 ± 1.6 mmHg, P = 0.005) and ASV (4.1 ± 2.6 to 6.8 ± 1.5 mmHg, P = 0.026). Cardiac index was significantly decreased by CPAP 10 cmH₂O (2.3 ± 0.4 to 1.9 ± 0.3 L/minute/m², P = 0.048), but was not changed by ASV (2.3 ± 0.4 to 2.0 ± 0.3 L/ minute/m², P = 0.299). There was a significant positive correlation between baseline PCWP and % of baseline SVI by CPAP 10 cmH₂O (r = 0.705, P < 0.001) and ASV (r = 0.750, P < 0.001). ASV and CPAP 10 cmH₂O had significantly greater slopes of this correlation than CPAP 5 cmH₂O, suggesting that patients with higher PCWP had a greater increase in SVI by ASV and CPAP 10 cmH₂O. The relationship between baseline PCWP and % of baseline SVI by ASV was shifted upwards compared to CPAP 10 cmH₂O. Furthermore, based on the results of a questionnaire, patients accepted CPAP 5 cmH₂O and ASV more favorably compared to CPAP 10 cmH₂O.
ASV had more beneficial effects on acute hemodynamics and acceptance than CPAP in HF patients.

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The modified Blalock-Taussig shunt (mBTS) is one of the most important palliative procedures in congenital heart surgery. However, in neonates and small infants, operative mortality and morbidity due to excessive pulmonary blood flow or shunt failure remains high. In this study, a small shunt graft (3.0-mm diameter) was estimated to determine the optimal shunt graft size of BTS as an initial palliation for ultimate biventricular circulation. Eighteen patients weighing an average 3.5 kg who underwent mBTS from July 2004 to January 2013 at our institute were reviewed. We divided the study cohort into two groups: group S (n = 10) included patients with 3.0-mm diameter shunt grafts, and group L (n = 8) included patients with 3.5-mm diameter shunt grafts. There were no hospital deaths or shunt occlusion in either group. One group L patient (12.5%) had cardiogenic shock due to excessive pulmonary blood flow. There were no differences in postoperative arterial oxygen saturation (SaO₂) between the groups. There were no differences in body weight at intracardiac repair (ICR) between the groups. During the interstage to ICR, body weight gain was significantly greater in group S than in group L (P = 0.008). The small shunt graft (3.0-mm diameter) in BTS was safe, provided adequate pulmonary blood flow, and led to significant weight gain between mBTS and ICR for ultimate biventricular circulation in neonates and small infants with low body weight.

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Stress cardiomyopathy is characterized by transient apical hypokinesia related to catecholamine overflow. Recently, excessive epinephrine administration was shown to recapitulate stress cardiomyopathy through β₂-adrenoceptor (AR)-inhibitory G protein (Gi) coupling in rats. We aimed to study whether α₂-AR and Gi affect cardiac contraction in rats in which emotional stress was evoked using immobilization (IMO). Echocardiography results showed that when male rats were exposed to IMO for 30 minutes and then injected with the α₂-AR agonist xylazine (Xy), ejection fraction and the movement of the anterior wall (AW) were suppressed, maximally at 5 minutes post-injection, whereas posterior wall (PW) movement was preserved. At the same time points, the phosphorylation of Ser282 in myosin-binding protein-C (MyBP-C-Ser282) was higher in the PW than in the AW. Pretreatment with the Gi inhibitor pertussis toxin (PTX) reversed the low contractility and MyBP-C-Ser282 phosphorylation in the AW, but induced lethal heart failure in 3 out of 11 rats. Moreover, at 5 minutes after Xy injection following 30 minutes of IMO, serum epinephrine levels were increased. Thus, in rats exposed to psychological stress, α₂-AR stimulation triggered transient hypo-contractility and MyBP-C-Ser282 hypo-phosphorylation in the AW, in association with an epinephrine surge. PTX treatment reversed the AW hypo-contractility and MyBP-C hypo-phosphorylation, but induced acute heart failure. These findings suggest α₂AR/Gi-dependent signaling attenuates MyBP-C phosphorylation and contractility in the AW through an epinephrine surge in rats subjected to IMO and α₂-AR stimulation. This model can recapitulate stress cardiomyopathy and thereby deepen our understanding of regional cardiac hypo-contractility and prosurvival mechanisms.

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Cell migration, proliferation, and differentiation of cardiac fibroblasts (CFs) play a central role in cardiac fibrosis. Factor Xa (FXa)-dependent protease-activated receptor (PAR)-1 and PAR-2 have been reported as important targets in proinflammatory and fibroproliferative diseases. From this viewpoint, we aimed to investigate whether treatment of rivaroxaban, an approved oral direct FXa inhibitor, attenuates functional changes in angiotensin (Ang) II-induced mouse CFs.
Confluent cultured mouse CFs were pretreated with or without rivaroxaban. Ang II-induced cell migration was decreased by 73% in rivaroxaban induced cells. Rivaroxaban inhibited Ang II-induced cell proliferation by 27% at 0.01 μg/ mL, 69% at 0.1 μg/mL, 71% at 1 μg/mL, and 69% at 5 μg/mL. In mouse cytokine array measuring 40 cytokines, the productions of interleukin-16, TIMP-1, and tumor necrosis factor-α (TNF-α) were significantly reduced with 0.1 μg/mL of rivaroxaban pretreatment (all P < 0.05). TIMP-1 levels in the culture supernatant measured by ELISA were also decreased by rivaroxaban pretreatment in Ang II-induced CFs (35% decrease at 0.01 μg/mL, 47% at 0.1 μg/mL, 47% at 1 μg/mL, and 57% at 5 μg/mL). In the dual reporter assay analysis, rivaroxaban inhibited various inflammatory signal pathways, including the nuclear factor-kappa B (NF-κB), active protein-1 (AP-1), and mitogen-activated protein kinase (MAPK) pathways (decreases of 82%, 78%, and 75%, respectively).
These data suggest that rivaroxaban inhibits Ang II-induced functional activation in cultured mouse CFs via inhibiting NF-κB and MAPK/AP-1 signaling pathways, which may be a possible target of heart failure, through the antifibrotic and anti-inflammatory efficacy of rivaroxaban in Ang II-stimulated cardiac fibroblasts.

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Coronary arterial complications associated with Kawasaki disease (KD), such as a giant coronary aneurysm, determine the relative risk of future cardiac events and require lifelong medical treatment. Here, we describe a 24-year-old man who developed myocardial infarction due to poor adherence to medical treatment for a giant coronary aneurysm in the chronic phase of KD. He was hospitalized two hours after the onset of chest pain. The presence of the giant coronary aneurysm made primary percutaneous coronary intervention (PCI) difficult. However, we were able to perform primary PCI successfully utilizing previous coronary computed tomography (CT) angiographic pictures as a reference. This case provides valuable insight for the management of coronary arterial complications associated with KD. Patients in the chronic phase of KD are usually asymptomatic, even in the presence of giant coronary aneurysms which have been reported to have a high risk of morbidity and mortality. Therefore, patient education is critical for preventing poor adherence to medical treatment for coronary arterial complications. In preparation for potential coronary intervention in the future, it is also useful to perform coronary CT angiography, coronary magnetic resonance (MR) angiography, and/or coronary angiography on a regular basis while patients remain free from serious cardiac events.

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Electrical storm (ES) was observed in an 82-year-old man with recent myocardial infarction. Conventional therapy, including amiodarone, could not suppress the ES. After more than 100 electrical defibrillations, we were finally able to control the ES with the administration of landiolol. It is known that landiolol can inhibit ES. However, we hesitate to use landiolol in patients with low cardiac output. We would like to emphasize that careful use of landiolol should be considered in patients with refractory ES after myocardial infarction, although cardiac output is severely reduced.

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A 68-year-old man with sick sinus syndrome (SSS) was referred to our department for pacemaker implantation. After implantation of a pacemaker with rate-responsive dual chamber (DDDR) mode and minimized ventricular pacing (MVP) functions, paroxysmal atrial fibrillation (PAF) repeatedly developed. Pacemaker memory showed that the intrinsic atrioventricular (AV) (atrial pacing-ventricular sensing [Ap-Vs]) interval was paradoxically prolonged during rate-responsive atrial single-chamber (AAIR) mode rapid pacing because of MVP. Accordingly, to eliminate the paradoxical prolongation of the AV interval during rapid atrial pacing, we changed MVP to medium AV hysteresis and conducted DDDR mode pacing with rate-dependent AV delay. PAF then sharply decreased without antiarrhythmic drugs.

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Tachyarrhythmias such as atrial fibrillation (AF) or atrial flutter (AFL) sometimes invoke life-threatening collapse of hemodynamics in patients with severe heart failure. Recently, landiolol, an ultra-short acting β1-selective antagonist, has been reported to be safe and useful for the treatment of supraventricular tachyarrhythmias with reduced left ventricular function. Here we report a case of advanced heart failure with severe hypotension who was treated successfully by landiolol for rapid AF. The patient was a 20-year old male with dilated cardiomyopathy. He presented with low output syndrome in spite of optimal medical therapy and was referred to our department to consider ventricular assist device implantation and heart transplantation. Soon after admission, he developed rapid atrial fibrillation at 180 beats per minute (bpm) followed by severe hypotension and liver enzyme elevation. Low dose landiolol at 2 μg/kg/minute was started because digoxin was not effective. After landiolol administration, his heart rate decreased to 110 bpm, and finally returned to sinus rhythm without hemodynamic deterioration. Intra-aortic balloon pumping was inserted soon after sinus recovery and he was discharged successfully with an implantable left ventricular assist device.

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“Shoshin beriberi”, which is a fulminant form of cardiovascular beriberi accompanied by hemodynamic deterioration with high cardiac output and decreased systemic blood pressure, caused by thiamine deficiency due to alcoholic abuse or malnutrition, is often difficult to address because of its rarity and non-specific symptoms. We here present a patient with a history of alcoholic abuse who had suffered hemodynamic deterioration with extremely low cardiac output refractory to extracorporeal membrane oxygenation and intravenous catecholamine support, which was improved dramatically by bolus intravenous thiamine administration. Such a type with low cardiac output would be the most severe form of Shoshin beriberi, and cannot be rescued without diagnostic administration of thiamine.

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We present a case of POEMS syndrome in which cardiac MRI (CMR) revealed cardiac involvement. POEMS syndrome is a very rare disease and cardiac involvement in POEMS syndrome is rarely reported. In the present case, echocardiography revealed left ventricular hypertrophy with moderately impaired systolic function and moderate pulmonary hypertension. CMR examination showed a typical circular subendocardial type of late gadolinium enhancement, which is a classic pattern of cardiac amyloidosis. The diagnosis of cardiac amyloidosis in POEMS would be helpful for further risk stratification and treatment strategies.

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The use of implantable continuous-flow left ventricular assist devices (LVADs) as a bridge to transplant is effective for patients with congestive heart failure (HF). However, some patients develop congestive symptoms due to right-sided HF even with LVAD support. Tolvaptan, a vasopressin type 2 receptor antagonist, corrects both congestion and hyponatremia in patients with advanced HF. We report herein a case involving a patient who underwent LVAD implantation and developed hyponatremia and congestive symptoms after negative-pressure wound therapy and omental transposition for postoperative mediastinitis. Hemodynamic evaluation performed after negative-pressure wound therapy revealed elevation of both right arterial pressure and pulmonary capillary wedge pressure, and suggested biventricular dysfunction despite LVAD support. Symptoms improved after starting administration of tolvaptan. Tolvaptan may be useful for correcting hyponatremia and volume overload in patients under LVAD support.

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Dear Editor,
We have read with great interest the article discussing an improvement of cardiac function by increasing stimulus strength during left ventricular pacing in cardiac resynchronization therapy (CRT) by Ishibashi, et al.¹⁾ The authors investigated whether increasing stimulus strength of left ventricle (LV) pacing improves LV mechanical dyssynchrony and cardiac function in patients treated with CRT. According to their observation higher stimulus strength may result in statistically significant decreases in QRS duration, septal-posterior wall motion delay, and standard deviation of time from QRS, and increases in LV ejection fraction and LV stroke volume. Thus, increasing stimulus strength of LV pacing in patients treated with CRT improves LV mechanical dyssynchrony and cardiac function.
One of the limitations of CRT in clinical practice is the high percentage of patients not responding to the therapy. Clinical or echocardiographic improvement is not recorded in 20 to 45% of patients after implantation of CRT.²⁾ Many physicians used to believe optimal selection of patients and LV lead placement were crucial for efficient CRT. Based on current knowledge we predict that optimal device programming influences cardiac function.³⁾
Ishibashi, et al state that LV pacing with higher energy should result in depolarization of the enlarged myocardial area. Assuming this mechanism is true, it is possible to reduce myocardium depolarization time in patients with suboptimal placement of the LV lead, such as near the infarction area. It is a very important observation as LV stimulus strength is often being programmed close to capture the threshold to save battery life and avoid phrenic nerve stimulation. Moreover, for a long time physicians have been striving to avoid high LV pacing energy to reduce the risk of anodal pacing.
Influenced by Ishibashi, et al we decided to check if increasing stimulus strength of LV pacing would affect cardiac function in our patients who were not responding to CRT. We chose two men with significant QRS complex narrowing when increasing the energy of LV pacing and carefully assessed LV function with echocardiography. Both of them had ischemic heart failure with significantly reduced ejection fraction (25% and 15%). First, we assessed QRS complex width, rate of LV pressure rise [dP/dt], and LV velocity-time integral [VTI] pacing at LV capture threshold. Then, we assessed those parameters doubling the energy of LV pacing. Our observation was consistent with the results of the trial; LV systolic function was more efficient when conducting LV pacing with increased energy (Table).
We must remember that increased stimulus strength results in increased energy consumption and faster battery depletion. Reducing device battery longevity may increase the number of device replacements in a patient’s lifetime. However, CRT is a treatment option for symptomatic patients on top of optimal heart failure therapy. Only responders benefit from CRT. In our opinion if no clinical (or other) symptoms of improvement are observed and the patient is classified as a non-responder, every possible and rational opportunity should be evaluated – even if it results in faster battery depletion.
Based on our review of the literature and on our observations, we are strongly convinced that the results of the published trial may have significant influence in clinical practice. We would like to encourage Ishibashi, et al to perform a longterm observation to confirm the possible positive impact of increasing stimulus strength of LV pacing on the response to CRT.

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We thank Cacko, et al for their interest in our clinical study article,¹⁾ which describes increasing stimulus strength (SS) of left ventricular (LV) pacing in cardiac resynchronization (CRT) improves LV mechanical dyssynchrony and cardiac function. Moreover, we would like to congratulate them for achieving improvement of cardiac function in their two patients with ischemic cardiomyopathy (ICM) who were not responding to CRT.
There are 2 types of LV electrical activation with a line of block in patients with left bundle branch block (type I pattern: homogenous spread from septum to lateral wall pattern, and type II pattern; presence of block with a subsequent U-shaped electrical activation pattern).²⁾ Non-ischemic cardiomyopathy (NICM) patients are significantly more likely to have a type II pattern than ICM patients, and the presence of a type II pattern predicts a favorable response to CRT. The type I pattern is more frequent in ICM patients and may explain the lower response rates to CRT. The rates of CRT responders are lower in ICM patients because of the scarred myocardium.³⁾ The scar tissue at the region of the LV lead inhibits effective pacing of myocardium.⁴⁾ As increasing SS of LV pacing in CRT captures an enlarged myocardial area and provides a pacing response beyond a discrete region with conduction block, this optimization might be appropriate for ICM. Both patients of Cacko, et al were ICM patients and increasing SS of LV pacing seemed to be effective for them.
We believe that increasing the SS of LV pacing in CRT might be practical in the clinical setting despite the dramatic battery consumption. Multipoint LV pacing (MPP) can capture an enlarged myocardial area and improve LV mechanical dyssynchrony and cardiac function similar to high SS of LV pacing.⁵⁾ However, almost all patients with CRT cannot use MPP therapy as MPP needs a special lead. Furthermore, MPP cannot necessarily stimulate myocardium beyond a conduction block area. Increasing SS of LV pacing is one useful optimization method for every CRT non-responder. Thus, we completely agree with their opinion and strongly recommend increasing the SS of LV pacing in CRT as one option for non-responders.
We would like to use increasing SS of LV pacing for appropriate patients in the clinical setting and evaluate the long-term prognosis to confirm the possible positive impact of increasing the SS of LV pacing on the response to CRT in a future study.

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The following errors appeared in the article titled “Effectiveness and Adverse Events of Tolvaptan in Octogenarians With Heart Failure : Interim Analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study)” by Koichiro Kinugawa, Takayuki Inomata, Naoki Sato, Moriyoshi Yasuda, Toshiyuki Shimakawa, Kosuke Bando, Kazuki Mizuguchi (Vol. 56, No. 2, 137-143, 2015).
In Table I, the values of “Aldosterone antagonist, (%)” in “All patients”, “7” should be replaced by “44”, in “U-80”, “9” by “49”, in “Aged”, “5” by “39”, and in “P”, “0.0025^**” by “< 0.0001^***”.
The corrected table is given below;

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An error appeared in the article titled “Improvement of Predictive Value for Thromboembolic Risk by Incorporating Left Atrial Functional Parameters in the CHADS2 and CHA2DS2-VASc Scores” by Mi-Na Kim, Su-A Kim, Jong-il Choi, Seoung-Mi Park, Sang Won Park, Young Hoon Kim, Wan Joo Shim (Vol. 56, No. 3, 286-292, 2015).
The name of the last author on page 286 and the back cover should be “Seong-Mi Park” and not “Seoung-Mi Park”.

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