BACKGROUND: Recurrent ventricular tachycardia (VT) can be treated by substrate modification of the myocardial scar by catheter ablation during sinus rhythm without VT induction. Better defining this arrhythmic substrate could help improve outcome and reduce ablation burden.
OBJECTIVE: The study aimed to limit ablation within postinfarction scar to conduction channels within the scar to reduce VT recurrence.
METHODS: Patients undergoing catheter ablation for recurrent implantable cardioverter-defibrillator therapy for postinfarction VT were recruited at 5 centers. Left ventricular maps were collected on CARTO using a Pentaray catheter. Ripple mapping was used to categorize infarct scar potentials (SPs) by timing. Earliest SPs were ablated sequentially until there was loss of the terminal SPs without their direct ablation. The primary outcome measure was sustained VT episodes as documented by device interrogations at 1 year, which was compared with VT episodes in the year before ablation.
RESULTS: The study recruited 50 patients (mean left ventricular ejection fraction, 33% ± 9%), and 37 patients (74%) met the channel ablation end point with successful loss of latest SPs without direct ablation. There were 16 recurrences during 1-year follow-up. There was a 90% reduction in VT burden from 30.2 ± 53.9 to 3.1 ± 7.5 (P < .01) per patient, with a concomitant 88% reduction in appropriate shocks from 2.1 ± 2.7 to 0.2 ± 0.9 (P < .01). There were 8 deaths during follow-up. Those who met the channel ablation end point had no significant difference in mortality, recurrence, or VT burden but had a significantly lower ablation burden of 25.7 ± 4.2 minutes vs 39.9 ± 6.1 minutes (P = .001).
CONCLUSIONS: Scar channel ablation is feasible by ripple mapping and can be an alternative to more extensive substrate modification techniques.

UNASSIGNED: Left atrial dysfunction has shown to play a prognostic role in patients with ischemic cardiomyopathy (ICM) and is becoming a therapeutic target for pharmacological and non-pharmacological interventions. The effects of exercise training on the atrial function in patients with ICM have been poorly investigated. In the present study, we assessed the effects of a 12-week combined training (CT) program on the left atrial function in patients with ICM.
UNASSIGNED: We enlisted a total of 45 clinically stable patients and randomly assigned them to one of the following three groups: 15 to a supervised CT with low-frequency sessions (twice per week) (CTLF); 15 to a supervised CT with high-frequency sessions (thrice per week) (CTHF); and 15 to a control group following contemporary preventive exercise guidelines at home. At baseline and 12 weeks, all patients underwent a symptom-limited exercise test and echocardiography. The training included aerobic continuous exercise and resistance exercise. The analysis of variance (ANOVA) was used to compare within- and inter-group changes.
UNASSIGNED: At 12 weeks, the CTLF and CTHF groups showed a similar increase in the duration of the ergometric test compared with the control (ANOVA p < 0.001). The peak atrial longitudinal strain significantly increased in the CTHF group, while it was unchanged in the CTLF and control groups (ANOVA p = 0.003). The peak atrial contraction strain presented a significant improvement in the CTHF group compared with the CTLF and control groups. The left ventricular global longitudinal strain significantly increased in both the CTHF and the CTLF groups compared with the control group (ANOVA p = 0.017). The systolic blood pressure decreased in the CTHF and CTLF groups, while it was unchanged in the control group. There were no side effects causing the discontinuation of the training.
UNASSIGNED: We demonstrated that a CT program effectively improved atrial function in patients with ICM in a dose-effect manner. This result can help with programming exercise training in this population.

Background and Objective: In the landscape of heart failure, non-cardiac comorbidities represent a formidable challenge, imparting adverse prognostic implications. Holter ECG monitoring assumes a supplementary role in delineating myocardial susceptibility and autonomic nervous system dynamics. This study aims to explore the potential correlation between Holter ECG parameters and comorbidities in individuals with ischemic cardiomyopathy experiencing heart failure (HF), with a particular focus on the primary utility of these parameters as prognostic indicators. Materials and Methods: In this prospective inquiry, a cohort of 60 individuals diagnosed with heart failure underwent stratification into subgroups based on the presence of comorbidities, including diabetes, chronic kidney disease, obesity, or hyperuricemia. Upon admission, a thorough evaluation of all participants encompassed echocardiography, laboratory panel analysis, and 24 h Holter monitoring. Results: Significant associations were uncovered between diabetes and unconventional physiological indicators, specifically the Triangular index (p = 0.035) and deceleration capacity (p = 0.002). Pertaining to creatinine clearance, notable correlations surfaced with RMSSD (p = 0.026), PNN50 (p = 0.013), and high-frequency power (p = 0.026). An examination of uric acid levels and distinctive Holter ECG patterns unveiled statistical significance, particularly regarding the deceleration capacity (p = 0.045). Nevertheless, in the evaluation of the Body Mass Index, no statistically significant findings emerged concerning Holter ECG parameters. Conclusions: The identified statistical correlations between non-cardiac comorbidities and patterns elucidated in Holter ECG recordings underscore the heightened diagnostic utility of this investigative modality in the comprehensive evaluation of individuals grappling with HF. Furthermore, we underscore the critical importance of the thorough analysis of Holter ECG recordings, particularly with regard to subtle and emerging parameters that may be overlooked or insufficiently acknowledged.

In 2016, the DANISH study reported negative results regarding the efficacy of implantable cardioverter-defibrillators (ICDs) in patients with non-ischemic cardiomyopathy (NICM) and reduced left ventricular ejection fraction (LVEF). In this study we determined the efficacy of using ICDs for primary prophylaxis in patients with NICM.
We selected 1,274 patients with underlying cardiac disease who were enrolled in the Nippon Storm Study. We analyzed the data of 451 patients with LVEF ≤35% due to NICM or ischemic cardiomyopathy (ICM) who underwent ICD implantation for primary prophylaxis (men, 78%; age, 65±12 years; LVEF, 25±6.4%; cardiac resynchronization therapy, 73%; ICM, 33%). After propensity score matching, we compared the baseline covariates between groups: NICM (132 patients) and ICM (132 patients). The 2-year appropriate ICD therapy risks were 27.7% and 12.2% in the NICM and ICM groups, respectively (hazard ratio, 0.390 [95% confidence interval, 0.218-0.701]; P=0.002).
This subanalysis of propensity score-matched patients from the Nippon Storm Study revealed that the risk of appropriate ICD therapy was significantly higher in patients with NICM than in those with ICM.

Stem cell-secreted extracellular vesicles (EVs) play essential roles in intercellular communication and restore cardiac function in animal models of ischemic heart disease. However, few studies have used EVs derived from clinical-grade stem cells and their derivatives with stable quality. Moreover, there is little information on the mechanism and time course of the multifactorial effect of EV therapy from the acute to the chronic phase, the affected cells, and whether the effects are direct or indirect.
Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) were produced using a clinical-grade differentiation induction system. EVs were isolated from the conditioned medium by ultracentrifugation and characterized in silico, in vitro, and in vivo. A rat model of myocardial infarction was established by left anterior descending artery ligation and treated with iPSCM-derived EVs.
iPSCM-derived EVs contained microRNAs and proteins associated with angiogenesis, antifibrosis, promotion of M2 macrophage polarization, cell proliferation, and antiapoptosis. iPSCM-derived EV treatment improved left ventricular function and reduced mortality in the rat model by improving vascularization and suppressing fibrosis and chronic inflammation in the heart. EVs were uptaken by cardiomyocytes, endothelial cells, fibroblasts, and macrophages in the cardiac tissues. The pleiotropic effects occurred due to the direct effects of microRNAs and proteins encapsulated in EVs and indirect paracrine effects on M2 macrophages.
Clinical-grade iPSCM-derived EVs improve cardiac function by regulating various genes and pathways in various cell types and may have clinical potential for treating ischemic heart disease.

UNASSIGNED: YS-1402, which is a polymerized form of the synthetic prostacyclin agonist ONO-1301, has been proven in several preclinical studies to induce therapeutic effects for patients with ischemic cardiomyopathy (ICM). In this human study, we assessed the safety, tolerability, and efficacy of YS-1402, combined with coronary artery bypass grafting (CABG), for ICM.
UNASSIGNED: Twenty-four patients with ICM whose left ventricular ejection fraction was <40% with an indication for CABG were double-blindly assigned to four groups: placebo, 10-mg YS-1402, 30-mg YS-1402, and 100-mg YS-1402. YS-1402 or placebo medications were administered on the surface of the left ventricle at the time of the CABG. Pre- and postoperative cardiac function and myocardial blood flow were assessed for 6 months postoperatively, along with a safety assessment.
UNASSIGNED: No severe adverse events were related to YS-1402. The maximum blood concentration of ONO-1301 was less than that of the no observable adverse effect level. Significantly increased myocardial blood flow (MBF) and cardiac function were observed in the YS-1402 group 26 weeks postoperatively, although no improvement in MBF occurred in the placebo group.
UNASSIGNED: This Phase I/IIa parallel group-controlled, dose-escalation study of YS-1402 combined with CABG for ICM demonstrated the safety, tolerability, and potential efficacy of YS-1402.

UNASSIGNED: Ischemic cardiomyopathy (ICM) with high morbidity and mortality is closely associated with an abnormal equilibrium of circulation selenium levels. The oxidative stress theory is the most accepted theory of selenium causing ischemic cardiomyopathy. However, the role of inflammatory responses in ICM has received limited attention.
UNASSIGNED: This study included 119 subjects, 43 of whom were patients with ICM, and 76 were healthy controls. Blood specimens were collected from subjects and serum levels of inflammatory and oxidative stress indicators and plasma levels of selenium were measured.
UNASSIGNED: When plasma selenium and indicators of inflammation and oxidative stress were compared between groups, plasma selenium levels were significantly lower in the ICM group than in the control group (68.83874 vs 104.39775, p=0.02032), while indicators of inflammation such as tumour necrosis factor-alpha (TNF-α) (79.09773 vs 46.15634, p<0.001), interleukin-6 (IL-6) (49.41484 vs 38.46923, p<0.01) and neutrophil/lymphocyte ratio (3.696574 vs 2.383658, p<0.001) were significantly higher in the ICM group than in the control group (all of these results were statistically different). Additionally, malondialdehyde (MDA), a marker of oxidative stress, was considerably higher in the ICM group than in the control group (61.63078 vs 39.0609, p<0.01). In contrast, there were no significant differences in superoxide dismutase (SOD) levels between groups (p>0.05). The Poisson regression analysis revealed a significant association between selenium and high levels of MDA, IL-6 and TNF-α (p<0.05). Additionally, selenium was negatively connected with SOD levels and the neutrophil/lymphocyte ratio, but this relationship was not statistically significant (p=0.96, 0.15, respectively).
UNASSIGNED: Selenium deficiency is strongly associated with the development of ICM, and with levels of inflammation and oxidative stress in patients with ICM. Selenium can prevent the development and delay the progression of ICM by alleviating inflammatory responses.

(1) Background: Immunoglobulin gamma subclass 4 (IgG4) is a serum protein belonging to the immunoglobulin superfamily. It has a central role in certain immune-mediated conditions defined as IgG4-related disease. There is a paucity of data regarding the potential association of IgG4 and cardiovascular diseases. Our aim is to study the serum levels of IgG4 in patients with ischemic and non-ischemic dilated cardiomyopathy (DCM). (2) Methods: patients with ischemic and non-ischemic DCM were included in this study. Non-ischemic DCM was defined as a left ventricular ejection fraction (LVEF) < 40% without coronary artery disease (CAD). Ischemic DCM was defined as a LVEF < 40% and proven CAD. The serum concentrations of IgG4 were measured by turbidimetry. (3) Results: Overall 98 patients with cardiomyopathy had significantly higher levels of IgG4 compared with the control group (77.4 ± 64.0 vs. 50.3 ± 28.8 mg/dL, p < 0.01). Although there was no difference in the total IgG levels in patients with ischemic DCM, the serum concentrations of IgG4 were significantly higher than the corresponding values in the control group (89.8 ± 67.3 vs. 50.3 ± 28.8 mg/dL; interquartile ranges: 40.4−126.5 vs. 31.8−66.8 mg/dL, p < 0.01). This was altered by gender and smoking. (4) Conclusions: The patients with ischemic DCM had increased serum concentrations of IgG4. Future studies are warranted to explore the potential role of an IgG4-mediated process in patients with heart failure with reduced LVEF.

UNASSIGNED: Congestive heart failure is a complex multifactorial syndrome due to tissue hypoperfusion that is affected by some factors like inflammatory cytokines. In our study, we investigated the exact gene expression of three inflammatory cytokines in ischemic and idiopathic cardiomyopathy patients.
UNASSIGNED: From 49 studied recipients in the ischemic group, 23 (46.9%) were male and from 40 studied recipients in the idiopathic dilated cardiomyopathy group, 19 (47.5%) were male. For the quantitative analysis of interleukin (IL)-1, IL-27, and tumor necrosis factor (TNF)-α messenger RNAs expression level, the SYBR Green real-time polymerase chain reaction method was performed using SYBRPremix Ex TaqTM II (Tli RNaseH Plus; Takara) and designed primers specific for each gene in an iQ5 thermocycler (BioRad Laboratories) according to the manufacturer\'s instructions.
UNASSIGNED: Our results showed that the expression level of IL-1 and TNF-α were significantly higher in the ischemic patients compared to healthy controls (p < 0.001, p < 0.01, respectively); also, we found higher levels of IL-1 and IL-27 gene expressions in idiopathic patients compared to healthy controls (p < 0.001, p < 0.001, respectively). There were not any significant differences in IL-1, IL-27, and TNF-α expression levels between ischemic patients and idiopathic ones.
UNASSIGNED: Although we would introduce IL-1, IL-27, and TNF-α as effective inflammatory cytokines on myocardial functions in ischemic and idiopathic cardiomyopathy patients, there is not any difference between these two groups in gene expression of three main inflammatory cytokines.

OBJECTIVE: The role of surgical ventricular reconstruction (SVR) in patients with ischemic cardiomyopathy is controversial. Observational series and the Surgical Treatment of IsChemic Heart failure (STICH) trial reported contradictory results. SVR is highly dependent on operator experience. The aim of this study is to compare the long-term results of SVR between a high-volume SVR institution and the STICH trial using individual patient data.
METHODS: Patients undergoing SVR at San Donato Hospital (Milan) were compared with patients undergoing SVR in STICH (as-treated principle) by inverse probability treatment-weighted Cox regression. The primary outcome was all-cause mortality.
RESULTS: The San Donato cohort included 725 patients, whereas the STICH cohort included 501. Compared with the STICH-SVR cohort, San Donato patients were older (66.0, lower quartile, upper quartile [Q1, Q3: 58.0, 72.0] vs 61.9 [Q1, Q3: 55.1, 68.8], P < .001) and with lower left ventricular end-systolic volume index at baseline (LVESVI: 77.0 [Q1, Q3: 59.0, 97.0] vs 80.8 [Q1, Q3: 58.5, 106.8], P = .02). Propensity score weighting yielded 2 similar cohorts. At 4-year follow-up, mortality was significantly lower in the San Donato cohort compared with the STICH-SVR cohort (adjusted hazard ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .001). Greater postoperative LVESVI was independently associated with mortality (hazard ratio, 1.02; 95% confidence interval, 1.01-1.03). At 4 to 6 months of follow-up, the mean reduction of LVESVI in the San Donato cohort was 39.6%, versus 10.7% in the STICH-SVR cohort (P < .001).
CONCLUSIONS: Patients with postinfarction LV remodeling undergoing SVR at a high-volume SVR institution had better long-term results than those reported in the STICH trial, suggesting that a new trial testing the SVR hypothesis may be warranted.