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Introduction: Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective: This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-β agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom’s use in managing these conditions and identify avenues for future research. Methods: Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results: Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction [standardized mean difference (SMD) −4.61, 95% CI −6.77 to −2.44, P < 0.0001], NASH resolution without worsening fibrosis [risk ratio (RR) 2.51, 95% CI 1.74–3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20–4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion: Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.

Abstract Aims The viability of cardiac resynchronization therapy (CRT) in inotrope-dependent heart failure (HF) has been a matter of debate. Methods and results We searched Medline, EMBASE, Scopus, and the Cochrane Library until 31 December 2022. Studies were included if (i) HF patients required inotropic support at CRT implantation; (ii) patients were ≥18 years old; and (iii) they provided a clear definition of ‘inotrope dependence’ or ‘inability to wean’. A meta-analysis was performed in R (Version 3.5.1). Nineteen studies comprising 386 inotrope-dependent HF patients who received CRT (mean age 64.4 years, 76.9% male) were included. A large majority survived until discharge at 91.1% [95% confidence interval (CI): 81.2% to 97.6%], 89.3% were weaned off inotropes (95% CI: 77.6% to 97.0%), and mean discharge time post-CRT was 7.8 days (95% CI: 3.9 to 11.7). After 1 year of follow-up, 69.7% survived (95% CI: 58.4% to 79.8%). During follow-up, the mean number of HF hospitalizations was reduced by 1.87 (95% CI: 1.04 to 2.70, P &lt; 0.00001). Post-CRT mean QRS duration was reduced by 29.0 ms (95% CI: −41.3 to 16.7, P &lt; 0.00001), and mean left ventricular ejection fraction increased by 4.8% (95% CI: 3.1% to 6.6%, P &lt; 0.00001). The mean New York Heart Association (NYHA) class post-CRT was 2.7 (95% CI: 2.5 to 3.0), with a pronounced reduction of individuals in NYHA IV (risk ratio = 0.27, 95% CI: 0.18 to 0.41, P &lt; 0.00001). On univariate analysis, there was a higher prevalence of males (85.7% vs. 40%), a history of left bundle branch block (71.4% vs. 30%), and more pronounced left ventricular end-diastolic dilation (274.3 ± 7.2 vs. 225.9 ± 6.1 mL). Conclusions CRT appears to be a viable option for inotrope-dependent HF, with some of these patients seeming more likely to respond.

Background: Many cardiac implantable devices have the capability of monitoring the volume status in patients with heart failure by tracking the intra-thoracic impedance changes over time measured by OptiVol fluid index. Objective: The aim of this study is to evaluate the association between the intra-thoracic impedance measured by OptiVol fluid index and the onset of tachyarrhythmias. Methods: We searched Medline and EMBASE databases through January 2021 looking for studies evaluating intra-thoracic impedance measured by OptiVol with either ventricular tachycardia/ventricular fibrillation (VT/VF) or atrial tachycardia/atrial fibrillation (AT/AF). After extracting the data from each study, we calculated the odds ratio with 95% confidence intervals using RevMan 5 software. Results: Ten studies met our inclusion criteria with a total of 118,504 patients were included in our analysis. Seven studies measured VT/VF included 94,816 patients and 5 studies measured AT/AF included 23,688 patients. Two studies measured both AT/AF and VT/VF. The odds ratio for developing VT/VF with OptiVol fluid index crossing a threshold of 60 Ω-days was 1.55 (95% CI 1.35, 1.78) (P<0.00001) and for developing AT/AF was 1.79 (95% CI 1.43, 2.24) (P<0.00001) {Figure1} Conclusion: The decrease in intra-thoracic impedance measured by OptiVol fluid index threshold crossing of 60 Ω-days is associated with higher risk for developing new onset AT/AF and VT/VF. Key Words: intra-thoracic impedance; OptiVol; tachyarrhythmia Figure1: Forest Plot for risk of developing VT/VF Figure: Forest Plot for risk of developing AT/AF

Introduction: Remote monitoring using implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy defibrillator (CRT-D) can be used as an adjunctive diagnostic tool to traditional hospital and clinic visits to monitor the volume status of patients with heart failure (HF). Methods: We searched PubMed, Cochrane Library, and ClinicalTrials.gov (inception through February 4th, 2021) for randomized controlled trials (RCTs) evaluating ICDs/CRT-D remote monitoring versus standard of care in patients with HF. Of 642 articles retrieved after removing duplicate items, we included 11 RCTs encompassing 5,965 patients. Absolute risk difference (ARD) with 95% credible interval (CrI) was estimated. Pooled (posterior) risk difference was computed using Bayesian hierarchical methods, random effects model and weakly informative prior. Results: The ARD for mortality was centered at -0.01 (95%CrI: -0.03; 0.01, Tau: 0.02), with 82% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for cardiovascular mortality was centered at -0.03 (95%CrI: -0.11; 0.05, Tau: 0.10), with 84% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for HF admissions was centered at -0.00 (95%CrI: -0.07; 0.06, Tau: 0.08), with 57% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0 [Figure]. Conclusions: This meta-analysis suggests that ICD/CRT-D remote monitoring in patients with HF is associated with a higher probability of reduced all-cause mortality, and cardiovascular mortality compared with standard care. However, ICD-CRT/D remote monitoring was associated with minimal probability of difference in HF hospitalizations.

Abstract Aims ECG abnormalities are often the first signs of arrhythmogenic right ventricular cardiomyopathy (ARVC) and we hypothesized that an artificial intelligence (AI)-enhanced ECG could help identify patients with ARVC and serve as a valuable disease-detection tool. Methods and results We created a convolutional neural network to detect ARVC using a 12-lead ECG. All patients with ARVC who met the 2010 task force criteria and had disease-causative genetic variants were included. All case ECGs were randomly assigned in an 8:1:1 ratio into training, validation, and testing groups. The case ECGs were age- and sex-matched with control ECGs at our institution in a 1:100 ratio. Seventy-seven patients (51% male; mean age 47.2 ± 19.9), including 56 patients with PKP2, 7 with DSG2, 6 with DSC2, 6 with DSP, and 2 with JUP were included. The model was trained using 61 case ECGs and 5009 control ECGs; validated with 7 case ECGs and 678 control ECGs and tested in 22 case ECGs and 1256 control ECGs. The sensitivity, specificity, positive and negative predictive values of the model were 77.3, 62.9, 3.32, and 99.4%, respectively. The area under the curve for rhythm ECG and median beat ECG was 0.75 and 0.76, respectively. Conclusion Our study found that the model performed well in excluding ARVC and supports the concept that the AI ECG can serve as a biomarker for ARVC if a larger cohort were available for network training. A multicentre study including patients with ARVC from other centres would be the next step in refining, testing, and validating this algorithm.

Abstract Background Inotrope-dependent heart failure (HF) carries a poor prognosis. Advanced mechanical supports have been viewed as primary treatment modalities for these patients, but cardiac resynchronization therapy (CRT) is an emerging alternative. Whether CRT is viable in HF patients who require inotropic support is uncertain. Purpose To assess outcomes of CRT in end-stage inotrope-dependent HF. Methods Following PRISMA guidelines, we searched Medline, EMBASE, Scopus, and Cochrane Library until December 31st 2022, with the following terms: "end-stage heart failure," "catecholamine-dependent overt heart failure," "inotrope-dependent heart failure," "advanced heart failure," "New York Heart Association class IV," "NYHA class IV." These terms were combined with "cardiac resynchronization therapy" OR "CRT" OR "biventricular device". Studies were included if: 1) HF patients required on inotropic support at CRT implantation; 2) patients were at least 18 years old; and 3) provided a clear definition of "inotrope dependence" or "inability to wean." A meta-analysis with random effects was performed in R (Version 3.5.1) with data presented as mean ± standard error. Results 19 studies comprised of 386 inotrope-dependent HF patients (mean age 64.4 ± 1.2 years, 76.9% male, 54.6% non-ischemic cardiomyopathy, mean QRS duration 168.0 ± 4.6 ms, mean follow-up 778 ± 110.7 days) were included for meta-analysis. A large majority of patients survived until discharge at 90% (95% CI: 81.0%-96.8%, I2=51%, p=0.04, Figure 1A), 88.6% were weaned off inotropes (95% CI: 77.5%-96.8%, I2=64%, p&lt;0.01), and mean time to discharge post-CRT was 7.8 days (95% CI: 3.9-11.7, I2= 84%, p&lt;0.01). After one year of follow-up 69.5% survived (95% CI: 59.2%-78.9%, I2=53%, p=0.02, Figure 1B) and 59.1% (95% CI: 50.1%-67.8%, I2=58%, p&lt;0.01, Figure 1C) were alive at the end of follow-up. During follow-up the mean number of hospital admission for HF was reduced by 1.87 (95% CI: 2.70-1.04, I2=77%, p=0.04). Post-CRT mean QRS duration was reduced by 29.0 ms (95% CI: 41.33-16.68, I2=69%, p=0.006, Fig) and mean left ventricular ejection fraction increased by 4.83% (95% CI: 3.09%-6.57%, I2=16%, p=0.31, Fig). The mean NYHA class post-CRT was 2.7 (95% CI: 2.5-3.0, I2=56%, p=0.03, Figure 2A), 39.6% (95% CI: 18,.7%-62.3%, I2=83%, p&lt;0.01, Figure 2C) improved to NYHA class III and 34.6% (95% CI: 16.4%-55.2%, I2=79%, p&lt;0.01, Figure 2D) improved to NYHA class II. Responders to CRT tended be male (85.7% vs. 40%, p=0.015), have a history of left bundle branch block (71.4% vs. 30%, p=0.036) or an increased left ventricular end-diastolic volume (274.3 mL vs. 225.9 mL, p=0.038). Conclusion(s) Our results suggest that CRT is an alternative option for end-stage inotrope-dependent HF, improving survival, NYHA status, and HF readmission. CRT responders appear to be male with evidence of preserved diastolic function or a history of a left bundle branch block.

Purpose: To highlight spontaneous resolution or improvement of myopic retinoschisis (MR) in actively surveilled patients. Methods: Case series of five patients diagnosed with MR who did not undergo pars plana vitrectomy and were carefully monitored by a single retina specialist. Ocular and medical history were reviewed, and clinical characteristics including visual acuity and the status of the MR were monitored with spectral domain optical coherence tomography (SD-OCT) at each clinic visit. Results: Five patients were identified to have MR without vitreomacular traction, or macular hole formation. Two patients exhibited spontaneous and complete resolution of MR without surgical intervention over an average observation time of 52.5 months. In these cases, a clinical posterior vitreous detachment was documented preceding the resolution of MR over an average time of 26.5 months. Snellen best-corrected visual acuity in these patients improved (Case 1 from 20/50 to 20/40, Case 2 from 20/30 to 20/25). The remaining three patients were monitored for an average of 52 months and showed improvement of MR via OCT imaging. Snellen best-corrected visual acuity either remained stable or improved from baseline (Case 3 stable at 20/30, Case 4 improved from 20/40 to 20/30, and Case 5 stable at 20/20). Conclusion: These findings suggest that conservative management of MR with observation can be considered especially in patients with challenging comorbidities (such as monocular status), and with a clinically identified posterior vitreous detachment without vitreomacular traction.