Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells, which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardio-myopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based model for therapeutic discovery.

Background: The global myocardial work index (GWI), a novel, valid, and non-invasive method based on speckle-tracking echocardiography, could provide value for calculating left ventricular (LV) function and energy consumption in athletes. Materials and Methods: We prospectively analyzed a single-center cohort of Spanish First-Division football players who attended a pre-participation screening program from June 2020 to June 2021, compared to a control group. All the individuals underwent an electrocardiogram and echocardiography, including two-dimensional speckle tracking and 4D-echo. The study aimed to evaluate the feasibility of myocardial work in professional football players and its correlations with other echocardiographic parameters. Results: The study population comprised 97 individuals (49 professional players and 48 controls). The mean age was 30.48 +/- 7.20 years old. The professional football players had significantly higher values of LVEDV (p < 0.001), LVESV (p < 0.001), LV-mass index (p = 0.011), PWTd (p = 0.023), and EA (p < 0.001) compared with the control group. In addition, the professional players had lower GCW (p = 0.003) and a tendency to show lower GWI values (p < 0.001). These findings could suggest that professional football players have more remodeling and less MW, related to their adaptation to intensive training. Significant differences in GLS (p = 0.01) and GWE (p = 0.04) were observed as a function of the septal thickness of the athletes. Irrespective of the MW variable, the parameters with better correlations across all the populations were SBP, DBP, and GLS. Conclusions: The GWI is a novel index to assess cardiac performance, with less load dependency than strain measurements. Future GWI analyses are warranted to understand myocardial deformation and other pathological differential diagnoses.

BACKGROUND Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 +/- 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across alt patients, mean z-scores for T1 and T2 values were 2.9 +/- 1.9 (p < 0.001) and 2.2 +/- 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1(1,079.0 +/- 55.5 ms vs. 1,000.3 +/- 221 ms; p < 0.001) and 12 (56.2 +/- 4.9 ms vs. 49.8 +/- 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91(95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. CONCLUSIONS The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis. (C) 2021 by the American College of Cardiology Foundation.

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

The combination of CA and percutaneous LAAC in a single procedure is technically feasible in patients with symptomatic drug-refractory AF, high risk of stroke, and contraindications to OACs, although it is associated with a significant risk of major complications

The present document reviews various aspects of the current status of cardiac resynchronization therapy: mechanisms of action, current indications and implantation technique.