No abstract

In DCM, increased FXR1 expression appears to play an important role in disease progression by regulating gap junction remodeling. Together this study provides a novel function of FXR1, namely, that it directly regulates major gap junction components, contributing to proper cell-cell communication in the heart.

Although radiofrequency ablation has revolutionized the management of tachyarrhythmias, the rate of arrhythmia recurrence is a large drawback. Successful substrate identification is paramount to abolishing arrhythmia, and bipolar voltage electrogram’s narrow field of view can be further reduced for increased sensitivity. In this report, we perform cardiac mapping with monophasic action potential (MAP) amplitude. We hypothesize that MAP amplitude (MAPA) will provide more accurate infarct sizes than other mapping modalities via increased sensitivity to distinguish healthy myocardium from scar tissue. Using the left coronary artery ligation Sprague-Dawley rat model of ischemic heart failure, we investigate the accuracy of in vivo ventricular epicardial maps derived from MAPA, MAP duration to 90% repolarization (MAPD90), unipolar voltage amplitude (UVA), and bipolar voltage amplitude (BVA) compared with gold standard histopathological measurement of infarct size. Numerical analysis reveals discrimination of healthy myocardium versus scar tissue using MAPD90 ( P = 0.0158) and UVA ( P < 0.001, n = 21). MAPA and BVA decreased between healthy and border tissue ( P = 0.0218 and 0.0015, respectively) and border and scar tissue ( P = 0.0037 and 0.0094, respectively). Contrary to our hypothesis, BVA mapping performed most accurately regarding quantifying infarct size. MAPA mapping may have high spatial resolution for myocardial tissue characterization but was quantitatively less accurate than other mapping methods at determining infarct size. BVA mapping’s superior utility has been reinforced, supporting its use in translational research and clinical electrophysiology laboratories. MAPA may hold potential value for precisely distinguishing healthy myocardium, border zone, and scar tissue in diseases of disseminated fibrosis such as atrial fibrillation. NEW & NOTEWORTHY Monophasic action potential mapping in a clinically relevant model of heart failure with potential implications for atrial fibrillation management.

Purpose of reviewHeart failure often progresses despite optimal medical and device therapies, and advanced mechanical circulatory support has limited availability and substantial associated morbidity. Cardiac contractility modulation (CCM) provides nonexcitatory stimulation to ventricular myocardium which increases cardiac contractility without increasing oxygen demand. This review describes the emerging role of CCM in heart failure treatment. Recent findingsThe FIX-HF-5C2 study demonstrated similar safety and efficacy profile of the two-lead Optimizer device in comparison with the prior three-lead system, thereby decreasing procedural complexity and minimizing endocardial hardware. The FIX-HF-5C trial underscored the benefit of CCM in patients with mild-moderate left ventricular dysfunction (ejection fraction, 25-45%) with New York Heart Association (NYHA) Class III symptoms. The summarized randomized trial data show consistent improvements in peak VO 2 , 6-min walk distance, and NYHA functional class with CCM. Future trials are planned to determine the role of CCM in heart failure patients with preserved ejection fraction, obligate ventricular pacing, and atrial arrhythmias. SummaryNonexcitatory extracellular electric potentials can facilitate inotropic improvements in the failing heart. The mechanism of CCM does not increase myocardial oxygen consumption and has been shown to mitigate heart failure symptoms, decrease hospitalizations, and work in synergy with guideline-directed therapy for heart failure.

This review will outline cell-based therapy for heart failure focusing on tissue engineering to deliver cells to the damaged heart. We will present an overview of the central approaches focusing on pluripotent stem cell-derived cells, mechanisms of action, autologous vs. allogeneic cell approaches, immunologic modulation, and safety considerations. We will outline the progress that has been made to-date and define the areas that still need to be investigated in order to advance the field.