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Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, and cardiac amyloidosis (CA) is one of the causes of HFpEF, that has established and emerging treatment options. However, it remains an underdiagnosed and often overlooked cause of HFpEF. The importance of early diagnosis cannot be emphasized enough, as emerging therapies are more effective early in the course of the disease. Further, because of the unique physiologic and hemodynamic features of CA, patients poorly tolerate traditional heart failure medications and experience worse outcomes compared with other causes of HFpEF. With the aging of the population, transthyretin (ATTR) CA, once thought to be a rare disease, will become the most common type of systemic amyloidosis. ATTR-CA is increasingly recognized due to enhanced clinical awareness; advances in diagnostic imaging that have led to a diagnostic approach that does not require a biopsy, as well as the recent introduction of novel disease-modifying treatments. ATTR-CA causes restrictive and infiltrative cardiomyopathy that results in heart failure, atrial and ventricular arrhythmias, and conduction disease, and is associated with significant morbidity and mortality. Our goal in this review is to provide an overview of the historical, epidemiologic, diagnostic, and therapeutic evolution of ATTR-CA, and to emphasize the importance of early suspicion and detection of HFpEF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The cardiac regenerative capacity of MRL/MpJ mouse remains a controversy. Although the MRL mouse has been reported to exhibit minimal scarring and subsequent cardiac regeneration after cryoinjury of the right ventricle, multiple studies have been unable to replicate this cardiac regenerative capacity after both cryogenic and coronary ligation cardiac injury. Therefore, we evaluated the cardiac regenerative wound-healing response and functional recovery of MRL mice compared to C57 mice, in response to a clinically relevant left ventricular (LV) coronary ligation. Male MRL/MpJ+/+ and C57BL/6 mice underwent left coronary artery ligation followed by reperfusion. Cardiac function was evaluated by echocardiography [LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV mass, wall thickness] at 24 hours post-ischemia and weekly for 13 weeks thereafter. Hearts were also analyzed histologically for individual cardiomyocyte hypertrophy and cardiac fibrosis. Our results show that contrary to prior reports of cardiac regenerations, MRL mice progress to heart failure more rapidly following I/R injury as marked by a significant decrease in LVEF, increase in LVEDV, LV mass, individual myocyte size, and fibrosis in the post-ischemic myocardium. Therefore, we conclude that MRL mice do not exhibit regeneration of the LV or enhanced functional improvement in response to coronary ligation. However, unlike prior studies, we matched initial infarct size in MRL and C57 mice, used high frequency echocardiography, and histological analysis to reach this conclusion. The prospect of cardiac regeneration after ischemia in MRL mice seems to have attenuated interest, given the multiple negative studies and the promise of stem cell cardiac regeneration. However, our novel observation that MRL may possess an impaired compensated hypertrophy response makes the MRL mouse strain an interesting model in the study of cardiac hypertrophy., (Copyright © 2014 Elsevier Inc. All rights reserved.)