LVAD as a Bridge to Remission from Advanced Heart Failure: Current Data and Opportunities for Improvement

Left ventricular assist devices (LVADs) are an established treatment modality for advanced heart failure (HF). It has been shown that through volume and pressure unloading they can lead to significant functional and structural cardiac improvement, allowing LVAD support withdrawal in a subset of patients. In the first part of this review, we discuss the historical background, current evidence on the incidence and assessment of LVAD-mediated cardiac recovery, and out-comes including quality of life after LVAD support withdrawal. In the second part, we discuss current and future opportunities to promote LVAD-mediated reverse remodeling and improve our pathophysiological understanding of HF and recovery for the benefit of the greater HF population

Effect of Portable, In-Hospital Extracorporeal Membrane Oxygenation on Clinical Outcomes

The time between onset of cardiogenic shock and initiation of mechanical circulatory support is inversely related to patient survival as delays in transporting patients to the operating room (OR) for venoarterial extracorporeal membrane oxygenation (VA ECMO) could prove fatal. A primed and portable VA ECMO system may allow faster initiation of ECMO in various hospital locations and subsequently improve outcomes for patients in cardiogenic shock. We reviewed our institutional experience with VA ECMO based on two time periods: beginning of our VA ECMO program and from initiation of our primed and portable in-hospital ECMO system. The primary endpoint was patient survival to discharge. A total of 137 patients were placed on VA ECMO during the study period; n = 66 (48%) before and n = 71 (52%) after program initiation. In the second era, the proportion of OR ECMO initiation decreased significantly (from 92% to 49%, p < 0.01) as more patients received ECMO in other hospital units, including the emergency department (p < 0.01) and during cardiac arrest (12% vs. 38%, p < 0.01). Survival to hospital discharge was equivalent between the two groups (30% vs. 42%, p = 0.1) despite more patients being placed on ECMO during ongoing cardiac arrest. Finally, we observed increased clinical volume since initiation of the in-hospital, portable ECMO system. Developing an in-hospital, primed and portable VA ECMO program resulted in increased clinical volume with equivalent patient survival despite a sicker cohort of patients. We conclude that more rapid deployment of VA ECMO may extend the treatment eligibility to more patients and improve patient outcomes

Cardiogenic Shock Management: International Survey of Contemporary Practices

BACKGROUND: Limited data exist on current cardiogenic shock (CS) management strategies. METHODS: A 48-item open- and closed-ended question survey on the diagnosis and management of CS. RESULTS: A total of 211 respondents (3.2%) completed the survey, including 64% interventional cardiologists, 14% general cardiologists, 11% advanced heart failure cardiologists, 5% intensivists, 3% cardiothoracic surgeons; the remainder were internists, emergency medicine, and other physicians. Nearly half (45%) reported practicing at sites without advanced heart failure support/resources, with neither durable ventricular assist devices nor heart transplant available; 16% practice at sites without on-site cardiac surgery and 6% do not offer 24/7 percutaneous coronary intervention (PCI) coverage. The majority (70%) practice in closed intensive care units with multidisciplinary rounding (73%), cardiologists frequently involved in patient care (89%), and involving cardiology-intensivist co-management (41%). Over half (55%) reported use of CS protocols, 61% reported routine arterial line use, 25% reported routine use of pulmonary artery catheter use to guide management and 9% did not. The preferred vasopressor and/or inotrope was norepinephrine (68%). For coronary angiography and PCI, 53% use transradial access, 72% only revascularize the culprit vessel, and 44% institute mechanical circulatory support (MCS) prior to revascularization. Percutaneous MCS availability was as follows: intra-aortic balloon pump (92%), Impella (78%), peripheral veno-arterial extracorporeal membrane oxygenation (66%), and TandemHeart (28%). Most respondents (58%) do not use a scoring system for risk stratification and most (62%) reported that CS-specific cardiac rehabilitation programs were unavailable at their sites. CONCLUSION: Wide variation exists in the care delivered and/or resources available for patients with CS. Our survey suggests opportunities for standardization of care

Perm1 regulates cardiac energetics as a downstream target of the histone methyltransferase Smyd1.

The transcriptional regulatory machinery in mitochondrial bioenergetics is complex and is still not completely understood. We previously demonstrated that the histone methyltransferase Smyd1 regulates mitochondrial energetics. Here, we identified Perm1 (PPARGC-1 and ESRR-induced regulator, muscle specific 1) as a downstream target of Smyd1 through RNA-seq. Chromatin immunoprecipitation assay showed that Smyd1 directly interacts with the promoter of Perm1 in the mouse heart, and this interaction was significantly reduced in mouse hearts failing due to pressure overload for 4 weeks, where Perm1 was downregulated (24.4 ± 5.9% of sham, p<0.05). Similarly, the Perm1 protein level was significantly decreased in patients with advanced heart failure (55.2 ± 13.1% of donors, p<0.05). Phenylephrine (PE)-induced hypertrophic stress in cardiomyocytes also led to downregulation of Perm1 (55.7 ± 5.7% of control, p<0.05), and adenovirus-mediated overexpression of Perm1 rescued PE-induced downregulation of estrogen-related receptor alpha (ERRα), a key transcriptional regulator of mitochondrial energetics, and its target gene, Ndufv1 (Complex I). Pathway enrichment analysis of cardiomyocytes in which Perm1 was knocked-down by siRNA (siPerm1), revealed that the most downregulated pathway was metabolism. Cell stress tests using the Seahorse XF analyzer showed that basal respiration and ATP production were significantly reduced in siPerm1 cardiomyocytes (40.7% and 23.6% of scrambled-siRNA, respectively, both p<0.05). Luciferase reporter gene assay further revealed that Perm1 dose-dependently increased the promoter activity of the ERRα gene and known target of ERRα, Ndufv1 (Complex I). Overall, our study demonstrates that Perm1 is an essential regulator of cardiac energetics through ERRα, as part of the Smyd1 regulatory network