Despite efforts to improve treatment of refractory cardiogenic shock (rCS), prognosis remains poor. Multidisciplinary Shock Teams have been proposed as a strategy to streamline care delivery and improve outcomes despite the lack of strong evidence 1-5. This study sought to determine the feasibility and efficacy of the Shock Team approach for rCS at our tertiary care institution.
Aims
Adjuvant heart failure (HF) drug therapy in patients undergoing chronic mechanical circulatory support (MCS) is often used in conjunction with a continuous‐flow left ventricular assist device (LVAD), but its potential impact is not well defined. The objective of the present study was to examine the effects of conventional HF drug therapy on myocardial structure and function, peripheral organ function and the incidence of adverse events in the setting of MCS.
Methods and results
Patients with chronic HF requiring LVAD support were prospectively enrolled. Paired myocardial tissue samples were obtained prior to LVAD implantation and at transplantation for histopathology. The Meds group comprised patients treated with neurohormonal blocking therapy (concurrent beta‐blocker, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, and aldosterone antagonist), and the No Meds group comprised patients on none of these. Both the Meds (n = 37) and No Meds (n = 44) groups experienced significant improvements in cardiac structure and function over the 6 months following LVAD implantation. The degree of improvement was greater in the Meds group, including after adjustment for baseline differences. There were no differences between the two groups in arrhythmias, end‐organ injury, or neurological events. In patients with high baseline pre‐LVAD myocardial fibrosis, treatment with HF drug therapy was associated with a reduction in fibrosis.
Conclusions
Clinical and histopathological evidence showed that adjuvant HF drug therapy was associated with additional favourable effects on the structure and function of the unloaded myocardium that extended beyond the beneficial effects attributed to LVAD‐induced unloading alone. Adjuvant HF drug therapy did not influence the incidence of major post‐LVAD adverse events during the follow‐up period.
BACKGROUND:
Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed “responders”). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown.
METHODS:
To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders.
RESULTS:
These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions.
CONCLUSIONS:
This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets.
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