Publications by authors named "Rami Alharethi"

Article Synopsis
  • Peripartum cardiomyopathy (PPCM) poses serious health risks, and while recovery of heart function is important, it doesn't guarantee better long-term outcomes; additional assessments using cardiac MRI (CMR) can reveal further risks.
  • The study analyzed 51 PPCM patients, highlighting that lower left ventricular ejection fraction (LVEF), peak global longitudinal strain (GLS), and higher extracellular volume (ECV) were linked to worse outcomes, including the need for heart assist devices or transplants.
  • Findings suggest CMR might help identify patients at higher risk for serious adverse outcomes beyond what LVEF can indicate, potentially revealing future treatment targets like diffuse myocardial fibrosis.
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Article Synopsis
  • The study explores how incorporating patient-reported outcomes (PROs) can enhance the prediction of hospitalization and mortality risks in patients with heart failure (HF).
  • The research involved 1165 patients with heart failure with reduced ejection fraction (HFrEF) and 456 with preserved ejection fraction (HFpEF), utilizing advanced statistical methods to analyze risk over time.
  • Findings indicated that models including PROs significantly improved risk prediction, demonstrating their value alongside traditional clinical assessments in managing outpatient heart failure.
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Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT). We evaluated donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker of CAV development after HT. The INSPIRE registry at the Intermountain Medical Center was queried for stored plasma samples from HT patients with and without CAV.

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Background: Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients.

Methods And Results: Consecutive patients with an LVAD were prospectively evaluated (n=531).

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A previously healthy man presented in shock due to incessant tachycardia. He ultimately required extracorporeal membrane oxygenation for support and clipping of his appendage for arrhythmia control. This case highlights the importance of early recognition of cardiogenic shock, aggressive hemodynamic support, and a multidisciplinary approach to managing these challenging arrhythmias.

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Article Synopsis
  • The HeartMate 3 (HM3) is the only fully magnetically levitated left ventricular assist device (LVAD) available for advanced heart failure patients, but its impact on heart function post-implantation hasn't been fully explored.
  • A study comparing HM3 to older LVADs (HeartWare Ventricular Assist Device and HeartMate II) found no significant differences in heart function improvements after implantation.
  • The proportion of patients showing significant reverse heart remodeling was similar across all devices, indicating that HM3 technology may be just as effective as older models in supporting heart recovery.
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Article Synopsis
  • Mechanical unloading with left ventricular assist devices (LVADs) can significantly improve heart function in some advanced heart failure patients, and researchers are studying the related clinical and biological changes.
  • In a study involving 208 patients, a combination of clinical data and RNA sequencing was used to identify predictors of heart recovery after LVAD implantation, focusing on factors like ejection fraction and heart size.
  • The results showed that specific clinical indicators and a biological variable (LRRN4CL) were linked to potential recovery, suggesting that this research could enhance diagnosis and treatment strategies for advanced heart failure.
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Importance: The existing models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support might be limited, partly due to lack of external validation, marginal predictive power, and absence of intraoperative characteristics.

Objective: To derive and validate a risk model to predict RVF after LVAD implantation.

Design, Setting, And Participants: This was a hybrid prospective-retrospective multicenter cohort study conducted from April 2008 to July 2019 of patients with advanced heart failure (HF) requiring continuous-flow LVAD.

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Background: Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to cardiovascular death (CV death). We hypothesized that a donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CV death.

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Article Synopsis
  • Activin A, a protein, is linked to chronic hypertension, heart failure, and hypertensive pregnancy disorders but its role in blood pressure during peripartum cardiomyopathy (PPCM) was previously unexplored.
  • A study of 82 women with PPCM examined the relationship between blood pressure and serum levels of activin A and another biomarker, finding significant correlations specifically in those with a history of hypertensive disorders.
  • The strongest correlation was observed between activin A and diastolic blood pressure in women with preeclampsia, indicating its potential importance in regulating blood pressure for those affected by hypertensive disorders during pregnancy.
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Background: The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy.

Objectives: The aim of this study was to characterize the pathophysiology of PPCM through serum proteomic analysis.

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By unloading the failing heart, left ventricular (LV) assist devices (LVADs) provide a favorable environment for reversing adverse structural and functional cardiac changes. Prior reports have suggested that an improved native LV function might contribute to the development of LVAD thrombosis. We used the Interagency Registry for Mechanically Assisted Circulatory Support and found that LV functional improvement is associated with a lower risk for device thrombosis.

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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.

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Background: Donor heart scarcity remains the fundamental barrier to increased transplant access. We examined whether 2018 United Network for Organ Sharing (UNOS) policy changes have had an impact on donor heart acceptance rates.

Methods And Results: We performed an interrupted time series analysis in UNOS to evaluate for abrupt changes in donor heart-acceptance rates associated with the new policy.

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Objective: In chronic heart failure (HF) patients supported with continuous-flow left ventricular assist device (CF-LVAD), we aimed to assess the clinical association of pre-LVAD QRS duration (QRSd) with post-LVAD cardiac recovery, and its correlation with pre- to post-LVAD change in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD).

Methods: Chronic HF patients ( = 402) undergoing CF-LVAD implantation were prospectively enrolled, at one of the centers comprising the U.T.

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Background: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF.

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Background: A growing proportion of transplant donors and recipients have a history of COVID-19 infection. This study sought to characterize clinical practice after recipient or donor COVID-19 infection.

Methods: An online survey was distributed to heart transplant clinicians through a professional society message board and social media.

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Background: Extrinsic control of cardiomyocyte metabolism is poorly understood in heart failure (HF). FGF21 (Fibroblast growth factor 21), a hormonal regulator of metabolism produced mainly in the liver and adipose tissue, is a prime candidate for such signaling.

Methods: To investigate this further, we examined blood and tissue obtained from human subjects with end-stage HF with reduced ejection fraction at the time of left ventricular assist device implantation and correlated serum FGF21 levels with cardiac gene expression, immunohistochemistry, and clinical parameters.

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Background Recent prospective multicenter data from patients with advanced heart failure demonstrated that left ventricular assist device (LVAD) support combined with standard heart failure medications, induced significant cardiac structural and functional improvement, leading to high rates of LVAD weaning in selected patients. We investigated whether preintervention myocardial and systemic inflammatory burden could help identify the subset of patients with advanced heart failure prone to LVAD-mediated cardiac improvement to guide patient selection, treatment, and monitoring. Methods and Results Ninety-three patients requiring durable LVAD were prospectively enrolled.

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It is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF.

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Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD.

Methods: The study enrolled consecutive LVAD patients across 4 study sites.

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Background: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in (TTNtvs).

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Objective: Using augmented intelligence clinical decision tools and a risk score-guided multidisciplinary team-based care process (MTCP), this study evaluated the MTCP for heart failure (HF) patients' 30-day readmission and 30-day mortality across 20 Intermountain Healthcare hospitals.

Background: HF inpatient care and 30-day post-discharge management require quality improvement to impact patient health, optimize utilization, and avoid readmissions.

Methods: HF inpatients (N = 6182) were studied from January 2013 to November 2016.

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Background: The coronary vasculature encounters a reduction in pulsatility after implementing durable continuous-flow left ventricular assist device (CF-LVAD) circulatory support. Evidence exists that appropriate pulsatility is required to maintain endothelial cell homeostasis. We hypothesized that coronary artery endothelial function would be impaired after CF-LVAD intervention.

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