Publications by authors named "Ravi Karra"

The adult mammalian heart harbors minute levels of cycling cardiomyocytes (CMs). Large numbers of images are needed to accurately quantify cycling events using microscopy-based methods. CardioCount is a new deep learning-based pipeline to rigorously score nuclei in microscopic images.

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Article Synopsis
  • LMNA-CM is a type of heart disease caused by changes in specific proteins that can lead to serious heart problems and requires special treatment.
  • People usually show signs of LMNA-CM in their 30s or 40s, and doctors can recognize it early by looking for heart rhythm issues even before major heart damage appears.
  • It's important for doctors to know how to test for LMNA-CM and be aware of new treatments being studied, as this helps manage patients' health better.
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Cardiac sarcoidosis (CS) is a relapsing-remitting disease, and immune suppression (IS) is the mainstay of therapy. Predictors of relapse for patients with CS in remission are not well characterized. We assessed incidence of relapse in consecutive patients with CS treated with high-dose steroids and/or steroid-sparing agents (SSA) in our center from 2000 to 2020.

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This Editorial introduces DMM's new Special Issue on ‘Moving heart failure to heart success’. The Guest Editors reflect on how articles in the issue advance the cardiac research field.

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Background: We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF).

Methods: We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT study. Protein levels were evaluated for association with echocardiographic parameters and the incidence of all-cause death and hospitalization for heart failure (HHF).

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Article Synopsis
  • Current gene therapy methods struggle with precise control of how and when therapeutic genes are delivered to damage sites.
  • Researchers discovered that "tissue-regeneration enhancer elements" (TREEs) from zebrafish can effectively guide gene expression related to tissue healing in both small and large mammals.
  • When combined with CRISPR tools in mice, TREEs improved cardiac regeneration and function after heart damage, suggesting they could be used for more effective, targeted therapies in tissue repair.
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Purpose Of Review: Cardiac sarcoidosis (CS) is an important cause of non-ischemic cardiomyopathy and has specific diagnostic and therapeutic considerations. With advances in imaging techniques and treatment approaches, the approach to monitoring disease progression and management of CS continues to evolve. The purpose of this review is to highlight advances in CS diagnosis and treatment and present a center's multidisciplinary approach to CS care.

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Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled.

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Background: The significance of recovered left ventricular ejection fraction (LVEF) in LVAD recipients, outside of pump explantation, is unclear.

Methods: Patients undergoing first LVAD implantation at Duke University Hospital between 2006 and 2017 were evaluated for LVEF recovery up to 2 years following implant. Occurrence of gastrointestinal bleeding (GIB), hospitalization for heart failure (HF), pump thrombosis and death were assessed before and after LVEF recovery.

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Human cardiac organoid systems hold significant promise for mechanistic studies of early heart morphogenesis and an improved understanding of congenital cardiac disease.

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Background: Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets.

Methods: We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays.

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We report the first patient roadmap in severe chronic low back pain (cLBP) in Europe, assessing the views of cLBP patients and general practitioners (GPs) who treat cLBP with regard to current cLBP management. Patient journey mapping was conducted in four European countries to assess the views of cLBP patients (n = 20) and GPs (n = 40). Four broad phases of cLBP, subdivided into eight individual steps, were identified as part of the patient journey, showing a disconnect between patients' and physicians' treatment goals, and expectations regarding pain relief levels for some patients.

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Background Although technological advances to pump design have improved survival, left ventricular assist device (LVAD) recipients experience variable improvements in quality of life. Methods for optimizing LVAD support to improve quality of life are needed. We investigated whether acoustic signatures obtained from digital stethoscopes can predict patient-centered outcomes in LVAD recipients.

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Purpose Of Review: The replenishment of lost or damaged myocardium has the potential to reverse heart failure, making heart regeneration a goal for cardiovascular medicine. Unlike adult mammals, injury to the zebrafish or neonatal mouse heart induces a robust regenerative program with minimal scarring. Recent insights into the cellular and molecular mechanisms of heart regeneration suggest that the machinery for regeneration is conserved from zebrafish to mammals.

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Aims: Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF).

Methods And Results: In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days.

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Objective: LVADs are surgically implanted mechanical pumps that improve survival rates of individuals with advanced heart failure. LVAD therapy is associated with high morbidity, which can be partially attributed to challenges with detecting LVAD complications before adverse events occur. Current methods used to monitor for complications with LVAD support require frequent clinical assessments at specialized LVAD centers.

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A survey of European Pain Federation 2019 attendees was conducted to identify unmet needs in chronic pain patients. Four questions were asked focusing on functional impairment in chronic pain, including who are at increased risk and ways to better identify and manage these patients. In total 143 respondents indicated that key issues were lack of knowledge, lack of resources/time to assess and manage chronic pain and lack of sufficient tools to identify patients at risk for functional impairment.

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To investigate quality of life (QOL) and functionality changes in chronic pain during tapentadol prolonged release (PR) treatment. analysis of data from three Phase III trials in patients with osteoarthritis knee pain or low back pain. QOL and functionality changes were assessed by SF-36 scores.

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To explore fracture outcomes with tapentadol or oxycodone, two opioids with differing mechanisms of action. Retrospective cohort pilot study, using MarketScan Commercial and Medicare Supplemental claims databases, on patients with postoperative pain, back pain, or osteoarthritis and ≥1 claim for tapentadol (n = 16,457), oxycodone (n = 1,356,920), or both (n = 15,893) between June 2009 and December 2015. During 266,826 and 9,007,889 days of tapentadol and oxycodone treatment, patients evidenced 1080 and 72,275 fractures, respectively.

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Objectives: This study characterized the relationship between conduction disease and cardiac amyloidosis (CA) through longitudinal analysis of cardiac implantable electronic device (CIED) data.

Background: Bradyarrhythmias and tachyarrhythmias are commonly reported in CA and may precede a CA diagnosis, although the natural history of conduction disease in CA is not well-described.

Methods: Patients with CA (transthyretin amyloidosis cardiomyopathy [ATTR-CM] and light-chain amyloidosis [AL-CA]) and a CIED were identified within the Duke University Health System.

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By replacing lost or dysfunctional myocardium, tissue regeneration is a promising approach to treat heart failure. However, the challenge of detecting bona fide heart regeneration limits the validation of potential regenerative factors. One method to detect new cardiomyocytes is multicolor lineage tracing with clonal analysis.

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