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Archive for the ‘Frontiers in Cardiology and Cardiovascular Disorders’ Category

Multiple Barriers Identified Which May Hamper Use of Artificial Intelligence in the Clinical Setting

Reporter: Stephen J. Williams, PhD.

From the Journal Science:Science  21 Jun 2019: Vol. 364, Issue 6446, pp. 1119-1120

By Jennifer Couzin-Frankel

3.3.21

3.3.21   Multiple Barriers Identified Which May Hamper Use of Artificial Intelligence in the Clinical Setting, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

In a commentary article from Jennifer Couzin-Frankel entitled “Medicine contends with how to use artificial intelligence  the barriers to the efficient and reliable adoption of artificial intelligence and machine learning in the hospital setting are discussed.   In summary these barriers result from lack of reproducibility across hospitals. For instance, a major concern among radiologists is the AI software being developed to read images in order to magnify small changes, such as with cardiac images, is developed within one hospital and may not reflect the equipment or standard practices used in other hospital systems.  To address this issue, lust recently, US scientists and government regulators issued guidance describing how to convert research-based AI into improved medical images and published these guidance in the Journal of the American College of Radiology.  The group suggested greater collaboration among relevant parties in developing of AI practices, including software engineers, scientists, clinicians, radiologists etc. 

As thousands of images are fed into AI algorithms, according to neurosurgeon Eric Oermann at Mount Sinai Hospital, the signals they recognize can have less to do with disease than with other patient characteristics, the brand of MRI machine, or even how a scanner is angled.  For example Oermann and Mount Sinai developed an AI algorithm to detect spots on a lung scan indicative of pneumonia and when tested in a group of new patients the algorithm could detect pneumonia with 93% accuracy.  

However when the group from Sinai tested their algorithm from tens of thousands of scans from other hospitals including NIH success rate fell to 73-80%, indicative of bias within the training set: in other words there was something unique about the way Mt. Sinai does their scans relative to other hospitals.  Indeed, many of the patients Mt. Sinai sees are too sick to get out of bed and radiologists would use portable scanners, which generate different images than stand alone scanners.  

The results were published in Plos Medicine as seen below:

PLoS Med. 2018 Nov 6;15(11):e1002683. doi: 10.1371/journal.pmed.1002683. eCollection 2018 Nov.

Variable generalization performance of a deep learning model to detect pneumonia in chest radiographs: A cross-sectional study.

Zech JR1, Badgeley MA2, Liu M2, Costa AB3, Titano JJ4, Oermann EK3.

Abstract

BACKGROUND:

There is interest in using convolutional neural networks (CNNs) to analyze medical imaging to provide computer-aided diagnosis (CAD). Recent work has suggested that image classification CNNs may not generalize to new data as well as previously believed. We assessed how well CNNs generalized across three hospital systems for a simulated pneumonia screening task.

METHODS AND FINDINGS:

A cross-sectional design with multiple model training cohorts was used to evaluate model generalizability to external sites using split-sample validation. A total of 158,323 chest radiographs were drawn from three institutions: National Institutes of Health Clinical Center (NIH; 112,120 from 30,805 patients), Mount Sinai Hospital (MSH; 42,396 from 12,904 patients), and Indiana University Network for Patient Care (IU; 3,807 from 3,683 patients). These patient populations had an age mean (SD) of 46.9 years (16.6), 63.2 years (16.5), and 49.6 years (17) with a female percentage of 43.5%, 44.8%, and 57.3%, respectively. We assessed individual models using the area under the receiver operating characteristic curve (AUC) for radiographic findings consistent with pneumonia and compared performance on different test sets with DeLong’s test. The prevalence of pneumonia was high enough at MSH (34.2%) relative to NIH and IU (1.2% and 1.0%) that merely sorting by hospital system achieved an AUC of 0.861 (95% CI 0.855-0.866) on the joint MSH-NIH dataset. Models trained on data from either NIH or MSH had equivalent performance on IU (P values 0.580 and 0.273, respectively) and inferior performance on data from each other relative to an internal test set (i.e., new data from within the hospital system used for training data; P values both <0.001). The highest internal performance was achieved by combining training and test data from MSH and NIH (AUC 0.931, 95% CI 0.927-0.936), but this model demonstrated significantly lower external performance at IU (AUC 0.815, 95% CI 0.745-0.885, P = 0.001). To test the effect of pooling data from sites with disparate pneumonia prevalence, we used stratified subsampling to generate MSH-NIH cohorts that only differed in disease prevalence between training data sites. When both training data sites had the same pneumonia prevalence, the model performed consistently on external IU data (P = 0.88). When a 10-fold difference in pneumonia rate was introduced between sites, internal test performance improved compared to the balanced model (10× MSH risk P < 0.001; 10× NIH P = 0.002), but this outperformance failed to generalize to IU (MSH 10× P < 0.001; NIH 10× P = 0.027). CNNs were able to directly detect hospital system of a radiograph for 99.95% NIH (22,050/22,062) and 99.98% MSH (8,386/8,388) radiographs. The primary limitation of our approach and the available public data is that we cannot fully assess what other factors might be contributing to hospital system-specific biases.

CONCLUSION:

Pneumonia-screening CNNs achieved better internal than external performance in 3 out of 5 natural comparisons. When models were trained on pooled data from sites with different pneumonia prevalence, they performed better on new pooled data from these sites but not on external data. CNNs robustly identified hospital system and department within a hospital, which can have large differences in disease burden and may confound predictions.

PMID: 30399157 PMCID: PMC6219764 DOI: 10.1371/journal.pmed.1002683

[Indexed for MEDLINE] Free PMC Article

Images from this publication.See all images (3)Free text

 

Surprisingly, not many researchers have begun to use data obtained from different hospitals.  The FDA has issued some guidance in the matter but considers “locked” AI software or unchanging software as a medical device.  However they just announced development of a framework for regulating more cutting edge software that continues to learn over time.

Still the key point is that collaboration over multiple health systems in various countries may be necessary for development of AI software which is used in multiple clinical settings.  Otherwise each hospital will need to develop their own software only used on their own system and would provide a regulatory headache for the FDA.

Other articles on Artificial Intelligence in Clinical Medicine on this Open Access Journal include:

Top 12 Artificial Intelligence Innovations Disrupting Healthcare by 2020

The launch of SCAI – Interview with Gérard Biau, director of the Sorbonne Center for Artificial Intelligence (SCAI).

Real Time Coverage @BIOConvention #BIO2019: Machine Learning and Artificial Intelligence #AI: Realizing Precision Medicine One Patient at a Time

50 Contemporary Artificial Intelligence Leading Experts and Researchers

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scPopCorn: A New Computational Method for Subpopulation Detection and their Comparative Analysis Across Single-Cell Experiments

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

4.2.5

4.2.5   scPopCorn: A New Computational Method for Subpopulation Detection and their Comparative Analysis Across Single-Cell Experiments, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 4: Single Cell Genomics

Present day technological advances have facilitated unprecedented opportunities for studying biological systems at single-cell level resolution. For example, single-cell RNA sequencing (scRNA-seq) enables the measurement of transcriptomic information of thousands of individual cells in one experiment. Analyses of such data provide information that was not accessible using bulk sequencing, which can only assess average properties of cell populations. Single-cell measurements, however, can capture the heterogeneity of a population of cells. In particular, single-cell studies allow for the identification of novel cell types, states, and dynamics.

One of the most prominent uses of the scRNA-seq technology is the identification of subpopulations of cells present in a sample and comparing such subpopulations across samples. Such information is crucial for understanding the heterogeneity of cells in a sample and for comparative analysis of samples from different conditions, tissues, and species. A frequently used approach is to cluster every dataset separately, inspect marker genes for each cluster, and compare these clusters in an attempt to determine which cell types were shared between samples. This approach, however, relies on the existence of predefined or clearly identifiable marker genes and their consistent measurement across subpopulations.

Although the aligned data can then be clustered to reveal subpopulations and their correspondence, solving the subpopulation-mapping problem by performing global alignment first and clustering second overlooks the original information about subpopulations existing in each experiment. In contrast, an approach addressing this problem directly might represent a more suitable solution. So, keeping this in mind the researchers developed a computational method, single-cell subpopulations comparison (scPopCorn), that allows for comparative analysis of two or more single-cell populations.

The performance of scPopCorn was tested in three distinct settings. First, its potential was demonstrated in identifying and aligning subpopulations from single-cell data from human and mouse pancreatic single-cell data. Next, scPopCorn was applied to the task of aligning biological replicates of mouse kidney single-cell data. scPopCorn achieved the best performance over the previously published tools. Finally, it was applied to compare populations of cells from cancer and healthy brain tissues, revealing the relation of neoplastic cells to neural cells and astrocytes. Consequently, as a result of this integrative approach, scPopCorn provides a powerful tool for comparative analysis of single-cell populations.

This scPopCorn is basically a computational method for the identification of subpopulations of cells present within individual single-cell experiments and mapping of these subpopulations across these experiments. Different from other approaches, scPopCorn performs the tasks of population identification and mapping simultaneously by optimizing a function that combines both objectives. When applied to complex biological data, scPopCorn outperforms previous methods. However, it should be kept in mind that scPopCorn assumes the input single-cell data to consist of separable subpopulations and it is not designed to perform a comparative analysis of single cell trajectories datasets that do not fulfill this constraint.

Several innovations developed in this work contributed to the performance of scPopCorn. First, unifying the above-mentioned tasks into a single problem statement allowed for integrating the signal from different experiments while identifying subpopulations within each experiment. Such an incorporation aids the reduction of biological and experimental noise. The researchers believe that the ideas introduced in scPopCorn not only enabled the design of a highly accurate identification of subpopulations and mapping approach, but can also provide a stepping stone for other tools to interrogate the relationships between single cell experiments.

References:

https://www.sciencedirect.com/science/article/pii/S2405471219301887

https://www.tandfonline.com/doi/abs/10.1080/23307706.2017.1397554

https://ieeexplore.ieee.org/abstract/document/4031383

https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0927-y

https://www.sciencedirect.com/science/article/pii/S2405471216302666

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First Surgical Robot Making Surgeon’s Life More Efficient

Reporter : Irina Robu, PhD

A team of microsurgeons and engineers, developed a high-precision robotic assistant called MUSA which is clinically and commercially available. The high precision robotic assistant is compatible with current operating techniques, workflow, instruments and other or instrument.   Microsure is a medical device company in The Netherlands founded by Eindhoven University of Technology and Maastricht University Medical Center in 2016. Microsure’s focus is to improve patients’ quality of life through developing robot systems for microsurgery.

The Microsure’s MUSA enhances surgical performance by stabilizing and scaling down the surgeon’s movements during complex microsurgical procedures on sub-millimeter scale. The surgical robot, allows lymphatic surgery on lymph vessels smaller than 0.3 mm in diameter. Microsure received the ISO 13485 certificate which assures that Microsure is adhering to the highest standards in quality management and regulatory compliance procedures to develop, manufacture, and test its products and services.

MUSA provides superhuman precision for microsurgeons, enabling new interventions that are currently impossible to perform by hand.

SOURCE

https://www.businesswire.com/news/home/20190607005175/en/

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New Neuromodulation Device to Treat Migraines

Reporter: Irina Robu, PhD

Theranica, Israeli startup is developing a non-invasive medical device that treats migraine pain through smartphone-controlled electric pulses unlike existing pharmaceutical solutions like triptans and ergotamine. The company recently received FDA De-novo clearance on Nerivio Migra, a class II medical device to treat acute migraine pain.

The non-invasive medical device, Nerivio Migra contains a bioelectric patch which is placed on the upper arm and a linked smartphone app which controls the electrical impulses and records data. The device’s electric pulses excite C-fiber nerves, generating an analgesic mechanism in the brain that lightens migraine pain.

In order to diminish the overuse of painkillers, the company developed the non-invasive device and tested it among acute migraine patients both two and 48 hours after treatment. Side effects from the device were mild and resolved within 24 hours.

Theranica’s product is lower in price than the existing alternatives and it is using existing smartphone technology. Their initial focus is on marketing to headache clinics as a start. And hoping to expand the indications for its device to the pediatric migraine population and finally use its platform to treat other idiopathic pain conditions like cluster headaches.

SOURCE

Israeli startup gets FDA nod for neuromodulation device to treat migraines

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@ClevelandClinic – Cardiac Consult: Catheter Ablation vs Antiarrhythmic Drug Therapy in Atrial Fibrillation: CABANA – What Did We Learn?

Reporter: Aviva Lev-Ari, PhD, RN

 

AUDIT PODCAST

https://my.clevelandclinic.org/podcasts/cardiac-consult/catheter-ablation-vs-antiarrhythmic-drug-therapy-in-atrial-fibrillation-cabana?_ga=2.88658141.711601484.1558922695-amp-RRJ7UwWd4zu5JL6IeLrcYA

 

The international CABANA trial (Catheter Ablation versus Arrhythmia Drug Therapy for Atrial Fibrillation) was the biggest buzz at the Heart Rhythm Society Scientific Sessions earlier this year, and it’s still making waves several months later.

Cleveland Clinic is among the 120 centers participating in the trial, and electrophysiologist Bruce Lindsay, MD, is the site’s principal investigator for the study. He recently sat down with Oussama Wazni, MD, Cleveland Clinic’s Section Head of Cardiac Electrophysiology and Pacing, to discuss the CABANA trial’s findings and implications. Below is an edited transcript of their conversation.

The problem was this: About 9 percent of the patients who were supposed to get ablations never did, and it’s not clear why. The reasons could have been financial issues or patients merely changing their mind or perhaps being too sick. If it was the latter reason, that would of course bias the results. But the problem is we don’t know.

On the other side, a substantial number of patients assigned to drug therapy — 27.5 percent — crossed over and received ablation. That rate of crossover was a bit higher than anticipated.

It’s difficult to use an intention-to-treat analysis when there’s a large crossover and a lot of people don’t get the treatment they were supposed to get. Nonetheless, the study design specified an intention-to-treat analysis, which found no significant differences between the groups in the composite primary end point or any of its components. There were, however, significant reductions in hospitalization for cardiovascular problems and in time to atrial fibrillation recurrence in the ablation group, and the latter finding is consistent with results from past studies.

Because of the large number of crossovers, there was much interest in the as-treated analysis, which was prespecified as a sensitivity analysis of the primary results.

  • This analysis showed a 3.9 percent absolute risk reduction — and
  • a 27 percent relative reduction — in the primary end point with ablation versus drug therapy.
  • That was a statistically significant effect, as was the 3.1 percent absolute reduction in all-cause death with ablation versus drug therapy.

SOURCE

https://consultqd.clevelandclinic.org/ablation-vs-medical-therapy-for-atrial-fibrillation-putting-cabana-in-perspective/?utm_campaign=qd%20tweets&utm_medium=social&utm_source=twitter&utm_content=180920%20ablation%20fibrillation&cvosrc=social%20network.twitter.qd%20tweets&cvo_creative=180920%20ablation%20fibrillation

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Clever experiment: GWAS of 500 time points in an EKG – The genetic makeup of the electrocardiogram

Reporter: Aviva Lev-Ari, PhD, RN

The genetic makeup of the electrocardiogram

Niek VerweijJan-Walter BenjaminsMichael P. MorleyYordi van de VegteAlexander TeumerTeresa TrenkwalderWibke ReinhardThomas P. CappolaPim van der Harst

Abstract

Since its original description in 1893 by Willem van Einthoven, the electrocardiogram (ECG) has been instrumental in the recognition of a wide array of cardiac disorders1,2. Although many electrocardiographic patterns have been well described, the underlying biology is incompletely understood. Genetic associations of particular features of the ECG have been identified by genome wide studies. This snapshot approach only provides fragmented information of the underlying genetic makeup of the ECG. Here, we follow the effects of individual genetic variants through the complete cardiac cycle the ECG represents. We found that genetic variants have unique morphological signatures not identified by previous analyses. By exploiting identified abberations of these morphological signatures, we show that novel genetic loci can be identified for cardiac disorders. Our results demonstrate how an integrated approach to analyse high-dimensional data can further our understanding of the ECG, adding to the earlier undertaken snapshot analyses of individual ECG components. We anticipate that our comprehensive resource will fuel in silico explorations of the biological mechanisms underlying cardiac traits and disorders represented on the ECG. For example, known disease causing variants can be used to identify novel morphological ECG signatures, which in turn can be utilized to prioritize genetic variants or genes for functional validation. Furthermore, the ECG plays a major role in the development of drugs, a genetic assessment of the entire ECG can drive such developments.

SOURCE

https://www.biorxiv.org/content/10.1101/648527v1

made available under a CC-BY-ND 4.0 International license.

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The role of PET/CT in diagnosing giant cell arteritis (GCA) and assessing the risk of ischemic events

 

Reporter: Aviva Lev-Ari, PhD, RN

 

 

May 20, 2019 — PET/CT images are offering evidence of a link between vascular patterns at the time of diagnosis for giant cell arteritis (GCA) and a patient’s risk of an ischemic event, Spanish researchers explained in a study published online on 12 May in the European Journal of Nuclear Medicine and Molecular Imaging.

The group found that patients with inflammation in vertebral arteries, which causes blood vessels to narrow, were five times more likely to develop ischemic symptoms. The information may be particularly helpful because GCA is difficult to diagnose in its early stages.

“Bearing in mind these results and our findings, we consider that the vertebral arteries should be carefully studied in patients with suspected GCA, not only to support the diagnosis but also to assess the risk of development of ischemic events,” wrote lead author Dr. Jaume Mestre-Torres and colleagues from Hospital Vall d’Hebron in Barcelona.

GCA’s challenges

Giant cell arteritis is an inflammatory disease that causes the large blood vessels to narrow and restrict blood flow. The affliction is typically seen in the temporal arteries and the aorta in adults older than 50. Currently, there is little information on how the disease develops, although there are indications that it may be linked to genetics.

The challenge for clinicians is that there are “no specific clinical symptoms that lead to the diagnosis of GCA, but headache and ischemic symptoms such as jaw claudication and transient visual loss or permanent visual loss may raise suspicion [of the disease],” the authors noted.

Results

In assessing visual loss, the team found no significant differences between patients with vertebral artery involvement and permanent visual loss (61.5%) and patients with vertebral artery issues and no permanent visual loss (58.8%) (p = 0.88). Interestingly, the presence of intrathoracic large-vessel vasculitis tended to protect against a patient’s likelihood of permanent visual loss.

In addition, “all patients with vertebral involvement but no aortic involvement showed ischemic manifestations at disease onset,” the researchers noted. “In contrast, none of the patients with aortic involvement but no vertebral hypermetabolism showed ischemic symptoms.”

SOURCE

https://www.auntminnieeurope.com/index.aspx?sec=sup&sub=mol&pag=dis&ItemID=617395

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Society for Cardiovascular Angiography and Interventions (SCAI) Released Classification Stages of Cardiogenic Shock

Reporter: Aviva Lev-Ari, PhD, RN
NEWS | CARDIOGENIC SHOCK | MAY 20, 2019

SCAI Releases New Consensus Document on Classification Stages of Cardiogenic Shock

New classification system endorsed by multiple societies was developed to describe five stages of shock

SCAI Releases New Consensus Document on Classification Stages of Cardiogenic Shock

Image courtesy of the Society for Cardiovascular Angiography and Interventions (SCAI).

May 20, 2019 – A newly released expert consensus statement proposes a classification schema for cardiogenic shock (CS) that will facilitate communication in both the clinical and research settings. The document was published online in the Society for Cardiovascular Angiography and Interventions (SCAI)’s Catheterization and Cardiovascular Interventions journal,1 and is endorsed by the American College of Cardiology, American Heart Association, the Society of Critical Care Medicine and the Society of Thoracic Surgeons.

Cardiogenic shock is a condition in which the heart, often abruptly, cannot pump enough blood to meet the body’s needs, according to the Mayo Clinic, most often accompanying larger heart attacks such as myocardial infarction (MI). Outcomes for patients with cardiogenic shock complicating MI have not significantly improved over the last 30 years despite the development of various percutaneous mechanical circulatory support technologies and the national standard of emergent angioplasty and stenting.

SCAI convened a multidisciplinary writing group comprised of leading experts in interventionaland advanced heart failure, non-invasive cardiology, emergency medicine, critical care and cardiac nursing to represent the team-based care of these patients. The writing group developed a new five-stage system that is defined by narrative patient descriptions, physical findings, and biochemical/hemodynamic markers, creating a new language that will facilitate rapid assessment, reassessment over time and communication between providers including hospital systems.

The new CS definition is intended to provide clinicians and researchers with a unified and standardized vocabulary that will translate across all settings. Additionally, the definition aims to facilitate recognition of risk for adverse outcomes and the potential benefit from various interventions and prognosis. The goal is to reduce mortality on both an individual and national scale.

“The main areas we may have failed in the fight to improve mortality in cardiogenic shock is, quite simply, not speaking the same language when describing these patients,” said Srihari S. Naidu, M.D., FSCAI, former SCAI Trustee and chair of the writing group. “Without that, we can’t even begin to understand these patients, how sick they are, what might work and what does not work. This is the most important first step, and it is important to use this classification system to reset our understanding of cardiogenic shock and restart the trials very much needed in this space.”

For more information: http://www.scai.org

Related Cardiogenic Shock Content

VIDEO: Cardiogenic Shock Case with Impella CP Support

VIDEO: Analysis of Outcomes for 15,259 U.S. Patients with AMICS Supported with the Impella Device

VIDEO: How to Reduce Cardiogenic Shock Mortality by 50 Percent

Reference

1. Baran D.A., Grines C.L., Bailey S., et al. SCAI clinical expert consensus statement on the classification of cardiogenic shock. Catheterization and Cardiovascular Interventions, May 19, 2019. https://doi.org/10.1002/ccd.28329

SOURCE

https://www.dicardiology.com/content/scai-releases-new-consensus-document-classification-stages-cardiogenic-shock?eid=333021707&bid=2450760

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The Promise of MicroRNA Therapy to Stimulates Uncontrolled Cardiac Repair in Animal Trials of Large Mammals

 

Reporter: Aviva Lev-Ari, PhD, RN

start quote

Here we show that expression of human microRNA-199a in infarcted pig hearts can stimulate cardiac repair. One month after myocardial infarction and delivery of this microRNA through an adeno-associated viral vector, treated animals showed marked improvements in both global and regional contractility, increased muscle mass and reduced scar size. These functional and morphological findings correlated with cardiomyocyte de-differentiation and proliferation. However, subsequent persistent and uncontrolled expression of the microRNA resulted in sudden arrhythmic death of most of the treated pigs. Such events were concurrent with myocardial infiltration of proliferating cells displaying a poorly differentiated myoblastic phenotype.

End quote

 

Abstract

Prompt coronary catheterization and revascularization have markedly improved the outcomes of myocardial infarction, but have also resulted in a growing number of surviving patients with permanent structural damage of the heart, which frequently leads to heart failure. There is an unmet clinical need for treatments for this condition1, particularly given the inability of cardiomyocytes to replicate and thereby regenerate the lost contractile tissue2. Here we show that expression of human microRNA-199a in infarcted pig hearts can stimulate cardiac repair. One month after myocardial infarction and delivery of this microRNA through an adeno-associated viral vector, treated animals showed marked improvements in both global and regional contractility, increased muscle mass and reduced scar size. These functional and morphological findings correlated with cardiomyocyte de-differentiation and proliferation. However, subsequent persistent and uncontrolled expression of the microRNA resulted in sudden arrhythmic death of most of the treated pigs. Such events were concurrent with myocardial infiltration of proliferating cells displaying a poorly differentiated myoblastic phenotype. These results show that achieving cardiac repair through the stimulation of endogenous cardiomyocyte proliferation is attainable in large mammals, however dosage of this therapy needs to be tightly controlled.

References

  1. 1.

    Roth, G. A. et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J. Am. Coll. Cardiol70, 1–25 (2017).

  2. 2.

    Eschenhagen, T. et al. Cardiomyocyte regeneration: a consensus statement. Circulation 136, 680–686 (2017).

SOURCE

https://www.nature.com/articles/s41586-019-1191-6

 

ALTERNATIVE methods of Cardiac Repair were published in this Open Access Online Scientific Journal:

 

Stem Cells and Cardiac Repair: Content Curation & Scientific Reporting: Aviva Lev-Ari, PhD, RN

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/17/stem-cells-and-cardiac-repair-content-curation-scientific-reporting-aviva-lev-ari-phd-rn/

 

Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/02/27/arteriogenesis-and-cardiac-repair-two-biomaterials-injectable-thymosin-beta4-and-myocardial-matrix-hydrogel/

 

Human Embryonic-Derived Cardiac Progenitor Cells for Myocardial Repair

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

https://pharmaceuticalintelligence.com/2012/08/01/human-embryonic-derived-cardiac-progenitor-cells-for-myocardial-repair/

 

 

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@Cleveland Clinic – Serial measurements of high-sensitivity C-reactive protein (hsCRP) post acute coronary syndrome (ACS) may help identify patients at higher risk for morbidity and mortality

 

Reporter: Aviva Lev-Ari, PhD, RN

 

Original Investigation
March 6, 2019

Association of Initial and Serial C-Reactive Protein Levels With Adverse Cardiovascular Events and Death After Acute Coronary Syndrome, A Secondary Analysis of the VISTA-16 Trial

Key Points

Question  Are initial and serial increases in high-sensitivity C-reactive protein levels after acute coronary syndrome in medically optimized patients associated with increased risk of a major cardiac event, cardiovascular death, and all-cause death?

Findings  In this secondary analysis of the VISTA-16 randomized clinical trial that included 5145 patients, baseline and longitudinal high-sensitivity C-reactive protein levels were independently associated with increased risk of a major adverse cardiac event, cardiovascular death, and all-cause death during the 16-week follow-up.

Meaning  Monitoring high-sensitivity C-reactive protein levels in patients after acute coronary syndrome may help better identify patients at greater risk for recurrent cardiovascular events or death.

Abstract

Importance  Higher baseline high-sensitivity C-reactive protein (hsCRP) levels after an acute coronary syndrome (ACS) are associated with adverse cardiovascular outcomes. The usefulness of serial hsCRP measurements for risk stratifying patients after ACS is not well characterized.

Objective  To assess whether longitudinal increases in hsCRP measurements during the 16 weeks after ACS are independently associated with a greater risk of a major adverse cardiac event (MACE), all-cause death, and cardiovascular death.

Results  Among 4257 patients in this study, 3141 (73.8%) were men and the mean age was 60.3 years (interquartile range [IQR], 53.5-67.8 years). The median 16-week low-density lipoprotein cholesterol level was 64.9 mg/dL (IQR, 50.3-82.3 mg/dL), and the median hsCRP level was 2.4 mg/L (IQR, 1.1-5.2 mg/L). On multivariable analysis, higher baseline hsCRP level (hazard ratio [HR], 1.36 [95% CI, 1.13-1.63]; P = .001) and higher longitudinal hsCRP level (HR, 1.15 [95% CI, 1.09-1.21]; P < .001) were independently associated with MACE. Similar significant and independent associations were shown between baseline and longitudinal hsCRP levels and cardiovascular death (baseline: HR, 1.61 per SD [95% CI, 1.07-2.41], P = .02; longitudinal: HR, 1.26 per SD [95% CI, 1.19-1.34], P < .001) and between baseline and longitudinal hsCRP levels and all-cause death (baseline: HR, 1.58 per SD [95% CI, 1.07-2.35], P = .02; longitudinal: HR, 1.25 per SD [95% CI, 1.18-1.32], P < .001).

Conclusions and Relevance  Initial and subsequent increases in hsCRP levels during 16 weeks after ACS were associated with a greater risk of the combined MACE end point, cardiovascular death, and all-cause death despite established background therapies. Serial measurements of hsCRP during clinical follow-up after ACS may help to identify patients at higher risk for mortality and morbidity.

SOURCE

https://jamanetwork.com/journals/jamacardiology/fullarticle/2725734

 

Inflammation’s role in residual risk

Residual risk of cardiovascular events or death remains high following ACS, despite coronary revascularization and optimal guideline-directed treatment with antiplatelet and LDL cholesterol-lowering agents. Inflammation is thought to drive this risk, but no effective treatment for such inflammation is commercially available. The secretory phospholipase A2 inhibitor varespladib was developed to meet this need, and it was evaluated in VISTA-16.

VISTA-16 was an international, multicenter clinical trial that randomized 5,145 patients in a double-blind manner to varespladib or placebo on a background of atorvastatin treatment within 96 hours of presentation with ACS. The trial was terminated early due to futility and likely harm from the drug, which was subsequently pulled from development.

Implications for practice

The association of increasing CRP levels with residual cardiovascular risk may prompt more intensive treatment to lower this risk. In particular, a secondary analysis showed that use of antiplatelet agents (clopidogrel, ticlopidine and prasugrel) was associated with stable or decreasing hsCRP levels.

“Monitoring not only lipids but also hsCRP after ACS may help us better identify patients at increased risk for recurrent cardiovascular events or death,” notes Dr. Puri. “High or increasing CRP levels could be an indication to optimize dual antiplatelet therapy post-ACS, along with high-intensity statin therapy (and possibly PCSK9 inhibitors) and antihypertensive therapy, in addition to instituting measures that are globally beneficial, such as dietary modifications and cardiac rehabilitation/exercise.”

SOURCE

https://consultqd.clevelandclinic.org/increasing-inflammation-correlates-with-residual-risk-after-acute-coronary-syndrome/amp/?__twitter_impression=true

 

Other related articles published in this Open Access Online Scientific Journal, include the following:

 

Biomarkers and risk factors for cardiovascular events, endothelial dysfunction, and thromboembolic complications

Larry H Bernstein, MD, FCAP, Curator

https://pharmaceuticalintelligence.com/2014/09/09/biomarkers-and-risk-factors-for-cardiovascular-events-endothelial-dysfunction-and-thromboembolic-complications/

 

A Concise Review of Cardiovascular Biomarkers of Hypertension

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/04/25/a-concise-review-of-cardiovascular-biomarkers-of-hypertension/

 

Acute Coronary Syndrome (ACS): Strategies in Anticoagulant Selection: Diagnostics Approaches – Genetic Testing Aids vs. Biomarkers (Troponin types and BNP)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/03/13/acute-coronary-syndrome-acs-strategies-in-anticoagulant-selection-diagnostics-approaches-genetic-testing-aids-vs-biomarkers-troponin-types-and-bnp/

 

In Europe, BigData@Heart aim to improve patient outcomes and reduce societal burden of atrial fibrillation (AF), heart failure (HF) and acute coronary syndrome (ACS).

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/10/in-europe-bigdataheart-aim-to-improve-patient-outcomes-and-reduce-societal-burden-of-atrial-fibrillation-af-heart-failure-hf-and-acute-coronary-syndrome-acs/

 

Cardiovascular Diseases and Pharmacological Therapy: Curations by Aviva Lev-Ari, PhD, RN, 2006 – 4/2018

https://pharmaceuticalintelligence.com/2014/04/17/cardiovascular-diseases-and-pharmacological-therapy-curations-by-aviva-lev-ari-phd-rn/

 

 

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