Frontiers in Cardiology and Cardiovascular Disorders | Leaders in Pharmaceutical Business Intelligence Group, LLC, Doing Business As LPBI Group, Newton, MA

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

Most Popular According To Cardiologists in Circulation, AHA, European Heart Journal and Medscape Medical News

Posted in Frontiers in Cardiology and Cardiovascular Disorders on January 31, 2021| Leave a Comment »

Most Popular According To Cardiologists in Circulation, AHA, European Heart Journal and Medscape Medical News

Reporter: Aviva Lev-Ari, PhD, RN

Left Ventricular Volume Reduction and Reshaping as a Treatment Option for Heart Failure

Posted in Assist Devices: LV, Cardiomyopathy, congestive heart failure, Frontiers in Cardiology and Cardiovascular Disorders, Heart Failure (HF) on January 22, 2021| Leave a Comment »

Left Ventricular Volume Reduction and Reshaping as a Treatment Option for Heart Failure

Reporter: Aviva Lev-Ari, PhD, RN

Left Ventricular Remodeling and Its Reversal

When the myocardium is subjected to abnormal mechanical and neurohormonal stresses, left ventricular remodeling ensues with a progression of structural, cellular, molecular, metabolic, and functional changes.

In chronic heart failure with reduced ejection fraction, this remodeling affects the left ventricle with consequences that include ventricular dilation, transition of the chamber shape from elliptical to spherical, and the shifting of papillary muscles and mitral valve apparatus into abnormal positions. Ironically, while remodeling is an outgrowth of the initial hemodynamic and metabolic insults that lead to heart failure, it is also self-propagating, contributing to the progressive loss of ventricular function over time.

In the July 20 online issue of Structural Heart, heart failure specialists at Columbia University Vagelos College of Physicians and Surgeons present a comprehensive review of treatment options that focus on restoring the normal ventricular size and preventing the remodeling process from continuing. But can preventing or limiting left ventricular remodeling following an insult or reversing it once it is present reduce cardiovascular morbidity?

Their article provides insight into this question with a view toward better understanding the impact of remodeling on ventricular dysfunction and an in-depth look at therapeutic approaches, including those that are well-established, several that are currently under investigation, as well as those that have been invalidated and no longer used. The authors focus on two fundamental therapeutic approaches – those that rely primarily on

biological mechanisms to induce responses in the myocardium and improve myocardial function, and

physical mechanisms, involving procedures where a portion of the heart is either removed or excluded and devices to reduce myocardial wall stress through ventricular constraint or reshaping.

Left Ventricular Volume Reduction and Reshaping as a Treatment Option for Heart Failure.
https://doi.org/10.1080/24748706.2020.1777359

Retrospective Study of National Danish Registry Sheds Light on Cardiotoxic Risks of Immune Checkpoint Inhibitors

Posted in Cardiotoxic Risks of Immune Checkpoint Inhibitors, Electrophysiology, Epigenetics and Cardiovascular Risks, Frontiers in Cardiology and Cardiovascular Disorders, Rare heart rhythm disorders and Long QT syndrome (LQTS), tagged arrhythmia, cardiac arrhythmia myocarditis heart failure cardiac event denmark lymphocytes melanoma lung cancer pharmacovigilance cardiovascular death immune checkpoint inhibitors danish study, Cardio-Oncology, Cardiotoxic Risks of Immune Checkpoint Inhibitors, Cardiovascular death, Heart Failure, Immune checkpoint inhibitors, Myocarditis on January 8, 2021| Leave a Comment »

Retrospective Study of National Danish Registry Sheds Light on Cardiotoxic Risks of Immune Checkpoint Inhibitors

Reporter: Adina Hazan, PhD

Immune checkpoint inhibitors are used to treat over 12 different types of cancers, as a way of encouraging T cells of the immune system to target and kill cancer cells. While this method has proved to be an incredibly important mechanism in fighting deadly cancers, the enhanced immune response has been documented to produce a wide array of side effects, including an increased incidence of cardiovascular events such as arrhythmias and sudden cardiac arrest. Due to the nature of the disease and treatment, most evidence of cardiotoxicity from the treatment comes from small cohorts of patients or individual case studies.

D’Souza and colleagues used four Danish healthcare registries to collect data from over 13,000 patients with malignant melanoma, and over 25,000 patients with lung cancer, starting from 2011 with the introduction of checkpoint inhibitors up until 2017. Each group included patients who received checkpoint inhibitors and those that did not, providing the basis of their retrospective study to determine the risk of developing cardiac events with treatment over a long period of time. The study was published in the European Heart Journal in December 2020.

The authors confirmed the increased risk of cardiac events with the treatment of immune checkpoint inhibitors PD1i and CTLA-4i.

The relative rate of cardiovascular deaths were increased in patients with lung cancer treated with PD1i by three-fold, and
eight times higher in patients with malignant melanoma treated with CTLA-4i.
Moreover, they show increased relative rates of arrhythmias in both diseases treated with PD1i, and malignant melanoma treated with CTLA-4i.
This was also true of the timeframe of treatment, where it was previously believed that most cardiac events would develop within the first six months of checkpoint inhibitor use.
By using data from patients over years, this study shows that these adverse events develop even after the first six months.

The myocardium, or heart muscle tissue, has previously been reported to be damaged with the use of checkpoint inhibitors, suspected to be due to

increasing inflammatory cytokines and enhanced inflammatory pathways. Significantly, previous pharmacovigilance studies have suggested a rate of developing myocarditis at less than 1%, but
data from this study shows that the 1 year risk was 1.8%, “suggesting that the risk may be higher than previously estimated”.

Even though Immune checkpoint inhibitors have been shown to be invaluable tools in the treatment of certain cancers, “the findings [in this study] urge increased awareness of cardiac events in patients receiving ICI”.

Abstract

Aims

The study aimed to estimate the risk of cardiac events in immune checkpoint inhibitor (ICI)-treated patients with lung cancer or malignant melanoma.

Methods and results

The study included consecutive patients with lung cancer or malignant melanoma in 2011–17 nationwide in Denmark. The main composite outcome was cardiac events (arrhythmia, peri- or myocarditis, heart failure) or cardiovascular death. Absolute risks were estimated and the association of ICI and cardiac events was analysed in multivariable Cox models. We included 25 573 patients with lung cancer. Of these, 743 were treated with programmed cell death-1 inhibitor (PD1i) and their 1-year absolute risk of cardiac events was 9.7% [95% confidence interval (CI) 6.8–12.5]. Of the 13 568 patients with malignant melanoma, 145 had PD1i and 212 had cytotoxic T-lymphocyte-associated protein-4 inhibitor (CTLA-4i) treatment. Their 1-year risks were 6.6% (1.8–11.3) and 7.5% (3.7–11.3). The hazard rates of cardiac events were higher in patients with vs. without ICI treatment. Within 6 months from 1st ICI administration, the hazard ratios were 2.14 (95% CI 1.50–3.05) in patients with lung cancer and 4.30 (1.38–13.42) and 4.93 (2.45–9.94) in patients with malignant melanoma with PD1i and CTLA-4i, respectively. After 6 months, HRs were 2.26 (1.27–4.02) for patients with lung cancer and 3.48 (1.91–6.35) for patients with malignant melanoma and CTLA-4i.

Conclusions

Among patients with lung cancer and malignant melanoma, ICI treated had increased rates of cardiac events. The absolute risks were higher in these data compared with previous pharmacovigilance studies (e.g. 1.8% peri-/myocarditis 1-year risk).

Cardio-oncology, Immune checkpoint inhibitors, Arrhythmia, Myocarditis, Heart failure, Cardiovascular death

Issue Section:

Clinical Research

SOURCES

https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa884/6027871

Diagnostic and Interventional Cardiology (DAIC): 2020 Top 25 Best Performing Articles

Posted in Frontiers in Cardiology and Cardiovascular Disorders on December 29, 2020| Leave a Comment »

Diagnostic and Interventional Cardiology (DAIC): 2020 Top 25 Best Performing Articles

Reporter: Aviva Lev-Ari, PhD, RN

Here are the top 25 best performing articles on the Diagnostic and Interventional Cardiology (DAIC) website from 2020. This is based on the analytics of DAIC’s record 3.3 million pages views in 2020:

1. Kawasaki-like Inflammatory Disease Affects Children With COVID-19

2. COVID-19 Hydroxychloroquine Treatment Brings Prolonged QT Arrhythmia Issues

3. ESC Council on Hypertension Says ACE-I and ARBs Do Not Increase COVID-19 Mortality

4. The Cardiac Implications of Novel Coronavirus

5. FDA Approves ECMO to Treat COVID-19 Patients

6. World’s First Transcatheter Mitral Valve Approved in Europe

7. New Guidelines for Stress Echocardiography in Ischemic Heart Disease

8. First Large-scale U.S. Study on Hydroxychloroquine COVID-19 Prophylaxis Begins in Detroit

9. ACC COVID-19 Clinical Guidance For the Cardiovascular Care Team

10. FDA Reports of Deaths and Injuries From Use of Antimalarial hydroxychloroquine in COVID-19 Patients

11. 8 Cardiovascular Technologies to Watch in 2020

12. FDA Clears Medtronic Micra AV to Treat AV Block

13. ACC 2020 Late-breaking Presentations

14. Abbott Recalls Two Coronary Balloon Catheters That May Not Deflate

15. New Heart Failure Devices and Drugs to Treat Heart Failure

16. Italian Cardiologist Maurizio Galderisi Died From COVID-19

17. ASE Guidelines for the Protection of Echocardiography Providers During the COVID-19 Outbreak

18. CMS Calls For Postponing All Elective Cardiac Tests and Procedures to Aid COVID-19 Containment

19. COVID-19 Genetic PCR Tests Give False Negative Results if Used Too Early

20. ISCHEMIA Trial Results Find Interventions for Stable Heart Disease No better Than Drug Therapy

21. Image Gallery Showing Impact of the COVID-19 Pandemic

22. WHO Database Shows Serious Health Impact of Hydroxychloroquine and Azithromycin Being Used to Treat COVID-19

23. A Double-Edged Sword: How Over-the-Counter ECG Devices are Impacting Cardiac Care

24. AI Tool Allows Automated ECG Interpretation for Cardiac Diagnostics

25. Medtronic Resolute Onyx Drug Eluting Stent First to Receive One-Month DAPT Indication

Related Content:

Top 25 Cardiology Videos on DAIC in 2020

Most Popular Cardiology Technology Content in November 2020

The Most Popular Cardiology Topics in 2019

Top 25 Cardiology Videos on DAIC in 2019

Top 25 Stories in Radiology in 2020

Top 25 Videos For Radiology on ITN in 2020

SOURCE

https://www.dicardiology.com/article/top-25-stories-cardiology-2020?oly_enc_id=9685J9265356C8S

Read Full Post »

Bioresorbable Stent Clinical Trials with New Esprit Below-the-knee Scaffold

Posted in Cardiac and Cardiovascular Surgical Procedures, Medical Devices R&D and Inventions, Peripheral Arterial Disease & Peripheral Vascular Surgery, Stents & Tools, tagged biodegradable scaffold, Clinical Trials, critical limb ischemia (CLI), Esprit BTK System, everolimus on October 9, 2020| Leave a Comment »

Bioresorbable Stent Clinical Trials with New Esprit Below-the-knee Scaffold

Reporter: Irina Robu, PhD

Abbott announced on September 3, 2020, the beginning of the LIFE-BTK clinical trial to evaluate effectiveness and safety of the Esprit BTK Everolimus Eluting Resorbable Scaffold System. The Esprit BTK System consists of a thin strutted scaffold made of poly-L-lactide, a semi-crystalline bioresorbable polymer engineered to resist vessel recoil and provide a platform for drug delivery. The scaffold is coated with poly-D, L-lactide (PDLLA) and the cytostatic drug, everolimus.

This trial is the first Investigational Device Exemption in the US to assess a fully bioresorbable stent to treat blocked arteries below the knees, also known as critical limb ischemia in people battling advanced stages of peripheral artery disease. For people with CLI, blocked vessels weaken blood flow to the lower extremities, which can lead to severe pain, wounds, and in severe cases, limb amputation.

At this time, the standard of care for patients battling critical limb ischemia is balloon angioplasty, which depend on on a small balloon delivered via a catheter to the blockage to compress it against the arterial wall, opening the vessel and restoring blood flow. Yet, blockages treated only with balloon angioplasty have poor short- and long-term results, and in many cases the vessels become blocked again, lacking additional treatment.

Patients treated with balloon angioplasty often require several procedures on treated arteries, and a drug eluting resorbable device is if at all possible suited to provide mechanical support, decrease the chance of the vessel re-narrowing and then slowly disappear over time. At this time, there are no drug eluding stents, drug coated balloons or bare metal stents approved for use below the knee. Since, there is a limited number of options for stents below the knee, the FDA has granted Esprit BTK breakthrough device designation, which simplifies review and pre-market approval timelines.

According to Abbott, Espirit BTK System is not a permanent implant, but it does provide support to an artery right after a balloon angioplasty, stopping the vessel from reclosing. As soon as it is implanted, the scaffold distributes a drug over a few months that encourages healing and keeps the artery open. The scaffold is naturally resorbed into the body over time, like dissolving sutures, and eventually leaves only a healed artery behind.

The LIFE-BTK trial is the first Investigational Device Exemption trial in the U.S. to evaluate a fully dissoluble device to treat critical limb ischemia in people battling advanced stages of peripheral artery disease (PAD). The trial will be run by principal investigators Brian DeRubertis, M.D. (vascular surgeon, UCLA), Sahil Parikh M.D., (interventional cardiologist, New York-Presbyterian/Columbia University Irving Medical Center.

SOURCE

https://www.dicardiology.com/article/abbott-restarts-bioresorbable-stent-clinical-trials-new-esprit-below-knee-scaffold

Read Full Post »

Precision Cardiology to Benefit from New Atlas of Cells of the Adult Human Heart

Posted in Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, Origins of Cardiovascular Disease, Resident-cell-based, Single Cell Genomics, Single-cell sequencing, Systemic Inflammatory Diseases as CVD Risk, Variation in human protein-coding regions on September 29, 2020| Leave a Comment »

Precision Cardiology to Benefit from New Atlas of Cells of the Adult Human Heart

Reporters: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

The Voice of Dr. Pearlman on potential clinical implications of the New Atlas:

Published on 9/24/2020 in Nature

Litviňuková, M., Talavera-López, C., Maatz, H. et al. Cells of the adult human heart. Nature (2020). https://doi.org/10.1038/s41586-020-2797-4

Abstract

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require deeper understanding of the healthy heart’s molecular processes. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using state-of-the-art analyses of large-scale single-cell and nuclei transcriptomes, we characterise six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes, and fibroblasts, revealing distinct atrial and ventricular subsets with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment we identify cardiac resident macrophages with inflammatory and protective transcriptional signatures. Further, inference of cell-cell interactions highlight different macrophage-fibroblast-cardiomyocyte networks between atria and ventricles that are distinct from skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a healthy reference for future studies.

Author information

Author notes

These authors contributed equally: Monika Litviňuková, Carlos Talavera-López, Henrike Maatz, Daniel Reichart

These authors jointly supervised this work: J. G. Seidman, Christine E. Seidman, Michela Noseda, Norbert Hubner, Sarah A. Teichmann

Affiliations

Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom

Monika Litviňuková, Carlos Talavera-López, Krzysztof Polanski, Kenny Roberts, Liz Tuck, Eirini S. Fasouli, Hongbo Zhang, Omer Bayraktar & Sarah A. Teichmann

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany

Monika Litviňuková, Henrike Maatz, Catherine L. Worth, Eric L. Lindberg, Masatoshi Kanda, Giannino Patone & Norbert Hubner

EMBL – EBI, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom

Carlos Talavera-López

Department of Genetics, Harvard Medical School, Boston, MA, United States

Daniel Reichart, Emily R. Nadelmann, Daniel M. DeLaughter, Hiroko Wakimoto, Joshua M. Gorham, J. G. Seidman & Christine E. Seidman

Dept Physics/Cavendish Laboratory, University of Cambridge, JJ Thompson Ave, Cambridge, CB3 0EH, United Kingdom

Sarah A. Teichmann

Department of Cardiology, University Heart & Vascular Center, University of Hamburg, Hamburg, Germany

Daniel Reichart

National Heart and Lung Institute, Imperial College London, London, United Kingdom

Michael Lee, Sara Samari, Joseph J. Boyle & Michela Noseda

British Heart Foundation Centre of Research Excellence and Centre of Regenerative Medicine, Imperial College London, London, United Kingdom

Michela Noseda

Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Centre, and Cambridge Biorepository for Translational Medicine, Cambridge, United Kingdom

Krishnaa T. Mahbubani & Kourosh Saeb-Parsy

Charité-Universitätsmedizin, Berlin, Germany

Norbert Hubner

Berlin Institute of Health (BIH), Berlin, Germany

Norbert Hubner

DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany

Barbara McDonough & Norbert Hubner

Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, United States

Barbara McDonough & Christine E. Seidman

Howard Hughes Medical Institute, Chevy Chase, MD, United States

Christine E. Seidman

Institute of Computational Biology (ICB), HMGU, Neuherberg, Germany

Matthias Heinig

Department of Informatics, Technische Universitaet Muenchen (TUM), Munich, Germany

Matthias Heinig

Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

Hao Zhang, Anissa Viveiros & Gavin Y. Oudit

Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

Hao Zhang, Anissa Viveiros & Gavin Y. Oudit

Department of Histology and Embryology of Zhongshan School of Medicine, Sun-Yat Sen University, Guangzhou, China

Hongbo Zhang

Department of Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan

Masatoshi Kanda

Corresponding authors

Correspondence to J. G. Seidman or Christine E. Seidman or Michela Noseda or Norbert Hubner or Sarah A. Teichmann.

Read Full Post »

COVID concern in Cardiology: Asymptomatic patients who have been previously infected demonstrating evidence on MRI of scarring or myocarditis

Posted in Atherogenic Processes & Pathology, Biomarkers: Inflammation, Cardio-Oncology, COVID-19, COVID-19 effects on Human Heart, Frontiers in Cardiology and Cardiovascular Disorders, inflammation independent of lipid levels, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Origins of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, Systemic Inflammatory Diseases as CVD Risk, Treatment Protocols for COVID-19, Virus Infective Acute Respiratory Syndrome: SARS-CoV on September 21, 2020| Leave a Comment »

COVID concern in Cardiology: Asymptomatic patients who have been previously infected demonstrating evidence on MRI of scarring or myocarditis

Reporters: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC

Indeed, many viruses can cause inflammation and weakening of the heart.

So far there is no established action to take for prevention, and management is based on clinical manifestations of heart failure: shortness of breath, particularly if worse laying flat or worse with exertion, leg swelling (edema), blood tests showing elevated brain natriuretic peptide (BNP or proBNP, a marker of heart muscle strain), and a basic metabolic panel that may show “pre-renal azotemia” (elevation of BUN and Creatinine, typically in a ratio >20:1) and/or hyponatremia (sodium concentration below 135 mEq/dL). If any of the above are suspected, it is reasonable to get transthoracic echocardiography for systolic and diastolic function. If either systolic or diastolic function by ultrasound show significant impairment not improved by usual therapy (diuretic, ACEI/ARB/ARNI, blocker, aldosterone inhibitor e.g. spironolactone) then an MRI scar map may be considered (MRI scar maps show retention of gadolinium contrast agent by injured heart muscle, first demonstrated by Dr. Justin Pearlman during angiogenesis research MRI studies).

There is no controversy in the above, the controversy is a rush to expanded referral for cardiac MRI without clear clinical evidence of heart impairment, at a stage when there is no established therapy for possible detection of myocarditis (cardiac inflammation). General unproven measures for inflammation may include taking ginger and tumeric supplements if well tolerated by the stomach, drinking 2 cups/day of Rooibos Tea if well tolerated by the liver.

Canakinumab was recommended by one research group to treat inflammation and risk to the heart if the blood test hsCRP is elevated (in addition to potential weakening of muscle, inflammation activates complement, makes atherosclerosis lesions unstable, and thus may elevate risk of heart attack, stroke, renal failure or limb loss from blocked blood delivery). The canakinumab studies were published in NEJM and LANCET with claims of significant improvement in outcomes, but that was not approved by FDA or confirmed by other groups, even though it has biologic plausibility. https://www.thelancet.com/journals/lancet/article/PIIS0140-67361732247-X/fulltext

Some Heart Societies Agree on Cautions for COVID-Myocarditis Screening

— Official response has been modest, though

by Crystal Phend, Senior Editor, MedPage Today September 18, 2020

Such evidence of myocardial injury and inflammation on CMR turned up in a German study among people who recovered from largely mild or moderate cases of COVID-19 compared with healthy controls and risk factor-matched controls.

Then an Ohio State University study showed CMR findings suggestive of myocarditis in 15% of collegiate athletes after asymptomatic or mild SARS-CoV-2 infection.

But an open letter from some 50 medical professionals across disciplines emphasized that “prevalence, clinical significance and long-term implications” of such findings aren’t known. The letter called on the 18 professional societies to which it was sent on Tuesday to release clear guidance against CMR screening in the general population to look for post-COVID heart damage in the absence of symptoms.

The Society for Cardiac Magnetic Resonance quickly responded with a brief statement from its chief executive officer, Chiara Bucciarelli-Ducci, MD, PhD, agreeing that routine CMR in asymptomatic patients after COVID-19 “is currently not justified… and it should not be encouraged.”

She referred clinicians to the multisociety guidelines on clinical indications of CMR when deciding whether to scan COVID-19 patients. “While CMR is an excellent imaging tool for diagnosing myocarditis in patients with suspected disease, we do not recommend its use in patients without symptoms,” she added.

The American Heart Association didn’t put out any written statement but offered spokesperson Manesh Patel, MD, chair of its Diagnostic and Interventional Cath Committee.

“The American Heart Association’s position on this is that in general we agree that routine cardiac MRI should not be conducted unless in the course of a study” for COVID-19 patients, he said. “There’s a lot of evolving information around people with COVID, and certainly asymptomatic status, whether it’s recent or prior, it’s not clearly known what the MRI findings will mean or what the long-term implications are without both a control group and an understanding around population.”

The ACC opted against taking a stand. It provided MedPage Today with the following statement from ACC President Athena Poppas, MD:

“We appreciate the authors’ concerns about the potential mischaracterization of the long-term impact of myocarditis after a COVID-19 diagnosis and the need for well-designed clinical trials and careful, long term follow-up. The pandemic is requiring everyone make real-time decisions on how to best care for heart disease patients who may be impacted by COVID-19. The ACC is committed to helping synthesize and provide the most up-to-date, high quality information possible to the cardiovascular care team. We will continue to review and assess the scientific data surrounding cardiac health and COVID-19 and issue guidance to help our care team.”

While the open letter noted that some post-COVID patients have been asking for CMR, Walsh noted that primary care would likely see the brunt of any such influx. She personally has not had any patients ask to be screened.

SOURCE

https://www.medpagetoday.com/infectiousdisease/covid19/88704?xid=nl_covidupdate_2020-09-21

Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial

Published:August 27, 2017DOI:https://doi.org/10.1016/S0140-6736(17)32247-X

Summary

Background

Inflammation in the tumour microenvironment mediated by interleukin 1β is hypothesised to have a major role in cancer invasiveness, progression, and metastases. We did an additional analysis in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised trial of the role of interleukin-1β inhibition in atherosclerosis, with the aim of establishing whether inhibition of a major product of the Nod-like receptor protein 3 (NLRP3) inflammasome with canakinumab might alter cancer incidence.

Methods

We did a randomised, double-blind, placebo-controlled trial of canakinumab in 10 061 patients with atherosclerosis who had had a myocardial infarction, were free of previously diagnosed cancer, and had concentrations of high-sensitivity C-reactive protein (hsCRP) of 2 mg/L or greater. To assess dose–response effects, patients were randomly assigned by computer-generated codes to three canakinumab doses (50 mg, 150 mg, and 300 mg, subcutaneously every 3 months) or placebo. Participants were followed up for incident cancer diagnoses, which were adjudicated by an oncology endpoint committee masked to drug or dose allocation. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT01327846. The trial is closed (the last patient visit was in June, 2017).

Findings

Baseline concentrations of hsCRP (median 6·0 mg/L vs 4·2 mg/L; p<0·0001) and interleukin 6 (3·2 vs 2·6 ng/L; p<0·0001) were significantly higher among participants subsequently diagnosed with lung cancer than among those not diagnosed with cancer. During median follow-up of 3·7 years, compared with placebo, canakinumab was associated with dose-dependent reductions in concentrations of hsCRP of 26–41% and of interleukin 6 of 25–43% (p<0·0001 for all comparisons). Total cancer mortality (n=196) was significantly lower in the pooled canakinumab group than in the placebo group (p=0·0007 for trend across groups), but was significantly lower than placebo only in the 300 mg group individually (hazard ratio [HR] 0·49 [95% CI 0·31–0·75]; p=0·0009). Incident lung cancer (n=129) was significantly less frequent in the 150 mg (HR 0·61 [95% CI 0·39–0·97]; p=0·034) and 300 mg groups (HR 0·33 [95% CI 0·18–0·59]; p<0·0001; p<0·0001 for trend across groups). Lung cancer mortality was significantly less common in the canakinumab 300 mg group than in the placebo group (HR 0·23 [95% CI 0·10–0·54]; p=0·0002) and in the pooled canakinumab population than in the placebo group (p=0·0002 for trend across groups). Fatal infections or sepsis were significantly more common in the canakinumab groups than in the placebo group. All-cause mortality did not differ significantly between the canakinumab and placebo groups (HR 0·94 [95% CI 0·83–1·06]; p=0·31).

Interpretation

Our hypothesis-generating data suggest the possibility that anti-inflammatory therapy with canakinumab targeting the interleukin-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality. Replication of these data in formal settings of cancer screening and treatment is required.

Funding

Novartis Pharmaceuticals.

SOURCE

https://www.thelancet.com/journals/lancet/article/PIIS0140-67361732247-X/fulltext

Read Full Post »

The Role of Cholesterol Crystals in increase of NLRP3 Inflammasome affecting Coronary Artery Disease & Carotid Atherosclerosis

Posted in Atherogenic Processes & Pathology, Frontiers in Cardiology and Cardiovascular Disorders, Origins of Cardiovascular Disease, Systemic Inflammatory Diseases as CVD Risk, Vascular Diseases on September 15, 2020| Leave a Comment »

The Role of Cholesterol Crystals in increase of NLRP3 Inflammasome affecting Coronary Artery Disease & Carotid Atherosclerosis

Reporters: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC

Justin D. Pearlman, MD, PhD, FACC – Scientific Expert & Key Opinion Leader on Cardiovascular Diseases, Cardiac Imaging & Complex Diagnosis in Cardiology: Senior Editor & Author

The study published in Lancet https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30361-3/fulltext

shows plausible evidence for a sequence of events following atheroma crystal formation in blood vessel walls leading to inflammation and consequential injuries from atherosclerosis. The liquid crystal behavior of atheroma was first demonstrated in original PhD dissertation by JDPearlman MD PhD who demonstrated that 0.5 C temperature shift at body temperature converts the physical state of atheroma lipids to crystalline, known as liquid-crystal behavior, and studies he performed with NMR (nuclear magnetic resonance) and EPR (electron paramagnetic resonance) demonstrated that triglyceride levels impact the transition temperature. The current study shows a cascade of responses to the atheroma crystallization that leads to damaging inflammation and risk of acute obstruction. In particular, the current study demonstrates accumulation of blood complement factor complexes C1q and C5b-9, along with increases in complement receptors C5aR1, C5aR2 and C3aR1. Priming human carotid plaques with C5a followed by cholesterol crystal incubation resulted in pronounced release of interleukins IL-1β, IL-18 and IL-1α. Further understanding of the dominant pathways linking atheroma crystallization to unstable plaque with clinical consequences (heart attack, stroke) points to additional opportunities for medication or gene therapy to mitigate the harm.

Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis

Open AccessPublished:September 11, 2020 DOI:https://doi.org/10.1016/j.ebiom.2020.102985

Abstract

Background

During atherogenesis, cholesterol precipitates into cholesterol crystals (CC) in the vessel wall, which trigger plaque inflammation by activating the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. We investigated the relationship between CC, complement and NLRP3 in patients with cardiovascular disease.

Methods

We analysed plasma, peripheral blood mononuclear cells (PBMC) and carotid plaques from patients with advanced atherosclerosis applying ELISAs, multiplex cytokine assay, qPCR, immunohistochemistry, and gene profiling.

Findings

Transcripts of interleukin (IL)-1beta(β) and NLRP3 were increased and correlated in PBMC from patients with acute coronary syndrome (ACS). Priming of these cells with complement factor 5a (C5a) and tumour necrosis factor (TNF) before incubation with CC resulted in increased IL-1β protein when compared to healthy controls. As opposed to healthy controls, systemic complement was significantly increased in patients with stable angina pectoris or ACS. In carotid plaques, complement C1q and C5b-9 complex accumulated around CC-clefts, and complement receptors C5aR1, C5aR2 and C3aR1 were higher in carotid plaques compared to control arteries. Priming human carotid plaques with C5a followed by CC incubation resulted in pronounced release of IL-1β, IL-18 and IL-1α. Additionally, mRNA profiling demonstrated that C5a and TNF priming followed by CC incubation upregulated plaque expression of NLRP3 inflammasome components.

Interpretation

We demonstrate that CC are important local- and systemic complement activators, and we reveal that the interaction between CC and complement could exert its effect by activating the NLRP3 inflammasome, thus promoting the progression of atherosclerosis.

Keywords

Read Full Post »

Heart Failure in Women With Hypertensive Disorders of Pregnancy

Posted in Frontiers in Cardiology and Cardiovascular Disorders, Heart Failure (HF) on August 26, 2020| Leave a Comment »

Heart Failure in Women With Hypertensive Disorders of Pregnancy

Reporter: Aviva Lev-Ari, PhD, RN

Heart Failure in Women With Hypertensive Disorders of Pregnancy

Insights From the Cardiovascular Disease in Norway Project

Michael C. Honigberg

Hilde Kristin Refvik Riise

Anne Kjersti Daltveit

Janet W. Rich-Edwards

Originally published24 Aug 2020 https://doi.org/10.1161/HYPERTENSIONAHA.120.15654Hypertension. ;0

Abstract

Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84–2.35], P=0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50–2.68, P<0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery (P_interaction=0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.

SOURCE

https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.15654?utm_campaign=sciencenews20-21&utm_source=weekly-sn&utm_medium=email&utm_content=phd08-26-20&j=72055108&sfmc_sub=1648404797&l=7991033_HTML&u=633892723&mid=10171707&jb=0

Read Full Post »

Targeting Atherosclerotic Plaques with Stents made of Drug-eluting Biomaterials

Posted in Biodegradable Drug-eluting Material, Bioresorbable Vascular Scaffold (BVS), Cardiac and Cardiovascular Surgical Procedures, Frontiers in Cardiology and Cardiovascular Disorders, PCI, Peripheral Arterial Disease & Peripheral Vascular Surgery, Stents & Tools, Vascular Diseases on June 9, 2020| Leave a Comment »

Targeting Atherosclerotic Plaques with Stents made of Drug-eluting Biomaterials

Reporter: Daniel Menzin, BSc BioMedical Engineering, expected, May 2021, Research Assistant 4, Core Applications Developer and Acting CTO

Atherosclerosis is a chronic cardiovascular disease with a multitude of different implications. A coronary artery plaque may lead to congestive heart failure while an aortic plaque may cause angina. Both can quite possibly lead to a heart attack unless properly managed. One way to manage this condition is through the use of stents made of a mesh that is expanded following placement into the diseased vessel.

Unfortunately, stents are oftentimes initially effective but eventually restenosis occurs. Restenosis is a condition in which the affected vessel becomes blocked again. Cholesterol-rich blood vessel environments oftentimes lead to an irritation that results in white blood cells aggregating in the area and releasing proinflammatory chemokines and cytokines, which cause fibrosis. To make matters worse, the cholesterol plaques undergo compression against the vessel wall which causes vessel injury and further inflammation. This leads to thrombus formation and may potentiate neointimal hyperplasia, an abnormal proliferation and migration of smooth muscle cells in the tunica intima. Neointimal hyperplasia plays a major role in restenosis.

Recent research has found that interfacing drug eluting biomaterials with stents may help prevent restenosis. One study showed that rapamycin delivered with acid labile and ROS-sensitive forms of Beta-cyclodextrin produced promising results when treating atherosclerosis in rat models (Dou, et al). In this promising new paradigm of treatment, non-proinflammatory biomaterials are interfaced with stents. Once inflammation appears the biomaterial will begin to degrade, slowly releasing the drug which suppresses the underlying immune reaction and the resulting inflammation.

SOURCE

Dou Y;Chen Y;Zhang X;Xu X;Chen Y;Guo J;Zhang D;Wang R;Li X;Zhang J; “Non-Proinflammatory and Responsive Nanoplatforms for Targeted Treatment of Atherosclerosis.” Biomaterials, U.S. National Library of Medicine, 29 July 2017, pubmed.ncbi.nlm.nih.gov/28778000/.

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

Drug Eluting Stents: On MIT‘s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES

Author: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/25/contributions-to-vascular-biology/

Read Full Post »

« Newer Posts - Older Posts »

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

Most Popular According To Cardiologists in Circulation, AHA, European Heart Journal and Medscape Medical News

Most Popular According To Cardiologists

Share this:

Like this:

Left Ventricular Volume Reduction and Reshaping as a Treatment Option for Heart Failure

Left Ventricular Remodeling and Its Reversal

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

Share this:

Like this:

Retrospective Study of National Danish Registry Sheds Light on Cardiotoxic Risks of Immune Checkpoint Inhibitors

Original Research

The risk of cardiac events in patients receiving immune checkpoint inhibitors: a nationwide Danish study

Abstract

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

Share this:

Like this:

Diagnostic and Interventional Cardiology (DAIC): 2020 Top 25 Best Performing Articles

Share this:

Like this:

Bioresorbable Stent Clinical Trials with New Esprit Below-the-knee Scaffold

Share this:

Like this:

Precision Cardiology to Benefit from New Atlas of Cells of the Adult Human Heart

The Voice of Dr. Pearlman on potential clinical implications of the New Atlas:

Abstract

Author information

Affiliations

Corresponding authors

Share this:

Like this:

COVID concern in Cardiology: Asymptomatic patients who have been previously infected demonstrating evidence on MRI of scarring or myocarditis

The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC

Some Heart Societies Agree on Cautions for COVID-Myocarditis Screening

Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial

Share this:

Like this:

The Role of Cholesterol Crystals in increase of NLRP3 Inflammasome affecting Coronary Artery Disease & Carotid Atherosclerosis

The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC

Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis

Abstract

Background

Methods

Findings

Interpretation

Keywords

Share this:

Like this:

Heart Failure in Women With Hypertensive Disorders of Pregnancy

Heart Failure in Women With Hypertensive Disorders of Pregnancy

Abstract

Share this:

Like this:

Targeting Atherosclerotic Plaques with Stents made of Drug-eluting Biomaterials

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

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents

Drug Eluting Stents: On MIT‘s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES

Share this:

Like this:

Follow Blog via Email

Recent Posts

Archives

Categories

Meta