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Genetics

VA/Yale Researchers Lead Multi-ancestry Study of Genetics of Problematic Alcohol Use – Yale School of Medicine

A study led by VA Connecticut Healthcare Center/Yale researchers reveals ancestries around the world possess a shared genetic architecture for problematic alcohol use (PAU) habitual heavy drinking, accompanied by harmful consequences.

The findings, published in Nature Medicine, could help scientists understand the genetic basis of PAU, a major cause of health problems in many age groups. It is a leading cause of death in those it afflicts.

This study is the largest to date for PAU it identified many new risk genes and uncovered a large amount of new biology. With a better understanding of PAU biology, scientists will have new possibilities in developing treatments.

Hang Zhou, PhD, assistant professor of psychiatry and of biomedical informatics & data science at Yale School of Medicine and VA Connecticut, and first author of the study, said, Research with the primary focus on understanding the molecular mechanism underlying PAU and identification of gene targets for potential pharmacological studies is extremely important for future treatments and could help mitigate the consequences of excessive alcohol use.

Researchers studied more than 1 million people with PAU and included as many genetic ancestral groups as possible, including people with European, African, Latin American, East Asian, and South Asian ancestries.

The Million Veteran Program (MVP), funded by the U.S. Department of Veterans Affairs, was a major source of data for this study MVP data were combined with data from many other sources to create the analyses.

Compared to previous research, this work broadened the findings and demonstrated that the genetic architecture of PAU is substantially shared across these populations. There are genetic differences in different populations for PAU, but the similarities are greater. Cross-ancestry information allowed the researchers to improve the power of gene discovery.

By leveraging the multi-ancestry information, we identified 110 gene regions and had an improved fine-mapping of the potential causal variants in each region, Zhou said.

The researchers also used various methods to prioritize multiple genes with convergent evidence linking association to PAU with brain biology through gene expression (transcriptional-wide association study in 13 brain tissues) and chromatin interaction analyses in the brain. This work will provide valuable resources and targets for future functional analyses and drug development.

Joel Gelernter, MD, Foundations Fund Professor of Psychiatry, and professor of genetics and of neuroscience at Yale School of Medicine and VA Connecticut, was the study's senior author.

One of the most important products of this research is the information provided about PAU risk across the entire genome," Gelernter said. "The resulting data allowed us to understand the biology of PAU better, suggesting some already-approved drugs that might become tools for treating PAU in the future, with additional research. The data we produced will be shared with the research community, and this will aid greatly in future research by other scientists.

The drug-repurposing analyses identified several existing medications as potential treatments for PAU, which are described in the published article.

One of the outputs from this study is genomewide association data, and this kind of information can be used to compute polygenic risk scores, or PRS, that can be used to estimate an individuals genetic risk for PAU.

The researchers stressed that the PRS they computed is not yet ready for use in the clinic, but they also tested the association of the PRS for PAU with hundreds of medical traits in multiple biobanks including Vanderbilt University Medical Centers Biobank, Mount Sinais BioMe, the Mass General Brigham Biobank, and Penn Medicine Biobank. This analysis identified genetic correlations between PAU and many other mental and neurological disorders.

Other Yale contributors include Joseph D. Deak, Lu Wang, Jiayi Xu, Keira J.A. Johnston, Marco Galimberti, Cecilia Dao, Daniel F. Levey, Cassie Overstreet, Ke Xu, Hongyu Zhao, Laura M. Huckins, John H. Krystal, and Amy C. Justice. The investigators also worked with scientists from the University of Pennsylvania and many other institutions.

Funding was provided by the U.S. Department of Veterans Affairs and National Institutes of Health.

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VA/Yale Researchers Lead Multi-ancestry Study of Genetics of Problematic Alcohol Use - Yale School of Medicine

Genetics

Sunday Links from Etalon Equine Genetics – Eventing Nation

The 2023 USEA Annual Meeting & Convention comes to a close today, and we have all been watching and waiting patiently to hear news on the many proposed rule changes, USEA Board nominees, and end-of-year award recipients.

Yesterdays schedule featured several highlight meetings, including the open forum regarding proposed rule changes and the keynote presentation by prolific animal welfare activist and animal science professor Dr. Temple Grandin.

Here are some numbers and statistics on and from this year-end convention!

Number of committee meetings that took place: 41 Number of educational seminars, sessions, and forums that took place: 40

Incoming Area Chairs:

New Board of Governors:

Current number of USEA members to date: 477,055 Number of active competing USEA members: 80,623 Number of USEF-licensed competitions in 2023: 2,128

USEA Governors Cup recipients: John Bourgoin, Rebecca Brown, Loris Henry, Kathy Kerns, Mark Andreason Andrew H. Popiel Memorial Trophy recipients: Lena and Mark Warner USEA Presidents Lifetime Achievement Award: Sharon Gallagher

Find all awards recipients here, as well as the USEA CEOs Report.

U.S. Weekend Action

USEA Annual Meeting and Convention (St. Louis, MO): [Information Hub] [Schedule] [Fast Facts]

Full Gallop Farm Jingle Bells H.T (Aiken, SC) [Website] [Entries] [Ride Times] [Volunteer] [Scoring]

Links to Start Your Sunday:

EquiRatings Horse of the Year voting is on to the semi-finals! Vote here for one of the final four.

While youre at it, dont forget to send in a nomination for The One #Supergroom to Rule Them All!

Test the Best Without Hurting the Rest: Barnard and Donovan Lead Show Jumping Seminar at USEA Annual Meeting & Convention

Horse Community Controversy: The Future of Wellington

Meet Cascada: a smart auto-waterer that sends alerts to your phone

Just in time for the holidays: Hallmark Channel to release A Blacksmith for Christmas movie

Sponsor Corner: What are equine performance genetics? Etalon Equine Genetics can identify your horses strengths and weaknesses in the competition ring according to their DNA.

Morning Viewing: Everyone has their own ASMR genres dont deny it, I saw you watching those satisfying farrier videos. While my in-the-background choices lately may have included some very cool leatherworking close-ups (its also a ploy to get my husband to think its cool; homemade halters may be in my future), Horse Grooming ASMR might just be added into my playlists. All the satisfaction of watching a horse meticulously cleaned and none of the impending arthritis flares from doing it yourself? This may just bring balance to my life.

And yes, Im that girl at the barn who uses two different stiff brushes and three soft brushes before every ride. I like shiny ponies, sue me.

Excerpt from:
Sunday Links from Etalon Equine Genetics - Eventing Nation

Genetics

Study reveals genetic roots of hodgkin lymphoma, offering hope for new treatments – News-Medical.Net

A Stanford Medicine-led, international study of hundreds of samples from patients with Hodgkin lymphoma has shown that levels of tumor DNA circulating in their blood can identify who is responding well to treatment and others who are likely to experience a disease recurrence -; potentially letting some patients who are predicted to have favorable outcomes forgo lengthy treatment.

Surprisingly, the study also revealed that Hodgkin lymphoma, a cancer of the lymph nodes, can be divided into two groups, each with distinct genetic changes and slightly different prognoses. These changes hint at weaknesses in the cancer's growth mechanisms that could be targeted by new, less toxic therapies.

The idea of establishing molecular profiles of tumors is not new. But unlike other cancers, Hodgkin lymphoma has resisted these types of analyses. That's because Hodgkin lymphoma cells are relatively scarce -; even within a large tumor.

This approach offers our first significant look at the genetics of classical Hodgkin lymphoma. Compared with other cancers, finding Hodgkin lymphoma cancer cells or cancer DNA to study is like searching for a needle in a haystack. A patient can have a football-sized tumor in their chest, but only about 1% of the cells in the mass are cancer cells, with the remainder representing an inflammatory response to the tumor. This has made it very difficult to find the smoking guns that drive the disease."

Ash Alizadeh, MD, PhD, professor of medicine, Stanford

Alizadeh, who is the Moghadam Family Professor, and Maximilian Diehn, MD, PhD, professor of radiation oncology and the Jack, Lulu, and Sam Willson Professor, are the senior authors of the research, which will be published Dec. 11 in Nature. Former postdoctoral scholar Stefan Alig, MD; instructor of medicine Mohammad Shahrokh Esfahani, PhD; and graduate student Andrea Garofalo are the lead authors, as is graduate student Michael Yu Li at British Columbia Cancer.

About 8,500 people are diagnosed with Hodgkin lymphoma each year in the United States. The disease primarily affects people between the ages of 15 and 35, and people older than 55.

Just over 60 years ago, Stanford radiologist Henry Kaplan, MD pioneered the use of targeted radiation to treat Hodgkin lymphoma. The new therapy, delivered by a high-energy linear accelerator Kaplan developed in the 1950s for medical use, was the first step in a Stanford-driven effort to turn the once fatal cancer of the lymph nodes into one that is now highly curable. Soon thereafter, Kaplan was joined by medical oncologist Saul Rosenberg, MD, and the two worked out ways to combine radiation therapy with chemotherapy regimens, including one known simply as the Stanford 5 (named because it was the fifth in a series of gradually less toxic treatments).

During the subsequent decades, however, the genetic changes that cause the cancer have remained mysterious. That's because, unlike many other cancers, Hodgkin lymphoma tumors are made up primarily of immune cells that have infiltrated the cancer, making it difficult to isolate the diseased cells for study. Today, patients are treated with chemotherapy, radiation or a combination of both; about 89% of patients survive five years or more after their initial diagnosis.

Alizadeh, Diehn and their colleagues used an optimized DNA sequencing technique called PhasED-Seq, or phased variant enrichment and detection sequencing, they developed at Stanford Medicine in 2021 to home in on vanishingly rare bits of DNA in a patient's bloodstream to identify genetic changes that drive the growth of Hodgkin lymphoma.

PhasED-Seq builds upon a technique called CAPP-Seq, or cancer personalized profiling by deep sequencing, developed in 2014 by Alizadeh and Diehn to assess lung cancer levels and response to treatment. But PhasED-Seq is much more sensitive.

"CAPP-Seq could detect as few as one cancer DNA sequence in 10,000 non-cancer DNA sequences," Diehn said. "But PhasED-Seq can detect less than one cancer DNA sequence in 1 million non-cancer DNA sequences."

Their goal was to learn more about what drives the cancer and how to make successful treatments even easier for patients.

"We typically can cure most patients with one line of therapy," Alizadeh said. "But we are always trying to figure out less toxic chemotherapeutic agents that are gentler to the bone marrow, lungs and other organs, and ways to more precisely target radiation therapy. And a small minority of patients experience a recurrence that can be challenging to treat successfully."

The researchers used CAPP-Seq and PhasED-Seq to analyze blood samples from 366 people treated for Hodgkin lymphoma at three medical centers including Stanford Medicine. The technique was remarkably sensitive.

"Surprisingly, we detected more cancer DNA in the blood than in the cancer tissue itself," Alizadeh said. "That seemed hard to believe until we had analyzed enough samples to show that it was reproducible."

The researchers used machine learning techniques to categorize the different types of genetic changes present in the cancer cells. They found that patients could be separated into two groups: one that predominantly has mutations in several cancer-associated genes implicated in cellular survival, growth and inflammation, and another with a type of genetic change called copy number alterations that affects larger swathes of the genome, subbing in or excising regions of DNA that influence cell growth and cancer.

"We adapted a method from natural language processing to find these two Hodgkin subtypes, and then used a variety of methods to identify key biological and clinical features and to confirm that the subtypes are also seen in other groups of patients," Esfahani said.

The first group, which makes up about one-half to two-thirds of patients, occurs primarily in younger patients and has a comparatively more favorable outcome. About 85-90% of these people survive for three years without disease recurrence. The second, which makes up about one-half to one-third of the total, occurs in both younger and older patients and has a less favorable, although still good outcome. About 75% of these people live for at least three years without recurrence.

Critically, a subset of both groups contained a unique mutation in a gene for the receptor for cellular signaling proteins called interleukin 4 and interleukin 13.

"We discovered a new class of mutations in the interleukin 4 receptor gene that enhance a key pathway characteristic to Hodgkin lymphoma," Alig said. "These mutations may be indicative of unique vulnerabilities of the tumor that can be exploited therapeutically."

The researchers also showed that patients who had no detectable circulating tumor DNA in their blood shortly after starting treatment were much less likely to have disease recurrence than those who had even small amounts of residual circulating cancer DNA at the same time point -; a distinction researchers had hoped to see, but were unsure about being able to detect even with PhasED-Seq.

"I was surprised that we could predict which patients would recur," Diehn said. "Even with our ultrasensitive assay there was a significant chance that the signal from the cancer DNA could become undetectable after treatment, even in patients who eventually recurred. But this didn't happen."

The researchers seeking to understand more about the biology of Hodgkin lymphoma have one key goal: the improvement of care for patients.

"The number of people who experience recurrence is small, but, like Henry Kaplan and Saul Rosenberg, we want to save every one of them," Diehn said. "They would have been amazed and gratified by these findings, which build upon their important work from decades ago. We look forward to an era in which we can cure every patient with no toxicity."

Researchers from British Columbia Cancer, University Hospital Franois Mitterand, St. Jude Children's Research Hospital, the Oncology Institute of Southern Switzerland, KU Leuven, the University of Strasbourg, Emory University, the Fred Hutchinson Cancer Research Center, the Hospices Civils de Lyon, and the Universit Catholique de Louvain contributed to the work.

This work was supported by the National Institutes of Health (grants R01CA257655, R01CA233975 and R03CA21765), the Department of Defense, the Virginia and D.K. Ludwig Fund for Cancer Research, a Hanna and Michael Murphy family gift, the Stanford Cancer Institute, the Damon Runyon Cancer Research Foundation, an American Society of Hematology Scholar Award, the V Foundation for Cancer Research, the Emerson Collective Cancer Research Fund, a Stinehart/Reed Award, the CRK Faculty Scholar Fund, the Lung Cancer Research Foundation and the SDW/DT, the Shanahan Family Foundations, the Terry Fox Research Institute, the Canadian Institutes of Health Research, an Elizabeth C. Watters Research Fellowship, and the American Syrian Lebanese Associated Charities.

Diehn, Alizadeh, Alig and Esfahani have filed patents related to cancer biomarkers. Diehn has multiple issued and pending patents licensed to Foresight Diagnostics and Roche. He holds interests in CiberMed, Inc.; Foresight Diagnostics; and Gritstone Bio. Alizadeh has multiple issued and pending patents licensed to Foresight Diagnostics, CiberMed Inc. and Idiotype Vaccines. He holds interests in CiberMed, Inc.; Foresight Diagnostics; FortySeven Inc.; and CARGO Therapeutics.

Source:

Journal reference:

Alig, S. K., et al. (2023). Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling. Nature. doi.org/10.1038/s41586-023-06903-x.

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Study reveals genetic roots of hodgkin lymphoma, offering hope for new treatments - News-Medical.Net

Genetics

Experts in Animal, Human Genetics Talk Innovation at Angus Convention – Morning Ag Clips –

From left, Kelli Retallick-Riley, AGI; Debbie Plouffe, Center for Aquaculture Technologies; and Kristin Brogaard, Inherent Biosciences, present during the second general session of the 2023 Angus Convention held in Orlando, Fla., Nov. 3-6. (Courtesy photo)

SAINT JOSEPH, Mo. Cattle producers and Angus Genetics Inc. (AGI) are not the only ones thinking about advancements in genetic selection. Genetic tools and research in fields such as aquaculture and human health are also exploring ways to improve tools and industry methods.

On November 4 at Angus Convention in Orlando, FL, a panel presentation featured Kristin Brogaard, co-founder and chief scientific officer of Inherent Biosciences; Debbie Plouffe, vice president of business development for the Center for Aquaculture Technologies; and Kelli Retallick-Riley, president of AGI. The session was sponsored by Neogen.

Following the conventions theme of experiencing innovation, they discussed how genomics has transformed how people think about breeding cattle today and connections seen across their research and business fields.

In 2009, the first genomic-enhanced EPDs were released through the American Angus Association, Retallick-Riley said. Since that time, the rate of adoption and the rate of adoption by producers in this room has grown astronomically. Nearly 60% of [Association members] registrations submitted in 2023 were accompanied by genotypes.

Collectively, this amounts to 1.5 million genotypes being included in Anguss weekly genetic evaluation. Both Retallick-Riley and Plouffe agree there are several reasons the agricultural industry has seen a shift toward more genetic testing.

I think the drive towards genomic selection is really being fueled by, and agriculture is being fueled by, this desire to improve animal welfare, reduce the treatments that were doing, and therefore improve overall productivity and sustainability of the industry, Plouffe said.

Retallick-Riley said genomically enhanced EPDs present themselves as a marketing tool but are more importantly a breeding and herd management tool. She told the audience 45% of the Associations available genotypes are from females.

That tells me that the people in this room are not only committed to making sure commercial cattlemen have their individual information to select bulls but are using genomics to ensure theyre making genetic progress on the female side as well, said Retallick-Riley.

From a research perspective, studying disease resistance through genetics is of interest to all three fields beef cattle, aquaculture, and human health. Aquaculture has experienced some significant wins using genomics, especially with a particular viral disease that affects Atlantic salmon, rainbow trout, and all their relatives.

Plouffe said the disease was unique and rare in that it is controlled by a single gene.

Using that information, we were able to build a genetic test that could be used to accurately predict which fish, which breeders, were going to produce animals that were resistant, she said.

The success helped aquaculture increase the technologys adoption rate for genomic testing among salmon, rainbow trout, tilapia, and more recently some shellfish species.

When it comes to human health, Brogaard said she has seen growth in her companys products, which focus on male fertility, due to how common infertility is among couples and their desire for better fertility treatment options.

One in six couples suffer from infertility, she said. There is usually two years of trying, $80,000 on average out-of-pocket (costs) to go through a single fertility journey. There are three times more divorces in couples seeking fertility care.

In a word, she described the typical fertility treatment process as awful. In response, Brogaard and her colleagues have developed a sperm test, SpermQTTMfor male fertility, which analyzes the expression of 1,233 genes in a sample. Test results help couples determine the best next steps for them.

We can now very accurately predict the likelihood of artificial insemination success, pregnancy and live birth based on how your genes are being expressed, looking at those 1,233 genes, she said.

Brogaards background is in epigenetics, which is the science where nature and nurture meet. In other words, epigenetics is influenced by the individuals environment as well as gene expression.

Whats probably the most important part of this is that those guys that we identified as having abnormal epigenetics, four out of five of them had normal semen parameters, she said. Talking to some people last night, it sounds like thats sometimes the case in this (cattle) industry where you have semen parameters, but theyre not usually predictive of fertilization outcomes. So thats interesting because we are seeing the same thing in men.

Comparing industries, Brogaard said she finds herself jealous of the volume of data and research conditions available to Retallick-Riley and Plouffe as animal genetics researchers, and she said she is excited about what epigenetics could bring to the table in their fields.

You can just move a lot quicker, Brogaard said. I think theres huge potential of identifying epigenetics that are important for [proper fertilization, embryo development with your embryo transfers and offspring health] for your industry, and Im really excited about it.

Breeders utilizing contemporary groups and submitting data, especially through Inventory Reporting, help tie phenotypic and genomic information together and move the needle on industry progress.

If we didnt have this large database, our genomic predictions wouldnt nearly be as accurate, they wouldnt be as useful, and wed be stifled by the rate of genetic change that we can make for that reason, Retallick-Riley said. Luckily for me, I get to work for an organization that allows us to be able to put out some of the most accurate genetic evaluations in the industry.

The trio also discussed how researching environmental impact on gene expression combined with traditional genetics research could help us understand more about complex diseases in animals and humans.

AGIcontinues to work on its heart health initiative for cattle and the study of more complex traits like functional longevity. Brogaard shared Inherent Biosciences is branching out and working on detection tools for male urological cancers, while Plouffe and her team work on furthering breeding strategies using genomic selections in aquaculture, including gene editing.

Plouffe said gene editing gives them more flexibility in how they can introduce some traits. Her companys view is responsible application of genome editing requires sterility, she said, so breeding for sterility has been another focus of their research.

We dont see it replacing traditional selective breeding, Plouffe said. This is just going to be another tool in the breeders toolbox that they can use to introduce traits of interest.

She continued, I think if you find the traits that are both interesting for the consumers and the producers, thats where youre going to be most successful.

For more stories from the 2023 Angus Convention, visit angus.org and view News & Announcements.

Sarah Kocher Angus Communications

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Experts in Animal, Human Genetics Talk Innovation at Angus Convention - Morning Ag Clips -

Genetics

NIH statement on new FDA-approved gene therapies for sickle cell disease – National Human Genome Research Institute

The U.S. National Institutes of Health (NIH) has long invested in basic genetics and genomics research, clinical trials, as well as translational medicine and social science studies, to advance our understanding of this widespread illness to help develop effective therapies.

For example:

"NIH celebrates this enormous milestone in treatment for sickle cell disease, the first human genetic disease that was understood at the protein and DNA levels. Researchers have worked hard to find a long-term, durable therapy for sickle cell disease. Research has enabled the use of gene therapy to make genetic changes in the bone marrow of sickle cell patients, leading to normal red blood cell levels. None of this would be possible without federal investments in basic science research."

Eric Green, M.D., Ph.D., Director of the National Human Genome Research Institute

"We have made some exciting research advances over the years and are ready to collect on our scientific investments in sickle cell research. However, we must remember that these advances need to go hand-in-hand with scalable innovations that will ensure equitable access to life-altering care and that we must continue to engage in additional research endeavors that will minimize or eliminate potential risks that might be associated with these therapies."

Gary H. Gibbons, M.D., Director of the National Heart, Lung, and Blood Institute

The sickle cell disease community has historically been underserved and underacknowledged when it comes to rare genetic conditions, so it is heartening to see sickle cell disease at the forefront of gene therapy. It is critical that people with sickle cell disease who are considering gene therapy fully understand the treatment so they can make an informed decision on whether it is appropriate for them. Patients need accessible, understandable and actionable educational materials to help them make such decisions, as well as support from practitioners and the healthcare system to consider these therapies.

Vence L. Bonham, Jr., J.D., Acting Deputy Director of the National Human Genome Research Institute

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NIH statement on new FDA-approved gene therapies for sickle cell disease - National Human Genome Research Institute

Cardiology

BLOG: Combining Local Impedance with Contact Force to Perform RF Ablation – Diagnostic and Interventional Cardiology

When performing radiofrequency (RF) ablation to treat cardiac arrhythmia, medical professionals must balance the safety of the patient with the efficacy of the procedure. Several important safety considerations are at play.

Physicians want to avoid mechanical perforation of the cardiac tissue, which can be caused by applying too much force in positioning the catheter. They also want to avoid unintentional damage to tissue or nontargeted structures during RF delivery.

Among the rare but serious complications associated with RF ablation are steam pops, which occur when ablated tissue is heated above 100 C, causing an explosion of steam to be released and unwanted damage to the tissue. In a worst-case scenario, a steam pop can tear a hole in the wall of the cardiac tissue allowing blood to leak into the pericardium. This can lead to cardiac tamponade, when the pressure from the blood surrounding the heart prevents it from beating.

Since the introduction of RF ablation as a cardiac arrhythmia therapy, advances have been made in the technologies and methods of delivering RF. These include the introduction of advanced mapping, multi-electrode and irrigated catheters, contact force, and the use of measures of tissue resistivity, or impedance, as a means to track RF delivery and lesion development.1

Boston Scientific offers RF ablation catheters with technology that enables capture of impedance metrics nearer the tissue to be treated. With the DIRECTSENSE Technology-enabled catheters, impedance can be measured around the tip of the catheter, avoiding the interference of far-field signals and capturing insights on cardiac tissue resistivity.

Local impedance has been demonstrated to more accurately indicate subsurface tissue temperature and lesion formation than does surface temperature. In tissue tests with embedded thermocouples, local impedance drop followed the rate and magnitude of the rise in intra-lesion temperature, demonstrating a correlation between the metric and volumetric heating as it occurs.2 Local impedance has also been found to respond with greater specificity and sensitivity in identifying abnormal substrate all valuable feedback in helping inform optimal delivery of ablation therapy.

Boston Scientific has now incorporated contact force capabilities into their DIRECTSENSE-enabled ablation catheters.

The investigational device INTELLANAV STABLEPOINT Ablation Catheter brings together the handling and inputs of contact force catheters with the ablation feedback offered by DIRECTSENSE local impedance. Available with RHYTHMIA HDx Mapping System (pictured above), the STABLEPOINT catheter is designed to help physicians verify contact, discern tissue characteristics, monitor subsurface tissue heating for predictable and controlled delivery of RF.

With the addition of force technology, the STABLEPOINT catheter can help confirm tissue contact and catheter-tip stability for the duration of RF delivery. In one study, force readings enabled two independent users to maintain a stable average force of +/- 5 grams, compared to starting force, for the full duration of >90 percent of point-by-point PVI applications.3

Using local impedance, physicians gain insights into tissue characteristics and resistivity, input that can help guide the ablation strategy. Changes in local impedance during ablation offer information on lesion development and feedback that can help safeguard against tissue overheating.

Recent studies have examined the STABLEPOINT catheters use in clinical settings. In a multicenter, prospective study conducted across Europe, Asia, and the United States, 299 patients treated for de novo atrial fibrillation (AF) underwent pulmonary vein isolation with the STABLEPOINT catheter guided by RHYTHMIA HDx Mapping System. STABLEPOINT in the NEwTON AF Study met the 30-day and 12-month primary safety endpoints as well as the acute, 6-month and 12-month primary effectiveness performance criteria for the use of the catheter in this patient population.4 At 12 months, data indicated a 4 percent incidence of adverse events. Freedom from atrial flutter and atrial tachycardia in the study group was 90.2 and 97.6 percent, respectively.4

A separate, multicenter study of 212 consecutive patients treated for AF with the STABLEPOINTcatheter assessed results across 13,891 RF applications of a 3 second duration. High-power, short-duration ablation with contact force and local impedance resulted in a 93.3 percent rate of successful first-pass isolation with no reported steam pops or major complications. Researchers also noted that the combination of local impedance drop with good contact led to a reduction in the duration of RF.5

Editor's note: This is the conclusion of a three-part series on cardiac ablation technology.Part one,Pulsed Field Ablation: A New Ablation Method,addressed pulsed field ablation; Part two, Cryoablation Gets New Tech," covers next-generation cryoballoon technology.

1. Habibi M, Berger RD, Calkins, H. Radiofrequency ablation: technological trends, challenges, and opportunities. EP Europace. 2021;23(4): 511519. doi.org/10.1093/europace/euaa328

2. Garrott KE, et al. Intra-lesion temperature rise and local impedance drop predictive of lesion growth on RF ablation catheter with mini electrodes. Abstract. Heart Rhythm Annual Meeting. May 2020.

3. Internal BSC Report 92464384.

4. NEwTON AF: Clinical Evaluation of the STABLEPOINTTM Catheter and Force Sensing System for Paroxysmal Atrial Fibrillation. NEwTON AF Study (NCT04580914) presented at AHA, November 2023.

5. Lepillier A, Maggio R, De Sanctis V, et al. Insight into contact force local impedance technology for predicting effective pulmonary vein isolation. Front Cardiovasc Med. 2023;10. doi.org/10.3389/fcvm.2023.1169037

Caution: Investigational device. Limited by Federal (or U.S.) law to investigational use only. Not available for sale. 2023 Boston Scientific Corporation or its affiliates. All rights reserved. All trademarks are the property of their respective owners. EP-1755903-AA

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BLOG: Combining Local Impedance with Contact Force to Perform RF Ablation - Diagnostic and Interventional Cardiology

Cardiology

Heart attack breakthrough: New protocol saves 71% of patients with deadly complication – News-Medical.Net

Published results of a large, national heart attack study show that patients with a life-threatening complication known as cardiogenic shock survived at a significantly higher rate when treated with a protocol developed by cardiologists at Henry Ford Health, in collaboration with 80 hospitals nationwide.

Cardiogenic shock is a critical condition in which the heart is unable to pump enough blood to sustain the body's needs, depriving vital organs of blood supply. This can cause those organs to eventually stop functioning. The typical survival rate of this deadly complication during a heart attack has historically hovered around 50%.

Led by a cardiology research team based at Henry Ford Hospital in Detroit, the National Cardiogenic Shock Initiative (NCSI) results demonstrate a survival rate of 71% in patients whose heart attack was complicated by cardiogenic shock and were treated with the protocol. Final results from the national study published in the Journal of the American Heart Association were achieved from looking at 406 patients from hospitals across 29 states.

The National Cardiogenic Shock Initiative is the largest prospective study of therapy for severe heart attack cardiogenic shock done in the United States in the past two decades. The impressive results from our study in the U.S. have also prompted the use of our protocol in Japan where they are experiencing similar great outcomes."

William O'Neill, M.D., medical director emeritus of Henry Ford's Center for Structural Heart Disease and principal investigator of the study

The treatment algorithm, available at henryford.com/cardiogenicshock, emphasizes quick recognition of the condition, then inserting a temporary straw-sized pump into the heart to keep blood flowing throughout the body. The Impella heart pump, an FDA-approved device, is inserted through a catheter in the groin as soon as the patient arrives at the hospital. Doctors then treat the cause of the heart attack, either inserting a stent, removing a clot or taking other necessary action.

The NCSI study involved cardiologists at both community hospitals, where many patients with heart attack first present, and large academic centers. Of the more than 1,100 patients who were screened, 406 were enrolled into the study. The study also isolated predictive markers that indicate a patient's condition, an invaluable tool in determining treatment.

The NCSI participating hospitals agreed to treat patients who presented with acute myocardial infarction and cardiogenic shock using a standard protocol, which involved rapid initiation of mechanical circulatory support (MCS) with an Impella 2.5 or Impella CP heart pump, along with right heart catheterization to assess status of right and left ventricular heart function. Patients were enrolled between July 2016 and December 2020.

"The study results show remarkable survival, the highest we've seen in any study so far," said Babar Basir, D.O., Director of Acute Mechanical Circulatory Support at Henry Ford Health and principal investigator of the study. "The results show that we now have therapy that can save lives and improve outcomes for people who've had severe heart attacks and we haven't had results like these in 20 years. The protocol has already saved many lives and will continue to do so as more hospitals adopt its principles."

In the U.S., approximately 80,000 people are diagnosed with cardiogenic shock as a result from a heart attack each year according to data from a published study that looked at a 15-year trend from 2004 to 2018.

Dr. O'Neill will continue to lead research in the next NCSI phase in an upcoming study titled Recover IV Trial.

"Implementing this protocol has truly been a joint effort with hospitals that have experienced the devastating burden of cardiogenic shock," said Sarah Gorgis, M.D., a cardiologist at Henry Ford Health and co-researcher for the study. "Our work has just begun, but this protocol gives us hope since we have seen first-hand the impact it can make on survival."

"The NCSI initiative was critically important. It changed how we approach the management of patients with cardiogenic shock, and with those changes, we witnessed improvements in survival , for the first time in decades," said Herb Aronow, M.D., medical director of Heart & Vascular Services at Henry Ford Health.

"Bringing together 80 different sites to investigate an innovative treatment protocol for Acute myocardial infarction complicated by cardiogenic shock is an incredible accomplishment by our NCSI team and heralds highly promising new approaches to improving outcomes in this challenging patient population," said Henry Kim, M.D., Division Head of Cardiology at Henry Ford Health.

Source:

Journal reference:

Basir, M. B., et al. (2023) Early Utilization of Mechanical Circulatory Support in Acute Myocardial Infarction Complicated by Cardiogenic Shock: The National Cardiogenic Shock Initiative. Journal of the American Heart Association. doi.org/10.1161/JAHA.123.031401.

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Heart attack breakthrough: New protocol saves 71% of patients with deadly complication - News-Medical.Net