Thomas M. Roston, MD, FRCPC from The University of British Columbia speaks about Burst Exercise Testing Can Unmask Arrhythmias in Patients With Incompletely Penetrant Catecholaminergic Polymorphic Ventricular Tachycardia.

Link to Article:
https://www.jacc.org/doi/10.1016/j.jacep.2021.02.013?utm_medium=social&utm_source=twitter_post&utm_campaign=twitter_post

Synopsis:

Cardiac arrest following abrupt exercise is a symptom of catecholaminergic polymorphic ventricular tachycardia (CPVT). Standard exercise stress testing (EST), on the other hand, is insensitive, resulting in misdiagnosis and undertreatment. We report on six patients who had a unique burst exercise test, which was characterized by a sudden high workload at the start of testing, after a nondiagnostic conventional progressive EST. Compared to conventional EST, burst EST caused new and more complicated arrhythmias in 5 of 6 patients, necessitating medication treatment in 3 individuals. This minor EST adjustment might increase diagnostic sensitivity and treatment decision-making by better mimicking a common CPVT triggering event.

C. Michael Gibson, MD, CEO non-profit Baim / PERFUSE Research Institute, Harvard Professor, Cardiologist BIDMC, Founder & Chairman WikiDoc.org speaks about ACC 2021 Abstract - 1063-07 - Association Of Cholesterol Efflux Capacity With Adverse Cardiovascular Outcomes - A Meta Analysis


Link to Article:
https://www.abstractsonline.com/pp8/#!/9228/presentation/13693


Summary -

Background information:

The principal process by which macrophages remove cholesterol from atherosclerotic plaque is reverse cholesterol transport. A systematic literature review and meta-analysis were done to investigate the relationship between cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and poor cardiovascular (CV) events.

Methodologies:

A literature study was conducted to gather papers that looked at the link between CEC and CV outcomes. Adverse CV events, a composite of incident atherosclerotic CV disease (acute coronary syndrome, stroke/transient ischemic attack, revascularization, or new atherosclerotic plaque), or all-cause death, were the main outcomes.

The following are the outcomes:

Twenty investigations yielded a total of 25,132 individuals. High CEC levels were linked with a 37 percent decreased risk of the main outcome when compared to low CEC levels (RR=0.63; 95 percent CI, 0.52-0.76; P0.00001; Figure A). A 20 percent decreased risk of unfavorable CV events was related with every SD rise in CEC (HR=0.80; 95 percent CI, 0.66-0.97; P=0.02). After controlling for CV risk factors, medicines, and HDL concentration, the link remained significant (HR=0.76; 95 percent CI, 0.63-0.91; P=0.004). There was a 5% risk decrease in unfavorable CV events for every 0.1 unit rise in CEC (RR=0.95; 95 percent CI, 0.91-0.99; Figure B).

Final Thoughts:

Higher CEC is linked to less negative CV outcomes. These findings call for more research on CEC as a possible therapeutic target in order to enhance clinical outcomes.

C. Michael Gibson, MD, CEO non-profit Baim / PERFUSE Research Institute, Harvard Professor, Cardiologist BIDMC, Founder & Chairman WikiDoc.org speaks about ACC 2021 Abstract - Early And Late Recurrent Cardiovascular Risk In Patients With Recent Acute Coronary Syndrome - Meta-Analysis And Implications In Trial Design

Link to Article:
abstractsonline.com/pp8/#!/9228/presentation/22780

Summary -

Background information:

Despite receiving excellent medical treatment, people with an acute coronary syndrome have a significant residual atherosclerotic risk (ACS). The goal of this research was to calculate the risk of early and late major adverse cardiovascular events (MACE) and consider the implications for trial design.
Methodologies: To find phase III interventional studies on high-risk ACS patients, a thorough search was conducted. Meta-analytic techniques were used to estimate pooled incident rates at 90 and 360 days by fitting a random-effects model using the DerSimonian-Laird technique. The connection between power and relative risk reduction (RRR) or absolute risk reduction (ARR) for early vs. late MACE endpoints was investigated using the log-rank test (n=10,000; 1-sided=0.025).

The following are the outcomes:

A total of 82,727 high-risk individuals with recent ACS were examined from seven studies. After 90 days, the pooled rate of recurrent MACE was 4.1 percent (95 percent CI: 3.0 percent-5.7 percent), and at 360 days, the rate was 8.3 percent (95 percent CI: 7.1 percent -9.8 percent). Within the first 90 days, approximately 49% of incidents happened. For late MACE, a lower RRR (22 percent vs. 30 percent) is required to achieve 90 percent statistical power, but for early MACE, a lower ARR is required (1.2 percent vs. 1.8 percent ).

Final Thoughts:

The first 90 days after an ACS occurrence are most sensitive to recurrent MACE. Determining a clinically meaningful benefit by relative vs. absolute risk reduction may impact the choice of early vs. late MACE as the research endpoint from a trial design standpoint.

Ian A. White, MS, Ph.D., Founder, President & Chief Scientific Officer at Neobiosis speaks about the Breakthrough Paper Outlines Path to Heart Regeneration After Cardiac Injury.

Link to Article:
https://www.pubstemcell.com/epub/016010300010EPA121120.htm?fbclid=IwAR3HybxbXXEBRK4FXsfcUc-MBImTiSc1USuIg-J_8f0JLuwKL3O_oWa1qf4

Cardiovascular disorder claims the lives of over 650,000 Americans per year. (1) Those who survive a myocardial infarction are still at risk of dying because the human heart's capacity to heal itself is limited. No one has yet discovered a mechanism for regenerating a weakened human heart's cardiovascular system. But it could all improve due to a groundbreaking medical paper written by Dr. Ian White, President and Chief Scientific Officer of Neobiosis, a regenerative medicine corporation.

A mouse heart, like the hearts of other mammals, has a very brief time (1-7 days) after birth where it maintains its primordial regenerative powers. White's latest approach, however, maintains a neonatal mouse heart alive and beating in a stable environment for up to a month, extending the regenerative cycle. This gives scientists more time to figure out how various treatments or medications can help the weakened organ heal or rebuild.

The epicardium, a single layer of cells that protects the nucleus, is involved in neonatal cardiac recovery, according to White's article. In response to injury, the cells proliferate before successfully migrating to the damaged area.

The discovery has far-reaching health consequences, especially for those who have suffered heart damage as a result of COVID-19 exposure.

White is happy to share his creations with the rest of the world. He also urged colleagues to conduct their own studies using the same neonatal heart preservation process. Neobiosis is a pioneer in the field of regenerative science, as shown by the dissemination of this research.

Regenerative medicine, according to White and his colleagues at the University of Florida's Sid Martin Innovate Biotechnology Institute, carries the promise of long-term survival and wellbeing. Many concerned with the new laboratory are optimistic that their findings and affiliation with the University of Florida would lead to new health therapies, and they also urge the FDA to reconsider its position on this groundbreaking area of science.


Regenerative Therapy's Advantages

Regenerative medicine has the ability to revolutionize healthcare and combat illness. The medications focus on assisting the body in healing, regenerating, and rebuilding itself. These are some of the advantages:

* Using biochemical guidance and raw biomaterials to stimulate the body's own repair processes to functionally restore previously irreparable tissues and organs.

* Reducing inflammation to help with healing and tissue repair.

* Use alternative methods to treat trauma and illness without the use of surgery or opioids.

Rohan Khera, MD, MS, Assistant Professor at Yale School of Medicine speaks about A phenomapping-derived tool to personalize the selection of anatomical vs. functional testing in evaluating chest pain (ASSIST).

Link to Lab's ASSIST:
https://www.cards-lab.org/assist

Link to Article:
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab223/6242724?utm_medium=Email&utm_source=My%20ESC%20News&utm_campaign=ESC+-+Newsletter+-+week+17+-+2021

Summary

Objectives

Coronary artery disease is often identified after anatomical or clinical examination is used to evaluate persistent chest pain. Personalized testing could be possible with a more detailed knowledge of patient phenotypes that benefit from either approach.


Methods and outcomes

We generated a topological representation of the sample population based on 57 pre-randomization variables using participant-level results from 9572 patients undergoing anatomical (n = 4734) vs. functional (n = 4838) research in the PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) trial. Cox regression models presented individual patient-centered hazard ratios for significant adverse cardiovascular outcomes within each patient's 5% topological neighbourhood and showed marked heterogeneity around the phenomap [median 1.11 (10th to 90th percentile: 0.52–2.61]], suggesting distinct phenotypic neighbourhoods favoring anatomical or functional research. We used an intense gradient boosting algorithm in 80% of the PROMISE population to estimate the personalized value of anatomical vs. functional tests using 12 model-derived, regularly collected variables and generated a decision support method called ASSIST based on this vulnerability phenomap (Anatomical vs. Stress teSting decIsion Support Tool). The testing strategy recommended by ASSIST was associated with a significantly lower incidence of each study's primary endpoint in both the remaining 20% of PROMISE and an external validation set consisting of patients from SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) undergoing anatomical-first vs. functional-first assessment (P = 0.0024 and P = 0.0321 for interaction, respectively) in both the remaining 20% of PROMISE and an external validation set consist

Final thoughts

We suggest a new phenomapping-based decision support method to standardize the use of structural vs. functional research in the treatment of controlled chest pain, which has been tested in two broad and geographically disparate clinical trial populations.

Dino Mehic, MD from the Medical University of Vienna speaks about Elevated levels of tissue factor pathway inhibitor in patients with mild to moderate bleeding tendency.

Link to Abstract:
https://ashpublications.org/bloodadvances/article/5/2/391/474924/Elevated-levels-of-tissue-factor-pathway-inhibitor

Points to Remember -

* TFPI levels are higher in patients with minor bleeding disorders, especially those that have BUC or PFDs.

* There were no genetic changes in the F5 gene that were related to increased TFPI levels.

Synopsis:

High levels of tissue factor pathway inhibitor (TFPI) were recently discovered in two families with an unknown bleeding propensity, due to a longer TFPI half-life after binding to a factor V splice variant and variations in the F5 gene. The aim of this research was to look at the relationship between free TFPI and genetic alterations in the F5 gene in a well-characterized population of 620 patients with mild to moderate bleeding tendencies. Patients with leakage have higher TFPI values than stable controls (median [interquartile range], 8.2 [5.5-11.7] vs 7.8 [4.3-11.1]; P =.026). In comparison to stable samples, a higher percentage of patients had free TFPI ratios greater than or equal to the 95th percentile (odds ratio [OR] [95 percent confidence interval (CI)], 2.82 [0.98-8.13]). This was particularly noticeable in patients with no documented bleeding condition (bleeding of uncertain origin [BUC; n = 420]; OR [95 percent CI], 3.03 [1.02-8.98]) and platelet function defects (PFDs) (n = 121; OR [95 percent CI], 3.47 [1.09-11.08]). A rise in free TFPI was linked to a slight thrombin generation delay (longer lag time and time to peak), but not to changes in commonly used global clotting tests. In our patient cohort, we were unable to find any new or established genetic variants in the F5 gene that are linked to free TFPI levels, nor any effect of the single-nucleotide variant rs10800453 on free TFPI levels. Unexpected bleeding, which is more often multifactorial in the majority of patients, maybe caused or contributed by an excess of natural coagulation inhibitors such as TFPI.

Learn more about the American College of Cardiology and what it's like to work there. #LifeAtACC

Dr. Kim Eagle provides a weekly tip for clinicians on the front lines of the COVID-19 pandemic. This week's tip provides an interim update on the Oxford COVID (ChAdOx1 nCoV-19) vaccine (https://www.acc.org/latest-in-cardiol...).

The ACC's Sandra J. Lewis Cardiovascular Women's Leadership Institute will support the unique needs of mid-career women as they continue to sustain and grow their leadership skills. Part of the ACC's Campaign for the Future, the Institute will further the College's Strategic Goals to foster a diverse pipeline of leaders within the profession and the ACC itself. "For many women, 15 to 20 years into their career, changes in responsibilities serve as an opportunity to reassess, reimagine and reinvent their professional lives," says Sandra J. Lewis, MD, FACC, whose transformational gift to the Campaign for the Future is making the Institute possible. "While this stage may serve as a professional renaissance for many, it is also a stage with opportunities for unique guidance and targeted leadership development to successfully transition forward 'to the next'.” Read more: http://bit.ly/2KefKk1 #ACCFuture #ACCWIC

Watch a COVID-19: Protecting Patients at Greatest Risk mini-course for NCD Academy on “Building Back Better to Put People First in the NCD Response: Views From Africa and the Middle East.” Learn more about the NCD Academy by visiting ACC.org/NCDAcademy.

Watch a COVID-19: Protecting Patients at Greatest Risk mini-course for NCD Academy on “Building Back Better to Put People First in the NCD Response.” Learn more about the NCD Academy by visiting ACC.org/NCDAcademy.

Watch a COVID-19: Protecting Patients at Greatest Risk mini-course for NCD Academy on “Building Back Better to Put People First in the NCD Response: Views From Asia.” Learn more about the NCD Academy by visiting ACC.org/NCDAcademy.

We discuss several of the important data coming out the American Heart Association 2020 meeting.

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We have a multispecialty panel discussion on the cardiorenal benefits of newer antidiabetic agents with Drs Rangaswami, Vaduganathan, Tuttle and Bhalla.

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We have a multispecialty panel discussion on the cardiorenal benefits of newer antidiabetic agents with Drs Rangaswami, Vaduganathan, Tuttle and Bhalla.
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We discuss several of the important data coming out the European Society of Cardiology 2020 meeting.

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We discuss cardiogenic shock and decision making in the case of a young female presenting to the ER. We have a panel of cardiologists guide the discussion. Drs Rene Alvarez, Daniel Sims and Alec Vishnevski discuss the case presented by cardiology fellow Rachna Kataria, MD.
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We discuss the various aspects of cardiogenic shock including definition, heterogeneity, classification and management with an internationally renowned expert in the field Dr Navin Kapur. Dr Kapur is the Director of the Acute Mechanical Circulatory Support Program at Tufts University School of Medicine, Boston, MA.

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Paul W. Armstrong, MD from the Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada and the Merck speaks about the ACC 2021 Abstract - Coronary Artery Disease and Cardiovascular Outcomes in Heart Failure: Insights from the VerICiguaT Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA).

Link to Study:
https://www.acc.org/latest-in-cardiology/clinical-trials/2020/03/26/19/43/victoria#references-for-article

Detailed description:

The trial's purpose was to compare vericiguat to placebo in individuals with chronic heart failure (CHF) caused by a low ejection fraction (EF). Vericiguat boosts the activity of soluble guanylate cyclase. This may assist to enhance cardiac and vascular function by increasing the generation of cyclic guanosine monophosphate.

Design of the Research

* This is a randomized sample.

* Double-blind study

* Concurrent

Vericiguat (n = 2,526) versus placebo (n = 2,524) were given to CHF patients. Vericiguat was begun at 2.5 mg per day, then raised to 5 mg, then 10 mg per day.


* The total number of students enrolled is 5,050.

* Follow-up period: 12 months

* The average patient is 68 years old.

* Females account for 24% of the total.



Criteria for inclusion:

* CHF; New York Heart Association class II-IV, left ventricular EF 45%, and heart failure treatment based on guidelines.

* A recent hospitalization for heart failure or the administration of an intravenous diuretic

* Natriuretic peptides elevated; N-terminal pro–B-type natriuretic peptide (NT-proBNP) 1000 pg/ml (1600 pg/ml if atrial fibrillation) or BNP 300 pg/ml (500 pg/ml if atrial fibrillation).

* Clinically stable (systolic blood pressure 100 mm Hg for 24 hours and no IV diuretics)



Criteria for exclusion:

* Nitrates with a lengthy half-life, phosphodiesterase type 5 inhibitors, and riociguat

* Awaiting a heart transplant, using continuous intravenous diuretics, or using a ventricular assist device now or in the future.

* Dialysis or chronic renal disease (evaluated glomerular filtration rate of 15 ml/min/1.73 m2)

* Severe pulmonary illness that necessitates the use of oxygen on a continual basis

* Hepatic insufficiency (severe)

* Cardiovascular comorbidities that can be treated

Other noteworthy features/characteristics include:

* The average EF is 29%.

* In 89 percent of cases, the target dosage of vericiguat was met.

The Most Important Findings:

Cardiovascular mortality or heart failure hospitalization occurred in 35.5 percent of the vericiguat group compared to 38.5 percent of the placebo group (hazard ratio [HR] 0.90, p = 0.019). The major outcome risk for vericiguat vs. placebo was 0.84% for those aged 75 years and 1.04% for those aged 75 years (p for interaction = 0.030).

Secondary effects include:

* Cardiovascular death: 16.4% in the vericiguat group vs. 17.5 percent in the placebo group (p = 0.27)

* Death from any cause: 20.3 percent in the vericiguat group vs. 21.2 percent in the placebo group (p = 0.38)

* Hospitalization for heart failure: 27.4 percent of the vericiguat group vs. 29.6 percent of the placebo group (p = 0.048).

* Serious adverse event: 32.8 percent of the vericiguat group versus 34.8 percent of the placebo group had a serious adverse event.

Contextualization:

A new technique of boosting soluble guanylate cyclase activity with vericiguat proved successful in individuals with CHF who had recently decompensated. Vericiguat was shown to be more efficacious than placebo in lowering cardiovascular mortality and hospitalization for heart failure. There was a possibility of a greater advantage for those above the age of 75. Vericiguat did not appear to reduce all-cause mortality when compared to placebo. Vericiguat was well tolerated and did not need renal function or electrolyte monitoring. Vericiguat might be a potential therapy option for individuals who have recently had heart failure decompensation.

Naveen L. Pereira, MD, Consultant for the Department of Cardiovascular Diseases and Professor of Medicine and Associate Professor of Pharmacology, Mayo Clinic College of Medicine speaks about ACC 2021 - Late-Breaking Clinic Science - Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy: A Meta-Analysis.

Link to Abstract:
https://www.jacc.org/doi/full/10.1016/j.jcin.2021.01.024

 Summary

The aim of this research was to compare the effects of ticagrelor or prasugrel versus clopidogrel treatment on clinical results in patients with coronary artery disease (CAD) who were primarily treated with percutaneous coronary intervention (PCI).

Background: The impact of CYP2C19 genotype on ticagrelor or prasugrel patient results relative to clopidogrel is unknown.

Methods: Experiments comparing the effects of CYP2C19 genotype on ischemic results during ticagrelor or prasugrel versus clopidogrel therapy were scanned through February 19, 2020. Results for CYP2C19 genotype status, clopidogrel, and alternative P2Y12 inhibitors in patients with CAD with at least 50% undergoing PCI are expected for study eligibility. The main focus of the study was on randomized controlled trials (RCTs). Non-RCTs are added to the main analysis as a supplementary analysis. Cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, and extreme chronic ischemia were the main outcomes. To analyze the two-drug regimens and assess the relationship with the CYP2C19 genotype, a meta-analysis was performed.

Seven RCTs were found among the 1,335 studies found (15,949 patients, mean age 62 years; 77 percent had PCI, 98 percent had acute coronary syndromes). The probability of prejudice was poor, and statistical variability was small. When ticagrelor and prasugrel were linked to clopidogrel, there was a substantial decrease in ischemic incidents (relative risk: 0.70; 95 percent confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 0.70; 95 percent confidence interval: 0.59 to 0.83). (relative risk: 1.0; 95 percent confidence interval: 0.80 to 1.25). The association test on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), implying that the genotype of CYP2C19 altered the effect. Four further observational experiments were discovered, and when they were used in the study, the results were the same (p-value of the interaction test 0.001).

Conclusions: The role of ticagrelor or prasugrel in minimizing ischemic events in patients with CAD who specifically experience PCI is dependent on the existence of CYP2C19 loss-of-function carrier status when opposed to clopidogrel. These findings back up genetic tests before administering P2Y12 inhibitors.

Giuseppina Caligiuri, MD, Ph.D. from the Laboratory for Vascular Translational Science, Université de Pari speaks about Coronary Stent CD31-mimetic Coating Favours Endothelialization And Reduces Local Inflammation And Neointimal Development In Vivo.

Link to Article:
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab027/6134553

Synopsis:

The rapid endothelialization of bare-metal stents (BMS) is counterbalanced by neointimal growth caused by inflammation. Drug-eluting stents (DES) inhibit endothelialization thereby preventing leukocyte activation, slowing successful system penetration into arterial walls. We previously demonstrated that the vascular CD31 co-receptor is necessary for endothelial and leukocyte homeostasis as well as arterial healing. Furthermore, we have demonstrated that P8RI, a soluble synthetic peptide, acts as a CD31 agonist. The aim of this study was to see how a CD31-mimetic metal stent coating affected endothelial cell (EC) and blood element adherence in vitro, as well as strut coverage and neointimal growth in vivo.

Methods and Actual outcomes: We used two methods to coat Cobalt-Chromium discs and stents with a CD31-mimetic peptide: plasma amination and dip-coating, both of which achieved comparable results. In vitro, CD31-mimetic discs significantly decreased EC and blood platelet/leukocyte activation in primary human coronary arteries. At 7 and 28 days after implantation in pig coronary arteries, CD31-mimetic stent properties were compared to those of DES and BMS using coronarography and microscopy (n = 9 stents/group/time point). Only CD31-mimetic struts were completely endothelialized seven days after implantation, with no activated platelets or leukocytes. On day 28, neointima formation was substantially reduced over CD31-mimetic stents compared to BMS, appearing as a normal arterial media with no thrombosis, in contrast to DES.

Response: The CD31-mimetic coating promotes vascular homeostasis and arterial wall healing, avoiding stenosis and thrombosis within the stent. As a result, such coatings seem to increase the biocompatibility of metal stents.

Summary

We looked at the associations between plant-based diet quality and the risk of complete, ischemic, and hemorrhagic stroke to see whether a healthy plant-based diet is linked to a lower risk of stroke.

The study included 73,890 women in the Nurses' Health Study (NHS; 1984 to 2016), 92,352 women in NHSII (1991 to 2017), and 43,266 men in the Health Professionals Follow-Up Study (1986 to 2012) who were free of cardiovascular disease and cancer at the start. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI were used to assess the consistency of plant-based diets (uPDI). Participants who recorded none or less than one serving of meat or fish per month were classified as vegetarians, while those who reported more than one serving per month were classified as non-vegetarians. Ischemic and hemorrhagic strokes were classified based on medical records.

Results: A total of 6,241 stroke cases were reported during the follow-up period (including 3,015 ischemic and 853 hemorrhagic strokes). The hazard ratios (HRs) for total stroke among participants with the highest PDIs were 0.94 (95 percent confidence interval 0.86 to 1.03) for PDI, 0.90 (0.83 to 0.98) for hPDI, and 1.05 (0.96 to 1.15) for uPDI, compared to participants with the lowest PDIs. Participants with the highest hPDI had a slightly lower HR for ischemic stroke (0.92 [0.82 to 1.04]) but no stable relationships for hemorrhagic stroke. Despite the limited number of cases, we found no connection between a vegetarian diet and total stroke (1.00 [0.76 to 1.32]).

Conclusions: Those who followed a healthy plant-based diet had a lower risk of total stroke.

JACC: Case Reports Editor-in-Chief Dr. Julia Grapsa is joined by Deputy Editor Dr. Eric Bates, Associate Editors Drs. David Fischman and Mladen Vidovich, and a panel of other experts including Drs. George Dangas, Ajay Kirtane, and Poonam Velagapudi. The panel discusses a selection of newly published cases from the January 2021 issue that focus on interesting procedural complications. Please visit https://www.jacc.org/ and https://www.acc.org/ for more information.

JACC: Case Reports Editor-in-Chief Dr. Julia Grapsa is joined by Associate Editor Dr. Maurizio Taramasso, co-host Dr. Ana Paula Tagliari, and other experts Drs. Francesco Maisano, Bernard Prendergast, Tiffany Patterson, Simon Redwood. The panel discusses a selection of newly published cases from the January 2021 issue and focus on cases that present interesting structural complications. Please visit https://www.jacc.org/ and https://www.acc.org/ for more information. 

JACC: Case Reports Editor-in-Chief Dr. Julia Grapsa is joined by Editorial Consultant Yevgeniy “Eugene” Brailovsky; authors Drs. Mohammad Sarraf, Daniel Burkhoff, and Michael I. Brener; as well as Prof. Nicolas van Mieghem from Erasmus University to discuss a case reporting the first-in-man description of pressure–volume analysis in all four cardiac chambers before and after transcatheter aortic valve replacement. Pressure–volume analysis demonstrated that the hemodynamic consequences of valve replacement are chamber-specific and influenced by all aspects of the procedure (i.e., rapid ventricular pacing), not just valve deployment. #JACCCardioOnc Please visit https://www.jacc.org/ and https://www.acc.org/

Journal Editor-in-Chief Bonnie Ky, MD, MSCE, FACC, moderates a video case presentation on Early Immune Checkpoint Inhibitor Cardiotoxicity presented by Han Zhu, MD, with associate editor discussants Dan Lenihan, MD, FACC; Ana Barac, MD, PhD, FACC; Ronald Witteles, MD, FACC; and Anne Blaes, MD. The experts discuss two newly published manuscripts related to the topic, “The Evolving Immunotherapy Landscape and the Epidemiology, Diagnosis, and Management of Cardiotoxicity,” by Lili Zhang, MD, ScM and Tomas G. Neilan, MD, MPH et al., and the French Working Group’s Viewpoint on “Management of Immune Checkpoint Inhibitor-Induced Myocarditis: Plea for a Pragmatic Approach,” led by Franck Thuny, MD, PhD, et al. Please visit https://www.jacc.org/ and https://www.acc.org/ for more information

Javid Moslehi, MD and Justin M. Balko, Pharm.D., Ph.D. from Vanderbilt-Ingram Cancer Center discuss A genetic mouse model recapitulates immune checkpoint inhibitor-associated myocarditis and supports a mechanism-based therapeutic intervention.


Instract
Cancer therapy has been transformed by immune control point inhibitors (ICI) targeting CTLA-4 or PD-1/PD-L1 but is associated with immune-related adverse effects (irAEs), including myocarditis. A robust preclinical mouse model of ICI-associated myocarditis is reported here, in which mono-allelic loss of Ctla4 in the sense of complete genetic absence of Pdcd1 leads to premature death in about half of the mice. Premature death results from T cell and macrophage myocardial invasion and significant electrocardiographic defects, closely recapitulating the clinical and pathological characteristics of ICI-associated myocarditis found in patients. Using this model, we demonstrate that in a gene dosage-dependent way, Ctla4 and Pdcd1 interact functionally, providing a mechanism by which myocarditis occurs in the setting of combination ICI therapy with increased frequency. We show that CTLA-4-Ig (abatacept) intervention is appropriate to boost the progression of the disease and also include a case series of patients in whom abatacept mitigates the fulminant course of ICI-myocarditis.

Maurice Sarano, MD of the Minneapolis Heart Institute speaks about STS 2021 Discussion - STS/CSCS: Tricuspid Valve Surgery Associated with Left Sided Cardiac Disease: When, What, and How?

Link to Abstract -
https://www.eventscribe.net/2021/STS/fsPopup.asp?efp=SEJKWElTSFExMjA3NA&PresentationID=815982&rnd=0.2613683&mode=sessionInfo


Diagnosis and treatment of tricuspid regurgitation associated with left-sided heart disease are difficult. A multidisciplinary group of experts will discuss the natural history of tricuspid regurgitation, diagnosis, and surgical and transcatheter management in this session.

Learning Goals:

Explain the natural history of left-side cardiac disease-related tricuspid regurgitation and its prognostic implications

Recognize tricuspid valve care timing and indications

Describe tricuspid regurgitation surgical and transcatheter therapies