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

Jeffrey J. Goldberger, MD, MBA from the University of Miami speaks about the Comparison of Metoprolol versus Carvedilol After Acute Myocardial Infarction.

Link to Article -
https://www.ajconline.org/article/S0002-9149(21)00155-7/fulltext#%20

• Beta-blockers are commonly administered after a heart attack, but no one brand has been recommended.

• In this analysis, metoprolol and carvedilol are compared in a post-MI cohort.

• Carvedilol and metoprolol had comparable overall survival rates in the sample.

• In the ejection fraction 40 percent subgroup, carvedilol outperformed metoprolol in terms of survival.

Summary

Following a myocardial infarction (MI), beta-blockers are commonly prescribed, although no particular beta-blocker is recommended. 4142 patients were discharged on metoprolol and 1487 on carvedilol from the OBTAIN multi-center list of patients with acute MI. The beta-blocker dose was calculated as a percentage of the target daily dose used in randomized clinical trials (metoprolol 200 mg; carvedilol 50 mg). >0 percent -12.5 percent (n=1428), >12.5 percent -25 percent (n=2113), >25 percent -50 percent (n=1392), and >50 percent (n=696) were the beta-blocker dose classes. Three-year survival was calculated using the Kaplan-Meier equation. A multivariable adjustment was used to correct for baseline variations. Carvedilol patients were older (64.4 vs. 63.3 years) and had more comorbidities, including hypertension, diabetes, previous MI, congestive heart failure, lower left ventricular ejection fraction, and a longer period of stay. The mean doses of metoprolol and carvedilol did not vary substantially (37.227.8% and 35.831.0%, respectively). The 3-year survival figures for metoprolol and carvedilol were 88.2% and 83.5 percent, respectively, with an unadjusted HR=0.72 (p0.0001), but HR=1.073 (p=0.43) after multivariable adjustment. In comparison to other dose ranges, patients in the >12.5-25 percent dose range had better survival. In a subgroup of patients with a left ventricular ejection fraction of less than 40%, metoprolol was found to have a worse survival rate than carvedilol (adjusted HR=1.281; 95 percent CI: 1.024-1.602, p=0.03). There were no variations in survival between carvedilol and metoprolol in patients with a left ventricular ejection fraction greater than 40%. Overall survival after acute MI was comparable in patients treated with metoprolol or carvedilol, but carvedilol could be superior in patients with a left ventricular ejection fraction of less than 40%.

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.

Prof. Dr. John J.P. Kastelein of the Department of Vascular Medicine, Amsterdam UMC, and the University of Amsterdam speaks about New and Emerging Therapies for Reduction of LDL-Cholesterol and Apolipoprotein B: JACC Focus Seminar 1/4.

Link to Article:
https://www.jacc.org/doi/10.1016/j.jacc.2020.11.079?utm_medium=social&utm_source=twitter_post&utm_campaign=twitter_post

Summary -

Novel, emerging low-density lipoprotein cholesterol (LDL-C)–lowering therapies are under development for the prevention of cardiovascular disease, adding to the base of statins, ezetimibe, and proprotein convertase subtilisin–kexin type 9 inhibitors (PCSK9i). Inclisiran, a PCSK9-inhibiting small interfering RNA molecule that only needs to be dosed twice a year, has the ability to help address existing obstacles to lipid-lowering therapy persistence and adherence. Patients with statin intolerance can benefit from bempedoic acid, which lowers LDL-C upstream from statins. In patients with homozygous familial hypercholesterolemia, angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering without the significant side effects seen with lomitapide and mipomersen, and may minimize the need for apheresis. Finally, with the production of obicetrapib, CETP inhibitors may still be effective. From primary prevention and secondary prevention to null-null homozygous hereditary hypercholesterolemia patients, these novel agents provide clinicians the resources they need to effectively lower LDL-C across the entire spectrum of LDL-C–induced elevations of cardiovascular danger.

Aspects to Consider

• Despite existing methods, atherosclerotic cardiovascular disease continues to be a major problem.

• Low-density lipoprotein cholesterol (LDL-C) is a significant cause of atherosclerotic cardiovascular disease.

• The most commonly used pharmacological agents for reducing LDL-C are statins, ezetimibe, and PCSK9 inhibitor monoclonal antibodies.

• Inclisiran, bempedoic acid, ANGPTL3, and CETP inhibitors, all of which are still in production, have the potential to reduce residual LDL-C risk.

Rozh H. Al-Mashhadi, MD from the Aarhus University Hospital discusses Local Pressure Drives Low-Density Lipoprotein Accumulation and Coronary Atherosclerosis in Hypertensive Minipigs.


Link to Research -
https://www.jacc.org/doi/10.1016/j.jacc.2020.11.059?utm_medium=social&utm_source=twitter_post&utm_campaign=twitter_post

Instract

Context
There is a limited understanding of the mechanisms by which hypertension accelerates coronary artery disease. There are sometimes confusing humoral changes in patients with hypertension, and to date, no experimental models have allowed the isolated effect of pressure on atherosclerosis to be studied in a setting that recapitulates the dimensions and biomechanics of human coronary arteries.

Targets
This thesis aimed to examine and explore the fundamental mechanisms of the impact of pressure on coronary atherosclerosis.

Methodology
Using inflatable suprarenal aortic cuffs, in the cephalad body portion of wild-type and hypercholesterolemic proprotein convertase subtilisin kexin type 9 (PCSK9)D374Y Yucatan minipigs, we increased mean arterial pressure by >30 mm Hg for >1 year. Pressures at the caudal remained natural.

Outcomes
Cephalad hypertension accelerated coronary atherosclerosis to nearly 5-fold under hypercholesterolemic conditions in transgenic PCSK9D374Y mini pigs, with the consistent development of fibroatheromas that were sufficiently large to induce computed tomography angiography stenosis. This was caused by local pressure forces since there were no changes in lesion formation in vascular beds shielded from hypertension but subjected to the same humoral influences. The same experiment was performed to investigate the underlying mechanisms under normocholesterolemic conditions in wild-type mini-pigs. Hypertension with increased abundance of mechanical strength proteins and decreased levels of infiltrating plasma macromolecules induced clear changes in the arterial proteome. Increased smooth muscle cells and increased intimate accumulation of low-density lipoproteins in the coronary arteries were parallel to this.

Findings
Coronary atherosclerosis is facilitated by elevated pressure per se. Our data show that redesign of the artery to balance higher tensile forces in hypertension changes the movement of macromolecules and contributes to the increased intimate accumulation of lipoproteins of low density.

Eric Y. Ding, Ms from the Division of Cardiology, Department of Medicine, University of Massachusetts Medical School speaks about the Survey of current perspectives on consumer-available digital health devices for detecting atrial fibrillation.

Link to Article:
https://www.sciencedirect.com/science/article/pii/S2666693620300049#!

Background
Patients have direct access to a variety of digital health services that can detect atrial fibrillation (AF). Heart rhythm healthcare practitioners' (HCPs) adaptation into clinical practice, on the other hand, is uncertain.


Goal
The aim of this study was to look into the perspectives of HCPs on the use of commercial technologies for AF detection and management.



Methodologies
We developed an electronic survey for HCPs to determine practice demographics and attitudes toward digital devices for AF identification and management. The survey was sent to all members of three heart rhythm professional societies via email.



Conclusions
Out of 73,563 e-mails sent, we got 1601 responses, with 43.6 percent coming from cardiologists, 12.8 percent from fellows, and 11.6 percent from advanced practice practitioners. The majority of respondents (62.3 percent) said they had advised patients to use a digital system for AF detection. Many that didn't were worried about their accuracy (29.6%), the clinical usefulness of the findings (22.8%), and incorporation into electronic health records (22.8%). (19.8 percent ). For patients at high risk of stroke, the findings of a 30-second single-lead electrocardiogram were enough for 42.7 percent of HCPs to prescribe oral anticoagulation. More data comparing the accuracy of digital devices versus traditional devices for AF monitoring was requested by respondents (64.9 percent ). A quarter of HCPs (27.3%) had no concerns about recommending digital devices for AF detection, and the majority (53.4%) required guidelines from their professional societies about how to use them properly.



Final Thoughts
Many healthcare professionals have already begun to incorporate digital technologies into their clinical practice. However, when using digital technology for AF detection, HCPs identified difficulties, and professional society guidelines are required.

Mehmet Asim Bilen, MD from Winship Cancer Institute of Emory University discusses the Evaluation of a novel blood pressure scoring method and its association with clinical response in cancer patients treated with anti-vascular endothelial growth factor therapy.

Link to Study -
https://pubmed.ncbi.nlm.nih.gov/24764123/

Instract

Background: In advanced cancer patients treated with anti-vascular endothelial growth factor (VEGF) therapies, the aim of this study was to develop a novel blood pressure (BP) scoring method and correlate it with clinical response.


Methods: We retrospectively evaluated data from 23 clinical trials involving at least one anti-VEGF agent for 368 patients. Using the standard Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and our latest system, BP scores were measured using both BP readings and the amount of anti-hypertensive drugs obtained by the patient. BP ratings at baseline and four months have been classified. Elevated scores were correlated with the clinical response through logistic regression analysis. An agreement was assessed between the CTCAE and the new system.



Results: Under the latest BP scoring system, partial response rates were 20 percent for four-month elevated patients versus 6 percent for non-elevated patients (P < 0.001). When adjusted for tumor type, age, sex, history of anti-VEGF treatment, and the number of anti-VEGF treatments, the odds ratio was 3.8 (95% confidence interval [CI]: 1.8, 8.2; P < 0.001) for elevated BP under the new scoring system. The kappa statistics were 0.57 (95 percent CI: 0.47, 0.67; P < 0.001) for agreement between the CTCAE and current scoring methods, suggesting substantial concordance.



Conclusion: The rise in BP scores was a proxy for favorable clinical response in patients receiving anti-VEGF therapy using the novel scoring system. Ultimately, this new approach offers details about the clinical tumor response over and above that given by the scoring method of CTCAE.

Milind Desai, MD, MBA of the Cleveland Clinic, speaks about Current Concepts in Diagnosis and Management of Hypertrophic Cardiomyopathy.


Link to what Hypertrophic Cardiomyopathy is -
https://www.ccjm.org/content/85/5/399/tab-figures-data


Link to Milind Desai, MD's Bio -
https://my.clevelandclinic.org/staff/6670-milind-desai#research-publications

Professor Murray Esler from the Baker Heart & Diabetes Institute discusses the Editorial - Reflections on the past four decades of mental stress research in autonomic cardiology.

Link to Full Article -
https://link.springer.com/article/10.1007/s10286-020-00761-7

This commentary, with some observations and a description of my experience in the field of mental stress science, is my contribution to the celebration of the thirtieth anniversary of Clinical Autonomic Research, a journal that has become the benchmark publication for all those interested in the autonomic nervous system in recent years, regardless of their primary medical specialty, which in my case is the automobile.

In 1977, I returned to the Baker Medical Research Institute and the Alfred Hospital in Melbourne, Australia, after 4 years of postgraduate research and clinical training with Prof. Stevo Julius in the Hypertension Division of the University of Michigan Medical Center, where I worked as a clinical cardiologist and founded a laboratory for cardiovascular neuroscience.



I recall being struck by how the involvement of patients with myocardial infarction or ventricular arrhythmias was often precipitated by emotional turmoil in my early clinical practice in Melbourne. "I saw patients in whom armed robbery, robberies, and even an owner's racehorse winning by a "nose" had induced a heart attack. I was delighted to accept, in 1985, an invitation to participate in what I expected would be an influential national panel to discuss the relationship between mental stress and heart disease with this clinical exposure. However, I was not ready for the meeting chair's opening remark (whose name I will not say): "There is no proof that stress causes heart disease, nor will there ever be." I was saddened, but not discouraged, as this could not be true, of course. Where was his crystal ball? Even if the comment captured the pessimism that was prevalent in that era's cardiology.



Faced with this setback, by researching cardiac sympathetic responses to mental stress, I applied my newly developed noradrenaline spillover methodology[4] to the stress-heart issue, tapping into research possibilities that are open to a cardiologist. I performed this study in a cardiac catheterization facility, using a tritiated noradrenaline infusion to measure the isotope dilution release of this catecholamine from sympathetic nerves, with sampling from the heart's coronary sinus. This was to make these measurements of noradrenaline release unique to the cardiac sympathetic nerves, all achieved during the study participants' exposure to laboratory mental stress (Fig. 1a)[4]. The applied stressor, as accepted by my institutional ethics committee, was 10 minutes of challenging mental arithmetic, only to surpass the arithmetic competence of the volunteer, and paced by a metronome. For the mathematically talented, an additional tweak was made by informing the individual that they were incorrect... when they were actually correct! In a standard experiment, we measured the secretion of adrenaline by the adrenal medulla, the release of noradrenaline from the sympathetic nerves and sympathetic nerves of the whole body, the concentrations of noradrenaline and adrenaline plasma sampled from the antecubital vein, and the firing of sympathetic outflow using microneurography in the innervation of the vasculature of the skeletal muscle in the leg.

Robert D. Schaller, DO, MS, FHRS from Perelman School of Medicine at the University of Pennsylvania speaks about Magnetic Resonance Imaging in Patients With Cardiac Implantable Electronic Devices With Abandoned Leads.


Link to Article:
https://jamanetwork.com/journals/jamacardiology/article-abstract/2776350?guestAccessKey=885c40e4-d529-4ca0-ac32-eea0224bf10d&utm_source=twitter&utm_medium=social_jamacard&utm_term=4499311282&utm_campaign=article_alert&linkId=111556719


Question about the main points Is it safe to use magnetic resonance imaging (MRI) on patients who have had their cardiac implantable electronic system (CIED) leads removed?


Conclusions 
There were no significant adverse effects recorded in this cohort study of 139 patients who had 200 MRIs of different anatomic regions, including the thorax. Transient decreases in lead sensing in 5 patients and subjective sternal heating in 1 patient with an abandoned subcutaneous array and sternal wires were among the CIED parameter changes.



In other words, The results of this analysis indicate that, regardless of the anatomic area being examined, the existence of abandoned CIED leads does not rule out MRI.



Summary

The meaning of for certain cases, magnetic resonance imaging (MRI) is the preferred method of diagnosis. Patients with legacy cardiac implantable electronic devices (CIEDs) now have more access to MRI thanks to conditional devices and innovative imaging protocols. The presence of abandoned leads, on the other hand, is an utter no-no.



The goal to see if performing an MRI in the presence of an abandoned CIED lead is safe and if there are any negative effects on active CIED leads nearby.



Participants, Design, and Setting Between January 2013 and June 2020, this cohort study included consecutive CIED recipients who underwent 1.5-T MRI with at least one abandoned lead. At the University of Pennsylvania Hospital, MRI scans were done. No patients were turned away.



Expositions 
CIEDs were reprogrammed to satisfy the pacing needs of individual patients. Electrocardiography telemetry and pulse oximetry were constantly tracked, and if possible, live visual and voice communication with the patient was maintained during the scan. The CIED assessment was replicated after the MRI, and the programming was reset to baseline or a clinically acceptable environment.



Measures and Key Outcomes 
Variations of 50% or more in pre-and post-MRI capture thresholds, ventricular sensing of 40% or more, and lead impedance of 30% or more, as well as clinical sequelae including pain and sustained tachyarrhythmia, were considered important. If data on long-term follow-up leads was available, it was analyzed.



Conclusions 
A total of 139 patients (110 men [79 percent]) with an average (SD) age of 65.6 (13.4) years had 200 MRIs of different anatomic regions, including the thorax, performed. Repeat examinations were normal, with one patient receiving up to 16 examinations. There were 243 discarded leads in total, with an average (SD) of 1.22 (0.45) per patient. The average (SD) number of active leads was 2.04 (0.78), with 64 patients (46%) requiring a pacemaker. In 41 patients (20.5%) who underwent MRI of the brain, a transmit-receive radiofrequency coil was used. There were no irregular vital signs or tachyarrhythmias that continued. There were no adjustments in battery voltage, power-on reset events, or pacing volume. There were transient CIED parameter shifts, including decreased right atrial sensing in four patients and decreased left ventricular R-wave amplitude in one patient. One patient who had a subcutaneous collection that had been discarded experienced sternal heating that went away when the analysis was stopped early.



Conclusions and Implications 
In this large observational study, which included patients who had their thorax examined, the risk of MRI in patients with abandoned CIED leads was minimal. The growing body of evidence casts doubt on the utter contraindication of MRI in patients with CIED leads that have been abandoned.

Frank Gommans, MD, PhD from the Radboud University Medical Centre speaks about Soluble Neprilysin and Corin Concentrations in Relation to Clinical Outcome in Chronic Heart Failure.


Link to Study -
https://www.jacc.org/doi/10.1016/j.jchf.2020.08.015

Summary -

Aims and goals

This research looked at whether soluble neprilysin and corin concentrations can be used to stratify patients with chronic heart failure (HF) and whether this is related to clinical outcomes.

Foreground

Corin and neprilysin, two enzymes that process natriuretic peptides, play a key role in the conversion of pro–natriuretic peptides to active natriuretic peptides as well as their degradation

Methodologies

A prospective cohort of 1,009 patients with chronic HF was divided into four equal classes based on their neprilysin/corin concentration relative to the median: 1) low neprilysin/low corin; 2) low neprilysin/high corin; 3) high neprilysin/low corin, and 4) high neprilysin/high corin. The composite primary outcome of cardiovascular mortality and HF hospitalization was subjected to a Cox regression survival study.

Conclusions

The median concentrations of neprilysin and corin were not associated (rho:0.04; p = 0.21). While there was no correlation with outcome in univariate research, after accounting for baseline variations in age and sex, a substantial association with survival was observed, with the highest survival in group 1 (low neprilysin/low corin) and the lowest in group 4 (high neprilysin/high corin) (adjusted hazard ratio: 1.56; p = 0.003) (adjusted hazard ratio: 1.56; p =

Final Thoughts

Clinical results are related to the stratification of patients with chronic HF based on circulating neprilysin and corin concentrations. These findings indicate that the control of these enzymes is important in chronic HF, and they may provide an intriguing mechanism for classifying patients with HF as the first step toward individualized HF patient care.

B. Daan Westenbrink, MD, Ph.D., Senior Author and Cardiologist at the University of Groningen, UMCG Cardiology speaks about Ketone Supplementation: A Novel Intervention for CVD?

Link to Article:
https://www.medscape.com/viewarticle/946647?src=soc_lk_share

According to a recent study, regardless of the procedure used to increase ketone bodies' presence in the heart, they could have therapeutic benefits for patients with cardiovascular disease (CVD).

The authors examined the current body of experimental and clinical research on the potential function of ketone bodies in improving CVD and discovered that increasing circulating ketone levels can provide protective benefits in patients with the disease.



A ketogenic diet, which consists of a very low carbohydrate and high-fat intake, is a common way to induce ketosis; however, exogenous ketones could be a viable and superior alternative to the diet for increasing circulating ketone bodies, according to the researchers.

The study was published in the Journal of the American College of Cardiology on February 23.


This realization prompted Westenbrink and colleagues to conduct a clinical trial to examine the impact of exogenous ketones on exercise efficiency in patients with heart failure.


The aim of this review was to "summarize the existing literature from animal and human studies, in the hopes of facilitating more research into the benefits of ketones as therapeutic agents in CVD."



Beyond Fuel Efficiency

The authors have looked at the processes of ketone metabolism, such as ketogenesis and ketolysis, as well as cardiac metabolism in both healthy and diseased hearts.


The reactions that lead to the formation of the ketone bodies acetoacetate (AcAc), -hydroxybutyrate (OHB), and acetone are known as ketogenesis.


Fasting causes a reduction in the insulin-to-glucagon ratio, which mobilizes fatty acids, which the liver then converts into ketone bodies. They are then moved to peripheral tissues, where they go through a process known as "terminal oxidation."


The heart appears to "reprogram metabolism to increased dependence on ketone bodies as a fuel source" as heart failure progresses, according to the authors, with increased circulating ketone concentrations and cardiac ketone consumption.

Paul W. Armstrong, MD Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada speaks about Merck Announces U.S. FDA Approval of VERQUVO® (vericiguat).



The primary efficacy objective of VICTORIA was to evaluate if VERQUVO, in conjunction with other heart failure therapies, is superior to placebo in reducing the risk of cardiovascular mortality or hospitalization for heart failure in adults with symptomatic recurrent heart failure and less than 45% of the ejection fraction following a worsening heart failure case. Based on a time-to-event study, VERQUVO reached the primary efficacy objective (hazard ratio [HR]: 0.90, 95 percent confidence interval [CI], 0.82-0.98; p=0.019). There was a 4.2 percent reduction in annualized absolute risk with VERQUVO compared to placebo over the course of the study. Therefore, to avoid one primary endpoint case, 24 patients will need to be monitored for an average of one year.

Information Supporting the Approval
VERQUVO approval was based on evidence from VICTORIA (NCT02861534), a randomized, concurrent, placebo-controlled, double-blind, event-driven, multi-center clinical trial comparing VERQUVO with placebo in 5,050 adult patients with New York Heart Association (NYHA) class II-IV symptomatic chronic heart failure and left ventricular ejection fraction (LVEF) less than 45% after a wound of symptomatic chronic heart failure (NYHA) class II-IV. A worsening case of heart failure was described as hospitalization for heart failure within six months or less prior to randomization or use for heart failure of outpatient IV diuretics within three months or less prior to randomization. In VICTORIA, the primary outcome was time-to-first cardiovascular death or heart failure hospitalization. The median follow-up time was 11 months for the primary endpoint. Based on a time-to-event analysis, VERQUVO was superior to placebo in reducing the risk of cardiovascular death or hospitalization for heart failure.



Patients were given VERQUVO 10 mg once daily or a matched placebo up to the target maintenance dose. Therapy started with VERQUVO 2.5 mg once daily and increased to 5 mg once daily and then 10 mg once daily, as tolerated, at roughly two-week intervals. The placebo doses were adjusted similarly. 90 percent of patients in both the VERQUVO and placebo arms were treated with the 10 mg target maintenance dose after approximately one year.



Participants in the study were: 76% male, 64% Caucasian, 22% Asian and 5% Black. The mean age was 67. 59 percent of patients were NYHA Class II at randomization, 40 percent were NYHA Class III and 1 percent were NYHA Class IV. The mean LVEF was 29 percent . Approximately half of all patients had an EF of less than 30%, and 14% of patients had an EF of between 40% and 45%. Sixty-seven percent of VICTORIA patients were enrolled within three months of a hospitalization index case for heart failure; 17 percent were enrolled within three to six months of hospitalization for heart failure; and 16 percent were enrolled within three months of outpatient care for worsening heart failure with IV diuretics. At randomization, the median NT-pro B-type natriuretic peptide (NT-proBNP) level was 2800 pg/mL.



Participants in the study were on quality of treatment. At baseline, 93 percent of patients received a beta-blocker, 73 percent received an angiotensin-converting enzyme (ACE) or angiotensin II receptor blocker (ARB) inhibitor, 70 percent received a mineralocorticoid receptor antagonist (MRA), 15 percent received an angiotensin receptor and neprilysin inhibitor (ARNI) combination, 28 percent had an implantable cardiac receptor antagonist (MRA), and 28 percent had an implantable cardiac inhibitor (ARNI). Ninety-one percent of patients were treated with two or more drugs for heart failure (beta-blocker, any receptor of the renin-angiotensin system [RAS], or MRA) and all three were treated in 60 percent of patients. At baseline, 6% of patients received an inhibitor of ivabradine and 3% of sodium glucose co-transporter 2 (SGLT2).



VERQUVO showed an adverse effect profile comparable to placebo in the VICTORIA trial. Hypotension (16% vs 15%) and anemia were the adverse drug reactions that occurred more frequently with VERQUVO than with placebo and in more than or equivalent to 5% of patients treated with VERQUVO in VICTORIA (10 percent vs 7 percent ). The VICTORIA trial included a total of 2,519 patients treated with VERQUVO (up to 10 mg once daily). The mean period of exposure to VERQUVO was one year, with a median duration of 2.6 years.

Professor Richard Sutton from the Department of Cardiology, Imperial College speaks about Tilt testing remains a valuable asset.

Link to Article:
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab084/6149003?login=true

Synopsis:

For more than 50 years, the head-up tilt test (TT) has been used to study heart rate/blood pressure adaptation to positional changes, model responses to haemorrhage, determine orthostatic hypotension, and analyze haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. Any of the participants in these studies encountered syncope as a result of the vasovagal reflex. As a consequence, tilt checking has become part of the clinical evaluation of syncope where the cause is unclear. As a consequence, clinical experience backs up TT's diagnostic importance. This is emphasized in evidence-based clinical practice guidelines, which provide recommendations for TT technique and analysis while also pointing out its weaknesses. As a result, TT continues to be a valuable therapeutic asset, one that has contributed greatly to our understanding of the pathophysiology of syncope/collapse and, as a result, has enhanced the treatment of syncopal patients.

The first paragraph is an introduction.

For more than half a century, physiologists and physicians have used the head-up tilt test (TT) to investigate heart rate and blood pressure adaptation to positional changes, to model responses to haemorrhage, to measure characteristics of orthostatic hypotension (OH), and to examine haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. Due to hypotension caused by TT (often followed by bradycardia/asystole), some participants suffered complete or near-total transient loss of consciousness (TLOC) during these studies. 1-4 As a result, starting in the late 1980s, TT was used in the clinical evaluation of syncope of unknown origin1 as a means of activating the vasovagal reflex in susceptible individuals by exposing them to a regulated orthostatic challenge in a healthy, monitored clinical laboratory setting. 0.5–8 However, Kulkarni et al.9 recently criticized the clinical usefulness of TT, promoting the less well-studied active stand test based on the assumption of lower cost and, possibly, greater convenience. Although recognizing TT's shortcomings, the aim of this analysis is to provide a counterpoint to Kulkarni et al.9's viewpoints by highlighting both TT's well-documented clinical importance and numerous practice guidelines' recommendations.

Tilt work is currently in progress:

When the past fails to offer a definitive reason for symptoms, a positive TT may be used to diagnose syncope/collapse.

ten, eleven If the history reveals a straightforward diagnosis, TT isn't necessary; however, TT may provide valuable patient education and reassurance, as well as pathophysiological proof of the underlying processes, which is crucial for choosing the right treatment. 12

Since its introduction into clinical practice, the approach and understanding of TT findings have grown.

1 Longer TTs, up to 2 hours at angles of 40–60 degrees, were used to cause vasovagal events in susceptible people at first. In order to improve test sensitivity, the test period was shortened, the head-up angle was specified as 60–80°, and other interventions were introduced. years 13–21 Drugs (e.g., isoproterenol, nitroglycerine, serotonin agonists) were administered alone or in combination with physical manoeuvres, such as carotid sinus massage. Several of these offensive steps increased TT sensitivity and are still used, but they may reduce specificity.

In a meta-analysis of 55 studies involving patients with unexplained syncope and asymptomatic controls without a history of syncope, Forleo et al.22 published a meta-analysis of patients with unexplained syncope and asymptomatic controls without a history of syncope. The authors omitted trials of less than ten patients and procedures with a tilt angulation of 60° or greater than 80°; the study included 4361 syncope patients (aged 41-17 years) and 1791 controls (aged 39-17 years). With a region under the curve of 0.84 [95 percent confidence interval (CI) 0.81–0.87], the overview receiver-operating curve showed strong overall ability to distinguish symptomatic patients from asymptomatic controls. Pharmacological protocols increased sensitivity but decreased specificity, as predicted. The highest diagnostic odds ratio (14.40; 95 percent CI 11.50–18.05) and sensitivity (66 percent; 95 percent CI 60–72 percent ) were found in tilt protocols that included nitroglycerine provocation.

The European Society of Cardiology (ESC)10 and the American College of Cardiology/American Heart Association/Heart Rhythm Society collaboration11 came to similar and closely coherent recommendations for TT in unexplained syncope after initial clinical assessment based on the preponderance of evidence and working independently (a few members of each group provided reviews of the other document). Furthermore, both groups suggested that when an autonomic disruption was suspected, TT (along with additional cardiovascular autonomic assessment, if necessary) could be the first step in the diagnostic process.

According to recent criticisms by Kulkarni et al.9, TT, like any diagnostic test, may be misused. Nonetheless, comprehensive experience and evidence-based practice guidance guidelines provide clear direction for its proper use and indicate when TT is a valuable, efficient diagnostic tool. Other orthostatic stressors (e.g., active standing, squat-stand test) may be considered, but they have not received the same level of scrutiny as TT as possible clinical methods, with the exception of initial and classic OH and postural orthostatic tachycardia syndrome, where active standing is well known, validated by data, and thus by guidelines. ten, eleven

Tilt and syncope testing:

Tilt-table imaging was used to evaluate sensitivity to the vasovagal reflex in patients with TLOC of unknown etiology. If the medical history is classic and diagnostic of reflex syncope, such testing is not needed for diagnosis. However, this is not always the case, particularly in older patients whose histories may be incomplete due to retrograde amnesia. 23

From history taking, four characteristics of TLOC can be deduced: I a propensity to fall as an expression of loss of motor control; (ii) amnesia for the duration of the TLOC; (iii) irregular reactions to speech/touch; and (iv) a limited duration (less than 5 minutes).

I concussion; (ii) syncope; (iii) epileptic seizures; (iv) psychogenic spells resembling syncope [psychogenic pseudosyncope (PPS)] or seizures [psychogenic non-epileptic seizures (PNES)]; and (v) intoxication/metabolic disorder (strictly not TLOC because length is >5 minutes).

It is frequently, but not always, possible to distinguish between these diagnostic agents using a thorough medical history that includes eyewitness reports.

TT is the safest next step in some patients with persistent apparent syncope for whom prior attempts at diagnosis have failed, and recommendations support this approach.

ten, eleven If PPS, PNES, or mechanical falls due to orthostatic intolerance are all possibilities, findings during TT would almost certainly be diagnostic. Electroencephalography (EEG) is commonly used in conjunction with TT and is considered important in PPS/PNES. 24 In OH, TT allows for safe long-term blood pressure monitoring without the possibility of falling or injury that may occur during active stand or squat-stand tests. When it comes to recording immediate OH, however, TT is less successful than active standing, which is why the latter is recommended. ten, eleven

Several findings indicate that observed syncope/collapse associated with positive TT is comparable to spontaneous vasovagal syncope (VVS), but it should be noted that tilt-induced syncope is not the same as VVS. On implantable loop recorders (ILR), for example, bradyarrhythmias are more prominent than during TT. 6 VVS diagnosis varies from TT in that it is based on the patient's recognition of symptom replication (Figure 1). As a consequence, TT can be helpful in VVS diagnosis but not so much in therapy selection.

Final Thoughts:

Tilt testing is an important and effective diagnostic method. The importance of it is endorsed by practice guidelines based on published and thoroughly vetted data. TT strengthens our comprehension of the pathophysiology of syncope/collapse and makes us to care for our patients. Active standing and ILR/ICMs can't replace TT; active standing is useful in certain types of OH but hasn't been shown to be useful in other syncope presentations, while ILR/ICMs are a useful addition to syncope workup.

R.S. is a consultant for Medtronic Inc., a member of Abbott Laboratories Inc.'s speakers bureau, and a stockholder in Edwards Lifesciences Corp. and Boston Scientific Inc. D.G.B. receives funding from the Dr Earl E Bakken Family for heart-brain research and reports consulting fees from Medtronic Inc. and Abbott Laboratories (SJM). Biotronik Inc. and Medtronic Inc. pay A.F. personal fees. Boston Scientific Inc., Medtronic Inc., and Abbott Laboratories have all provided H.A. research grants. NHLBI Grant RO1HL134674 has supported J.M.S. R.D.T. is funded by Medtronic for research, Theravance Biopharma for consulting, and Medtronic, Union Chimique Belge, and Novartis for lectures. Personal payments from Amarin, Boehringer Ingelheim, Sanofi Aventis, Respicardia, and Lundbeck were mentioned by B.O. There are no conflicts of interest declared by J.G.v.D., M.B., F.d.L., P.B.L., R.A.K., A.M., S.D.R., and V.R.

Professor David A. Kass, MD, Department of Medicine, Division of Cardiology, Department of Biomedical Engineering, Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine speaks about Review: Cellular and molecular pathobiology of heart failure with preserved ejection fraction.

Link to Review Article:
https://www.nature.com/articles/s41569-020-00480-6

Synopsis:

Heart failure with retained ejection fraction (HFpEF) affects half of all heart failure patients worldwide, is becoming more common, is associated with significant morbidity and mortality, and has few successful therapies. The largest unmet medical need in cardiovascular disease is probably HFpEF. While HFpEF was once thought to be a haemodynamic disorder characterized by hypertension, cardiac hypertrophy, and diastolic dysfunction, the pandemics of obesity and diabetes mellitus have changed the HFpEF syndrome, which is now recognized as a multisystem disorder involving the heart, lungs, kidneys, skeletal muscle, adipose tissue, vascular system, immune and inflammatory systems. Since the disorder is more than just cardiac hypertrophy and hypertension with abnormal myocardial relaxation, HFpEF is difficult to model in laboratory animals. New animal models of haemodynamic and metabolic disease, as well as increased efforts to investigate human pathophysiology, are revealing new signaling mechanisms and possible therapeutic targets. We address the cellular and molecular pathobiology of HFpEF in this Study, with a specific emphasis on mechanisms related to the heart, as most research has been done on this organ. Other critical organ systems, such as the lungs, kidneys, and skeletal muscle, are also involved, as are attempts to characterize patients using systemic biomarkers and ongoing therapeutic efforts. Our aim is to build a map of the signaling pathways and mechanisms of HFpEF that are currently being studied, with the intention of creating more patient-specific therapies and enhancing clinical outcomes.

Points to remember:

* Historically, diastolic dysfunction, cardiac hypertrophy, and myocardial fibrosis have been the subject of research into the pathophysiology of heart failure with preserved ejection fraction (HFpEF).


* Moreover, HFpEF is made up of a variety of factors that affect both systolic and diastolic heart function, as well as other organs and systems such as the lungs, kidneys, vasculature, adipose tissue, and skeletal muscle.


* Preclinical studies, especially those that combine obesity and metabolic defects with haemodynamic and cardiac disease, as most patients with HFpEF do, are revealing novel molecular mechanisms and therapeutic targets.


* Metabolic defects in fuel utilization and performance, inflammatory responses, lipotoxicity, pathological growth of myocytes, and lack of cytoprotective signaling are all proposed molecular and cellular abnormalities in HFpEF and those seen in diabetes mellitus and obesity.


*New therapies are targeting pleiotropic signaling cascades to reverse improvements in metabolic, inflammatory, and pathological stress pathways, in addition to developing innovative haemodynamic treatments with drugs and devices.

Ramin Ebrahimi, MD, Department of Medicine, Cardiology Section, Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California, and Department of Medicine, UCLA (University of California, Los Angeles) speaks about the Association of Posttraumatic Stress Disorder and Incident Ischemic Heart Disease in Women Veterans.

Link to Abstract:
https://jamanetwork.com/journals/jamacardiology/article-abstract/2777415


Points to Remember:

Inquiry Is a history of posttraumatic stress disorder (PTSD) related to an increased risk of ischemic heart disease (IHD) in female veterans?


Findings: Those with PTSD had a 44 percent higher risk of developing incident IHD in this longitudinal cohort analysis of 398 769 women veterans, including 132 923 with PTSD matched 1:2 to 265 846 without PTSD. Various risk factors, including common and female-specific cardiovascular risk factors, as well as mental and physical health conditions, were taken into account using propensity score matching.



Meaning: These results indicate that among female veterans, PTSD is linked to an increased risk of experiencing incident IHD.



Synopsis:

The significance of In primarily male populations or small group studies, posttraumatic stress disorder (PTSD) is linked to an increased risk of ischemic heart disease (IHD). Women veterans are an increasing but understudied demographic with high trauma exposure and specific cardiovascular risks, but there is little research on PTSD and IHD in this community.



The aim of this study was to see if PTSD is linked to incident IHD in female veterans.



Participants, Design, and Setting The a priori hypothesis that PTSD would be associated with a higher risk of IHD onset was tested in this retrospective, longitudinal cohort analysis of the national Veterans Health Administration (VHA) electronic medical records. Women veterans aged 18 and up, with or without PTSD, who were patients at the VHA between January 1, 2000, and December 31, 2017, were considered for the report. No VHA clinical experiences after the index visit, IHD diagnosis at or before the index visit, and IHD diagnosis within 90 days of the index visit were all exclusion criteria. Women veterans ever diagnosed with PTSD were compared in a 1:2 ratio to those never diagnosed with PTSD using propensity score matching based on age at index visit, number of previous visits, and prevalence of traditional and female-specific cardiovascular risk factors and mental and physical health conditions. From October 1, 2018, to October 30, 2020, data was analyzed.



PTSD diagnosis codes from inpatient or outpatient encounters, as specified by the International Classification of Diseases, Ninth Revision (ICD-9), or the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10).



Incident IHD, classified as new-onset coronary artery disease, angina, or myocardial infarction, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient experiences, and/or coronary procedures based on Current Procedural Terminology codes, are the main outcomes and measures.



The study included 398 769 women veterans, 132 923 of whom had PTSD, and 265 846 who had never been diagnosed with PTSD. The mean (SD) age at the start was 40.1 (12.2) years. 4381 women with PTSD (3.3%) and 5559 control persons (2.1%) developed incident IHD over a median follow-up of 4.9 (interquartile range, 2.1-9.2) years. In a Cox proportional hazards model, PTSD was linked to a higher risk of developing IHD (hazard ratio [HR], 1.44; 95 percent confidence interval [CI], 1.38-1.50). Secondary stratified tests revealed that women veterans with PTSD who were younger were at a higher risk of incident IHD. At baseline, effect sizes were highest for those under 40 years old (HR, 1.72; 95 percent CI, 1.55-1.93), and they decreased monotonically with age (HR for those 60 years old, 1.24; 95 percent CI, 1.12-1.38).



Conclusions and Consequences: This cohort study discovered that PTSD was linked to an increased risk of IHD in female veterans, which may have implications for assessing IHD risk in vulnerable people.

Sammy Zakaria, MD, MPH from Johns Hopkins University speaks about Acute Cardiac Effects of Severe Pre-Eclampsia.

Link to Article:
https://www.jacc.org/doi/10.1016/j.jacc.2018.04.048

Summary

Background: Pre-eclampsia with severe features (PEC) is a pregnancy-related condition marked by severe hypertension and end-organ dysfunction, as well as short-term adverse cardiovascular events such as heart failure, pulmonary edema, and stroke.

Objectives include:

The authors wanted to see how right ventricular (RV) systolic pressure (RVSP) and echocardiographic-derived diastolic, systolic, and speckle monitoring parameters changed over time in women with PEC.

Methodologies:

The authors enrolled 63 women with PEC and 36 pregnant control patients in this prospective retrospective study.

The following are the outcomes:

As compared to the control cohort, the PEC cohort had a higher RVSP (31.0 7.9 mm Hg vs. 22.5 6.1 mm Hg; p 0.001) and a lower global RV longitudinal systolic strain (RVLSS) (19.6 3.2 percent vs. 23.8 2.9 percent [p 0.0001]). There were significant differences (p 0.001) in mitral septal e′ velocity (9.6 2.4 cm/s vs. 11.6 1.9 cm/s), septal E/e′ ratio (10.8 2.8 vs. 7.4 1.6), left atrial area size (20.1 3.8 cm2 vs. 17.3 2.9 cm2), and posterior and septal wall thickness for left-sided cardiac parameters (median [interquartile range]: 1.0 cm [0.9 to 1.1 cm] vs. 0.8 cm [0.7 to 0.9 cm], and 1.0 cm [0.8 to 1.2 cm] vs. 0.8 cm [0.7 to 0.9 cm]). PEC was seen in eight women (12.7%) with grade II diastolic dysfunction and six women (9.5%) with peripartum pulmonary edema.

Final Thoughts:

When compared to healthy pregnant women, women with PEC have higher RVSP, higher rates of irregular diastolic activity, decreased global RVLSS, increased left-sided chamber remodeling, and higher rates of peripartum pulmonary edema.

Anders Holt, MD from Herlev and Gentofte University Hospital speaks about the Effect of long-term beta-blocker treatment following myocardial infarction among stable, optimally treated patients without heart failure in the reperfusion era: a Danish, nationwide cohort study.


Abstract:


Listen to this contribution's audio abstract at https://doi.org/10.1093/eurheartj/ehaa10588



Targets:


The goal was to research the long-term cardio-protective effect of beta-blocker (BB) therapy in healthy, optimally treated patients with myocardial infarction (MI) without heart failure (HF).



Methods and outcomes:

We included patients with first-time MI undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during admission and treated between 2003 and 2018 with both acetyl-salicylic acid and post-discharge statins using national registries. Patients with a previous history of MI, prior use of BB, or any alternative indication or contraindication to treatment with BB have been removed. Follow-up started with patients alive, free of cardiovascular (CV) incidents or treatments, 3 months after discharge. CV death, repeated MI, and a composite outcome of CV events were the primary outcomes. 3 years after MI, we used modified logistic regression and reported standardized absolute hazards and differences (ARD). In total, 30,177 healthy, optimally treated MI patients were included (58 percent acute PCI, 26 percent sub-acute PCI, 16 percent CAG without intervention). 82% of patients were on BB therapy at baseline (median age 61 years, 75% male) and 18% were not (median age 62 years, 68% male). Compared to no BB treatment [ARD (95 percent confidence intervals)], BB treatment was associated with a comparable risk of CV death, recurring MI, and the cumulative outcome of CV events; 0.1 percent (−0.3 percent to 0.5 percent), 0.2 percent (−0.7 percent to 1.2 percent), and 1.2 percent (−0.2 percent to 2.7 percent).



Findings:

No long-term effect of BB treatment on CV prognosis was found in this nationwide cohort study of healthy, optimally treated MI patients without HF in patients aged 3 months to 3 years after MI admission.

Timothy D. Henry, MD, MSCAI of The Christ Hospital Health Network speaks about his Physician Perspective: Chest Pain Linked to Underdiagnosed Heart Condition Affecting 8.3M Americans.


Link to Dr. Henry's Biography -

https://www.thechristhospital.com/physician-details?Provider=%230010BU225

Link to Dr. Henry's ResearchGate -

https://www.researchgate.net/profile/Timothy_Henry6

The Christ Hospital’s Women’s Heart Website -

https://www.thechristhospital.com/services/heart/specialized-care-and-treatment/womens-heart-disease

The FREEDOM Trial website -

https://www.freedom-trial.com/

Additional information on the trial can be found in this press release -

https://www.caladrius.com/press-release/caladrius-biosciences-treats-first-patient-in-the-phase-2b-freedom-trial-of-clbs16-for-the-treatment-of-coronary-microvascular-dysfunction/