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Akhil Narang, MD from the Bluhm Cardiovascular Institute at Northwestern University discusses AI guidance helps nurses with no experience obtain echocardiograms.

Link to Article -
https://www.cardiovascularbusiness.com/topics/imaging-physiology/ai-guidance-helps-nurses-no-experience-imaging?utm_source=newsletter&utm_medium=cvb_news

According to new research published in JAMA Cardiology, AI models will direct nurses with no previous experience through the method of obtaining 10-view transthoracic echocardiographic (TTE) studies.


To see if AI could help with this issue, Narang et al. used software designed to "emulate sonographer expertise" by tracking image quality and providing helpful cues when needed.


The team trained its AI model on images from a variety of suppliers, making it adaptable to a variety of platforms, and then put it to the test on a group of eight nurses who had never done an echocardiogram before. From March to May 2019, each nurse screened 30 adult patients who were scheduled for an echocardiogram at one of two facilities.


Each nurse's purchases were individually checked by a group of five experienced specialists. Overall, 98.8% of scans for left ventricular size, function, and pericardial effusion were of diagnostic quality, while 92.5 percent of scans for right ventricular size were of diagnostic quality.


The researchers believe that their work will help users get improved patient care in addition to improving access. If the AI model can assist nurses with no prior experience, it can also be useful for users with some prior experience, offering vital reminders that they can bring with them going forward.

The full analysis is available here -
https://jamanetwork.com/journals/jamacardiology/fullarticle/2776714

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.

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.

Carol Chiung-Hui Peng, MD from the University of Maryland Medical Center Midtown Campus, and Kashif Munir, MD from the University of Maryland School of Medicine, associate professor, and Medical Director of the University of Maryland Center for Diabetes and Endocrinology speak about Non‐vitamin K antagonist oral anticoagulants vs. warfarin for AFib patients: What the latest research tells us.

Twitter -

@UMMC @umms @UMmedschool 

Link to Abstract:
https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14243


Abstract 
Comparison of the risk of developing diabetes in patients with non-vitamin K antagonist oral anticoagulants (NOACs) treated with atrial fibrillation (AF) and warfarin.



Materials and Methods

Using Taiwan's National Health Insurance Research Database, we carried out a nationwide retrospective cohort analysis. Adult new-onset AF patients treated with NOACs or warfarin between 2012 and 2016 have been included. The NOAC cohort was further categorized into classes of dabigatran, rivaroxaban, and apixaban. Incident diabetes requiring treatment with antidiabetic medications was the primary outcome. Subdistribution hazard models of Fine and Gray were used to estimate the adjusted hazard ratio (aHR). For each head-to-head analysis, propensity score matching was conducted.



Outcomes
Our analysis included a total of 10,746 new-onset AF patients. NOACs were associated with a lower risk of developing diabetes than warfarin during the mean 2.4-year follow-up (aHR = 0.80, 95 percent confidence interval [CI]: 0.68-0.94, P = .007). Analyses of the subgroup indicated that dabigatran, rivaroxaban, and apixaban each had a decreased risk of diabetes. Stratified studies found that the lower risk of NOAC-related diabetes was specific for patients 65 years of age or older (aHR = 0.74, 95% CI: 0.62-0.89, P = .002) and those with strong adherence to medication (aHR = 0.70, 95% CI: 0.58-0.84, P < .001).



Findings
In patients with AF, taking NOAC was associated with a lower risk of developing diabetes compared to taking warfarin.

Laura M. Stevens, Ph.D. from the Computational Bioscience Program, Department of Pharmacology (L.M.S.), University of Colorado Anschutz Medical School, Aurora and The American Heart Association discusses Association Between Coffee Intake and Incident Heart Failure Risk.

Link to Abstract -
https://www.ahajournals.org/doi/full/10.1161/CIRCHEARTFAILURE.119.006799


Abstract -

Context:

Complex diseases with different phenotypes include coronary heart disease, heart failure (HF), and stroke. While several risk factors are well known for these diseases, researching as-yet unidentified risk factors will enhance risk evaluation and adherence to patients to preventive guidelines. In the FHS (Framingham Heart Study), CHS (Cardiovascular Heart Study), and ARIC (Atherosclerosis Risk in Communities) study, we investigated the diet domain to identify possible lifestyle and behavioral factors associated with coronary heart disease, HF, and stroke.


Methodology:

To classify possible risk factors associated with coronary heart disease, stroke, and HF in FHS, we used machine learning feature selection based on random forest analysis. Using univariable and multivariable Cox proportional hazards analysis optimized for known cardiovascular dangers, we assessed the importance of selected variables. Using CHS and ARIC, findings from FHS were then confirmed.


Outcomes:

Multiple dietary and behavioral risk factors for cardiovascular disease outcomes were reported, including marital status, consumption of red meat, consumption of whole milk, and consumption of coffee. Among these dietary variables, the increase in coffee intake in FHS, ARIC, and CHS was associated with a decrease in the long-term risk of HF.


Findings:
In all three studies, higher coffee intake was found to be associated with reduced HF risk. In order to better define the function, potential causality, and potential mechanism of coffee consumption as a potentially modifiable risk factor for HF, further research is warranted.

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.

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.

Khaled Ziada, MD from the Cleveland Clinic discusses Cangrelor in ST-Elevation Myocardial Infarction to Decrease Infarct Size.


Link to the Clinical Trial-
https://clinicaltrials.gov/ct2/show/NCT03043274?cond=Heart+Attacks&cntry=US&phase=123&draw=2&rank=9

Summary Brief:
This research evaluates variations in the degree of myocardial necrosis observed by cardiac MRI in patients with randomized ST-elevated myocardial infarction who received cangrelor during the percutaneous coronary intervention and contrasts them with patients who did not receive cangrelor randomly.

Description in detail:
Cangrelor is a direct-acting and reversible intravenously administered platelet inhibitor approved as an alternative to percutaneous intervention (PCI) for reducing the risk of periprocedural myocardial infarction, repeat coronary revascularization, and stent thrombosis. Cangrelor is emerging as an important new choice for use in patients undergoing percutaneous intervention who have not been treated with oral platelet inhibitors, as it has a fast onset of action (2 minutes) compared with conventional oral platelet inhibitors.



In addition, several studies have shown that patients undergoing emergent PCI with ST-elevation myocardial infarction (STEMI) do not have adequate platelet inhibition even after a loading dose of conventional oral platelet inhibitors has been given. The clinical meaning of maximum platelet inhibition at the time of PCI, however, is not fully understood.



The primary objective is to characterize the efficacy of intravenous cangrelor immediate platelet inhibition in patients with acute STEMI by determining the degree of infarct size (either enzymatically or by imaging). If the results are positive, this could indicate that in this patient population, immediate platelet inhibition is an important part of treatment.

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

David Conen, MD from the Population Health Research Institute and McMaster University, discusses Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance.

Link To Study -
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa955/6090247

Atrial fibrillation (AF) is associated with an increased risk of death and cardiovascular complications and has been described as one of the 21st century cardiovascular epidemics.1 AF pathogenesis is complex, but many risk factors for AF have been described previously, explaining the attributable risk of about 50 percent of the population.1-4 Enhancing our understanding of risk factors. Indeed, only oral anticoagulation has so far been undeniably shown to boost difficult results once AF.5 has been established by a patient.

Excessive alcohol intake is a significant modifiable risk factor that predisposes to AF. 6,7 The development of AF has been related to both acute and increased habitual drinking. As is apparent in the Holiday Heart Syndrome, acute alcohol intake has a direct impact on the heart, contributing to atrial tachyarrhythmias.8,9 Chronic alcohol consumption is also associated with an elevated risk of AF.6,7 In the Women's Health Study, women who drank > 2 alcoholic drinks per day had a 60% higher risk of AF incident after the multivariable change, while lower amounts did n.



In this issue of the Journal, in a very broad dataset, Csengeri et al.10 discussed the relationship between alcohol consumption and incident AF. Five prospective community-based cohorts totaling 107,845 individuals free of AF at baseline were combined by Csengeri et al.10, of whom 5854 developed new-onset AF over a median follow-up of 13.9 years. From patient self-report, alcohol intake was determined at baseline, while incident AF was determined from hospitalization data through ICD codes or comorbidities reported on death certificates. The median age was 47.8 years, 48.3 percent were men and 3 g/day was the median intake of alcohol. Consumption of 1 alcoholic beverage (defined as 12 g of alcohol) per day was correlated with a 16 percent increased risk of incident AF in Cox regression models stratified by sex and cohort [hazard ratio 1.16, 95 percent confidence interval (CI) 1.11–1.22, P < 0.001]. Importantly, at very low alcohol consumption levels, there was a substantial association between alcohol and increased AF risk. Even an average 3 g/day intake was closely correlated with the risk of AF (HR 1.04, 95% CI 1.02-1.05). Adjustment for other AF risk factors has not substantially attenuated this relationship. It is important to remember, while not mentioned in the manuscript, that the absolute risk of AF was likely low in participants who drank low to moderate amounts of alcohol.



The authors found a J-shaped association between alcohol intake and heart failure events, with the lowest risk reported at alcohol levels of up to 20 g per day. The relationship between alcohol- and time-dependent heart failure (HF) was not important when evaluating the intermediate function of incident heart failure in developing AF from alcohol intake. Finally, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-I (hsTnI) were weakly associated with alcohol intake and the association between alcohol and AF for these biomarkers was not attenuated.



There are some strengths in the current study 10. Harmonization of the outcome and covariates across five cohorts allowed the authors to conduct standardized studies with very broad sample size and great power to define important associations between alcohol intake and AF, including the lower alcohol consumption range where the probability of AF incident is expected to be minimal. This research, therefore, offers strong evidence that even very low alcohol levels (i.e. < 1 drink per day) remain substantially correlated with an increased risk of new-onset AF.



There are drawbacks to the Csengeri et al.10 analysis. First, from hospitalization results, AF episodes were not adjudicated and relied on the international classification of diseases (ICD codes), which may have contributed to bias in misclassification. In addition, AF instances that did not result in hospital presentation or were listed on death certificates may not have been reported. Second, the link between binge drinking and incident AF could not be investigated in this review. Third, absolute risks of AF associated with low levels of alcohol intake were not reported in the study. This important problem must also be taken into account when considering the potentially beneficial associations with other cardiovascular outcomes of moderate alcohol intake.11-14 Finally, the research was not intended to shed more light on the mechanisms that link habitual alcohol consumption and AF production. Although the authors explored the potential role of NT-proBNP and hsTnI in this relationship, only a minority of patients had biomarker data available, and only at baseline. The effects of alcohol on atrial electrophysiology are likely to rely on many variables, including changes in atrial repolarization, vagal sound, and direct myocardial injury and fibrosis.9 More studies are required to investigate how alcohol affects atrial electrophysiology across these possible pathways.



In conclusion, the current Article10 makes a significant contribution to our understanding of the relationship between alcohol intake and AF incidence, especially with the lower alcohol consumption continuum. There was a substantial association between alcohol and AF, and even small amounts of alcohol were associated with an increased, albeit small, risk of AF incidence. Together with a recent randomized study showing that a decrease in alcohol intake resulted in a decrease in AF recurrence,15 these data indicate that reducing alcohol intake may be relevant for AF prevention and management. Importantly, any decrease in low-to-moderate alcohol consumption to potentially prevent AF needs to be balanced with the potentially beneficial association of low amounts of alcohol with other cardiovascular findings (Graphical abstract).11-14 More research is needed for the net clinical advantage of consuming low amounts of alcohol, preferably in adequately powered randomized studies. Until then, each person has to make their own best-educated decision as to whether it is worthwhile and healthy to consume up to 1 alcoholic drink per day.

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/

Jason G. Andrade, MD from Vancouver Costal Health and L’Institut de Cardiologie de Montréal discusses Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation.


Instract
HINTERGROUNDS
Until catheter ablation is considered in patients with atrial fibrillation, guidelines prescribe a trial of one or more antiarrhythmic medicines. The first-line ablation, however, may be more effective in preserving sinus rhythm.



FOR METHODS
303 patients with symptomatic, paroxysmal, untreated atrial fibrillation were randomly assigned to undergo cryothermia balloon catheter ablation or receive antiarrhythmic drug therapy for initial rhythm regulation. To detect atrial tachyarrhythmia, all the patients obtained an implantable cardiac monitoring unit. The time for follow-up was 12 months. The first confirmed recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) between 91 and 365 days after catheter ablation or antiarrhythmic drug onset was the primary endpoint. Independence from symptomatic arrhythmia, the stress of atrial fibrillation and quality of life were the secondary endpoints.



OUTCOMES
At 1 year, 66 of 154 patients (42.9%) assigned to receive ablation, and 101 of 149 patients (67.8%) assigned to receive antiarrhythmic drugs (hazard ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66; P<0.001) had a recurrence of atrial tachyarrhythmia. In 11.0 percent of the patients who underwent ablation and in 26.2 percent of those who administered antiarrhythmic medications, symptomatic atrial tachyarrhythmia recurred (hazard ratio, 0.39; 95 percent CI, 0.22 to 0.68). The median percentage of atrial fibrillation duration was 0 percent with ablation (interquartile range, 0 to 0.08) and 0.13 percent with antiarrhythmic drugs (interquartile range, 0 to 1.60). Five patients (3.2 percent) who underwent ablation and six patients (4.0 percent) who received antiarrhythmic drugs reported severe adverse events.



CONCLUSIONS
There was a substantially lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation in patients undergoing initial care for symptomatic, paroxysmal atrial fibrillation than with antiarrhythmic drug therapy, as measured by continuous cardiac rhythm monitoring. (Funded by Canada's Cardiac Arrhythmia Network and others; the number of EARLY-AF ClinicalTrials.gov, NCT0282597.)

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.

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.