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.

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%.

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.

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.

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.

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.)

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.

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.

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

Mads Hashiba Jensen, a Medical Student at the Department of Cardiology at Herlev og Gentofle Hospital and the University of Copenhagen a presentation on DANish Patients With Atrial Fibrillation and Sleep Apnea Prevalence by Night Owl (DANAPNO).

Link to Study:
https://www.clinicaltrials.gov/ct2/show/NCT04760002?term=04760002&draw=2&rank=1

Description of the Research -

A study to see whether NightOwl could be used to detect the prevalence of obstructive sleep apnea (OSA) in patients with atrial fibrillation (AF). The long-term goal is to use the system to test for OSA in AF patients undergoing ablation and/or AF patients undergoing cardioversion in a randomized clinical trial.

Patients with some form of AF who are referred to a nurse-run ambulatory for anticoagulation initiation will be required to participate. The ambulatory consists of four regular nurse-led tracks at Herlev-Gentofte University Hospital's Department of Cardiology. In a formal partnership, Herlev-Gentofte University Hospital's Department of Pulmonology offers work-up with cardio-respiratory monitoring investigation and clinical assessment of starting sleep apnea care in patients referred from the study. Those in attendance Participants will be recruited from the Thrombosis unit (Tromboseklinikken) at Herlev-GentofteHospital who have AF without established sleep apnea and a need for anticoagulation. As part of their routine check at the anticoagulation outpatient clinic at Herlev and Gentofte Hospital, participants will be contacted and invited to participate in the research project by a local investigator or a project nurse. Participants will be given verbal details about the research project as well as the appropriate time to discuss recruitment during the interview. The written participant information will be given to the participants before the verbal information, and it will be given to them by a researcher or a project nurse who is well-versed in the project. Before a written informed consent is received, the investigators will be given the details they need to find eligible participants. The written informed consent enables the researchers to access the participant's medical health records for the purposes of the study.


The analysis is cross-sectional in nature. A third visit will be scheduled for the first 20 participants and those with an apnea-hypopnea index (AHI)>15 who are included in the sample.

The participant borrows a NightOwl and receives system guidance during the initial visit, which includes a clinical assessment and a questionnaire about OSA symptoms.

In a home setting, NightOwlTM was used for four nights of recording.

A follow-up visit to discuss the findings of the home surveillance and the soft node questionnaire.

A fourth visit to the sleep apnea clinic will be scheduled for the first 20 patients, as well as all patients whose home test shows (AHI>15).

The research will take about 6 months from the time the first patient is enrolled until the last patient is enrolled.

Carol Chiung-Hui Peng, MD and Kashif Munir, MD, Medical Director Of The University Of Maryland Center For Diabetes And Endrocrinology, University of Maryland Medical Center Midtown Campus, University of Maryland School of Medicine speaks about Fracture Risks in Patients Treated With Different Oral Anticoagulants: A Systematic Review and Meta‐Analysis.

Link To Abstract:
https://www.ahajournals.org/doi/10.1161/JAHA.120.019618

Summary -

Background: 
To evaluate the fracture risk associated with NOACs and warfarin, we performed a systematic review and meta-analysis.

Methods and Results: 
From inception to May 19, 2020, we searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. We included studies that recorded measurements for any fracture in NOAC and warfarin users (regardless of major, secondary, tertiary, or safety outcomes). Two or more reviewers worked together to screen relevant papers, extract data, and evaluate accuracy. To synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin, data were retrieved. For data synthesis, random-effects models were used. There were 388 209 patients in 29 studies (5 cohort studies and 24 randomized controlled trials). Patients taking NOACs had a lower risk of fracture than those taking warfarin (pooled RR, 0.84; 95 percent CI, 0.77–0.91; P0.001), and there was little variability (I2=38.9%). NOACs were also linked to a lower risk of hip fracture than warfarin (pooled risk ratio, 0.89; 95 percent confidence interval, 0.81–0.98; P=0.023). There was also a nonsignificant trend of NOAC users having a lower risk of vertebral fracture (pooled RR, 0.74; 95 percent CI, 0.54–1.01; P=0.061). Specific NOACs dabigatran, rivaroxaban, and apixaban were found to be significantly associated with lower fracture risks in subgroup analyses. Furthermore, the data synthesis results from randomized controlled trials and real-world cohort studies were remarkably consistent, suggesting the validity of our findings.

Conclusions:
NOACs are associated with a lower risk of bone fracture as compared to warfarin.

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.

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.

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/

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.

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.

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.

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.

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.