Prof. Giuseppe Tarantini, Chief of interventional Cardiology Unit - Associate Professor, University Medical school of Padua - GISE President speaks about Downstream or Upstream P2Y12 Receptor Blockers in NSTE-ACS: Primary Results of the DUBIUS Trial.

Link to Expert Analysis:
https://www.acc.org/latest-in-cardiology/articles/2021/03/15/13/39/downstream-or-upstream-p2y12-receptor-blockers?utm_medium=social&utm_source=twitter_post&utm_campaign=twitter_post

Quick Hits

* In the case of various P2Y12 inhibitors, the available data on the clinical effect of pretreatment has been insufficient and heterogeneous.

* The DUBIUS (Downstream Vs Upstream Strategy for the Administration of P2Y12 Receptor Blockers in Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication) trial found that both downstream and upstream oral P2Y12 inhibitor administration strategies were correlated with low rates of ischemic and bleeding events and a small numeric disparity between treatment groups.

* The widespread use of a radial method may have led to the low adverse event rates observed.

A brief introduction

In patients with non-ST-segment elevation acute coronary syndrome, dual antiplatelet therapy with aspirin and an oral P2Y12 inhibitor is the preferred treatment (NSTE-ACS). Ticagrelor and prasugrel, among P2Y12 inhibitors, are associated with better clinical results in patients with the acute coronary syndrome (ACS) than clopidogrel and are therefore favored unless contraindicated. 1 The timing of P2Y12 inhibitor administration has been a point of contention in recent years. 2 Their use prior to coronary angiography (also known as pretreatment) may minimize periprocedural ischemic events in patients undergoing percutaneous coronary intervention (PCI), but it may also increase the risk of significant bleeding. Furthermore, the available data on the clinical effects of pretreatment has been sparse and inconsistent across various P2Y12 inhibitors. 2


Prior Research
The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial) and CREDO (Clopidogrel for the Reduction of Events During Observation) trials on clopidogrel inspired the idea of starting dual antiplatelet therapy early in patients with NSTE-ACS. However, a significant percentage of CURE patients did not have coronary angiography, and the median time between enrollment and angiography for those who were treated invasively was several days. Patients for the CREDO trial were chosen after an angiography examination of their coronary anatomy.


In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 18,624 patients with ACS were randomly assigned to receive ticagrelor or clopidogrel. The PLATO study presented evidence in support of early initiation of ticagrelor therapy based on the observed early gain of ticagrelor over clopidogrel in terms of ischemic events (without a rise in the rate of overall significant bleeding). The research medications, however, were given before coronary angiography, and the study did not look into the issue of pretreatment.


In TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38), 13,608 patients with ACS were randomly assigned to receive prasugrel or clopidogrel. Prasugrel decreased the number of ischemic cases, but it came with a higher risk of significant bleeding. Patients in this study, however, were given prasugrel after coronary angiography if the need for PCI was verified.


Pretreatment with prasugrel was explicitly tested in the ACCOAST analysis (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction). Before coronary angiography, a total of 4,033 patients were randomized to receive prasugrel (pretreatment group) or a placebo (control group). Pretreatment with prasugrel was linked to a higher risk of major bleeding without a reduction in major ischemic incidents after 30 days.


In the ISAR-REACT 5 study (Intracoronary Stenting and Antithrombotic Regimen 5) 4,018 patients with ACS were randomly assigned to receive either ticagrelor or prasugrel.


3 The loading dose for the ticagrelor community was given as soon as possible after randomization. The loading dose was given as soon as possible in patients with ST-segment elevation ACS (41%) and after coronary anatomy was known in patients with NSTE-ACS in the prasugrel community. At one year, prasugrel substantially decreased ischemic events without raising the rate of serious bleeding. Because of the research nature, both the study drugs and the administration approach may have had a mixed impact on the observed outcomes.


Design of the DUBIUS Trial Study
The DUBIUS trial was a multicenter, randomized, adaptive, open-label trial that compared downstream and upstream oral P2Y12 inhibitor administration strategies in patients with NSTE-ACS who were undergoing invasive treatment.
4,5 patients were randomly allocated to receive ticagrelor or no ticagrelor before angiography (upstream group) (downstream group). All patients undergoing PCI were randomized to receive either ticagrelor or prasugrel in the downstream community.


In terms of net clinical gain on ischemic and haemorrhagic cases, the primary hypothesis was that the downstream administration strategy would be superior to the upstream administration strategy. At 30 days after randomization, the primary outcome was a combination of death from vascular causes (death from cardiovascular or cerebrovascular causes, and any death without another known cause), nonfatal myocardial infarction, or nonfatal stroke, and serious or fatal bleeding (BARC types 3, 4, and 5)


The DUBIUS Trial's Primary Findings
From December 2015 to May 2020, 1,449 patients were randomized from 30 Italian centers. The occurrence of the primary endpoint was measured at the second interim review. The steering committee agreed to halt enrollment for a futility scenario based on a predetermined stopping law. The research arms is well-balanced in terms of patient characteristics. Both groups had a median GRACE score of 122, and the downstream group had a median CRUSADE score of 22 and the upstream group had a median CRUSADE score of 21. More than 99 percent of patients had coronary angiography (median time: 23.3 hours), with the radial approach being the most common (94.5 percent of patients). In 72 percent of patients, PCI was used for revascularization, while coronary artery bypass graft was used in 6%. In 22% of patients, no revascularization was required.


The downstream and upstream classes had no variations in the rate of the primary endpoint (2.9 percent and 3.3 percent, respectively; absolute risk reduction –0.46; 95 percent confidence interval, –2.87 to 1.89). Significant or fatal bleedings were the most common adverse events, with no variations between categories. The timing of coronary angiography (within or after 24 hours of enrollment) and treatment with or without PCI had no effect on the results. In an exploratory study, the incidence of the primary endpoint did not vary substantially between patients treated with prasugrel and those treated with ticagrelor in the PCI subgroup of the downstream arm (4.1 percent and 3.1 percent, respectively; absolute risk reduction 0.9; 95 percent confidence interval, –3 to 5).


Medical Implications
The DUBIUS trial is the first to investigate the effects of ticagrelor pretreatment in patients with NSTE-ACS. Owing to the unlikelihood of detecting an advantage of one approach over the other with continued enrollments, the DUBIUS trial was prematurely stopped after an interim review due to a futility scenario. The DUBIUS trial found that both a downstream treatment approach with an oral P2Y12 inhibitor (prasugrel or ticagrelor) and a ticagrelor-based pretreatment strategy were correlated with low rates of ischemic and bleeding incidents in patients with NSTE-ACS who are undergoing scheduled invasive treatment. Several factors, including early coronary angiography and revascularization, very high rates of radial approach, and widespread adoption of secondary prevention steps, may have led to the trial's low adverse event rates.


Summary In patients with NSTE-ACS receiving early invasive care, both downstream and upstream oral P2Y12 inhibitor administration methods were linked to a low incidence of ischemic and bleeding events, with little numeric difference between treatment classes. The widespread use of a radial method may have led to the low adverse event rates observed.

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%.

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.

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.

Todd Chapin, PharmD, BCPS from Sanford Health speaks about Apixaban Versus Warfarin for the Management of Post-operative Atrial Fibrillation.

Link to Study:
https://clinicaltrials.gov/ct2/show/NCT02889562?recrs=dem&cond=Atrial+Fibrillation&cntry=US&phase=123&draw=2&rank=51

Patients who experience atrial fibrillation after isolated coronary artery bypass grafting surgery will be identified in this open-label, prospective, randomized pilot study. Patients with chronic prolonged atrial fibrillation (>2 episodes of atrial fibrillation lasting longer than 30 minutes) or persistent atrial fibrillation (>12 hours) would be qualified. Patients will be randomized to either the standard of care (warfarin per protocol) or the apixaban arms of the trial after meeting research inclusion and exclusion requirements and giving informed consent. Both groups will receive routine postoperative treatment after CABG. The anticoagulation clinic will treat anticoagulation in both classes after discharge. After surgery, patients will be monitored for 30 days.

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.

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.

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.

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/

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

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

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.

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.

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.

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.

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.

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.

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.

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