FLAME: FlowTriever use for PE associated with decreased in-hospital adverse outcomes

Key Points:

  • Mortality in high-risk PE remains unacceptably high (25%) despite advances in medical and interventional therapies.
  • The FLAME study was a prospective, multi-center non-randomized observational study to describe the outcomes of patients undergoing mechanical thrombectomy and other modern therapies and generate evidence in high-risk PE. The primary outcome was a composite of all-cause mortality, bailout to alternate thrombus removal strategy, clinical deterioration, and major bleeding.
  • Compared with a pre-established performance goal of 32%, patients treated with Flowtriever had a significant reduction in the primary endpoint. There was also significant reduction in in-hospital mortality (1.9% compared to 28.5%). There was no increase in adverse events in the FlowTriever group.
  • Randomized evidence will be required to follow-up this observational study, but FlowTriever appears to be a safe, effective treatment which may reduce mortality in high-risk PE.

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CLEAR Outcomes – Bempedoic Acid reduces Cardiovascular Events among Statin-Intolerant Patients

Key Points

Bempedoic acid, an ATP citrate lyase inhibitor, has been shown to reduce LDL cholesterol concentrations by 17% to 28% in clinical trials. However, data on whether bempedoic acid reduces cardiovascular events has been lacking.

The CLEAR Outcomes trial enrolled 13,970 statin-intolerant individuals at risk for, or with established cardiovascular disease, and randomized them to 180 mg of bempedoic acid per day or placebo.

Over a median follow-up of 40.6 months, treatment with bempedoic acid resulted in a 13% relative reduction in the composite primary endpoint of CV death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization).

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It’s Time to Randomize: Smartphone-Based Screening for Atrial Fibrillation – The Siteless, Digital, Randomized eBRAVE-AF Trial  

Key Points 

  • Wearable technologies based on photoplethysmographic measurements of irregular pulses can be ubiquitously distributed to perform opportunistic longitudinal monitoring of atrial fibrillation, the most common arrythmia worldwide, and potentially reduce its stroke risk by prompt initiation of anticoagulation.
  • The eBRAVE-AF trial is the first trial to randomize elderly patients free of atrial fibrillation to them to digital AF screening via a smartphone app (n=2,860) or usual care (n= 2,691). After 6 months of observation, the digital care approach generated an odds ratio of identifying and treating atrial fibrillation of 2.12 (1.19–3.76, p=0.010), compared to usual care. The stroke event rate was too low during this short observation period to draw any definitive conclusions about the long term clinical impact of either strategy. 

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Artificial Intelligence can improve detection of severe aortic stenosis from echocardiograms: AI-ENHANCED AS shows.

Key Points

  • Aortic stenosis, despite being life-threatening, is often underdiagnosed. It is understood that when the disease is diagnosed, it does remain undertreated as well.
  • An artificial-intelligence algorithm was developed with the intent of being a decision support algorithm, both to identify patients with aortic stenosis, and stratify those patients by risk.
  • Using the National Echo Database of Australia, containing 1 million echocardiograms, the algorithm was able to identify high-risk phenotypes, correctly identifying all of the patients diagnosed with severe aortic stenosis, and flagging others who were likely to have the disease but failed to meet criteria.

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Acetazolamide results in improved decongestion, faster: results from ADVOR

Key Points:

  • Residual decongestion after a hospitalization for acute decompensated heart failure is associated with poor outcomes.
  • In this double-blinded, placebo-controlled study, patients admitted to the hospital with heart failure were randomized to receive either acetazolamide or placebo in addition to standard high-dose loop diuretics.
  • Acetazolamide was associated with improved decongestion at 3 days and discharge, resulting in shorter hospital stays.
  • This is the first diuretic trial to use successful decongestion as a primary outcome.

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More Evidence For the Newest Guideline Directed Medical Therapy Pillar – Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (The DELIVER Trial)

Key Points:

  • The use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) in heart failure with preserved ejection fraction (HFpEF) has been previously established, but evidence in patients who are peri-hospitalization and with improved EF is lacking
  • The Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure (DELIVER) Trial shows that dapagliflozin resulted in a lower risk of the primary composite (including cardiovascular death, HF hospitalization or urgent HF visit) in patients with HF and mildly reduced or preserved EF
  • Benefit of dapagliflozin was seen irrespective of EF and with no attenuation of treatment benefit in patients with highest EF or in inpatient setting
  • Dapagliflozin was proven to be effective among patients with a prior reduced EF which had recovered to >40%

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Routine PCI confers no added benefit in severe left ventricular dysfunction: REVIVED

Key Points

  • REVIVED is the first large scale clinical trial to assess the effect of routine PCI in patients with severe left ventricular dysfunction, when compared to optimal medical therapy alone.
  • 700 patients with myocardial viability were randomized to receive PCI of indicated vessels (assessed by cardiac MR or echocardiography), or continue with optimal heart failure therapy alone.
  • At 2 years, there were no differences in all-cause mortality or heart failure hospitalization between the two groups. Furthermore, there was no significant difference in LVEF between the two strategies.

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VALOR-HCM: Treatment with mavacamten decreased need for septal reduction therapy in patients with hypertrophic cardiomyopathy.

Key Points:

    • In the VALOR-HCM study, patients with severely symptomatic obstructive HCM on maximally tolerated medical therapy were treated with either mavacamten (a novel cardiac myosin inhibitor) or placebo. The primary outcome was composite of patient decision to proceed with SRT or continue to meet 2011 ACC/AHA guideline eligibility for SRT after 16 weeks. Pre-specified secondary analyses included a) change in post-exercise LVOT gradient, b) number of patients with a ≥1 class of NYHA improvement, c) change in KCCQ clinical summary score, d) change in NT-proBNP, and e) change in Troponin I.
    • Treatment with mavacamten reduced the primary endpoint, which was largely driven by guideline eligibility for SRT 17.9% of patients were eligible for SRT therapy at 16 weeks in the mavacamten arm, compared to 76.8% in the placebo arm. Mavacamten also led to a reduction in resting and Valsalva LVOT gradient, troponin and BNP, and KCCQ score.

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Left atrial appendage closure is noninferior to NOACs for atrial fibrillation: PRAGUE-17

Key Points:

  • In the PRAGUE-17 study, patients with non-valvular atrial fibrillation were treated with either oral anticoagulants or left atrial appendage closure devices and followed over a median of 3.5 years of follow-up. The primary endpoint was a composite of stroke or TIA, systemic embolism, clinically relevant bleeding, CV death, or peri-procedural/device complication.
  • Treatment with left atrial appendage closure was noninferior to NOAC treatment at long-term follow-up and was associated with significantly less non-procedural bleeding. Continue reading

ACST-2: Largest trial to date comparing carotid artery stenting to carotid endarterectomy finds no difference in disabling stroke at 5 years.

Key Points:

  • Carotid artery stenting and carotid endarterectomy have both been employed to treat severely stenosed carotid arteries, a known risk factor for disabling stroke.
  • In ACST-2, patient with severe carotid artery stenosis were randomized in a 1:1 fashion to receive either carotid artery stenting or carotid endarterectomy.
  • Serious complications from either procedure were comparably rare. At 5 years, the nonprocedural stroke rate was 2.5% for both carotid artery stenting and endarterectomy.

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One month of dual antiplatelet therapy after PCI non-inferior to standard duration: results from MASTER DAPT.

Key Points:

  • Patients with high bleeding risk who were treated with PCI with an Ultimaster stent were randomized to either standard care dual antiplatelet therapy (DAPT) or abbreviated DAPT starting after 30 days of DAPT post PCI. Standard DAPT was defined as an additional 2 or 5 month duration (with or without anticoagulation, respectively) followed by single antiplatelet therapy (SAPT) for up to 11 months following randomization. Abbreviated DAPT was defined as immediate DAPT discontinuation followed by SAPT for 11 months (or 5 months if anticoagulation was indicated).
  • The three primary endpoints included the following outcomes at 1 year: a) net adverse clinical events (NACE), b) major adverse cardiac and cerebral events (MACCE), and c) major or clinically relevant non-major bleeding (MCB).
  • Treatment with abbreviated DAPT was noninferior to standard DAPT for NACE and MACCE. Abbreviated DAPT resulted in lower major or nonmajor bleeding.

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TOMAHAWK: no benefit in immediate angiography after out of hospital cardiac arrest without ST segment elevation

Key Points:

  • In patients with resuscitated out-of-hospital cardiac arrest (OHCA) of potential cardiac etiology with either shockable or non-shockable arrest rhythm, performing immediate nonselective coronary angiography did not reduce 30-day all-cause mortality compared with delayed, selective angiography.
  • Of those undergoing immediate angiography, a culprit lesion was identified in 38.1% of patients, compared with 43% of patients undergoing delayed selective angiography.

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APAF-CRT: AV junction ablation followed by biventricular pacing provides a significant mortality benefit among some patients with symptomatic atrial fibrillation

Key points:

• The APAF-CRT trial was a two-phase trial conducted among patients with permanent atrial fibrillation (AF) and narrow QRS (<110 ms) with ≥1 heart failure hospitalizations but considered unsuitable for AF ablation. The goal of this study was to compare two rate control strategies, and understand whether atrioventricular junction (AVJ) ablation followed by cardiac resynchronization therapy (CRT) is superior to pharmacological rate control.

• In 2018, the results from the first phase (APAF-CRT Morbidity) found that AVJ ablation + CRT significantly reduced the composite outcome of death due to heart failure (HF), heart failure hospitalizations (HHF) or worsening HF at 16 months, compared to pharmacological rate control.

• Now, the second phase of the trial (APAF-CRT Mortality) also found that AVJ ablation + CRT was associated with a 27% absolute reduction in all-cause mortality at 4 years of follow-up, compared to pharmacological rate control. Continue reading

MRI-guided ablation no better than conventional PVI for Atrial Fibrillation

Key Points:                                         

  • DECAAF-1 showed that higher volumes of atrial tissue fibrosis on cardiac MRI were associated with higher rates of atrial arrhythmia recurrence after catheter ablation.
  • Patients were randomized to undergo MRI-guided ablation in addition to pulmonary vein isolation verses conventional pulmonary vein isolation and followed for 12-18 months to assess for atrial arrhythmia recurrence.
  • MRI-guided ablation did not decrease rates of atrial arrhythmia recurrence, and was found to have higher adverse events, including stroke.

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Haemodynamic Guided Heart Failure Management as a Hospitalization Reduction Strategy – the GUIDE-HF Tria


· CardioMEMS, a wireless, battery-free pressure sensor implanted in the pulmonary artery that transmits real-time pressure data, is an established means of remote, longitudinal clinical assessment for ambulatory patients with symptomatic heart failure syndromes

· The benefits of CardioMEMS in patients across the spectrum of heart failure syndrome classes was previously unknown

· GUIDE-HF shows that the benefits of hemodynamic guided management extends to a larger group of heart failure patients including patients with New York Heart Association Class II-IV heart failure, those without prior heart failure hospitalization, and among patients with all ejection fractions

Heart failure is a chronic, progressive condition that typically worsens over time. As a result it is one of the leading causes of hospitalization in the United States, resulting in almost one million hospitalizations in this country annually. Pulmonary artery congestion is the cause of many associated symptoms and therefore has been a long-standing target of therapeutic intervention. One such tool is the CardioMEMS HF System (Abbot, Atlanta, GA), a wireless, battery-free sensor that is implanted into the pulmonary artery to transmit pulmonary artery pressures. The device allows clinicians to

titrate heart failure medications according to the data received from the device, thereby allowing optimal control over fluid levels and ideally preventing heart failure hospitalizations for pulmonary congestion. Previously, the CardioMEMS device had been approved in Europe and the US on the basis of the results of the CHAMPION Trial, which demonstrated that active heart failure management guided by remotely obtained PA pressures using CardioMEMS reduced heart failure hospitalizations and improved health-related quality of life only in patients with more advanced heart syndromes, defined as patients with New York Heart Association (NYHA) Class III heart failure with

an admission for heart failure in the previous year. Notably this improvement was seen in patients irrespective of ejection fraction, therefore providing clinicians with possible therapeutic targets across the spectrum of heart failure syndromes.

The haemodynamic-GUIDEed management of Heart Failure (GUIDE-HF) trial, presented August 27th, 2021 in a Hot Line Session at ESC Congress sought to determine whether other types of patients might benefit from this pulmonary artery pressure monitoring device. Specifically, they evaluated whether haemodynamic-guided management using CardioMEMS could reduce heart failure events and mortality in patients with heart failure across the range of symptom severity (NYHA functional class II–IV), including those with elevated biomarkers but without a recent heart failure hospitalization. Furthermore, whether remote monitoring of pulmonary artery pressures could lead to timely intervention that might actually improve mortality is unknown.

The GUIDE-HF Trail was a multicenter, single-blind study conducted at 118 centers in the USA and Canada. Following successful implantation of a pulmonary artery pressure monitor, 1,000 patients with both preserved and reduced ejection fractions, NYHA functional class II–IV chronic heart failure, and either a recent heart failure hospitalization or elevated natriuretic peptides (based on a-priori thresholds) were randomly assigned (1:1) to either haemodynamic-guided heart failure management based on transmitted pulmonary artery pressures or to a control group who did not have pulmonary artery pressure data available. Though patients were blinded to the treatment allocation investigators were not. However, investigators did not have access to pulmonary artery pressure data for control patients. The primary endpoint was

a composite of all-cause mortality and total heart failure events (including heart failure hospitalizations and urgent heart failure hospital visits) at 12 months assessed in all randomly assigned patients. A pre-COVID-19 impact analysis for the primary and secondary outcomes was prespecified. The details of the study’s methods were published in the American Heart Journal in August 2019 and further information can be found at ClinicalTrials.gov (NCT03387813).

The trial’s results showed that though the primary endpoint was not met for the overall analysis (HR 0.88, 95% CI 0.74-1.05, p=0.16), the primary endpoint was met in the pre-COVID-19 impact analysis alone (HR 0.81, 95% CI 0.66-1.00, p=0.049). Furthermore

there was a highly significant 28% reduction in heart failure hospitalizations for patients with CardioMEMS devices in the pre-COVID-19 impact analysis (HR 0.72, 95% CI 0.57-0.92, p=0.007). This data is consistent with results previously reported in the CHAMPION trial, which enrolled only NYHA Class III patients with a previous heart failure hospitalization. Overall, there was a consistent signal for benefit for hemodynamic guided monitoring for patients of all subgroups regardless of NYHA Class, ejection fraction, sex, biomarkers, heart failure hospitalization in prior year, age, race, or etiology of heart failure. Notably there were only 54 NYHA class IV patients enrolled in the study and results for this population were inconsistent.


The trial’s lead investigator, Dr. Lindenfeld, points out during the GUIDE-HF press presentation that this trial’s novel finding is that it shows significant reduction in heart failure hospitalizations for patients with NYHA class II symptoms with a prior heart failure hospitalization or elevated biomarkers, NYHA class III patients even without a prior heart failure hospitalizations though with elevated biomarkers, and for patients with all ejection fractions. Furthermore, the findings have important implications for patients with heart failure with preserved ejection fractions as few therapies have shown benefit for this group.

The associated manuscript for this study is published today in The Lancet https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01754-2/fulltext.

STOP AF First Trial: Cryoballoon Ablation Is Superior to Antiarrhythmic Drug Therapy for the Prevention of Atrial Arrhythmia Recurrence in Patients With Paroxysmal Atrial Fibrillation

A recent trial by Dr. Oussama M. Wazni, published in the New England Journal of Medicine, indicated that in patients with paroxysmal atrial fibrillation, cryoballoon ablation therapy is superior as compared with antiarrhythmic drug therapy, in the prevention of atrial fibrillation recurrence. The study also showed the non-inferiority of this procedure over the drug therapy approach in terms of safety.

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TIPS-3 Trial: The Combination of Polypill and Aspirin Administered to Patients at Intermediate Risk Led to a Lower Incidence of Cardiovascular Events Compared With Double Placebo

A recent trial by Dr. Salim Yusuf, published in The New England Journal of Medicine, indicated that combination therapy with aspirin plus a polypill (consisting of a statin plus three blood-pressure-lowering drugs) can reduce the incidence of cardiovascular events compared with placebo among participants without established cardiovascular disease, but at moderate cardiovascular risk.

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EMPEROR-Reduced Trial: Empagliflozin Use Was Associated With a Better Clinical Outcomes Among Patients With Heart Failure and a Reduced Ejection Fraction

A recent study by Dr. Milton Packer, published in Circulation, demonstrated that empagliflozin use has been associated with a reduction in the total number of inpatient and outpatient visits in patients with heart failure and a reduced ejection fraction. These benefits were observed within  12-28 days of treatment initiation and were persisted over the duration of the trial. Continue reading

COACT Trial Shows Immediate Coronary Angiography Does Not Change the 1-Year Clinical Outcomes of Patients After Cardiac Arrest Without ST-Segment Elevation

A trial by Dr. Jorrit S. Lemkes, published in JAMA Cardiology, demonstrated that immediate coronary angiography and percutaneous coronary intervention (PCI) does not improve the 1-year clinical outcomes of patients after successful resuscitation from non-ST segment elevation cardiac arrest. Also, the survival rate was comparable between patients whose angiography was performed immediately (61.4%) versus those whose angiography was delayed (64.0%).

Given the high prevalence of coronary artery disease among patients with cardiac arrest, coronary angiography and PCI should be considered in these patients with suggested evidence of coronary artery involvement. However, the current data regarding the appropriate timing of this intervention is lacking. The interim results of the Coronary Angiography after Cardiac Arrest (COACT) trial failed to find a significant difference between the 90-days clinical outcomes of patients with delayed coronary angiography versus patients with immediate coronary angiography after non-ST segment elevation cardiac arrest. The 1-year follow-up study investigated the long-term clinical outcomes of immediate coronary angiography in these patients.

COACT study, an open-label, multicenter, randomized trial, compared the short-term clinical outcomes of immediate versus delayed coronary angiography in patients resuscitated from cardiac arrest without ST-segment elevation on the electrocardiogram tracing. Briefly, a total of 552 patients with out-of-hospital arrest and no signs of ST-segment elevation myocardial infarction (STEMI) who successfully resuscitated from cardiac arrest were randomized in a 1:1 ratio to undergo immediate (within 2 hours of randomization) or delayed (after neurological recovery or discharge from intensive care unit) coronary angiography. The 1-year endpoints of the study included survival rate, myocardial infarction, repeated revascularization, hospitalization for heart failure, and implantable cardiac defibrillator (ICD) shock since the index hospitalization.

At 1-year follow-up, 94.6% of the participants (n=522) were available for analysis. The recent analysis of the data indicated no significant differences between the two groups. The survival rate was 61.4% and 64.0% in the immediate and delayed coronary angiography group, respectively (odds ratio (OR)=0.90; 95%Confidence Interval (CI):0.63-1.28). Additionally, the endpoints of the interest were equivalent in the 2 groups. For example, the rate of myocardial infarction was 0.8%in the immediate group and 0.4%in the delayed group (OR=1.96; 95%CI: 0.18-21.8). The study also showed that the post-cardiac arrest mortality usually occurs within the first 90 days after the arrest, and the survival rate after this period is relatively favorable.

The trial has some limitations that need to be taken into account. First, the study is not powered for a 1-year analysis. Second, the findings of this study are not generalizable to patients with shock, severe renal dysfunction, or persistent ST-segment elevation due to their exclusion from the trial.

The results of this trial suggest that in patients with out-of-hospital cardiac arrest with no signs of STEMI, the coronary angiography, if necessary, can be delayed until after neurological recovery.

Study Shows the Efficacy of Adding Corticosteroids to Initial Intravenous Immunoglobulin Therapy in the Prevention of Coronary Artery Abnormality Among Patients at High Risk for Kawasaki Disease

A recent study by Dr. Ryusuke Ae, published in the Journal of the American Heart Association, demonstrated the efficacy of combining the initial intravenous immunoglobulin (IVIG) treatment with multiple-dose corticosteroids in the prevention of coronary artery abnormalities in selected patients at high risk for Kawasaki disease. The study showed a reduction in coronary artery abnormalities and treatment failure after applying this treatment strategy.
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