The American College of Cardiology (ACC.19) Annual Scientific Sessions represents one of the most exalted venues for investigators to present the latest studies that could potentially impact cardiology practice. Held in New Orleans, US, from 16th – 18th March 2019, Drs Gerald Chi, Syed Hassan Abbas Kazmi and C Michael Gibson give their ‘quick takes’ from the meeting and summarise the main results from six landmark studies presented there: PARTNER 3, Evolut Low Risk, MOMENTUM 3, AUGUSTUS, COACT, and the Apple Heart Study.
PARTNER 3 and Evolut Low Risk add to evidence base for TAVR
Prior literature suggests that transcatheter aortic-valve replacement (TAVR) is non-inferior or even superior to standard surgical aortic-valve replacement (SAVR) among high and intermediate surgical risk patients with aortic stenosis (AS). Two pivotal studies have now addressed the efficacy and safety of TAVR in AS patients at low mortality risk from surgery.
PARTNER 3 (ClinicalTrials.gov: NCT02675114) was an open-label trial that randomised 1,000 subjects with severe AS at low mortality risk from surgery into either TAVR with a third-generation balloon-expandable valve (SAPIEN™ 3 system) or SAVR.1 The one-year risk of death, stroke, or rehospitalisation was lower in the TAVR group than the SAVR group (8.5% vs. 15.1%; hazard ratio [HR] =0.54 [95% confidence interval (CI): 0.37–0.79]; p=0.001 for superiority). TAVR was also associated with a lower 30-day risk of stroke (0.6% vs. 2.4%), death or stroke (1.0% vs. 3.3%), new-onset atrial fibrillation (AF) (5.0% vs. 39.5%), life-threatening or major bleeding (3.6% vs. 24.5%), and a shorter hospital stay (3 days vs. 7 days) compared to SAVR.
Evolut Low Risk (ClinicalTrials.gov: NCT02701283) was an open-label trial that randomised 1,468 low-risk severe AS patients into either TAVR with one of three self-expanding supraannular bioprosthesis valves (CoreValve™, Evolut R™, or Evolut PRO™) or SAVR.2 The two-year risk of death or disabling stroke was lower in the TAVR group than the SAVR group (5.3% vs. 6.7%; posterior probability of non-inferiority >0.999). TAVR was also associated with a lower 30-day risk of death or disabling stroke (0.8% vs. 2.6%), disabling stroke (0.5% vs. 1.7%), AF (7.7% vs. 35.4%), stage 2 or 3 acute kidney injury (0.9% vs. 2.8%), and life-threatening or disabling bleeding (2.4% vs. 7.5%) compared to SAVR.
While the long-term outcome and risk of subclinical leaflet thrombosis or structural valve degeneration remain uncertain, these studies expand the treatment avenue for a sizable number of patients with severe AS.
MOMENTUM 3 shows promise for new HeartMate 3™ device
Another noteworthy potential advance in the mechanical circulatory support for advanced heart failure (HF) is the HeartMate 3™ device, a fully magnetically levitated pulsatile centrifugal-flow system without mechanical bearings. Revamped from its previous generation (HeartMate II™, a continuous axial-flow system with mechanical bearings), HeartMate 3™was developed to further improve hemocompatibility-related adverse events including pump thrombosis, stroke, and bleeding.
MOMENTUM 3 (ClinicalTrials.gov: NCT03335800) was an open-label trial in 1,028 patients with advanced HF randomised to either a centrifugal-flow pump (HeartMate 3™) or an axial-flow pump (HeartMate II™), regardless of the intended goal of bridging to transplantation or destination therapy.3 Compared with the HeartMate II™ device, the early benefits of the HeartMate 3 device persisted for two years, with a favourable survival free from disabling stroke or reoperation to replace or remove a malfunctioning device (76.9% vs. 64.8%; relative risk [RR]=0.84 [95% CI: 0.78–0.91]; p<0.001 for superiority). Pump replacement (2.3% vs. 11.3%), pump thrombosis (1.4% vs. 13.9%), stroke (9.9% vs. 19.4%), disabling stroke (5.0% vs. 7.5%), bleeding (43.7% vs. 55.0%), and gastrointestinal bleeding (24.5% vs. 30.9%) were less frequent in the HeartMate 3™ group than in the HeartMate II™ group.
Data from the MOMENTUM 3 trial speak to the potential of a durable left ventricular assist device as a viable alternative to transplantation among patients with end-stage HF.
AUGUSTUS: apixaban in the treatment of ACS and AF
Lowering the ischaemic risk while controlling the bleeding risk with antithrombotic agents for acute coronary syndrome (ACS) AF has been a clinical conundrum.
AUGUSTUS (ClinicalTrials.gov: NCT02415400) was an open-label, randomised, two-by-two factorial trial comparing the safety of the direct oral anticoagulant (DOAC) apixaban versus a vitamin K antagonist (VKA) and aspirin versus placebo in 4,614 patients with AF and recent ACS or percutaneous coronary intervention (PCI) on background therapy with a P2Y12 inhibitor for six months.4 Compared with those receiving VKA, patients receiving apixaban had a lower rate of major or clinically relevant nonmajor bleeding (10.5% vs. 14.7%; HR=0.69 [95% CI: 0.58–0.81]) and death or hospitalisation (23.5% vs. 27.4%; HR=0.83; [95% CI: 0.74–0.93]) at six months. The aspirin group sustained more bleeding than the placebo group (16.1% vs. 9.0%; HR=1.89 [95% CI: 1.59–2.24]), but the incidence of ischaemic events was similar.
Consistent with the PIONEER AF-PCI and RE-DUAL PCI trials, the AUGUSTUS trial offers compelling evidence favouring a direct oral anticoagulant over VKA as the anticoagulant therapy for the AF-ACS population.
COACT sheds light on timing for coronary angiography
Although coronary artery disease is common in patients with cardiac arrest, the appropriate timing of coronary angiography is unclear when there is no evidence of ST-segment elevation on electrocardiography (ECG).
COACT (Netherlands Trial Register number: NTR4973) was an open-label, randomised trial comparing the strategy of immediate angiography versus delayed angiography among 552 successfully resuscitated patients following out-of-hospital cardiac arrest without ST-segment elevation on the ECG after the return of spontaneous circulation.5 At 90 days, 64.5% in the immediate angiography group and 67.2% in the delayed angiography group were alive (odds ratio [OR]=0.89 [95% CI: 0.62–1.27]; p=0.51). There was no significant difference in secondary end points, except that the immediate angiography group attained the target temperature later than the delayed angiography group (5.4 hours vs. 4.7 hours; ratio of geometric means=1.19 [95% CI: 1.04–1.36]).
Provided the low rate of thrombotic occlusion (5.0%) and lack of survival benefit, the COACT trial indicates that immediate angiography with intent to revascularise may not be necessary for patients without ST-elevation after a cardiac arrest.
Apple Heart Study
In the realm of digital health, there is an emerging interest in detecting arrhythmia by the wearable device, such as a smartwatch. The Apple Heart Study (ClinicalTrials.gov: NCT03335800) was an open-label study that assessed the ability of an irregular pulse notification-algorithm by The Apple Watch to identify AF and guide subsequent clinical evaluation in 419,297 self-enrolled participants.6
A notification was received by 2,161 (0.5%) participants, more frequently (3.1%) in those aged ≥65 years. A total of 450 participants had an ECG patch analysis after a telehealth consultation by the study physician and 34% had confirmed AF, yielding a positive predictive value of 84%. Among 1,376 subjects who completed the end-of-study survey at 90 days, 57% sought medical care outside the study for starting a new medication, referral to a specialist, or additional testing.
Building upon these results, the upcoming HEARTLINE trial will examine whether the use of ECG app on Apple Watch can improve AF diagnosis, clinical outcome, and medication adherence.
Each of these late-breaking studies represents a potential advance in their respective field of cardiovascular medicine. Whether these trials will be integrated into practice guidelines will be determined in the near future.
Conflicts of interest
GC and SHAK receive research grant support paid to the Beth Israel Deaconess Medical Center, Harvard Medical School from Portola Pharmaceuticals, Bayer, and Janssen Scientific Affairs. CMG receives consultant fees from Portola Pharmaceuticals and reports grants from Angel Medical Corporation and CSL Behring; grants and other support from Bayer Corporation; grants and personal fees from Janssen, Johnson & Johnson, and Portola Pharmaceuticals; and personal fees from The Medicines Company, Boston Clinical Research Institute, Cardiovascular Research Foundation, Eli Lilly, Gilead Sciences Inc, Novo Nordisk, Pfizer, Web MD, UpToDate in Cardiovascular Medicine, Amarin Pharma, Amgen, Arena Pharmaceuticals, Bayer Corporation, Boehringer Ingelheim, Chiesi, Merck & Co, PharmaMar, Sanofi, Somahlution, St Francis Hospital, and Verreseon Corporation.
Syed Hassan Abbas Kazmi
C Michael Gibson
Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 930 Commonwealth Avenue, Ste 3, Boston, Massachusetts 02215, United States
Correspondence to: Dr CM Gibson (firstname.lastname@example.org)
1. Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, Russo M, et al. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients. N Engl J Med. 2019;380(18):1695-705.
2. Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, O’Hair D, et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. 2019;380(18):1706-15.
3. Mehra MR, Uriel N, Naka Y, Cleveland JC, Jr., Yuzefpolskaya M, Salerno CT, et al. A Fully Magnetically Levitated Left Ventricular Assist Device – Final Report. N Engl J Med. 2019;380(17):1618-27.
4. Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med. 2019;380(16):1509-24.
5. Lemkes JS, Janssens GN, van der Hoeven NW, Jewbali LSD, Dubois EA, Meuwissen M, et al. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation. N Engl J Med. 2019;380(15):1397-407.
6. Turakhia M, Perez M. Results of a Large-scale, App-based Study to Identify Atrial Fibrillation Using a Smartwatch: The Apple Heart Study 2019 [Available from: https://www.acc.org/~/media/Clinical/PDF-Files/Approved-PDFs/2019/03/15/ACC19_Slides/Mar16_Sat/10amET_Apple-Heart-Study-acc-2019.pdf]