Important Trial Results for Interventional Cardiology From TCT 2017 and AHA 2017

By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on
Richmond, VA

Late Fall meetings in 2017 provided significant new study results, in some cases potentially changing the "the way we do things." Below is a compilation of selected studies impacting interventional cardiology that were presented at the 2017 Transcatheter Cardiovascular Therapeutics Meeting (TCT 2017) and the American Heart Association Scientific Sessions 2017 (AHA 2017). As we have done in the past, links to the trial descriptions are provided, but we focus on the comments of experts who discuss their perspectives on the relevance, significance, and even the limits of the trials, including opportunities for future investigations. As usual, I trust this will be beneficial to frame the scientific significance of these studies.

I thank my colleagues who have made this a reality with their hard work and thoughtful comments. Your comments are always welcome as well. I trust this will be a rewarding read.

CULPRIT-SHOCK: Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock
By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on
Richmond, VA

The CULPRIT-SHOCK trial, presented at TCT 2017, addressed an important, incompletely answered question regarding the management of cardiogenic shock: Should complete revascularization be performed at the time of culprit percutaneous coronary intervention (PCI)? Results from the CULPRI-SHOCK trial are a "No" based on a randomized strategy applied to 706 acute myocardial infarction (MI) patients undergoing PCI within 12 hours of the onset of shock, comparing complete revascularization, including chronic total occlusions (CTOs) versus culprit-only acute PCI. Patients undergoing complete revascularization had a significantly worse primary outcome of combined death and renal replacement therapy at 30 days. In a secondary analysis, mortality, therapy at 30 days was significantly higher in patients undergoing complete revascularization, and renal replacement therapy was more frequent but not significantly increased in patients undergoing complete revascularization. Patients received more contrast in the complete revascularization group, but given the lack of a significant impact of renal replacement therapy on the outcome, multiple factors affecting mortality likely drove the endpoint.

The study was well performed but emphasized the difficulties of studying a complex clinical problem. The patient profile was quite variable in terms of patient presentation and co-morbidities. The study population included patients post cardiac arrest, which imposes multiple external risk factors, and even patients up to 12 hours who may be late for a reasonable hope of salvage regardless of the therapeutic strategy of the PCI. Thus, universal applicability of the study may be guarded without perspective.

Randomized trials are excellent for comparing treatment strategies to avoid patient treatment biases, which may affect observed results. Conversely, in complex clinical circumstances with multiple variables, randomized trials may not provide needed flexibility to allow physician decision-making to target management. The CULPRIT-SHOCK trial is such an example because reasonable clinicians outside randomization might decide to limit multivessel PCI in cases in which additional vessel treated with PCI would be extremely complex, and thus it is not performed for a reasonable clinical reason. Whether such an individualized approach could improve outcomes is unknown; that may be a good question as this trial is assessed for changing guidelines, particularly regarding the impact of CTO revascularization in the setting of shock.

The overall high mortality for both strategies again reaffirms the high-risk nature of cardiogenic shock as a disease state and emphasizes the need to look for new strategies to significantly improve outcome. Renal failure1 might be ameliorated by improved cardiac output with hemodynamic support. Early unloading with Impella (Abiomed; Danvers, MA) mechanical cardiac support (as proposed by Dr. William O'Neil as the Detroit Cardiogenic Shock Initiative project,2 now expanding nationally) may provide an improved potential for outcome. Regarding the timing of complete revascularization, an individualized, selective approach that is based on the patient's renal function, probability of acute PCI success, likelihood of viability in each distribution, and CTOs based on a patient's response to initial culprit lesion PCI seems most appropriate.

ORBITA: Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina
By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on
Richmond, VA

Much and perhaps too much has already been stated, argued, and sometimes rationally discussed about this trial that was presented at TCT 2017 and included in every possible electronic and print media. I can hopefully add a few rational comments to this intense discussion.

First, the trial is unique because it is the first sham controlled trial looking at the potential benefits of PCI. Despite some discussion, the trial seems ethical given that patients understood the meaning and potential impact of the trial to them individually. This may lead to more such trials, but likely enrollment in a trial of a larger size may be challenging.

Second, the value of PCI for stable angina to date has focused on relief of symptoms. Thus, the trial was constructed to determine if PCI was better at symptom control than medical therapy. However, the probability that angina would be more effectively controlled with PCI seems a priori to be unlikely given the upfront patient management. These patients all were maximally medically managed before randomization and had excellent exercise performance before randomization. The probability that PCI could further benefit the patients by over 30 seconds of exercise time seems unlikely given the excellent baseline exercise performance of both groups. And at the end, the PCI arm showed significantly improved exercise performance by 28 seconds within group but was only 16.6 seconds better than the placebo group, which did not meet the pre-specified, 30-second improvement in exercise time compared to placebo.

The placebo patients had an 11-second, non-significant improvement in exercise time within group. Thus, PCI did improve exercise time but not sufficiently to make the preset bar. As noted above, given the study design, this does not seem a surprise. But as the presenter noted, the endpoint was only 6 weeks, and longer-term follow-up of the patients will be necessary to determine if compliance challenges and/or medication tolerance will affect outcome difference over time.

The last important point is the issue of whether eliminating ischemia, more effectively accomplished by PCI than medications in studies, will have an impact on outcome. The ongoing ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial3 will help answer that question related to PCI in general. However, multiple recent studies have suggested that more complete revascularization is associated with better outcomes in stable ischemia with multivessel disease. The most recent evidence for that comes from the New York Database which demonstrated advantages relating to multivessel disease including the proximal left anterior descending artery.4 One important point is that if one hopes to show a difference in outcome for PCI related to elimination of ischemia, late follow-up of patients for up to 5 years may be necessary to show a difference. This length of follow-up has been seen in the PCI multivessel disease studies, but in surgical studies, including the STICHES (STICH Extension Study) trial and ROOBY-FS (Randomized On/Off Bypass Trial Follow-up Extension),5 survival benefits are often not seen until 5-year follow-up.

In summary, the study is unique in adding a sham control to the assessment of PCI benefit or lack thereof in stable ischemia, but was structured in a way that PCI was unlikely to show an exercise benefit at 6 months. Longer-term follow-up relative to the issues of medical therapy versus the late complications of PCI will be necessary. Lastly, the need to assess the impact of ischemia may not be settled by such a small study but will likely will take a study with much longer follow-up to answer that question. In the meantime, clinicians and interventionalists must make the best clinical decisions for patients not based on an "oculostenotic" response but based on guidelines and honest judgement because many patients may be challenged by compliance or medical side effects or may not have excellent baseline exercise tolerance, in which case PCI remains a viable and beneficial option for selected patients.

SENIOR: A Randomized Trial of a Bioabsorbable Polymer-Based Metallic DES vs. a BMS With Short DAPT in Patients With Coronary Artery Disease Older Than 75 Years
By Mark B. Effron, MD, FACC
Ochsner Health System
New Orleans, LA

SENIOR, presented at TCT 2017 by Olivier Varenne and published simultaneously in The Lancet,6 showed that a bioabsorbable polymer drug-eluting stent (DES) (SYNERGY [Boston Scientific; Marlborough, MA]) reduced the 1-year primary endpoint of death, MI, stroke, or ischemic-driven target lesion revascularization (TLR) compared with a thin strut bare-metal stent (BMS) (OMEGA or REBEL, [Boston Scientific; Marlborough, MA]) in patients at higher risk of ischemia and bleeding (aged 75 years or older) treated with short-term dual antiplatelet therapy (DAPT): 6 months acute coronary syndrome (ACS); 1 month non-ACS] The difference was primarily driven by ischemic-driven TLR with a trend toward lower mortality in the DES group and no difference in definite or probable stent thrombosis (ST) or bleeding (Bleeding Academic Research Consortium [BARC] 2-5 or BARC 3-5).

What are the take-home messages from this study? First, in a high-risk group of patients for whom use of DAPT for any duration is of concern, there was no increase in the primary endpoint with DES compared with BMS. In fact, a decrease driven by reduced ischemic-driven TLR was seen with DES, which is the primary reason that DES were developed. Second, this reduction did not occur at the expense of increased ST, not even after DAPT was discontinued as seen in the DAPT (Dual Antiplatelet Therapy) study. Third, the bleeding rates were lower in SENIOR than in the same patients with similar ischemic rates in TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38 (prasugrel or clopidogrel) and PLATO (Platelet Inhibition and Patient Outcomes) (ticagelor or clopidogrel), suggesting that newer stents may be better tolerated than previous-generation DES without the need for prolonged DAPT. Finally, given the higher risk of procedures in this group of patients, less ischemic-driven TLR is a very desirable outcome that would affect quality of life for this patient group.

What questions are unanswered? The subgroup analysis shows no difference in women between the two stents and numerically more events in patients with atrial fibrillation. Further evaluation of these subgroups is needed, but there is still no clear signal that short-term DAPT in newer-generation DES will be worse than in patients with BMS. Additionally, part of the benefit of long-term DAPT is the reduction of non-stent-related events. The risk and benefit of long-term versus short-term DAPT in the elderly population still need to be addressed, but SENIOR shows that DES can be used in any such study so that ischemic-driven TLR will play less of a role in the outcome.

PROTECT-AF: WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation
PREVAIL: Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy

By Kenneth A. Ellenbogen, MD, FACC
Virginia Commonwealth University School of Medicine
Richmond, VA

PROTECT-AF and PREVAIL are the only two randomized trials performed that compare the WATCHMAN (Boston Scientific; Marlborough, MA) device with warfarin for prevention of cardiovascular/unexplained death, stroke, or system embolism.

The PROTECT-AF trial enrolled patients with a CHADS2 score of at least 1, and PREVAIL included patients with a CHADS2 score of ≥2. The primary safety endpoint was WATCHMAN retrieval, pericardial effusion, or any bleeding that required transfusion. PROTECT-AF was non-inferior to warfarin with respect to the primary endpoint, and PREVAIL, a smaller study, did not reach noninferiority likely because of a low incidence of stroke in the control (warfarin) arm. The take-home message from a pooled meta-analysis of these two studies shows that after 5 years of follow-up, cardiovascular/unexplained death, stroke, or systemic embolism was not different between the 2 groups. Major bleeding or non-procedure-related bleeding was reduced by over 50% in the WATCHMAN group.

The data from these trials with long-term follow-up show that over time, the WATCHMAN has a place in the prevention of stroke in patients who cannot take long-term anticoagulation and benefits patients by reducing the risk of future bleeding. Studies in progress will further define the role of left atrial appendage occlusion devices by comparing their efficacy and safety to novel oral anticoagulants (Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation [NCT02426944], Evaluation of WATCHMAN Left Atrial Appendage Occlusion Device in Patients With Atrial Fibrillation Versus Rivaroxaban [NCT02549963], and Left Atrial Appendage Occlusion Versus New Oral Anticoagulants for Stroke Prevention in Patients With Non-valvular Atrial Fibrillation [NCT03108872]). Additional future studies will test alternative strategies for anticoagulation in the post-implant period.

GEMINI-ACS-1: Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome
By Dominick J. Angiolillo, MD, PhD, FACC
University of Florida College of Medicine – Jacksonville
Jacksonville, FL

The GEMINI-ACS-1 study was a double-blind, multicenter, randomized trial assessing the safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor. In particular, the trial assessed rivaroxaban 2.5 mg bid versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomization), for patients with ACS (n = 3037) started within 10 days after presentation and continued for 6-12 months. The trial showed that low-dose rivaroxaban (2.5 mg bid) does not result in higher bleeding compared with aspirin 100 mg daily in patients already on a P2Y12 inhibitor post-ACS. Ischemic endpoints were also similar, but the trial was not powered to assess these independently.

In the trial, reporting of CYP2C19 metabolizer status was required for all subjects. The rationale for this was the potential for lack of efficacy (and potential harm) with low-dose rivaroxaban as the sole antithrombotic in clopidogrel nonresponders. The genetic information was sent from the central laboratory to investigators within 1 week of randomization. The results of genetic testing revealed the following: 34.4% were ultra-metabolizers, 37.8% were extensive metabolizers, 24.5% were intermediate metabolizers, and 3.2% were reduced metabolizers. This information was provided to the enrolling investigators, but no recommendations were given regarding P2Y12 inhibitor therapy choices. Only 6.5% of patients had their P2Y12 inhibitor drug changed after a mean of 40 days. Ticagrelor switching occurred more often than clopidogrel switching (p < 0.001). In fact, 144 patients switched from ticagrelor to clopidogrel after a mean 62.5 days, and 53 switched from clopidogrel to ticagrelor at a mean 30 days. Reasons for de-escalation switching from ticagrelor to clopidogrel were mostly due to nonbleeding adverse events, and CYP219 genotype status was the driver for most patients who escalated from clopidogrel to ticagrelor therapy. However, of the 611 clopidogrel-treated patients whom physicians initially said they would switch based on genetic information, only 34 switched. Similarly, of the 96 ticagrelor-treated patients whom physicians thought would be switched, only 14 switched. Switching was most common in patients with reduced metabolizer status and those who were in North America and Western Europe. Metabolizer status had no effect on ischemic or bleeding outcomes.

The take-home message from this analysis is that in GEMINI-ACS-1, switching of P2Y12 inhibitors was infrequent despite direct reporting of CYP2C19 metabolizer status to investigators. When switching occurred, this was more commonly from ticagrelor to clopidogrel due to adverse events, rather than from clopidogrel to ticagrelor. The results of this analysis argue against the utility of mandatory testing of CYP2C19 metabolizer status in this context because the majority of investigators did not act on the information. In fact, in 2010 the US Food and Drug Administration mandated the addition of box warning to the clopidogrel labeling information recommending pharmacogenomic testing for patients with two loss-of-function alleles of the CYP2C19 gene, and the agency required this testing in any clinical trial that uses clopidogrel. These findings overall are in line with the perception from practicing clinicians on the (lack of) utility of genetic testing. In fact, to date, there are no large scale, randomized clinical trials that have shown how switching therapy based on results of genetic testing can affect clinical outcomes. Indeed, several randomized trials assessing the clinical impact of personalizing antiplatelet treatment based on the results of genetic testing are still ongoing.

Moreover, a number of ongoing registry databases are currently ongoing assessing physician response to the results of genetic testing in real-world clinical practice (outside a clinical trial). The availability of rapid bedside genetic testing, which is able to provide results in 1 hour, have facilitated the conduct of these studies, which will provide more insights into this topic of personalized antiplatelet therapy.

POISE-2: Perioperative Ischemic Evaluation 2
By Peter B. Berger, MD, FACC
Carmel, NY

In this POISE-2 substudy, 457 patients were analyzed, representing only 4.6% of the 10,010 patients enrolled in the overall trial. Clinicians must recognize that the results of such subgroup analyses, even when they are pre-specified, should not be considered to represent even moderately strong evidence of "truth." With as many subgroups as are pre-specified in a modern large, randomized trial, the odds are that one or more will be positive purely by chance, when a 0.05 p-value is considered to represent statistical significance. Accordingly, a chi-square test with 0.05 representing significance (which appears to be what was done in this analysis) is not the appropriate way to examine a subgroup. Much stricter statistical tests should be used.

Furthermore, the pre-PCI group in this analysis included patients who received DES or BMS and patients who underwent balloon angioplasty; these 3 groups might well derive different benefits from perioperative aspirin. Acknowledging as much, inclusion criteria for the study required differential durations of time between the 3 different types of revascularization and enrollment. (Whether a stent was used, and what type of stent was used, is unknown in 12.1% of patients in this analysis.) Perhaps most importantly, however, proof of the definite role of chance in this analysis can be seen in the effect of aspirin on bleeding. In the overall POISE-2 trial, aspirin increased the frequency of major bleeding by 22%, consistent with virtually all prior studies of aspirin. In the PCI subgroup analysis, however, perioperative aspirin was associated with a 15% reduction in major bleeding. Clearly this represents the play of chance in this subgroup. Additional evidence of chance is suggested by the observation that because MI was reduced a whopping 56% by aspirin among patients with prior PCI, and because MI is often fatal in the postoperative setting, the observation that aspirin did not reduce mortality in the trial (there was 1 fewer death in the aspirin subgroup than the placebo subgroup) further demonstrates the play of chance in this analysis.

What, then, should clinicians recommend regarding perioperative aspirin in their patients with prior PCI? I would argue that 1) because it is highly unlikely that an appropriately sized randomized trial will be performed among such patients to definitively answer the question; 2) because aspirin alone has been studied early after balloon angioplasty and shown to be beneficial; 3) because DAPT is beneficial long after DES placement and even BMS placement, but P2Y12 inhibition is often not permitted during and immediately following major surgery; 4) because antiplatelet therapy is generally believed to be beneficial more broadly among patients with coronary artery disease; and 5) because surgery is a highly pro-thrombotic state due to the underlying disease requiring surgery, the anesthetics administered, and the surgery itself, I believe that aspirin should be continued perioperatively unless brain or spinal cord surgery or other types of surgery exquisitely sensitive to bleeding are planned.

PRAGUE-18: One Year Outcomes of Patients with Acute Myocardial Infarction Treated with Primary Angioplasty and Randomised to Prasugrel versus Ticagrelor
By Paul A. Gurbel, MD, FACC
Inova Center for Thrombosis Research and Translational Medicine
Falls Church, VA

The PRAGUE-18 trial was planned to be a head-to-head comparison of the effects of prasugrel versus ticagrelor on the primary endpoint of cardiovascular death, non-fatal MI, and stroke in patients treated with PCI who had ST-segment elevation myocardial infarction (STEMI) and high-risk non-STEMI with intended treatment duration of 12 months. The study had no industrial support. Enrollment was terminated early for futility with 1,230 patients randomized; the sample size estimated to determine a 2.5% difference in the primary endpoint was 1,250 per arm. No differences in the primary endpoint were observed between groups. The study protocol allowed patients who were unwilling to accept the cost of either prasugrel or ticagrelor to switch to clopidogrel; in the 2 arms, 34 and 44% switched for that reason and another 15 and 14% switched for other reasons, respectively. Patients who switched had overall lower Killip class and had a lower frequency of left main disease and suboptimal PCI results.

There are two major unresolved issues in the treatment of the high-risk ACS patient: 1) the comparative efficacy of the two most potent P2Y12 inhibitors and 2) the efficacy and safety of switching to clopidogrel. Although the primary endpoint of PRAGUE-18 was no different between arms, the sample size was inadequate to determine clinical differences between these two agents. Moreover, the high frequency of non-randomized switching to clopidogrel, and the differences in clinical and angiographic variables between those who switched versus those who didn't, limit any conclusions that can be made about comparative agent efficacy and the efficacy and safety of switching to clopidogrel.

PRESERVE: Prevention of Serious Adverse Events Following Angiography
By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on
Richmond, VA

The technical achievements of first coronary angiography and more recently PCI have been limited in many instances by the adverse consequences of the contrast used to achieve the procedural success because of contrast-induced nephropathy (CIN) leading to acute and late adverse clinical, and at times mortal, consequences.

Hydration and limiting contrast volume have been mainstays of minimizing adverse contrast effect. Multiple modifications of contrast agents and adjunctive therapies have been studied with limited to no benefit ultimately being achieved. Encouraged by the low cost of sodium bicarbonate and/or N-acetylcysteine and unhindered by results of registry and underpowered trials, there has been continued use of these strategies without definitive data.

In a trial lead by the VA Cooperative Trials team, two separate comparisons were made comparing sodium bicarbonate infusions with normal saline and a separate study of N-acetylcysteine to placebo in patients undergoing coronary and non-coronary angiography. The overall study comprised just under 5,000 patients and aimed to definitively answer the question of whether either of these agents provided benefit. The primary endpoints were death, dialysis, or persistent increase in serum creatinine ≥50% at 90 days after the procedure. Neither agent showed a significant benefit in these defined and important endpoints.

Although some may argue that there are still potential subgroups or circumstances in which one or the other agent might make a difference, it seems that most clinicians and investigators feel the question is answered and consider these interventions to reduce contrast risk not beneficial. Thus, the PRESERVE trial did a service in establishing once and for all that sodium bicarbonate and/or N-acetylcysteine are not of benefit to prevent CIN and thus clinicians must focus on important clinical strategies to hydrate patients well, maintain renal perfusion as best as possible in the setting of low output, and minimize contrast as much as feasible within the needs of achieving an optimal procedure.

STEMI ACCELERATOR-2 - Regional STEMI Systems of Care: Results of the Mission: Lifeline STEMI ACCELERATOR-2 Study
By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on
Richmond, VA

Training and organization make a difference!

Arguably, the most significant advancement in medical care related to PCI is the dramatic improvement in STEMI outcomes related to early reperfusion. Now, more than 10 years since the 90-minute door-to-balloon concept was put into action, the in-hospital mortality for STEMI without shock has decreased from 20-25% to less than 5%. Likewise, late outcomes have improved dramatically with STEMI; cardiogenic shock remains the "outlier" with no similar, significant improvement in outcome. With such progress in non-shock STEMI, it would be easy to stop looking for advancements because the potential for a significant, further improvement would seem unlikely.

Fortunately, Jolles et al. who presented STEMI ACCELERATOR-2 at AHA 2017 were not dissuaded from seeking further improvements. Recognizing that there remain significant regional variations in STEMI care coordination between Emergency Medical Services (EMS) and hospitals, these investigators set about testing the hypothesis that improved training and coordination could improve door-to-balloon and, ultimately, outcomes.

Incorporating training and organization recorded via the ACTION Registry-Get With The Guidelines for quarterly Mission: Lifeline reports, the study focused on 12 metropolitan regions across the United States with 132 PCI-capable hospitals and 946 EMS agencies. Over a 2-year period, advanced training and coordination resulted in the following improvements for these 12 regions:

  • First medical contact to device time of ≤90 minutes increased from 67 to 74%.
  • Catheterization laboratory activation time (from the field) <20 minutes increased from 38 to 56%.
  • Emergency department dwell time of <20 minutes improved from 33 to 43%.

These highly significant improvements resulted in a significant reduction in mortality; in-hospital mortality fell nearly 50% from 4.4 to 2.3% (p = 0.001). No improvement in outcomes was seen in non-participating hospitals during the same timeframe.

These results have significant implications for what organization and training can do even in the setting of assumed "good results." I hope this observation will lead to overall improvements in STEMI care nationally by emphasizing training and utilizing hospitals with the best overall organizational structures and outcomes. These results likely have similar implications for STEMI with cardiogenic shock where evolving research is being targeted to optimal and rapid complex treatment strategies.

REDUCE LAP-HF I Randomized Control Trial – Transcatheter InterAtrial Shunt Device for the Treatment of Heart Failure
By Keyur B. Shah, MD, FACC
The Pauley Heart Center, Virginia Commonwealth University
Richmond, VA

In contrast to heart failure (HF) with reduced ejection fraction, patients with symptomatic HF and preserved or mid-range ejection fraction (left ventricular ejection fraction = 40-50%) have few clinically impactful treatment options. Interatrial shunt devices are being explored as ways to reduce left atrial pressure and improve functional capacity. Data from a phase I, single-arm study established the safety and potential hemodynamic benefits of a device that creates an 8 mm atrial septal defect (IASD [Corvia Medical, Inc; Tewkesbury, MA]).

The phase II REDUCE LAP-HF randomized clinical trial data were presented at AHA 2017. The study randomized 44 patients with symptomatic HF (New York Heart Association III or IV) to either active treatment with the IASD device or a sham control group. The investigators reported on early results with 1-month data on hemodynamic and safety endpoints. From baseline, the investigators reported a decrease in exercise pulmonary capillary wedge pressure with bicycle exercise (20 watts) and with resting leg raise. At this short-term follow-up, there was no signal or event to suggest procedural harm or sub-acute shunt-related worsening of right heart function or pulmonary hypertension.

This comparative trial confirms the hemodynamics findings observed in the phase I single-arm study. The longer-term effects of an iatrogenic left to right shunt for patients with HF on quality of life, functional capacity, and survival will be addressed by the REDUCE LAP-HF II pivotal trial.


  1. Flaherty MP, Pant S, Patel SV, et al. Hemodynamic Support With a Microaxial Percutaneous Left Ventricular Assist Device (Impella) Protects Against Acute Kidney Injury in Patients Undergoing High-Risk Percutaneous Coronary Intervention. Circ Res 2017;120:692-770.
  2. O'Neill W. Outcomes for 15,259 US Patients With Acute MI Cardiogenic Shock (AMICS) Supported With Impella. Presented at the American College of Cardiology Annual 66th Annual Scientific Session & Expo. March 19, 2017;Washington, DC.
  3. International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) ( website). 2018. Available at: Accessed 01/17/2018.
  4. Hannan EL, Zhong Y, Berger PB, et al. Association of Coronary Vessel Characteristics With Outcome in Patients With Percutaneous Coronary Interventions With Incomplete Revascularization. JAMA Cardiol 2017;Dec 27:[Epub ahead of print].
  5. Shroyer AL, Hattler B, Wagner TH, et al. Five-Year Outcomes after On-Pump and Off-Pump Coronary-Artery Bypass. N Engl J Med 2017;377:623-32.
  6. Varenne O, Cook S, Sideris G, et al. Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial. Lancet 2018;391:41-50.

Keywords: AHA Annual Scientific Sessions, AHA17, Transcatheter Cardiovascular Therapeutics, TCT17, Heart Valve Diseases, Absorbable Implants, Acetylcysteine, Acute Coronary Syndrome, Adenosine, Aged, Alleles, Anesthetics, Angina, Stable, Angioplasty, Angioplasty, Balloon, Coronary, Anticoagulants, Aspirin, Arteries, Atrial Appendage, Atrial Fibrillation, Atrial Pressure, Blood Platelets, Brain, Cardiac Output, Catheterization, Chi-Square Distribution, Control Groups, Coronary Angiography, Coronary Artery Disease, Creatinine, Decision Making, Double-Blind Method, Drug-Eluting Stents, Embolism, Drug-Eluting Stents, Emergency Medical Services, Emergency Service, Hospital, Exercise Tolerance, Fibrinolytic Agents, Flavins, Genotype, Heart Arrest, Heart Failure, Heart Septal Defects, Atrial, Hemodynamics, Hemorrhage, Hospital Mortality, Hypertension, Pulmonary, Iatrogenic Disease, Incidence, Luciferases, Mandatory Testing, Medical Futility, Myocardial Infarction, Percutaneous Coronary Intervention, Pericardial Effusion, Platelet Aggregation Inhibitors, Polyethylene Glycols, Polymers, Pulmonary Wedge Pressure, Quality of Life, Random Allocation, Registries, Renal Replacement Therapy, Research Personnel, Risk Factors, Sample Size, Shock, Cardiogenic, Sodium Bicarbonate, Spinal Cord, Stents, Stroke, Stroke Volume, Thrombosis, Purinergic P2Y Receptor Antagonists, Ticlopidine, Warfarin

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