Introduction
The 2020 European Society of Cardiology Congress (ESC Congress 2020) offered a large number of important clinical trials, striking in the breadth of topics covered. Below are summaries of many of the trials and "Quick Takes" for each to provide targeted highlights. I must thank the contributors for their excellent commentary. I trust you will enjoy the many topics ranging from anticoagulation strategies to valve and coronary trials. As always, comments are appreciated.

ISCHEMIA: Treatment for Patients With Stable Ischemic Heart Disease and Heart Failure
By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on ACC.org
Richmond, VA

ISCHEMIA randomized stable patients with at least moderate ischemia on stress testing and an LVEF ≥35% to an initial invasive versus optimal medical treatment strategy. Patients with LVEF <35%, left main >50%, recent myocardial infarction (MI), New York Heart Association HF Class III or IV, severe renal dysfunction, and percutaneous coronary intervention (PCI) or coronary artery bypass grafting in the last year were excluded. Over 4-year follow-up, there was no difference between the groups for the primary outcome (cardiovascular death, nonfatal MI, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest) between treatment strategies (13.3% for the invasive group vs. 15.5% for the medical therapy group; p = 0.34). Subgroup outcomes were likewise not significantly different.

At ESC Congress 2020, Renato Lopes et al.¹ reported an analysis of outcomes for patients with a history of HF and/or a modest reduction in LVEF (35-45%) given the lower limit of ≤35% of left ventricular (LV) function allowed in the trial. The authors looked at overall risk for this cohort regardless of randomized treatment strategy as well as the potential for a treatment effect. The results are as follows:

• Patients (398) with HF/LVEF represented 7.7% of the entire trial, of which 44% had HF with LVEF >45% but no history of HF; 49% had LVEF 35-45%, and 7% had both HF and LVEF 35-45%.
• HF and/or LVEF 35-45% patients had more frequent baseline comorbidities of prior MI, stroke, and hypertension.
• The 4-year cumulative primary outcome occurred more often in the HF/LVEF 35-45% group compared to those without HF/LVEF 35-45% (22.7% vs. 13.8%; p = 0.004), with similar, significant differences for cardiovascular death or MI (19.7% vs. 12.3%) and all-cause death or HF (15.0% vs. 6.9%).
• For patients with HF/LVEF 35-45% randomized to an initial invasive strategy, the primary outcome was lower (17.2% vs. 29.3%; difference in 4-year event rate = -12.1%; 95% confidence interval [CI], -22.6, -1.6%) compared to those without HF/LVEF 35-45% (13.0% vs. 14.6%; difference in 4-year event rate = -1.6%; 95% CI, -3.8%, 0.7%; p-interaction = 0.055). Similar directional changes were seen for all-cause mortality, and cardiovascular mortality outcomes were analyzed with LVEF as a continuous variable comparing patients with or without a history of prior HF.

Although the overall numbers are small, these results suggest that future studies need to focus on the increased risk of ischemia in the setting of even modest reductions in LVEF and/or a history of HF. The impact of this comparison might be more striking if completeness of revascularization had been added to the analysis. In the setting of LV dysfunction with or without HF, this likely could offer insight into the importance of effectively alleviating ischemia on outcome.   

In summary, these results again suggest increased importance of ischemia treatment in patients with HF and/or even modest reductions of LVEF. Thus, individualized therapeutic decisions regarding treatment strategies focused on the most effective elimination of ischemia seem warranted in these patients to achieve optimum results while awaiting future study results.

BAMI: Autologous Cell Therapy for the Treatment of Acute Myocardial Infarction
By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on ACC.org
Richmond, VA

BAMI is another in a series of trials evaluating various regimens to improve myocardial recovery through the use of stem cells to stimulate effective myocardial cell regeneration following MI. BAMI involved 10 countries with 37 centers including 4 cell-processing centers. Patients were randomized 1:1 to standard therapy or cell therapy after STEMI presentation and successful reperfusion. Patients were included if LVEF by echocardiogram was ≤45%. Harvested bone marrow cells were injected 2-8 days post successful reperfusion. There were 185 patients analyzed in the treatment arm and 190 patients in the control arm. Interestingly, the treatment arm had significantly more insulin-treated diabetics and patients with prior MI and prior coronary interventions. The core laboratory LVEF was 39% for both groups, and the treated vessel was the left anterior descending in 86% of cases.

The primary endpoint at 2 years showed an all-cause mortality of 3.3% (6/185) in the bone marrow cell treatment group versus 3.8% (7/190) in the standard therapy group (p = 0.77). Secondary outcomes included cardiovascular death or HF hospitalization occurring in 4.9% of bone marrow treated patients compared to 9.7% in the control group. Despite the favorable numbers, this difference was NOT significant. These negative results were likely influenced by a significantly lower incidence of HF hospitalizations for this group than predicted.

BAMI was hampered by slow enrollment coupled with an unexpectedly low incidence in mortality and HF admissions. The impact of imbalances in important baseline characteristics is unknown. Thus, the trial as presented does not qualify as hypothesis generating; it is observational only. It should be noted that this is not the first negative trial of cell therapy. These results do not apply to other circumstances of low ejection fraction and HF. However, any future trials must carefully assess the numbers of expected endpoints, which for BAMI were significantly less than expected given improvements in acute MI outcomes over time.

DUBIUS: Downstream or Upstream P2Y12 Receptor Blockers in NSTE-ACS
By Subhash Banerjee, MD, FACC
University of Texas Southwestern Medical Center and VA North Texas Health Care System
Dallas, TX

The multi-center, randomized, and open-label strategy DUBIUS (Downstream Versus Upstream Administration of P2Y12 Receptor Blockers in Non-ST-Elevated Acute Coronary Syndromes With Initial Invasive Indication) trial compared the efficacy and safety of upstream ticagrelor with downstream (after defining coronary anatomy) administration of ticagrelor or prasugrel among patients with NSTE-ACS with planned invasive strategy. The primary endpoint, a composite of death, ischemic events, and significant bleeding events at 30 days, was similar between the strategies (upstream 3.3% vs. downstream 2.9%; absolute risk reduction -0.46; 95% CI, -2.87 to 1.89). Indeed, the trial was terminated early for futility. Further, the primary endpoint did not differ significantly between downstream use prasugrel or ticagrelor (4.1% vs. 3.1%; absolute risk reduction 0.9; 95% CI, -3 to 5). Major bleeding (BARC 3-5) was low across groups (upstream 1.9% vs. downstream 1.6%).

The study enrolled relatively low-risk patients with NSTE-ACS (based on reported GRACE and CRUSADE scores) (25% were diabetic) and had high (~95%) use of radial access. Use of radial access PCI in this trial is much higher than in the ISAR-REACT 5 (Intracoronary Stenting and Antithrombotic Regimen 5) trials. This may have contributed to the lower than anticipated rates of bleeding observed in the trial. In addition, the combination of relatively low-risk patients with NSTE-ACS and a short time interval (mean ~23 hours) to coronary angiography may have rendered the strategic comparisons inconsequential.

The American College of Cardiology and American Heart Association 2014 guidelines endorse upstream use of ticagrelor or clopidogrel in NSTE-ACS (Class I, Level of Evidence B).² The combined evidence of the ISAR-REACT 5 and DUBIUS trials may move the needle to qualify the next iteration of the guideline statement to include downstream use of all three contemporary oral P2Y12 inhibitors in patients with NSTE-ACS who are destined for an early invasive strategy. This could make the guideline more consonant with real-world practice where downstream use remains prevalent. I congratulate Dr. Giuseppe Tarantini and his colleagues for their efforts to undertake this critically relevant investigator-initiated clinical strategy trial.

SWEDEHEART Registry: Ticagrelor and Clopidogrel in Elderly with Acute Coronary Syndrome
By Subhash Banerjee, MD, FACC
University of Texas Southwestern Medical Center and VA North Texas Health Care System
Dallas, TX

This analysis from the SWEDEHEART Registry is the largest to explore the safety and efficacy of ticagrelor in an all-comer, elderly (>80 years) post-MI patient cohort discharged alive from the hospital. The primary ischemic outcome (death, MI, or stroke) was similar for ticagrelor-treated and clopidogrel-treated patients (hazard ratio 0.97; 95% CI, 0.88-1.06). Ticagrelor was associated with a 17% higher risk of death and a 48% higher risk of bleeding, both statistically significant. Incidence of MI and stroke were significantly lower. Although these data create some uncertainty reading the use of a P2Y12 inhibitor more potent than clopidogrel (in this case ticagrelor), it should be interpreted with some caution given inherent limitations of an observational study despite propensity matching. The authors, in an ahead-of-print version of their manuscript, provide a fair and balanced perspective of the inherent limitations. It is important to indicate that the study does not account for early termination, interruption, or crossover of the P2Y12 inhibitors, which is not uncommon in this age group.

Although age is a strong predictor of bleeding, not all 80-year-old patients are similar. This is perhaps best demonstrated by the lack of an interaction between age and treatment assignment in the PLATO (Platelet Inhibition and Patient Outcomes) randomized clinical trial. I must say, I am not surprised by the findings of this SWEEDHEART Registry analysis. More importantly than relying on an arbitrary age criterion for senior citizens, this study in my view calls for a more individualized and nuanced approach to the selection of P2Y12 inhibitors in elderly post-MI patients. Other options to mitigate the risk of excess bleeding in the elderly could include ticagrelor monotherapy, de-escalation to clopidogrel, low-dose prasugrel, an abbreviated (6-month) duration of dual antiplatelet therapy (DAPT), or a platelet-function-test guided approach. All in all, this analysis from the SWEDEHEART Registry sets the stage for a dedicated randomized clinical trial to guide antiplatelet strategy in elderly post-MI patients.

ATPCI: Trimetazidine in Angina Patients With Recent Successful Percutaneous Coronary Intervention
By Chalak O. Berzingi MD, FACC
Carilion Clinic
Christiansburg, VA

The ATPCI (Efficacy and Safety of Trimetazidine in Patients Having Been Treated by Percutaneous Coronary Intervention) trial is a well-designed and conducted trial that was presented at ESC Congress 2020 and simultaneously published in The Lancet. Trimetazidine is not approved by the US Food and Drug Administration for use in the United States but is commonly used outside of western Europe and North America as an add-on treatment for angina with the presumption of improving energy metabolism of ischemic myocardium, delaying the onset of angina, and decreasing severity and frequency of angina.

This study enrolled 6,007 subjects who underwent successful PCI and were randomly assigned to either trimetazidine (n = 2,998) or placebo (n = 3,009) and followed for 47.5 months. In this trial, it was found that routine use of trimetazidine after recent successful PCI in addition to optimal standard medical treatment did not prevent further cardiac events and did not improve further control of angina. There was no significant difference whether PCI was performed for stable coronary artery disease (CAD) versus unstable angina or non-STEMI. Although the prevalence of angina was relatively low post-PCI (18.1% at 1 month, 15.1% at 1 year, and 9.8% at the end of the study), it did not differ significantly between the 2 treatment groups.

A limitation of the applicability of this trial to clinical practice is that it applies only to a narrow spectrum of patients with angina who underwent a successful PCI as an add-on medication. These results cannot be generalized to the broader populations of patients with angina syndrome.
Although previous smaller-scale studies have suggested a favorable effect of trimetazidine in the control of angina and time to ischemia in patients with established CAD, these results were not replicated in this study. Given that this trial was larger in scale with a greater statistical power, the grounds for use of this medication regimen remains questionable.

POPular TAVI: Aspirin With or Without Clopidogrel After Transcatheter Aortic Valve Implantation
By Zachary M. Gertz, MD
Pauley Heart Center VCU Medical Center and VCU School of Medicine
Richmond, VA

The POPular TAVI (Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic-Valve Implantation) trial was designed to assess the utility of DAPT compared to single therapy in patients undergoing TAVR. Patients were excluded if they had an indication for oral anticoagulation or an indication for DAPT because of a recent coronary stent. The study showed that treatment with aspirin plus clopidogrel, as opposed to aspirin alone, resulted in a significant increase in bleeding events, with no reduction in thrombotic events such as stroke or MI. Although the majority of bleeding events were minor, the percentage of patients with major, life-threatening, or disabling bleeding was more than twice as high in the dual-therapy group. The findings of this trial reinforce those from the ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) trial, a smaller trial that was halted due to slow enrollment. Taken together, it is clear that in the absence of another indication, the addition of clopidogrel to aspirin is not worthwhile in patients undergoing TAVR because it exposes them to unnecessary risk. One would expect to see this reflected in the next iteration of guidelines, which should remove the current recommendation for DAPT for up to 6 months after TAVR.

Beyond the immediate impact of the POPular TAVI trial on treatment of TAVR patients, it raises new questions that should be considered in future trials. There is ongoing debate about whether to address coronary disease before or after TAVR. With this new information available, trial protocols should consider whether TAVR should be postponed for 3 months after coronary intervention to allow for clopidogrel to be completed, or whether shorter-duration DAPT is feasible in patients in whom TAVR cannot be postponed.

This trial also prompts us to consider whether even single antiplatelet therapy is beneficial in TAVR patients. Patients with aortic stenosis, who have higher bleeding risk due to the pathophysiology of the disease (a risk that may persist even after TAVR), may not benefit from even aspirin monotherapy. It appears that leaflet thrombosis, whether clinical or sub-clinical, is the most common thrombotic even after TAVR, and registry data suggest it is not impacted by antiplatelet therapy. The POPular TAVI trial supports this finding because there was no difference between single antiplatelet therapy or DAPT for clinical valve thrombosis or post-procedure transvalvular gradient. The GALILEO (Global Study Comparing a Rivaroxaban-based Antithrombotic Strategy to an Antiplatelet-based Strategy After TAVR to Optimize Clinical Outcomes) trial, which tested the utility of rivaroxaban after TAVR to reduce leaflet thrombosis, had to be stopped due to harm, despite showing that leaflet thrombosis was reduced in the treatment group. Considering the findings from POPular TAVI and GALILEO, one has to conclude that any use of anticoagulation or antiplatelet medication in TAVR patients should be undertaken only with a clear indication and not solely because the patient has had TAVR.

Early Hemodynamic and Structural Impact of Transcatheter Aortic Valve Replacement in Pure Aortic Regurgitation
By Rani K. Hasan, MD, MHS, FACC
Johns Hopkins University
Baltimore, MD

Graziani et al. report a contemporary retrospective single-center observational study of 22 patients with pure aortic regurgitation treated with TAVR using self-expanding prostheses.³ All patients had evidence of heart damage as indicated by increased LV dimensions or LV systolic dysfunction. Hemodynamic and echocardiographic parameters were compared at baseline, acutely post-TAVR (24-72 hours), and at short-term follow-up (3-12 months). Compared to prior series,^4-5 this study reported a higher procedural success rate (95.5%) with mild (24%) or no aortic regurgitation post-TAVR despite up to 33% of the included patients reported as having no calcification.

As expected, hemodynamic parameters including LV end-diastolic pressure (26.2 to 20.1 mmHg; p = 0.012) and estimated pulmonary artery systolic pressure (48.6 ± 17.3 to 32.9 ± 7.8 mmHg; p < 0.001) improved significantly post-TAVR. Echocardiographic LV parameters including LV diastolic diameter (60.0 ± 8.0 vs. 54.6 ± 8.1 mm; p = 0.002) and LV mass (163.2 ± 58.8 vs. 140.2 ± 45.6 g/m2; p = 0.004) improved acutely and at short-term follow-up, along with significant reductions in concomitant mitral and tricuspid regurgitation. Albeit a small and single-center study, it demonstrates improved procedural success of TAVR for pure aortic regurgitation with evidence of LV reverse remodeling as is seen following surgical aortic valve replacement.⁶ These findings are encouraging but warrant further evaluation in larger studies. Although less common than aortic stenosis, pure aortic regurgitation is a vexing problem with a paucity of therapeutic options other than surgery. Early TAVR experience with pure aortic regurgitation were suboptimal compared to outcomes with treatment of aortic stenosis, but as TAVR technology and techniques continue to improve, the scope of patients and pathologies that can be managed with this revolutionary technology continues to expand.

Left Ventricular Remodeling after Transcatheter Mitral Valve Replacement With Tendyne: New Insights from Computed Tomography
By Michael Lim, MD, FACC, FSCAI
St. Louis University
St. Louis, MO

During the recent ESC Congress 2020, there was a presentation describing the effects on LV characteristics of Tendyne mitral valve replacement in patients with chronic, severe mitral regurgitation (MR) that was subsequently published in JACC: Cardiovascular Interventions.⁷ The Tendyne system has a worldwide experience of >100 implants to date, with this study focusing on the changes to LV geometry in the first weeks after implantation. Using CTA assessment pre and post Tendyne implantation, the study showed an overall decrease in LV end-diastolic volumes (281-239 ml) in the 36 patients treated. However, although mitral insufficiency was reduced in all patients, there was patient-to-patient variability of these changes, with some patients having an increase in LV end-diastolic volumes as well as a decrease in LVEF (37% to 30%). One of the unique features of the Tendyne valve is the apical pad, which tethers the mitral apparatus to the apex. The study found that the specific placement location of this pad contributed to the variability of the response, with optimal reverse remodeling evident when the device was placed at the distal apical compared to the mid-apical area. This finding may have implications as this valve moves forward in its pivotal trial, SUMMIT (Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation).⁸

The investigators demonstrate efficacy of CTA as a tool to better understand the effects of mitral valve replacement on chamber geometry, with implications for the broader question of which patients will receive ultimate clinical benefit. This question has been long in the making, as Gaasch and Meyer⁹ outlined back in 2008 that there are many complex relationships at play involving MR and the LV. These authors outlined 3 stages of chronic MR:

• Stage 1: Patients with preserved LV systolic function
• Stage 2: Patients with reversible changes to their ventricles after surgical correction of the regurgitant lesion
• Stage 3: Patients with decompensated regurgitation with irreversible structural and functional changes within the ventricle

As we continue to strive for a better understanding of the patient-specific features of patients seeing profound benefit from studies such as COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation)¹⁰ compared with patients undergoing surgical mitral valve replacement without chordal sparing¹¹ or from the MITRA-FR (Percutaneous Repair With the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial¹² who seemingly did not have benefit, this study of the Tendyne valve gives us hope that utilization of CTA and in-depth evaluation of these patients pre- and post-procedure will give us better insights to predict treatment responses.

Results From the HOST-REDUCE-POLYTECH-ACS Trial
By Zuzana Motovska, MD, PhD
Cardiocentre, Charles University and University Hospital Kralovske Vinohrady
Prague, Czech Republic

HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases Trial - Comparison of REDUCTION of Prasugrel Dose & Polymer Technology in ACS Patients) is another contribution to the effort to maximize the benefit of combined antiplatelet therapy while reducing the risk of major ischemic events associated with the lowest possible risk of unwanted bleeding. The design was based on the premise of the greatest benefit of the potent antiplatelet therapy early after stent implantation for acute coronary syndrome and the persistent risk of therapy-associated bleeding in the chronic maintenance phase.

The study compared the net clinical benefit (all-cause death, non-fatal MI, stent thrombosis, clinically driven revascularization, stroke, and BARC ≥2 bleeding) of recommended DAPT based on aspirin plus prasugrel 10 mg daily for 12 months with de-escalation of prasugrel treatment after 1 month at a dose of 5 mg per day in patients after stent implantation (durable polymer drug-eluting stent in 50.3% and absorbable polymer drug-eluting stent in 49.7%) for an acute coronary syndrome. De-escalation of prasugrel reduced the risk of BARC 2 bleeding without increasing the risk of observed ischemic events.

HOST-REDUCE-POLYTECH-ACS was an investigator-initiated, randomized, open-label study in which 2,354 patients were randomized. The specifics of the population are also the potential limitations of this study: selectively from the east Asian region, lower mean age (58.7 years and 58.9 years), high proportion of men (89.7% and 88.7%), and number of patients with unstable angina (≈60%).

A reduction in the risk of bleeding by reducing the intensity of antiplatelet therapy can be expected, especially among east Asian patients who are known to have a higher bleeding risk. Although the younger age and higher proportion of men selects a group with a lower risk of bleeding, the ethnicity risk is not taken into account. The published study paper does not state whether the diagnosis of unstable angina (two-thirds of the study population) included patients with typical symptoms but negative high-sensitivity troponin given the low incidence of ischemic endpoints leading to a lack of power to detect differences in the risk of ischemic endpoints.

No difference in the net clinical events was found in a multicenter randomized study,¹³ which compared a 5-mg maintenance dose of prasugrel with clopidogrel 75 mg daily in patients older than 74 years with a PCI-treated acute coronary syndrome. The study, originally designed to assess the superiority of prasugrel, was terminated prematurely due to futility. It therefore remains unanswered whether de-escalation of the prasugrel dose would not have produced the same results as de-escalation of prasugrel to the cheaper clopidogrel, even in the regionally defined study population.

The VOYAGER PAD and THEMIS-PAD Trials
By Bryan Raybuck, MD, FACC
WVU Heart and Vascular Institute and West Virginia University School of Medicine
Morgantown, WV

THEMIS-PAD was a 1,687 patient substudy of THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) in patients with stable ischemic heart disease, type 2 diabetes, and PAD. Patients randomized to ticagrelor and aspirin versus placebo and aspirin demonstrated a significant reduction in major adverse limb events, which was greater in patients with PAD than patients without PAD but was associated with an increase in major bleeding events.

VOYAGER PAD (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) studied 6,564 patients with lower extremity PAD undergoing revascularization. Patients randomized to rivaroxaban 2.5 mg BID and aspirin had a significant reduction in major adverse limb events and cardiovascular events compared to those receiving placebo and aspirin. The benefit was greater in patients with both PAD and CAD, and the frequency of Thrombolysis in Myocardial Infarction major bleeding and intracranial hemorrhage was similar in both groups. But the incidence of ISTH (International Society on Thrombosis and Haemostasis) bleeding was higher in the rivaroxaban and aspirin group.

Similarly, in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial, patients with stable atherosclerotic disease randomized to receive low-dose rivaroxaban and aspirin demonstrated reduced cardiovascular events with an increased bleeding risk.

Further studies are needed to assess the overall cardiovascular benefit versus bleeding risk in patients with PAD with or without CAD stratified into low and high bleeding risk per Valve Academic Research Consortium definitions. Low bleeding risk patients with PAD may benefit the most from the addition of ticagrelor and low-dose rivaroxaban to aspirin.

References

1. Lopes RD, Alexander KP, Stevens SR, et al. Initial Invasive versus Conservative Management of Stable Ischemic Heart Disease Patients with a History of Heart Failure or Left Ventricular Dysfunction: Insights from the ISCHEMIA Trial. Circulation 2020;Aug 29:[Epub ahead of print].
2. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;64:e139-e228.
3. Graziani F, Mencarelli E, Burzotta F, et al. Early Hemodynamic and Structural Impact of Transcatheter Aortic Valve Replacement in Pure Aortic Regurgitation. JACC: Cardiovasc Interv 2020;Aug 19:[Epub ahead of print].
4. Roy DA, Schaefer U, Guetta V, et al. Transcatheter aortic valve implantation for pure severe native aortic valve regurgitation. J Am Coll Cardiol 2013;61:1577-84.
5. Yoon SH, Schmidt T, Bleiziffer S, et al. Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation. J Am Coll Cardiol 2017;70:2752-63.
6. Izumi C, Kitai T, Kume T, et al. Effect of Left Ventricular Reverse Remodeling on Long-term Outcomes After Aortic Valve Replacement. Am J Cardiol 2019;124:105-12.
7. Fukui M, Sorajja P, Gössl M, et al. Left Ventricular Remodeling After Transcatheter Mitral Valve Replacement With Tendyne: New Insights From Computed Tomography. JACC Cardiovasc Interv 2020;13:2038-48.
8. Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation (SUMMIT) (ClinicalTrials.gov website). June 1, 2020. Available at https://clinicaltrials.gov/ct2/show/NCT03433274. Accessed October 7, 2020.
9. Gaasch WH, Meyer TE. Left ventricular response to mitral regurgitation: implications for management. Circulation 2008;118:2298-303.
10. Stone GW, Lindenfeld J, Abraham WT, et al. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Eng J Med 2018;379:2307-18.
11. Obadia JF, Messika-Zeitoun D, Leurent G, et al. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Eng J Med 2018;379:2297-306.
12. Rozich JD, Carabello BA, Usher BW, Kratz JM, Bell AE, Zile MR. Mitral valve replacement with and without chordal preservation in patients with chronic mitral regurgitation. Mechanisms for differences in postoperative ejection performance. Circulation 1992;86:1718-26.
13. Savonitto S, Ferri LA, Piatti L, et al. Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization. Circulation 2018;137:2435-45.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Valvular Heart Disease, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Heart Failure, Cardiac Surgery and SIHD, Cardiac Surgery and VHD, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Structural Heart Disease, Interventions and Vascular Medicine, Angiography, Echocardiography/Ultrasound, Nuclear Imaging, Chronic Angina, Mitral Regurgitation

Keywords: ESC Congress, ESC20, Coronary Angiography, Acute Coronary Syndrome, American Heart Association, Angina, Stable, Angina, Unstable, Aortic Valve, Aortic Valve Insufficiency, Aortic Valve Stenosis, Aspirin, Blood Pressure, Bone Marrow, Confidence Intervals, Control Groups, Coronary Artery Disease, Diabetes Mellitus, Type 2, Drug-Eluting Stents, Diastole, Echocardiography, Ethnic Groups, Fibrinolytic Agents, Follow-Up Studies, Heart Valve Prosthesis, Incidence, Mitral Valve, Mitral Valve Insufficiency, Medical Futility, Myocardial Infarction, Numbers Needed To Treat, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Peripheral Arterial Disease, Patient Discharge, Disease-Free Survival, Pulmonary Artery, Prevalence, Purinergic P2Y Receptor Antagonists, Retrospective Studies, ST Elevation Myocardial Infarction, Stroke Volume, Transcatheter Aortic Valve Replacement, Tricuspid Valve Insufficiency, Thrombosis, United States Food and Drug Administration, Trimetazidine, Troponin, Ventricular Remodeling, Ventricular Function, Left


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