Gennaro Giustino

Stable coronary artery disease: revascularisation and invasive strategies.

Stable coronary artery disease is the most common clinical manifestation of ischaemic heart disease and a leading cause of mortality worldwide. Myocardial revascularisation is a mainstay in the treatment of symptomatic patients or those with ischaemia-producing coronary lesions, and reduces ischaemia to a greater extent than medical treatment. Documentation of ischaemia and plaque burden is fundamental in the risk stratification of patients with stable coronary artery disease, and several invasive and non-invasive techniques are available (eg, fractional flow reserve or intravascular ultrasound) or being validated (eg, instantaneous wave-free ratio and optical coherence tomography). The use of new-generation drug-eluting stents and arterial conduits greatly improve clinical outcome in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PCI is feasible, safe, and effective in many patients with stable coronary artery disease who remain symptomatic despite medical treatment. In patients with multivessel and left main coronary artery disease, the decision between PCI or CABG is guided by the local Heart Team (team of different cardiovascular specialists, including non-invasive and invasive cardiologists, and cardiac surgeons), who carefully judge the possible benefits and risks inherent to PCI and CABG. In specific subsets, such as patients with diabetes and advanced, multivessel coronary artery disease, CABG remains the standard of care in view of improved protection against recurrent ischaemic adverse events.

Prosthetic Heart Valve Thrombosis.

Although surgery was the mainstay of treatment for valvular heart disease, transcatheter valve therapies have grown exponentially over the past decade. Two types of artificial heart valve exist: mechanical heart valves (MHV), which are implanted surgically, and bioprosthetic heart valves (BHV), which can be implanted via a surgical or transcatheter approach. Whereas long-term anticoagulation is required to prevent thromboembolism after MHV replacement, its value in patients receiving BHVs is uncertain. Patients undergoing transcatheter BHV replacement are at risk for thromboembolism in the first few months, and recent data suggest that the risk continues thereafter. BHV thrombosis provides a substrate for subsequent thromboembolism and may identify a reversible cause of prosthesis dysfunction. Hereafter, the authors: 1) review the data on prosthetic valve thrombosis; 2) discuss the pathophysiological mechanisms that may lead to valve thrombus formation; and 3) provide perspective on the implications of these findings in the era of transcatheter valve replacement.

Conventional surgery and transcatheter closure via surgical transapical approach for paravalvular leak repair in high-risk patients: results from a single-centre experience.

OBJECTIVES Paravalvular leaks (PVL) occur in up to 17% of all surgically implanted prosthetic valves. Re-operation is associated with high morbidity and mortality. Transcatheter closure via a surgical transapical approach (TAp) is an emerging alternative for selected high-risk patients with PVL. The aim of this study was to compare the in-hospital outcomes of patients who underwent surgery and TA-closure for PVL in our single-centre experience. METHODS From October 2000 to June 2013, 139 patients with PVL were treated in our Institution. All the TA procedures were performed under general anaesthesia in a hybrid operative room: in all but one case an Amplatzer Vascular Plug III device was utilized. RESULTS Hundred and thirty-nine patients with PVL were treated: 122 patients (87.3%) underwent surgical treatment (68% mitral PVL; 32% aortic PVL) and 17 patients (12.2%) underwent a transcatheter closure via a surgical TAp approach (all the patients had mitral PVL; one case had combined mitral and aortic PVLs); in 35% of surgical patients and in 47% of TAp patients, multiple PVLs were present. The mean age was 62.5 ± 11 years; the Logistic EuroScore was 15.4 ± 3. Most of the patients were in New York Heart Association (NYHA) functional class III-IV (57%). Symptomatic haemolysis was present in 35% of the patients, and it was particularly frequent in the TAp (70%). Many patients had >1 previous cardiac operation (46% overall and 82% of TAp patients were at their second of re-operation). Acute procedural success was 98%. In-hospital mortality was 9.3%; no in-hospital deaths occurred in patients treated through a TAp approach. All the patients had less than moderate residual valve regurgitation after the procedure. Surgical treatment was identified as a risk factor for in-hospital death at univariate analysis (OR: 8, 95% CI: 1.8-13; P = 0.05). Overall actuarial survival at follow-up was 39.8 ± 7% at 12 years and it was reduced in patients who had >1 cardiac re-operation (42 ± 8 vs. 63 ± 6% at 9 years; P = 0.009). CONCLUSIONS A transcatheter closure via a surgical TAp approach appears to be a safe and effective therapeutic option in selected high-risk patients with PVL and is associated with a lower hospital mortality than surgical treatment, in spite of higher predicted risk. Long-term survival remains suboptimal in these challenging patients.

Trial design: Rivaroxaban for the prevention of major cardiovascular events after transcatheter aortic valve replacement: Rationale and design of the GALILEO study

Background Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR‐related thrombotic complications and premature valve failure. Design GALILEO is an international, randomized, open‐label, event‐driven, phase III trial in more than 1,520 patients without an indication for oral anticoagulation who underwent a successful TAVR (ClinicalTrials.gov NCT02556203). Patients are randomized (1:1 ratio), 1 to 7 days after a successful TAVR, to either a rivaroxaban‐based strategy or an antiplatelet‐based strategy. In the experimental arm, subjects receive rivaroxaban (10 mg once daily [OD]) plus acetylsalicylic acid (ASA, 75‐100 mg OD) for 90 days followed by rivaroxaban alone. In the control arm, subjects receive clopidogrel (75 mg OD) plus ASA (as above) for 90 days followed by ASA alone. In case new‐onset atrial fibrillation occurs after randomization, full oral anticoagulation will be implemented with maintenance of the original treatment assignment. The primary efficacy end point is the composite of all‐cause death, stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, and systemic embolism. The primary safety end point is the composite of life‐threatening, disabling, and major bleeding, according to the Valve Academic Research Consortium definitions. Conclusions GALILEO will test the hypothesis that a rivaroxaban‐based antithrombotic strategy reduces the risk of thromboembolic complications post‐TAVR with an acceptable risk of bleeding compared with the currently recommended antiplatelet therapy–based strategy in subjects without need of chronic oral anticoagulation.

Outcomes in Patients With Transcatheter Aortic Valve Replacement and Left Main Stenting : The TAVR-LM Registry

BACKGROUND A percutaneous approach with transcatheter aortic valve replacement (TAVR) and percutaneous coronary intervention (PCI) of the left main coronary artery (LM) is frequently used in high-risk patients with coexisting aortic stenosis and LM disease. Outcomes of TAVR plus LM PCI have not been previously reported. OBJECTIVES The primary objective of the TAVR-LM registry is to evaluate clinical outcomes in patients undergoing TAVR plus LM PCI. METHODS Clinical, echocardiographic, computed tomographic, and angiographic characteristics were retrospectively collected in 204 patients undergoing TAVR plus LM PCI. In total, 128 matched patient pairs were generated by performing 1:1 case-control matching between 167 patients with pre-existing LM stents undergoing TAVR and 1,188 control patients undergoing TAVR without LM revascularization. RESULTS One-year mortality (9.4% vs. 10.2%, p = 0.83) was similar between the TAVR plus LM PCI cohort and matched controls. One-year mortality after TAVR plus LM PCI was not different in patients with unprotected compared with protected LMs (7.8% vs. 8.1%, p = 0.88), those undergoing LM PCI within 3 months compared with those with LM PCI greater than 3 months before TAVR (7.4% vs. 8.6%, p = 0.61), and those with ostial versus nonostial LM stents (10.3% vs. 15.6%, p = 0.20). Unplanned LM PCI performed because of TAVR-related coronary complication, compared with planned LM PCI performed for pre-existing LM disease, resulted in increased 30-day (15.8% vs. 3.4%, p = 0.013) and 1-year (21.1% vs. 8.0%, p = 0.071) mortality. CONCLUSIONS Despite the anatomic proximity of the aortic annulus to the LM, TAVR plus LM PCI is safe and technically feasible, with short- and intermediate-term clinical outcomes comparable with those in patients undergoing TAVR alone. These results suggest that TAVR plus LM PCI is a reasonable option for patients who are at high risk for surgery.

Safety and Efficacy of New-Generation Drug-Eluting Stents in Women Undergoing Complex Percutaneous Coronary Artery Revascularization from the WIN-DES Collaborative Patient-Level Pooled Analysis

OBJECTIVES The purpose of this study was to investigate the safety and efficacy of new-generation drug-eluting stents (DES) versus early-generation DES in women undergoing complex percutaneous coronary intervention (CPCI). BACKGROUND Whether the benefits of new-generation DES are preserved in women undergoing complex percutaneous revascularization is unknown. METHODS We pooled patient-level data from women enrolled in 26 randomized trials of DES. Study population was categorized according to the presence or absence of CPCI, which was defined as the composite of total stent length >30 mm, ≥2 stents implanted, ≥2 lesions treated, or bifurcation lesion as target vessel. The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. RESULTS Of 10,241 women included in the pooled database, 4,629 (45%) underwent CPCI. Compared with non-CPCI, women who underwent CPCI had a higher 3-year risk of MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.45 to 1.83; p < 0.0001). In women who underwent CPCI, use of new-generation DES was associated with significantly lower 3-year risk of MACE (adjusted HR: 0.81; 95% CI: 0.68 to 0.96), target lesion revascularization (adjusted HR: 0.74; 95% CI: 0.57 to 0.95), and definite or probable stent thrombosis (ST) (adjusted HR: 0.50; 95% CI: 0.30 to 0.83). The benefit of new-generation DES on efficacy and safety outcomes was uniform between CPCI and non-CPCI groups, without evidence of interaction. By landmark analysis, new-generation DES were associated with low rates (≤0.4%) of very-late ST irrespective of procedural complexity. CONCLUSIONS Women undergoing CPCI remain at higher risk of adverse events. The long-term ischemic benefits of new-generation DES platforms are uniform among complex and non-complex percutaneous revascularization procedures in women.

DAPT Duration After DES: What Is the “Mandatory” Duration?

inhibitor and aspirin, remains unclear. Theneed for antiplatelet therapy post-DES implantationis predicated on mitigating risk for thromboticevents, which is highest in thefirst weeks to monthsafter percutaneous coronary intervention (PCI). Notsurprisingly, early cessation of DAPT has emerged asa strong, consistent, and independent risk factor forstent thrombosis (ST)(1,2).Thepotentialforasys-temic benefitofDAPTthatextendsbeyondthelocalstented segment to the remaining coronary vascula-ture, coupled with concerns for late ST with earlygeneration DES, provide a pathobiological rationaleforlonger(>1 year) DAPT durations. The unavoidablecorollary to extending the duration of antiplatelettherapy is increased bleeding, a complication thatmay have a more durable impact on long-term riskthan recurrent thrombosis(3). Indeed, bleeding con-cerns—in concert with the improved biocompatibilityand clinical safety of second-generation DES—haveled to clinical equipoise on the optimal DAPTduration after PCI on the basis of multiple random-ized comparisons. To date, 7 randomized controlledtrials (RCTs) (Figure 1) have reported similar is-chemic outcomes with 3- or 6-month DAPT durationcompared with longer DAPT regimens following DESimplantation. Conversely, with the exception of theDAPT study, 2 RCTs failed to demonstrate a reductionin ischemic events with DAPT prolongation beyond12 months(4–17).It is within this context that Palmerini et al.(18)report their findings from a patient-level pooledanalysis of 4 randomized trials (n¼ 8,180) comparingshorter (3- or 6-month) versus longer (12-month)DAPT durations after DES PCI in this issue of theJournal (18).Reflecting contemporary PCI practicepatterns, the most prevalent DES platforms inthe pooled cohort were everolimus-eluting andzotarolimus-eluting stents,respectively. The authorsfound nonsignificant differences in major adversecardiac events (MACE), defined as the composite ofcardiac death, myocardial infarction, and definite/probable ST, between groups at 12 months (hazardratio: 1.11; 95% confidence interval: 0.86 to 1.43;p ¼ 0.44). A shorter DAPT duration, however, yieldedsignificant reductions in bleeding (hazard ratio: 0.66;95% confidence interval: 0.46 to 0.94; p ¼ 0.03).Findings were concordant in several clinically re-levant subgroups (sex, age, diabetes, clinical pre-sentation, multivessel disease, and left anteriordescending artery as a target vessel) without evi-dence of statistical interaction for the primary MACEendpoint.In addition to the primary patient-level analysis,in which point estimates were stratified by trial,the authors also performed indirect comparisons be-tweenDAPTdurationsacrosstrialsusinganetworkapproach. Findings from these analyses were largely

Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women.

Routine Screening of Coronary Artery Disease With Computed Tomographic Coronary Angiography in Place of Invasive Coronary Angiography in Patients Undergoing Transcatheter Aortic Valve Replacement

Background—Coronary artery disease (CAD) screening is required before transcatheter aortic valve implantation (TAVR). Although invasive coronary angiography (CA) remains the gold standard for CAD assessment, computed tomographic CA (CTCA) could be a safe and effective noninvasive alternative for CAD screening in patients undergoing TAVR. Methods and Results—From November 2007 to May 2013, all patients undergoing TAVR at our institution were included in the study cohort. CTCA was used as first-line imaging tool for CAD screening. Invasive CA was performed when any of the following were present: coronary anatomy at CTCA was not evaluable and presence of significant CAD at CTCA. The primary objective was to compare major adverse cardiovascular and cerebrovascular events at 30 days and 1 year between patients who performed CTCA as only screening test and those who performed CTCA and invasive CA. Of 491 patients treated with TAVR, 375 (76.3%) performed only CTCA, whereas 116 (21.7%) underwent also CA. No differences were present in crude major adverse cardiovascular and cerebrovascular event rates at 30 days and 1 year between the 2 groups. After multivariable adjustment, CTCA performed alone was not associated with higher risk of MACE at 1 year of follow-up (hazard ratio, 0.89; 95% confidence interval, 0.49–1.60; P=0.69). Conclusions—CTCA performed as a routine noninvasive imaging tool in patients undergoing TAVR seems safe and effective allowing, with a single test, acquisition of information on aortic annulus anatomy, peripheral access sites, and evaluation of coronary anatomy.

TCT-658 Neurologic Outcomes with Embolic Protection Devices in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Clinical or subclinical cerebral embolization is a relatively frequent complication of transcatheter aortic valve replacement (TAVR). Randomized controlled trials (RCTs) investigating the efficacy of embolic protection devices during TAVR were relatively underpowered to detect meaningful differences in imaging and clinical endpoints. Methods: We performed a systematic review and study-level meta-analysis of RCTs that tested the efficacy and safety of EP during TAVR. RCTs using any type of EP and TAVR vascular access were included. Primary imaging efficacy endpoints were total lesion volume (TLV; in mm 3 ) and number of new ischemic lesions. Primary clinical efficacy endpoints were any deterioration in National Institute of Health Stroke Scale (NIHSS) and Montreal Cognitive Assessment (MoCA) score at hospital discharge. Primary analyses were performed with the intention-to-treat approach. Results: A total of 4 RCTs (total n=252) have been included. Use of EP was associated with lower TLV (Figure; standardized mean difference [SMD]: -0.65; 95% confidence interval [CI]: -1.06 to -0.25; p=0.002) and lower number of new ischemic lesions (Figure; SMD: -1.27; 95% CI: -2.45 to -0.09; p = 0.03). EP was associated with a trend to lower risk of deterioration in NIHSS at discharge (RR: 0.55; 95% CI: 0.27 to 1.09; p=0.09) and higher MoCA score (SMD: +0.40; 95% CI: +0.04 to +0.76; p = 0.03). Risk of overt stroke and all-cause mortality were non-significantly lower in the EP group. Conclusions: Use of EP seems to be associated with a reduction of imaging markers of cerebral infarction and early clinical neurologic effectiveness in patients undergoing TAVR. Key Words: TAVR; Embolic Protection; Stroke.