Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Small Aortic Annulus: A Randomized Clinical Trial.

BACKGROUND: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA. METHODS: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes. RESULTS: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P=0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P=1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P=0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P=0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P=0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P=0.80). CONCLUSIONS: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.

Acute advanced aortic stenosis.

Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the disease with a dismal impact on survival and quality of life. Several factors may derange the faint balance between left ventricular preload and afterload and precipitate the occurrence of symptoms and signs of acute heart failure (HF). A standardized approach for the management of this condition is currently lacking. Medical therapy finds very limited application in this setting, as drugs usually indicated for the control of acute HF might worsen hemodynamics in the presence of AS. Urgent aortic valve replacement is usually performed by transcatheter than surgical approach whereas, over the last decades, percutaneous balloon valvuloplasty gained renewed space as bridge to definitive therapy. This review focuses on the pathophysiological aspects of acute advanced AS and summarizes current evidence on its management.

Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial.

BACKGROUND: Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. METHODS: In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. RESULTS: 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3-2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3-2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR - 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43-150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. CONCLUSIONS: In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (NCT04766008).

Periprocedural myocardial infarction in patients undergoing complex versus noncomplex percutaneous coronary intervention.

BACKGROUND: Limited data are available on the risk of periprocedural myocardial infarction (MI) in patients undergoing complex versus noncomplex percutaneous coronary intervention (PCI). METHODS: We assessed the risk of periprocedural MI according to the fourth Universal definition of myocardial infarction (UDMI) and several other criteria among patients undergoing elective PCI in a prospective, single-center registry. Complex PCI included at least one of the following: 3 coronary vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, treatment of chronic total occlusion, and use of rotational atherectomy. RESULTS: Between 2017 and 2021, we included 1010 patients with chronic coronary syndrome, of whom 226 underwent complex PCI (22.4%). The rate of periprocedural MI according to the fourth UDMI was significantly higher in complex compared to noncomplex PCI patients (26.5% vs. 14.5%, p < 0.001). Additionally, periprocedural MI was higher in the complex PCI group using SCAI (4% vs. 1.1%, p = 0.009), ARC-2 (13.7% vs. 8.0%, p = 0.013), ISCHEMIA (5.8% vs. 1.7%, p = 0.002), and EXCEL criteria (4.9% vs. 2.0%, p = 0.032). SYNTAX periprocedural MI occurred at low rates in both groups (0.9% vs. 0.6%, p = 0.657). Complex PCI was an independent predictor of the fourth UDMI periprocedural MI (odds ratio [OR] 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.031). CONCLUSIONS: In patients with chronic coronary syndrome undergoing elective PCI, complex PCI is associated with a significantly higher risk of periprocedural MI using multiple definitions. These findings highlight the importance of considering upfront this risk in the planning of complex PCI procedures.

Platelet Inhibition with Ticagrelor 60 mg Versus 90 mg Twice Daily in Elderly Patients with Acute Coronary Syndrome: Rationale and Design of the PLINY THE ELDER Trial.

BACKGROUND: Elderly status is steadily increasing among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent thrombotic complications in patients with ACS. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. The aim of this study is to evaluate the pharmacodynamic and pharmacokinetic profile of a lower dose of ticagrelor (60 mg twice daily) among elderly patients during the early phase of ACS. STUDY DESIGN: PLINY THE ELDER (PLatelet INhibition with two different doses of potent P2y12 inhibitors in THE ELDERly population) (NCT04739384) is a prospective, randomized, open-label, crossover trial to evaluate the non-inferiority of a lower dose of ticagrelor (60 mg twice daily) compared with a standard dose (90 mg twice daily) among elderly patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 50 patients, aged 75 years or more, with indication to potent P2Y12 receptor inhibitors will be randomized within 3 days from PCI for the index ACS. Patients with indication to oral anticoagulant therapy, treatment with glycoprotein IIb/IIIa inhibitors, or active bleeding will be excluded. The primary endpoint is platelet reactivity determined by P2Y12 reaction units (PRU) (VerifyNow, Accumetrics, San Diego, CA, USA) after treatment with ticagrelor 60 or 90 mg twice daily for 14 days. Secondary endpoints will include other pharmacodynamic tests of ADP-induced aggregation (light transmittance aggregometry and multiple electrode aggregometry) and determination of pharmacokinetic profile (plasma levels of ticagrelor and its metabolite AR-C124910XX) by high performance liquid chromatography-tandem mass spectrometry. CONCLUSIONS: The PLINY THE ELDER trial will determine whether a lower dose of ticagrelor confers non-inferior platelet inhibition compared with the standard dose in the early phase of ACS among elderly patients undergoing PCI, informing future clinical investigation.

Incidence, predictors, and prognostic impact of temporary left bundle branch block after transcatheter aortic valve replacement.

BACKGROUND: Little is known about temporary Left Bundle Branch Block (LBBB) after transcatheter aortic valve replacement (TAVR). We aim to evaluate the incidence, prognostic impact and predictors of temporary LBBB in TAVR patients. METHODS: Electrocardiograms (ECGs) obtained before and after TAVR, at discharge and at 30-day follow-up were anonymously analyzed by 5 cardiologists. Temporary LBBB included transient LBBB or persistent LBBB. The primary endpoint was all-cause mortality at 1-year after TAVR. RESULTS: Out of 198 patients, 55 (27.7%) developed temporary LBBB. No differences between groups were observed in primary endpoint. Left ventricular ejection fraction (LVEF) was identified as predictive factor of transient LBBB. CONCLUSIONS: Temporary LBBB has no significant impact on survival at 1 year after the procedure.

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment-Elevation Myocardial Infarction: Primary Results of the FABOLUS-FASTER Trial.

BACKGROUND: Standard administration of newer oral P2Y12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. We aimed to investigate the effects of cangrelor, tirofiban, and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary percutaneous coronary intervention. METHODS: The FABOLUS-FASTER trial (Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over Prasugrel: A Multicenter Randomized Open-Label Trial in Patients with ST-Elevation Myocardial Infarction Referred for Primary Percutaneous Intervention) is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y12-naive patients with ST-segment-elevation myocardial infarction were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40) (both administered as bolus and 2-hour infusion followed by 60 mg of prasugrel), or 60-mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 subrandomization to chewed (n=21) or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (noninferiority of cangrelor compared with tirofiban using a noninferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel, and superiority of chewed prasugrel as compared with integral prasugrel, each with α=0.016 for the primary end point, which was 30-minute IPA at light transmittance aggregometry in response to 20 µmol/L adenosine diphosphate. RESULTS: At 30 minutes, cangrelor did not satisfy noninferiority compared with tirofiban, which yielded superior IPA over cangrelor (95.0±8.9 versus 34.1±22.5; P<0.001). Cangrelor or tirofiban were both superior to chewed prasugrel (IPA, 10.5±11.0; P<0.001 for both comparisons), which did not provide higher IPA over integral prasugrel (6.3±11.4; P=0.47), despite yielding higher prasugrel active metabolite concentration (ng/mL; 62.3±82.6 versus 17.1±43.5; P=0.016). CONCLUSIONS: Cangrelor provided inferior IPA compared with tirofiban; both treatments yielded greater IPA compared with chewed prasugrel, which led to higher active metabolite concentration but not greater IPA compared with integral prasugrel. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02978040; URL: https://www.clinicaltrialsregister.eu; EudraCT 2017-001065-24.

Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve.

BACKGROUND: Some components of Nutraceuticals (NUT) such as red yeast rice and Morus alba have demonstrated positive effects on the endothelial function in hypercholesterolemic subjects. Our aim was to compare the effects of two different NUT combinations on cold pressure test (CPT) derived coronary flow reserve (CFR) assessed by transthoracic echo-Doppler. RESULTS: In a randomized, single-blind study, 28 consecutive patients with a variety of cardiovascular risk factors received NUT A (LopiGLIK®: berberine, red yeast rice powder, and leaf extract of Morus alba) or B (Armolipid Plus®: policosanol, red yeast rice, berberine, astaxantine, folic acidandcoenzyme Q10). An echo-Doppler exam with evaluation of CFR was performed at baseline, 2 h (acute test) and 30 days after daily NUT assumption. Blood sampling for metabolic profile and platelet aggregometry was performed at baseline and after 30 days of daily NUT assumption. CFR was not significantly modified at the acute test. After 30 days, CFR improved with NUT A (p < 0.0001), because of the increase of hyperemic flow velocity (p = 0.007), but not with NUT B. CFR was comparable between the two groups at baseline but became significantly higher after 30 days in NUT A (p < 0.02), with a higher CFR percent variation versus baseline (p = 0.008). Total cholesterol and LDL-cholesterol were reduced with both NUT A (p < 0.001 and p < 0.002, respectively) and B (both p < 0.02), whereas platelet aggregation did not significantly change. In the pooled group of patients, after adjusting for age and percent changes of systolic blood pressure, heart rate, LDL-cholesterol and glycemia, NUT A - but not NUT B - was independently associated with CFR changes (ß = 0.599, p = 0.003). CONCLUSIONS: LopiGLIK® improved endothelial-derived CFR, independently of the beneficial effects exerted on the lipid profile. These findings can have clinical reflections on the prevention of age-related inflammatory diseases including coronary artery disease. TRIAL REGISTRATION: (NUTRENDO)″(ClinicalTrials.gov, NCT02969070).

Aortic Stenosis With Coronary Artery Disease: SAVR or TAVR-When and How?

The growing number of candidates for transcatheter aortic valve replacement (TAVR) has increased the interest in the concomitant presence of coronary artery disease (CAD) and severe aortic stenosis (AS), prompting the need to define the appropriate revascularization strategy for each case. The reported prevalence of concurrent AS and CAD has varied over the years on the basis of the CAD definition and the population evaluated. Revascularization for treating CAD in patients with severe AS involves additional interventions that could impact outcomes. The addition of coronary artery bypass grafting (CABG) to surgical aortic valve replacement (SAVR) has demonstrated favourable effects on long-term prognosis, while the impact of adding percutaneous coronary intervention (PCI) to TAVR may depend on the CAD complexity and the feasibility of achieving complete or reasonably incomplete revascularization. Furthermore, the comparison between SAVR+CABG and TAVR+PCI in low-intermediate surgical risk and low-intermediate complex CAD patients did not reveal differences in all-cause mortality or stroke between the groups. However, there is some evidence showing a lower incidence of major cardiovascular events with the SAVR+CABG strategy for patients with complex CAD. Thus, SAVR+CABG seems to be the best option for patients with low-intermediate surgical risk and complex CAD, and TAVR+PCI for high surgical risk patients seeking complete and/or reasonable incomplete revascularization. After deciding between TAVR+PCI or SAVR+CABG, factors such as timing for PCI, low ejection fraction, coronary reaccess, and valve durability must be considered. Finally, alternative methods for assessing CAD severity are currently under evaluation to ascertain their real value for guiding revascularization in patients with severe AS with CAD.

Incidence, Predictors, and Prognostic Impact of Neurologic Events After TAVR According to VARC-3 Criteria.

BACKGROUND: The Valve Academic Research Consortium (VARC)-3 definition for neurologic events after transcatheter aortic valve replacement (TAVR) lacks clinical validation. OBJECTIVES: This study sought to determine the incidence, predictors, and clinical impact of neurologic events following TAVR as defined by VARC-3 criteria. METHODS: This was a multicenter study including 2,924 patients with severe aortic stenosis undergoing TAVR. Based on Neurologic Academic Research Consortium (NeuroARC) classification, neurologic events were classified as NeuroARC type 1 (stroke), NeuroARC type 2 (covert central nervous system injury), and NeuroARC type 3 (transient ischemic attack and delirium). Baseline, procedural, and follow-up data were prospectively collected in a dedicated database. RESULTS: After a median follow-up of 13 (7-37) months, neurologic events occurred in 471 patients (16.1%), NeuroARC type 1, 2, and 3 in 37.4%, 4.7%, and 58.0% of cases, respectively, and the majority (58.6%) were periprocedural. Advanced age, chronic kidney disease, atrial fibrillation, major vascular complications, and in-hospital bleeding determined an increased risk of periprocedural events (P < 0.03 for all). Neurologic events occurring during the periprocedural time frame were independently associated with a substantial increase in mortality at 1 year after the intervention (HR: 1.91; 95% CI: 1.23-2.97; P = 0.004). However, although NeuroARC type 1 was associated with an increased mortality risk (IRR: 3.38; 95% CI: 2.30-5.56; P < 0.001 and IRR: 21.7; 95% CI: 9.63-49.1; P < 0.001 for ischemic and hemorrhagic stroke, respectively), the occurrence of NeuroARC type 3 events had no impact on mortality. CONCLUSIONS: Neurologic events after TAVR were associated with poorer short- and long-term survival. This correlation was related to the type of NeuroARC event defined by the VARC-3 criteria. Given the negative impact on clinical outcomes, every attempt should be made to reduce the risk of neurologic complications after TAVR.

Safety and Efficacy of Combined Coronary and Peripheral Percutaneous Revascularization: A Proof-of-Concept Study.

Background. Lower extremity peripheral artery disease (LEPAD) frequently coexists with coronary artery disease (CAD) in patients with multisite vascular disease (MVD). While percutaneous revascularization is well-established for both LEPAD and CAD, limited evidence exists for patients eligible for both procedures. Specifically, the feasibility of concomitant LEPAD and CAD percutaneous revascularization remains unknown. Objectives. To compare the efficacy and safety of concomitant coronary and lower extremity elective percutaneous revascularization. Methods. Between 2012 and 2021, we included 135 patients in an observational, retrospective single-center registry. The population was stratified into two groups: 45 patients (concomitant group) underwent simultaneous coronary and peripheral percutaneous interventions, and 90 patients (deferred group) underwent two separate procedures within one year. The primary efficacy endpoint was major adverse cardiovascular events (MACE) at one year, while the primary safety endpoint was in-hospital contrast-induced nephropathy (CIN). Results. Study groups were well-balanced in baseline characteristics. In terms of coronary features, the concomitant revascularization group more often underwent single-vessel percutaneous coronary intervention (PCI), while the deferred group had multivessel PCI with diffuse coronary disease. No differences were detected in the number of LEPAD lesions between groups. For the primary efficacy endpoint, the incidence of MACE at one year was 37.8% in the concomitant group vs. 34.4% in the deferred group (HR 1.20, 95% CI 0.64-2.10; p = 0.61). No significant differences were found in CIN occurrence between the concomitant and deferred groups (11.1% vs. 8.9%; OR 1.30; 95% CI 0.36-4.21; p = 0.68). Conclusions. Multisite vascular disease patients eligible for CAD and LEPAD percutaneous revascularization exhibited a high cardiovascular risk profile with diffuse multivessel coronary and lower extremity disease. Our study suggests the efficacy and safety of concomitant coronary and lower extremity percutaneous revascularization based on one-year MACE incidence and in-hospital CIN. However, dedicated studies are warranted to confirm the short- and long-term outcomes of the concomitant revascularization strategy.

Optimal oversizing in transcatheter aortic valve replacement with the self-expanding Evolut valve system.

OBJECTIVES: Valve oversizing has been associated with reduced paravalvular leaks (PVL) and valve migration risk. However, no optimal cut-off oversizing value has been defined for the Evolut system (Medtronic). The aim of this study was to assess the relationship between the degree of oversizing and moderate-to-severe PVL and determine the optimal oversizing cut-off value. METHODS: We conducted a multicenter study that included 740 consecutive patients with multidetector computed tomography (CT) data. Valve size was selected according to manufacturer recommendations, with oversizing ranging from 10% to 30%. The primary endpoint was moderate-to-severe PVL. RESULTS: The median age was 84 years (79-87 years), with 58.4% women, and a median EuroSCORE II of 4.1% (2.4-7.3%). Moderate-to-severe PVL was observed in 7.0% of the patients. An inverse relationship was found between oversizing and both PVL (11.3%, 8.6%, 5.4%, and 2.7% for quartiles Q1 to Q4; P = .007) and the need for post-dilation (P = .016). The multivariable analysis showed an association between oversizing and PVL (OR: 0.915 for each 1%-increase, P = .002). The optimal oversizing cut-off value to predict PVL was 20%, and PVL was significantly higher in patients with oversizing less than 20% (10.5% vs.4.2%, P less than .001). There were no differences in major clinical events according to the degree of oversizing, and a higher oversizing did not translate into an increased risk of permanent pacemaker (18.4% vs18.3%, P = .976). CONCLUSIONS: In TAVR with the Evolut valve, a higher oversizing was associated with lower rates of moderate-to-severe PVL and a lower need for post-dilation, with no negative impact on procedural and early clinical outcomes. A 20% oversizing threshold could be suggested to reduce PVLs. Further prospective studies are warranted to validate optimal oversizing for this valve system.

Five-year outcomes of transcarotid transcatheter aortic valve replacement.

BACKGROUND: Transcarotid transcatheter aortic valve replacement (TC-TAVR) has emerged as an alternative access route for transcatheter aortic valve replacement (TAVR). However, scarce data exist on long-term outcomes following TC-TAVR. This study aimed to evaluate clinical outcomes at 5 years after TC-TAVR. METHODS: A total of 110 consecutive patients who underwent TC-TAVR were included. Baseline, procedural, and follow-up data were collected prospectively in a dedicated database. The primary endpoint was the incidence of a composite outcome of all-cause mortality, stroke, and repeat hospitalization at 5-year follow-up. Echocardiography results, New York Heart Association (NYHA) class, and quality of life (QoL) as assessed with the EuroQol visual analog scale (EQ-VAS) were examined over the 5-year follow-up. RESULTS: The median patient age was 77 years (interquartile range [IQR], 72-82.2 years), 42.3% were women, and the median Society of Thoracic Surgeons (STS) risk score was 5.02% (IQR, 3.4%-7.5%). The incidence of the composite primary endpoint was 54.5%. Death from any cause occurred in 45.6% of patients (11.9 per 100 patient-years); stroke in 8.2% (1.9 per 100 patient-years); disabling stroke in 2.7% (0.7 per 100 patient-years); and rehospitalization in 27.2%. The improvements in valve hemodynamics, NYHA class, and EQ-VAS following the procedure persisted at 5-year follow-up (P < .001). The incidence of bioprosthetic valve failure was 0.9%. CONCLUSIONS: About half of the moderate-to high-risk patients undergoing TC-TAVR survived with no major cardiovascular events at the 5-year follow-up. The yearly incidence of stroke events was low, and early improvements in valve hemodynamics, functional status, and QoL persisted at 5 years. These results suggest the long-term safety and efficacy of TC-TAVR and would support this approach as an alternative to surgery in non-transfemoral candidates.

Ticagrelor 60 vs. 90 mg in Elderly ACS Patients undergoing PCI: a Randomized, Crossover Trial.

AIMS: Although dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remain challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6±4.0 years, females 44%) was included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4±32.1 vs. 30.4±39.0; least squares mean difference: -4; 95% confidence interval: -16.27 to 8.06; p for non-inferiority=0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29±312.36 ng/mL vs. 579.57±351.73 ng/mL, p=0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg. CONCLUSIONS: Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI. Clinical Trial registration: EudraCT 2019-002391-13. Clinicaltrials.gov NCT04739384.

Clinical impact of complex percutaneous coronary intervention in the pre-TAVR workup.

INTRODUCTION AND OBJECTIVES: In patients undergoing percutaneous coronary intervention (PCI) in the workup pre-transcatheter aortic valve replacement (TAVR), the clinical impact of coronary revascularization complexity remains unknown. This study sought to examine the impact of PCI complexity on clinical outcomes after TAVR in patients undergoing PCI in the preprocedural workup. METHODS: This was a multicenter study including consecutive patients scheduled for TAVR with concomitant significant coronary artery disease. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with 2 stents implanted, total stent length >60mm, or chronic total occlusion. The rates of major adverse cardiac events (MACE), including cardiovascular mortality, myocardial infarction, and coronary revascularization were evaluated. RESULTS: A total of 1550 patients were included, of which 454 (29.3%) underwent complex PCI in the pre-TAVR workup. After a median follow-up period of 2 [1-3] years after TAVR, the incidence of MACE was 9.6 events per 100 patients-years. Complex PCI significantly increased the risk of cardiac death (HR, 1.44; 95%CI, 1.01-2.07), nonperiprocedural myocardial infarction (HR, 1.52; 95%CI, 1.04-2.21), and coronary revascularization (HR, 2.46; 95%CI, 1.44-4.20). In addition, PCI complexity was identified as an independent predictor of MACE after TAVR (HR, 1.31; 95%CI, 1.01-1.71; P=.042). CONCLUSIONS: In TAVR candidates with significant coronary artery disease requiring percutaneous treatment, complex revascularization was associated with a higher risk of MACE. The degree of procedural complexity should be considered a strong determinant of prognosis in the PCI-TAVR population.

Redo-TAVR: Essential Concepts, Updated Data and Current Gaps in Evidence.

Within the last two decades, transcatheter aortic valve replacement (TAVR) has transformed the treatment strategy for symptomatic severe aortic stenosis (AS), representing a less invasive alternative to traditional open-chest surgery. With time, advances in device features, imaging planning, and implantation techniques have contributed to an improvement in safety as well as a reduction in procedural complications. This has led to the expansion of TAVR to lower-risk patients, where TAVR has shown favorable outcomes compared to surgical aortic valve replacement (SAVR). As TAVR expands to younger and lower-risk patients with longer life expectancies, the need for reintervention for failing transcatheter heart valves is expected to increase. Redo-TAVR has gained increasing relevance in the lifetime management of AS as one of the treatment strategies available for structural valve dysfunction (SVD). However, some issues are associated with this approach, including coronary re-access and the risk of coronary obstruction. In this review, we provide essential concepts to properly select candidates for Redo-TAVR, updated data on clinical outcomes and complication rates, and current gaps in evidence.

Bleeding Events After Transcatheter Aortic Valve Replacement: JACC State-of-the-Art Review.

Transcatheter aortic valve replacement (TAVR) has gained over time a major reduction in procedural complications. Despite this, clinically relevant bleeding still occurs in a non-negligible proportion of patients and adversely affects prognosis. Patients with severe aortic stenosis are at heightened risk for spontaneous bleeding due to advanced age and a high comorbidity burden. Also, procedural factors and antithrombotic management contribute to define individual bleeding susceptibility. Bleeding prevention represents an emerging area for improving patient care. Because of the tight hemorrhagic/ischemic balance, a tailored approach based on individual bleeding-risk profile, such as a less invasive antithrombotic regimen or appropriate diagnostic preprocedural evaluation, should be pursued to avoid bleeding events. This review aims to provide an in-depth overview of bleeding events in the TAVR field, including definitions, timing and the extent of risk, and clinical impact, as well as updates on antithrombotic management and its potential influence on bleeding complications.

Managing the challenge of a small aortic annulus in patients with severe aortic stenosis.

INTRODUCTION: Small aortic annulus (SAA) poses a challenge in the management of patients with severe aortic stenosis requiring aortic valve replacement - both surgical and transcatheter - since it has been associated with worse clinical outcomes. AREAS COVERED: This review aims to comprehensively summarize the available evidence regarding the management of aortic stenosis in patients with SAA and discuss the current controversies as well as future perspectives in this field. EXPERT OPINION: It is paramount to agree in a common definition for diagnosing and properly treating SAA patients, and for that purpose, multidetector computer tomography is essential. The results of recent trials led to the expansion of transcatheter aortic valve replacement among patients of all the surgical-risk spectrum, and the choice of treatment (transcatheter, surgical) should be based on patient comorbidities, anatomical characteristics, and patient preferences.

Renin-angiotensin system inhibitors reduce cardiovascular mortality in hypertensive patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: insights from the EffecTAVI registry.

Objectives: Arterial hypertension is associated with the triggering of the renin-angiotensin system, leading to left ventricle fibrosis and worse cardiovascular outcomes. In this study, patients with comorbid arterial hypertension and severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) were selected from the EffecTAVI registry to evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on cardiovascular mortality. Methods: We enrolled 327 patients undergoing TAVI from the EffecTAVI registry. Using Kaplan-Meier event rates and study-stratified multivariable Cox proportional hazards regression models, we evaluated 2-year clinical outcomes according to the ACEI/ARB therapy status at enrollment. Results: Among the included patients, 222 (67.9%) were on ACEIs/ARBs at baseline, whereas 105 (32.1%) were not. Treatment with ACEIs/ARBs was significantly associated with a 2-year decrease in the rate of cardiovascular mortality (HR = 0.44, 95% CI: 0.23-0.81, p = 0.009). This association remained stable after both multivariable adjustment and propensity score matching. Conclusion: In a cohort of hypertensive patients with severe AS who were selected from the EffecTAVI registry, ACEI/ARB treatment at baseline was found to be independently associated with a lower risk of 2-year cardiovascular mortality, suggesting a potential benefit of this treatment. More trials are needed to validate this finding and to understand the full benefit of this treatment.