German Experience with a Novel Balloon-Expandable Heart Valve Prosthesis for Transcatheter Aortic Valve Implantation-Outcomes of the MYLAND (MYvaL germAN stuDy) Study.

Background: The primary objective of this study was to evaluate the initial experience in Germany with the Meril Myval™ (MM) transcatheter heart valve (THV) system for the treatment of severe symptomatic aortic valve stenosis. The MM THV is a novel balloon-expandable valve with an expanded sizing matrix. Contemporary patients undergoing TAVI with the established Edwards Sapien™ (ES) THV served as the comparator group. Methods: Between 1st March and 31 August 2020 a total of 134 patients (33% female, 80.1 ± 6.7 years; EuroScore II 4.7 ± 4.8) underwent TAVI with an MM (95% transfemoral) for severe aortic stenosis at six German tertiary care centers. Results: Correct positioning of the THV was achieved in 98.5% (n = 132). Mean aortic gradients (MPG) were reduced from 42 ± 14 mmHg to 11 ± 5 mmHg. Mild postprocedural paravalvular leak (PVL) was observed in 62% (n = 82) patients, whereas only one patient had more than mild PVL. New permanent pacemaker implantation (PPI) was indicated in 15 patients (11%). Major vascular complications occurred in 6.7% (n = 9) patients. The in-hospital combined incidence of all-cause death and stroke was 4.5% (n = 6). In the comparator group that included 268 patients, the 30-day incidences of PPI, major vascular complications, and the composite of all-cause death and stroke were 16%, 1.9%, and 7.1%, respectively; MPGs were reduced from 44 ± 15 mmHg to 12.8 ± 4.6 mmHg and the more than mild PVL occurred in 0.7%. Conclusions: The MM is a promising novel THV system, with performance comparable to the established ES THVs. These findings await confirmation by ongoing randomized trials.

Incidence and pattern of urgent revascularization in acute coronary syndromes treated with ticagrelor or prasugrel.

BACKGROUND: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization - TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00-1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09-2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77-1.65]; p = 0.546). CONCLUSIONS: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels.

Coronary artery restenosis treatment with plain balloon, drug-coated balloon, or drug-eluting stent: 10-year outcomes of the ISAR-DESIRE 3 trial.

AIMS: The best interventional strategy for the treatment of drug-eluting stent (DES) in-stent restenosis (ISR) is still unclear and no data from randomized trials beyond 3-year follow-up are available. We aimed to define 10-year comparative efficacy and safety of plain balloon (PB), paclitaxel-coated balloon (PCB), and paclitaxel-eluting stent (PES) for percutaneous coronary intervention (PCI) of DES-ISR. METHODS AND RESULTS: Clinical follow-up of patients randomly assigned to PB, PCB, and PES in the ISAR-DESIRE 3 trial was extended to 10 years and events were independently adjudicated. The primary endpoint was a composite of cardiac death, target vessel myocardial infarction, target lesion thrombosis, or target lesion revascularization. The major secondary safety endpoint was a composite of cardiac death, target vessel myocardial infarction, or target lesion thrombosis. The major secondary efficacy endpoint was target lesion revascularization. Incidences by the Kaplan-Meier method were compared by the log-rank test. Risk estimation was primarily performed by Cox proportional hazards regression and supplemented by weighted Cox regression accounting for non-proportional hazards and Royston-Parmar flexible parametric regression with a time-varying coefficient. Primary results were further assessed by landmark, lesion-level, per-protocol, and competing risk analyses. A total of 402 patients (500 lesions) with DES-ISR were randomly assigned to PB angioplasty (134 patients, 160 lesions), PCB angioplasty (137 patients, 172 lesions), and PES implantation (131 patients, 168 lesions). Clinical follow-up did not significantly differ among treatments [PB, 9.62 (4.50-10.02) years; PCB, 10.01 (5.72-10.02) years; PES, 9.08 (3.14-10.02) years; P = 0.300]. At 10 years, the primary composite endpoint occurred in 90 patients (72.0%) assigned to PB, 70 patients (55.9%) assigned to PCB, and 72 patients (62.4%) assigned to PES (P < 0.001). The pairwise comparison between PCB and PES resulted in a non-significant difference [multiplicity-adjusted P = 0.610; Grambsch-Therneau P = 0.004; weighted Cox: hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.80-1.51; Cox: HR 1.10, 95% CI 0.79-1.52; Royston-Parmar: HR 1.08, 95% CI 0.72-1.60]. The major secondary safety endpoint occurred in 39 patients (34.1%) assigned to PB, 39 patients (34.0%) assigned to PCB, and 42 patients (40.0%) assigned to PES (P = 0.564). Target lesion revascularization occurred in 71 patients (58.0%) assigned to PB, 55 patients (43.9%) assigned to PCB, and 42 patients (38.6%) assigned to PES (P < 0.0001). The pairwise comparison between PES and PCB resulted in a non-significant difference (multiplicity-adjusted P = 0.282; Grambsch-Therneau P = 0.002; weighted Cox: HR 0.83, 95% CI 0.56-1.22; Cox: HR 0.81, 95% CI 0.54-1.21; Royston-Parmar: HR 0.75, 95% CI 0.47-1.20). Lesion-level and per-protocol analyses were consistent. At landmark analyses, an excess of death and cardiac death associated with PES compared with PCB was observed within 5 years after PCI, though 10-year differences did not formally reach the threshold of statistical significance after adjustment for multiplicity. Competing risk regression confirmed a non-significant difference in target lesion revascularization between PCB and PES and showed an increased risk of death associated with PES compared with PCB. CONCLUSION: Ten years after PCI for DES-ISR, the primary and major secondary endpoints between PCB and PES were not significantly different. However, an excess of death and cardiac death within 5 years associated with PES and the results of the competing risk analysis are challenging to interpret and warrant further analysis. PES and PCB significantly reduced target lesion revascularization compared with PB.

Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial.

OBJECTIVES: To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours. BACKGROUND: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown. METHODS: This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 12 months. RESULTS: The primary endpoint occurred in 80 patients (10.4%) in the ticagrelor group and 57 patients (7.3%) in the prasugrel group in patients presenting off-hours (hazard ratio [HR] = 1.45; 95% confidence interval [CI] 1.03-2.03; P = 0.033), and 104 patients (8.5%) in the ticagrelor group and 80 patients (6.7%) in the prasugrel group in patients presenting on-hours (HR = 1.29 [0.97-1.73]; P = 0.085), without significant treatment arm-by-presentation time interaction (Pint = 0.62). BARC type 3 to 5 bleeding occurred in 35 patients (5.1%) in the ticagrelor group and 37 patients (5.3%) in the prasugrel group (P = 0.84) in patients presenting off-hours, and 60 patients (5.9%) in the ticagrelor group and 43 patients (4.6%) in the prasugrel group in patients presenting on-hours (P = 0.17). CONCLUSIONS: In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel. CLINICAL TRIAL REGISTRATION: NCT01944800.

Incidence and predictors of radial artery occlusion following transradial coronary angiography: the proRadial trial.

OBJECTIVES: This study investigated the contemporary incidence and predictors of radial artery occlusion as well as the effectiveness of antithrombotic treatment for radial artery occlusion following transradial coronary angiography. BACKGROUND: The radial artery is the standard access for coronary angiography and even complex interventions. Postprocedural radial artery occlusion is still a common and significant complication. METHODS: This prospective study enrolled 2004 patients following transradial coronary angiography. After sheath removal, hemostasis was obtained in a standardized fashion. Radial artery patency was evaluated by duplex ultrasonography in all patients. In case of occlusion, oral anticoagulation was recommended and patients were scheduled for a 30-day follow-up including Doppler ultrasonography. RESULTS: A new-diagnosed radial occlusion was found in 4.6% of patients. The strongest independent predictors of radial occlusion were female sex and active smoking status. In the subgroup of patients with percutaneous coronary interventions, female sex followed by sheath size > 6 French were the strongest predictors of radial occlusion. 76 of 93 patients with radial occlusion received an oral anticoagulation for 30 days. However, reperfusion at 30 days was found in 32% of patients on oral anticoagulation. CONCLUSION: The incidence of radial artery occlusion following coronary angiography in contemporary practice appears with 4.6% to be lower as compared to previous cohorts. Female sex and smoking status are the strongest independent predictors of radial occlusion followed by procedural variables. The limited effectiveness of oral anticoagulation for treatment of radial artery occlusion suggests a primarily traumatic than thrombotic mechanism of this complication.

The Hemodynamic Performance of the Perceval Sutureless Aortic Valve in a Propensity-Matched Comparison to the Carpentier-Edwards Perimount and Perimount Magna Ease Valves for Aortic Valve Replacement.

OBJECTIVES: The Perceval valve was shown to facilitate minimal-invasive operations and shorten operative times. We aimed to compare the early results of the Perceval valve to those of well-established valves, namely the Carpentier-Edwards Perimount and Perimount Magna Ease valve protheses, in terms of their clinical and hemodynamic performances. METHODS: This is a single-center, retrospective, observational cohort study. For every patient operated with a Perceval valve, the last patient before and the next following patient receiving a Perimount valve was included in a control group leading to a 2:1 ratio (Perimount:Perceval). A propensity score matching was used and a subgroup analysis was performed to compare early and late Perceval patients as the sizing technique was changed over time. RESULTS: From November 2013 to November 2017, 423 patients were identified. These included 141 consecutive patients receiving a Perceval valve through a full- or a hemi-sternotomy. In addition, 282 patients receiving a Perimount or a Magna Ease valve were enrolled. After propensity score matching, 127 matched patients were compared. Operating times were shorter and postoperative transvalvular pressure gradients were lower in the Perceval group (15 vs. 17 mmHg, p = 0.002). There was no difference in mortality and stroke rates. The incidence of new pacemaker implantations was higher in the Perceval group (7.1 vs. 18.9%, p = 0.005), mainly due to a very high incidence in the early phase of our Perceval experience prior to a change in the Perceval implantation technique. Subgroup analysis showed significantly better results in the late Perceval group. CONCLUSION: Surgical outcome was good in both groups. The Perceval valve exhibited lower postoperative gradients, and the need for pacemaker implantation was higher and can be reduced by avoiding oversizing.

Serum Lipoprotein(a) and 3-Year Outcomes in Patients Undergoing Percutaneous Coronary Intervention.

We aimed at addressing the association between serum lipoprotein (a) levels and clinical outcomes of consecutive patients undergoing PCI. We used consecutive patients undergoing PCI at the Heart Center University of Freiburg, Bad Krozingen in Germany between January 2005 and November 2013. A total of 6679 patients (men [n = 5391] and women [n = 1288]) with mean age of 67.5 (± 11.1) years were assessed at baseline and prospectively followed for 3 years. Lp(a) measurement was performed at hospital admission as a routine laboratory parameter. Approximately 30% of PCI patients showed an elevated Lp(a) value of more than 50 mg/dL. In total, 736 Patients died during the follow-up, thereof 189 (11.3%) in the first quartile, 186 (10.7%) in the second quartile, 183 (11.5%) in the third quartile and 178 (10.7%) in the last quartile (P value 0.843 from LogRank test). The MACE rate showed consistent results with 409 (24.4%), 385 (22.1%), 395 (24.7%) and 419 (25.3%) in the different respective quartiles (P value 0.125 from LogRank test). In this large non-selected cohort of patients undergoing PCI followed by moderate intensity statin therapy, higher Lp(a) levels were not associated with worse clinical outcomes during a follow-up of 3 years.

Impact of On-Clopidogrel Platelet Reactivity on Incidence of Peri-Interventional Bleeding in Patients Undergoing Transcatheter Aortic Valve Implantation.

Dual anti-platelet therapy (DAPT) with clopidogrel and acetylsalicylic acid (ASA) has previously been recommended after transcatheter aortic valve implantation (TAVI) and is still the standard of care in patients who underwent coronary stent placement within 3 months prior to TAVI. This study sought to evaluate whether on-treatment platelet reactivity is a predictor for the occurrence of bleeding events after TAVI. This study enrolled 484 patients undergoing TAVI from November 2013 until April 2018. Patients were either on long-term DAPT with clopidogrel and ASA or received loading doses of both drugs before TAVI, reflecting the standard of care at the time of the patient's enrollment. Platelet reactivity was determined by multi-electrode impedance aggregometry before TAVI, at days 1 and 5 thereafter. Peri-interventional bleeding was assessed up to 5 days following TAVI and coded according to BARC-classification. Bleeding events were seen in 199 (41.1%) patients. The most frequent were BARC 2 bleeding cases (24.2%), followed by BARC 1 (6.0%), BARC 3b (5.2%), and BARC 3a (4.5%) cases. Low on-clopidogrel platelet reactivity before TAVI was present in 243 patients, of which 44.4% had a bleeding event. In contrast, the incidence of bleeding was 30.5% in the 95 patients with high on-clopidogrel platelet reactivity. Multivariate logistic regression analysis identified low/normal/high on-clopidogrel platelet reactivity (OR: 0.533; CI: 0.309-0.917; p = 0.023) and use of oral anticoagulation (OR: 1.766; CI: 1.209-2.581; p = 0.003) as strongest predictors for peri-interventional bleeding events. These findings support current recommendations advocating against the routine use of dual antiplatelet therapy following TAVI.

Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis.

BACKGROUND: Sepsis is associated with high platelet turnover and elevated levels of immature platelets. Changes in the platelet transcriptome and the specific impact of immature platelets on the platelet transcriptome remain unclear. Thus, this study sought to address whether and how elevated levels of immature platelets affect the platelet transcriptome in patients with sepsis. METHODS: Blood samples were obtained from patients with sepsis requiring vasopressor therapy (n = 8) and from a control group of patients with stable coronary artery disease and otherwise similar demographic characteristics (n = 8). Immature platelet fraction (IPF) was determined on a Sysmex XE 2100 analyser and platelet function was tested by impedance aggregometry. RNA from leukocyte-depleted platelets was used for transcriptome analysis by Next Generation Sequencing integrating the use of unique molecular identifiers. RESULTS: IPF (median [interquartile range]) was significantly elevated in sepsis patients (6.4 [5.3-8.7] % vs. 3.6 [2.6-4.6] %, p = 0.005). Platelet function testing revealed no differences in adenosine diphosphate- or thrombin receptor activating peptide-induced platelet aggregation between control and sepsis patients. Putative circular RNA transcripts were decreased in platelets from septic patients. Leukocyte contamination defined by CD45 abundance levels in RNA-sequencing was absent in both groups. Principal component analysis of transcripts showed only partial overlap of clustering with IPF levels. RNA sequencing showed up-regulation of 524 and down-regulation of 118 genes in platelets from sepsis patients compared to controls. Upregulated genes were mostly related to catabolic processes and protein translation. Comparison to published platelet transcriptomes showed a large overlap of changes observed in sepsis and COVID-19 but not with reticulated platelets from healthy donors. CONCLUSIONS: Patients with sepsis appear to have a less degraded platelet transcriptome as indicated by increased levels of immature platelets and decreased levels of putative circular RNA transcripts. The present data suggests that increased protein translation is a characteristic mechanism of systemic inflammation.

Body mass index and efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes.

INTRODUCTION AND OBJECTIVES: The efficacy and safety of ticagrelor vs prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unstudied. We assessed the efficacy and safety of ticagrelor vs prasugrel in patients with ACS according to BMI. METHODS: Patients (n=3987) were grouped into 3 categories: normal weight (BMI <25kg/m2; n=1084), overweight (BMI ≥ 25 to <30kg/m2; n=1890), and obesity (BMI ≥ 30kg/m2; n=1013). The primary efficacy endpoint was the 1 year incidence of all-cause death, myocardial infarction, or stroke. The secondary safety endpoint was the 1 year incidence of Bleeding Academic Research Consortium type 3 to 5 bleeding. RESULTS: The primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the normal weight group (11.7% vs 7.5%; HR, 1.62; 95%CI, 1.09-2.42; P=.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the overweight group (8.3% vs 6.2%; HR, 1.36; 95%CI, 0.97-1.91; P=.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the obesity group (8.6% vs 7.3%; HR, 1.18; 95%CI, 0.76-1.84; P=.451). The 1-year incidence of bleeding events did not differ between ticagrelor and prasugrel in patients with normal weight (6.5% vs 6.6%; P=.990), overweight (5.6% vs 5.0%; P=.566) or obesity (4.4% vs 2.8%; P=.219). There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=.578) or secondary endpoint (Pint=.596). CONCLUSIONS: In patients with ACS, BMI did not significantly impact the treatment effect of ticagrelor vs prasugrel in terms of efficacy or safety. CLINICAL TRIAL REGISTRATION: NCT01944800.

Association of lipoprotein(a) with intrinsic and on-clopidogrel platelet reactivity.

Lipoprotein(a) [Lp(a)] is an independent, genetically determined, and causal risk factor for cardiovascular disease. Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its interaction with platelet receptors. So far, the potential association of Lp(a) with platelet activation and reactivity has not been proven in larger clinical cohorts. This study analyzed intrinsic platelet reactivity before loading with clopidogrel 600 mg and on-treatment platelet reactivity tested 24 h following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry following stimulation with collagen or adenosine diphosphate as well as by flow cytometry. Lp(a) levels were directly measured in all patients from fresh samples. The present analysis included 1912 patients. Lp(a) levels ranged between 0 and 332 mg/dl. There was a significant association of rising levels of Lp(a) with a higher prevalence of a history of ischemic heart disease (p < 0.001) and more extensive coronary artery disease (p = 0.001). Results for intrinsic (p = 0.80) and on-clopidogrel platelet reactivity (p = 0.81) did not differ between quartiles of Lp(a) levels. Flow cytometry analyses of expression of different platelet surface proteins (CD41, CD62P or PAC-1) confirmed these findings. Correlation analyses of levels of Lp(a) with any of the tested platelet activation markers did not show any correlation. The present data do not support the hypothesis of an interaction of Lp(a) with platelet reactivity.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

Moderate or Severe Functional MR and Severe AS: Is Mitral Valve Surgery Justified?

OBJECTIVE: Mitral regurgitation (MR) and severe aortic valve stenosis often coexist. Concomitant replacement of both valves is associated with a significantly higher morbidity and mortality. This study sought to investigate the progression of MR after isolated aortic valve replacement. METHODS: We analyzed the severity and progression of MR, survival and echocardiographic parameters in 506 patients with severe aortic valve stenosis and moderate to severe functional MR who received isolated aortic valve replacement during a 9-year period. RESULTS: Transcatheter aortic valve implantation (TAVI) was performed in 381 patients and 125 patients received surgical aortic valve replacement (SAVR). The median age of the cohort was 82 years. Median ejection fraction before and after TAVI or SAVR was 35 and 36% respectively (p = 0.64). There was a statistically significant reduction in the MR (p < 0.001) within both groups. Survival in both groups at 5 years was at 25%. CONCLUSION: Isolated aortic valve replacement in patients with accompanying moderate to severe functional MR may present an adequate treatment option for this high-risk patient collective.

Prevalence and Causes of Myocardial Infarction with Non-Obstructive Coronary Arteries in a Contemporary Cohort of Patients with Suspected Myocardial Infarction.

BACKGROUND: A significant proportion of patients presenting with acute myocardial infarction (MI) has no coronary obstruction at coronary angiography and no other obvious non-coronary pathophysiology causing MI. These patients are classified as MI with non-obstructive coronary arteries (MINOCA). Data on incidence and predictors of MINOCA are still limited. METHODS: This study enrolled patients presenting symptoms suggestive of MI and undergoing a comprehensive cardiac work-up including an early invasive strategy. Patients with non-obstructive coronary arteries and without other obvious reasons for MI were scheduled for further work-up including magnetic resonance or intraluminal imaging. MINOCA was diagnosed according to the current European Society of Cardiology guidelines. RESULTS: From the 1532 patients enrolled, 730 had available coronary imaging and 546 were diagnosed with MI. No significant coronary obstructions were found in 117 patients with MI. After the exclusion of 6 patients with acute myocarditis or takotsubo-syndrome as well as 88 with type II MI, 23 patients were diagnosed with MINOCA (4% of all MIs). Among these 23 patients, the most common etiology of MINOCA was thromboembolic events followed by coronary spasm. Female sex, the absence of hypercholesterolemia, and a normal left-ventricular ejection fraction were independently predictive for MINOCA compared to patients with other causes of MI. CONCLUSION: More than 20% of patients presenting with acute MI showed no significant coronary obstruction. About 4% of these patients were diagnosed with MINOCA. Female sex, a lower cardiovascular risk profile, and normal left-ventricular function were predictive for MINOCA.

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to Estimated Glomerular Filtration Rate.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs). BACKGROUND: The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined. METHODS: Patients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m2), intermediate eGFR (≥60 and <90 mL/min/1.73 m2), and high eGFR (≥90 mL/min/1.73 m2). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year. RESULTS: Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding. CONCLUSIONS: These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800).

Ticagrelor or Prasugrel for Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention: A Prespecified Subgroup Analysis of a Randomized Clinical Trial.

Importance: It is unclear whether ticagrelor or prasugrel hydrochloride is superior for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Objective: To assess the safety and efficacy of ticagrelor vs prasugrel for patients with ACS treated with PCI. Design, Setting, and Participants: A prespecified analysis was performed of a postrandomization subgroup of 3377 patients who presented with ACS and were treated with PCI in the investigator-initiated, multicenter, phase 4, open-label Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 randomized clinical trial, conducted from September 1, 2013, to February 28, 2018. Statistical analysis was performed from September 1, 2020, to January 30, 2021. Analysis was performed according to the intention-to-treat principle. Interventions: Patients were randomly assigned to a ticagrelor-based or prasugrel-based strategy. This analysis focuses on the subgroup of patients who underwent PCI that was formed after randomization. Main Outcomes and Measures: The primary end point was a composite consisting of all-cause death, myocardial infarction, or stroke at 12 months. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Results: The ticagrelor group comprised 1676 patients (1323 men [78.9%]; mean [SD] age, 64.4 [12.0] years), and the prasugrel group comprised 1701 patients (1341 men [78.8%]; mean [SD] age, 64.7 [12.0] years). The primary end point occurred for 162 patients (9.8%) in the ticagrelor group and 120 patients (7.1%) in the prasugrel group (hazard ratio [HR], 1.41; 95% CI, 1.11-1.78; P = .005). Myocardial infarction occurred in 88 patients (5.3%) in the ticagrelor group compared with 55 patients (3.8%) in the prasugrel group (HR, 1.67; 95% CI, 1.19-2.34; P = .003). The safety end point, BARC type 3 to 5 bleeding, occurred in 84 of 1672 patients (5.3%) in the ticagrelor group and 78 of 1680 patients (4.9%) in the prasugrel group (HR; 1.10; 95% CI, 0.81-1.50; P = .54). Conclusions and Relevance: Among patients presenting with ACS who were treated with PCI, the incidence of the primary composite end point occurred less frequently for patients who received prasugrel compared with those who received ticagrelor. The incidence of bleeding events was comparable between the 2 groups. These results suggest that, for patients presenting with ACS who undergo PCI, a prasugrel-based strategy is superior to a ticagrelor-based strategy. However, because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis generating and dedicated randomized clinical trials may be warranted to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT01944800.

Transcatheter valve-in-valve implantation in degenerated aortic bioprostheses: are patients with small surgical bioprostheses at higher risk for unfavourable mid-term outcomes?

BACKGROUND: To examine outcomes of valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) according to the inner diameter (ID) of the degenerated aortic valve bioprosthesis. METHODS: We analyzed survival, stroke, permanent pacemaker (PPM) implantation, paravalvular (PV) leakage, acute kidney injury and vascular complications in fifty-nine patients during a ten-year period. Patients were stratified according to the ID of the indwelling degenerated biological aortic valve (true ID ≤ and >20 mm). Differences in post-procedural transvalvular gradients and hospital re-admissions were analyzed. RESULTS: The median age of the small diameter group and large diameter group was eighty-one and eighty years, respectively. Median logistic EuroSCORE I was 23.9% and 26.2% and median Society of Thoracic Surgeons (STS) score was 5.7% and 7.8% for the small and large groups, respectively. Survival, stroke, PPM implantation, PV leakage, acute kidney injury and vascular complications did not reach any statistically significant difference between both groups. Postprocedural transvalvular gradients differed significantly according to the true ID of the degenerated bioprosthetic valve and consequently of the respective TAVI valve. There was a significant difference with regard to hospital readmissions according to the true ID. CONCLUSIONS: TAVI ViV implantation for aortic bioprostheses with small true IDs of ≤20 mm is associated with comparable mid-term mortality and periprocedural stroke rate compared to implantation into larger bioprostheses. However, the periprocedural and mid-term transvalvular gradients, as well as hospital re-admission rates are significantly higher in the small diameter group.

Clinical Outcomes after Additional Dynamic Renal® Stent Implantation for Stent Recoil in Ostial Coronary Lesions.

BACKGROUND: Interventional treatment of aorto-ostial coronary stenoses is limited by stent recoil and suboptimal angiographic results, leading to restenosis and frequent re-interventions. As a potential bail-out strategy for stent recoil, implantation of an additional stent to increase radial force has been reported. Thus, we sought to investigate clinical outcomes after additional implantation of a Dynamic Renal® stent (DRS), a non-coronary; bare-metal stent with very high radial force, in aorto-ostial coronary stenoses. METHODS: Patients treated by implantation of DRSs for stent recoil in the ostial right coronary artery or the left main stem were identified from the hospital database. Baseline clinical and procedural characteristics were compared to patients who underwent re-intervention for in-stent-restenosis in similar segments by either implantation of conventional drug-eluting stents (DES) or paclitaxel-coated balloons (PCB). Clinical follow-ups were performed up to three years following re-intervention with the assessment of death, target lesion reintervention (TLR), and major adverse cardiac events (MACE) as a combination death, myocardial infarction and target vessel revascularization. Kaplan-Meier analyses were performed for event-free survival between the three groups. RESULTS: Between 05/2013 and 07/2019, 28 patients underwent DRS implantation of aorto-ostial coronary lesions. In comparison with 49 patients with DES implantation and 29 patients undergoing PCB treatment, no relevant differences in baseline parameters were identified. Median follow-up was 714 days, with an available follow-up of >1 year after intervention in 82.1% of patients. In the entire study cohort at two years after re-intervention, the TLR rate was 16% (17 patients), the MACE rate 37% (39 patients), and all-cause mortality 9% (10 patients), with no significant differences between the three groups. CONCLUSIONS: DRS implantation for treating stent recoil of aorto-ostial coronary lesions resulted in a high rate of TLR, and was associated with similar risk for death and MACE compared to treatment of in-stent-restenosis with DES or PCB. Randomized, larger comparisons of contemporary DES in patients exclusively presenting with stent recoil are necessary to further define the efficacy and safety of this approach.

Reticulated Platelets in Medicine: Current Evidence and Further Perspectives.

Reticulated platelets (RPs) are young thrombocytes, newly released from the bone marrow. The identification and quantification of these cells remained difficult for decades due to a lack of standardized preanalytical and analytical methods. With the introduction of automated hematology analyzers in clinical routine, the determination of RPs, either as a total count or as a fraction, became more reliable, faster and more affordable. Currently, RPs are the focus of research in multiple clinical settings. In cardiovascular medicine, recent studies have focused on the relationship between RPs, coronary artery disease (CAD) and clinical outcomes, as well as the impact of RPs on the effects of antiplatelet therapy. Cohort studies showed increased levels of RPs in patients with acute coronary syndrome (ACS) or cardioembolic stroke. In patients with ACS, increased levels of RPs were also associated with an increased incidence of major ischemic cardiovascular events during follow-up. Further studies showed an association of levels of RPs with the antiplatelet response to less-potent P2Y12 inhibitors. In patients with paroxysmal atrial fibrillation undergoing pulmonary vein isolation, levels of RPs differed significantly depending on the achieved rhythm (sinus rhythm vs. recurrent atrial fibrillation). Levels of RPs appear to also be predictive for bleeding events in patients with various hematological diagnoses. Although no causal relationship has so far been proven, RP values have been associated with a large number of pathologies and clinical scenarios. This review summarizes the current evidence with regard to RPs and their potential diagnostic and prognostic value for noncardiovascular patients and for cardiovascular patients in particular. It describes further perspectives on how the testing of these cells might improve the treatment of cardiovascular patients.