Publications by authors named "Jurrien M Ten Berg"

257 Publications

VA-ECMO With IABP is Associated With Better Outcome Than VA-ECMO Alone in the Treatment of Cardiogenic Shock in ST-Elevation Myocardial Infarction.

J Invasive Cardiol 2021 May 20;33(5):E387-E392. Epub 2021 Apr 20.

Koopvaardersplantsoen 83, 1034KE, Amsterdam, The Netherlands.

Objective: To assess whether combining venoarterial extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pump (IABP) improves outcomes in ST-segment elevation myocardial infarction (STEMI) over VA-ECMO alone.

Background: VA-ECMO is an upcoming technique in the treatment of cardiogenic shock (CS); however, it increases afterload. IABP + VA-ECMO has been suggested to reduce afterload and increase survival.

Methods: A multicenter in-hospital registry was maintained on all patients undergoing VA-ECMO or VA-ECMO + IABP treatment for CS in STEMI.

Results: Between 2015 and 2018, a total of 18 patients with STEMI underwent VA-ECMO ± IABP treatment for CS. The majority (n = 14; 78%) were male and median age was 59 years (interquartile range, 47-75 years). VA-ECMO + IABP was performed in 7 patients (39%) and VA-ECMO alone was performed in 11 patients (61%). The VA-ECMO + IABP group had more complex coronary anatomy and a higher number of patients with left main (LM) disease, LM + 3-vessel disease, or 3-vessel disease (VA-ECMO + IABP 86% vs VA-ECMO alone 18%; P=.03). The Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score did not differ between the groups (VA-ECMO alone -5.9 ± 2.4 vs VA-ECMO + IABP -6.1 ± 2.6; P=.88). The SYNTAX score was higher in the VA-ECMO + IABP group (32 ± 13 vs 22 ± 14 in the VA-ECMO alone group). In the total group, a SAVE score of -6 had a predicted survival of 25%-35%. Survival in the VA-ECMO + IABP group was 100% (7/7) and survival in the VA-ECMO group was 55% (6/11); P=.04. Good neurological outcome was achieved in more patients in the VA-ECMO + IABP group (VA-ECMO alone 45% vs VA-ECMO + IABP 100%; P=.04).

Conclusion: In STEMI complicated by CS, VA-ECMO + IABP leads to a lower observed mortality and higher observed good neurological outcome.
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May 2021

Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.

Int J Cardiol 2021 Apr 20. Epub 2021 Apr 20.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands. Electronic address:

Background: Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.

Methods: Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).

Results: A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.

Conclusion: In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.029DOI Listing
April 2021

Aspirin Alone Versus Dual Antiplatelet Therapy After Transcatheter Aortic Valve Implantation: A Systematic Review and Patient-Level Meta-Analysis.

J Am Heart Assoc 2021 Apr 16;10(8):e019604. Epub 2021 Apr 16.

Department of Cardiology St. Antonius Hospital Nieuwegein The Netherlands.

Background In patients undergoing transcatheter aortic valve implantation without an indication for oral anticoagulation, it is unclear whether single or dual antiplatelet therapy (DAPT) is necessary to minimize both the bleeding and thromboembolic risk. In this patient-level meta-analysis, we further investigate the effect of aspirin alone compared with DAPT for preventing both thromboembolic and bleeding events after transcatheter aortic valve implantation. Methods and Results We conducted a systematic review of all available randomized controlled trials comparing aspirin with DAPT. In total, 1086 patients were included across 4 eligible trials. The primary outcomes were the composite of all-cause mortality, major or life-threatening bleeding, stroke or myocardial infarction (first composite outcome), and the same composite excluding bleeding (second composite outcome), both tested at 30 days and 3 months. The first composite outcome occurred significantly less in the aspirin-alone group at 30 days (10.3% versus 14.7%, odds ratio [OR], 0.67; 95% CI, 0.46-0.97, =0.034) and 3 months (11.0% versus 16.5%, hazard ratio [HR], 0.66; 95% CI, 0.47-0.94, =0.02), compared with the DAPT group. The second composite outcome occurred in 5.5% and 6.6% at 30 days (OR, 0.83; 95% CI, 0.50-1.38, =0.47) and in 6.9% and 8.5% at 3 months in the aspirin-alone group compared with the DAPT group (HR, 0.82; 95% CI, 0.52-1.29, =0.39), respectively. Conclusions In patients without an indication for oral anticoagulation undergoing transcatheter aortic valve implantation, aspirin alone significantly reduced the composite of thromboembolic and bleeding events, and does not increase the composite of thromboembolic events after transcatheter aortic valve implantation, compared with DAPT.
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http://dx.doi.org/10.1161/JAHA.120.019604DOI Listing
April 2021

Incidence, predictors, and outcomes associated with acute kidney injury in patients undergoing transcatheter aortic valve replacement: from the BRAVO-3 randomized trial.

Clin Res Cardiol 2021 May 11;110(5):649-657. Epub 2021 Apr 11.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA.

Background: Acute kidney injury (AKI) is not uncommon in patients undergoing transcatheter aortic valve replacement (TAVR).

Objective: We examined the incidence, predictors, and outcomes of AKI from the BRAVO 3 randomized trial.

Methods: The BRAVO-3 trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin vs. unfractionated heparin (UFH). The primary endpoint of the trial was Bleeding Academic Research Consortium (BARC) type ≥ 3b bleeding at 48 h. Total follow-up was to 30 days. AKI was adjudicated using the modified RIFLE (Valve Academic Research Consortium, VARC 1) criteria through 30-day follow-up, and in a sensitivity analysis AKI was assessed at 7 days (modified VARC-2 criteria). We examined the incidence, predictors, and 30-day outcomes associated with diagnosis of AKI. We also examined the effect of procedural anticoagulant (bivalirudin or unfractionated heparin, UFH) on AKI within 48 h after TAVR.

Results: The trial population had a mean age of 82.3 ± 6.5 years including 48.8% women with mean EuroScore I 17.05 ± 10.3%. AKI occurred in 17.0% during 30-day follow-up and was associated with greater adjusted risk of 30-day death (13.0% vs. 3.5%, OR 5.84, 95% CI 2.62-12.99) and a trend for more BARC ≥ 3b bleeding (15.1% vs. 8.6%, OR 1.80, 95% CI 0.99-3.25). Predictors of 30-day AKI were baseline hemoglobin, body weight, and pre-existing coronary disease. AKI occurred in 10.7% at 7 days and was associated with significantly greater risk of 30-day death (OR 6.99, 95% CI 2.85-17.15). Independent predictors of AKI within 7 days included pre-existing coronary or cerebrovascular disease, chronic kidney disease (CKD), and transfusion which increased risk, whereas post-dilation was protective. The incidence of 48-h AKI was higher with bivalirudin compared to UFH in the intention to treat cohort (10.9% vs. 6.5%, p = 0.03), but not in the per-protocol assessment (10.7% vs. 7.1%, p = 0.08).

Conclusion: In the BRAVO 3 trial, AKI occurred in 17% at 30 days and in 10.7% at 7 days. AKI was associated with a significantly greater adjusted risk for 30-day death. Multivariate predictors of AKI at 30 days included baseline hemoglobin, body weight, and prior coronary artery disease, and predictors at 7 days included pre-existing vascular disease, CKD, transfusion, and valve post-dilation. Bivalirudin was associated with greater AKI within 48 h in the intention to treat but not in the per-protocol analysis.
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http://dx.doi.org/10.1007/s00392-020-01787-7DOI Listing
May 2021

Evaluation of Dual Versus Triple Therapy by Landmark Analysis in the RE-DUAL PCI Trial.

JACC Cardiovasc Interv 2021 Apr;14(7):768-780

Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts, USA.

Objectives: The aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.

Background: Patients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events.

Methods: A total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y inhibitor (and no aspirin), or warfarin plus a P2Y inhibitor plus aspirin. Landmark analysis was performed at 30 and 90 days.

Results: There was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p < 0.0001; 150 mg: HR: 0.46; 95% CI: 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg: HR: 0.65; 95% CI: 0.47 to 0.88; p = 0.0062; 150 mg: HR: 0.54; 95% CI: 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin.

Conclusions: In RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events.
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http://dx.doi.org/10.1016/j.jcin.2021.02.022DOI Listing
April 2021

Diagnostic performance and clinical implications for enhancing a hybrid quantitative flow ratio-FFR revascularization decision-making strategy.

Sci Rep 2021 Mar 19;11(1):6425. Epub 2021 Mar 19.

Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands.

Invasive fractional flow reserve (FFR) adoption remains low mainly due to procedural and operator related factors as well as costs. Alternatively, quantitative flow ratio (QFR) achieves a high accuracy mainly outside the intermediate zone without the need for hyperaemia and wire-use. We aimed to determine the diagnostic performance of QFR and to evaluate a QFR-FFR hybrid strategy in which FFR is measured only in the intermediate zone. This retrospective study included 289 consecutive patients who underwent invasive coronary angiography and FFR. QFR was calculated for all vessels in which FFR was measured. The QFR-FFR hybrid approach was modelled using the intermediate zone of 0.77-0.87 in which FFR-measurements are recommended. The sensitivity, specificity, and accuracy on a per vessel-based analysis were 84.6%, 86.3% and 85.6% for QFR and 88.0%, 92.9% and 90.3% for the QFR-FFR hybrid approach. The diagnostic accuracy of QFR-FFR hybrid strategy with invasive FFR measurement was 93.4% and resulted in a 56.7% reduction in the need for FFR. QFR has a good correlation and agreement with invasive FFR. A hybrid QFR-FFR approach could extend the use of QFR and reduces the proportion of invasive FFR-measurements needed while improving accuracy.
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http://dx.doi.org/10.1038/s41598-021-85933-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979768PMC
March 2021

Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead.

Thromb Haemost 2021 Mar 7. Epub 2021 Mar 7.

Department of Cardiology, Zuyderland Medical Centre, Heerlen, The Netherlands.

Early recanalization of the infarct-related artery to achieve myocardial reperfusion is the primary therapeutic goal in patients with ST-elevation myocardial infarction (STEMI). To decrease the duration of ischaemia, continuous efforts have been made to improve pre-hospital treatment and to target the early period after symptom onset. In this period the platelet content of the fresh coronary thrombus is maximal and the thrombi are dynamic, and thus more susceptible to powerful antiplatelet agents. There have been substantial advances in antiplatelet therapy in the last three decades with several classes of oral and intravenous antiplatelet agents with different therapeutic targets, pharmacokinetics, and pharmacodynamic properties. New parenteral drugs achieve immediate inhibition of platelet aggregation, and fast and easy methods of administration may create the opportunity to bridge the initial gap in platelet inhibition observed with oral P2Y inhibitors. Moreover, potential future management of STEMI could directly involve patients in the process of care with self-administered antiplatelet agents designed to achieve rapid reperfusion. However, the potential anti-ischaemic benefits of potent antiplatelet agents will need to be balanced against their risk of increased bleeding. This study presents a comprehensive and updated review of pre-hospital antiplatelet therapy among STEMI patients undergoing primary percutaneous intervention and explores new therapies under development.
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http://dx.doi.org/10.1055/a-1414-5009DOI Listing
March 2021

Patient-tailored antithrombotic therapy following percutaneous coronary intervention.

Eur Heart J 2021 Mar;42(10):1038-1046

Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice.
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http://dx.doi.org/10.1093/eurheartj/ehaa1097DOI Listing
March 2021

Effect of aortic cross-clamp time on late survival after isolated aortic valve replacement.

Interact Cardiovasc Thorac Surg 2021 Jan;32(2):222-228

Department of Cardiothoracic Surgery, Amsterdam University Medical Center, Location Academic Medical Center, Amsterdam, Netherlands.

Objectives: Longer aortic cross-clamp (ACC) time is associated with decreased early survival after cardiac surgery. Because maximum follow-up in previous studies on this subject is confined to 28 months, it is unknown whether this adverse effect is sustained far beyond this term. We aimed to determine whether longer ACC time was independently associated with decreased late survival after isolated aortic valve replacement in patients with severe aortic stenosis during 25 years of follow-up.

Methods: In this retrospective cohort study, multivariable analysis was performed to identify possible independent predictors of decreased late survival, including ACC and cardiopulmonary bypass (CPB) time, in a cohort of 456 consecutive patients with severe aortic stenosis, who had undergone isolated aortic valve replacement between 1990 and 1993.

Results: Mean follow-up was 25.3 ± 2.7 years. Median (interquartile range) and mean ACC times were normal: 63.0 (20.0) and 64.2 ± 16.1 min, respectively. Age, operative risk scores and New York Heart Association class were similar in patients with ACC time above, versus those with ACC time below the median. Longer ACC time was independently associated with decreased late survival: hazards ratio (HR) 1.01 per minute increase of ACC time (95% confidence interval [CI] 1.00-1.02; P = 0.012). Longer CPB time was not associated with decreased late survival (HR 1.00 per minute increase of CPB time [95% CI 1.00-1.00; P = 0.30]).

Conclusions: Longer ACC time, although still within normal limits, was independently associated with decreased late survival after isolated aortic valve replacement in patients with severe aortic stenosis.
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http://dx.doi.org/10.1093/icvts/ivaa244DOI Listing
January 2021

The effect of transcatheter aortic valve implantation approaches on mortality.

Catheter Cardiovasc Interv 2021 Jan 14. Epub 2021 Jan 14.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.

Objectives: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality.

Background: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF).

Methods: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models.

Results: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches.

Conclusions: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.
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http://dx.doi.org/10.1002/ccd.29456DOI Listing
January 2021

Single or Dual Antiplatelet Treatment after TAVI. Reply.

N Engl J Med 2021 01;384(1):90-91

St. Antonius Hospital, Nieuwegein, the Netherlands.

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http://dx.doi.org/10.1056/NEJMc2032808DOI Listing
January 2021

NT-proBNP level before primary PCI and risk of poor myocardial reperfusion: Insight from the On-TIME II trial.

Am Heart J 2021 03 31;233:78-85. Epub 2020 Dec 31.

Department of Cardiology, Isala Heart Center, Zwolle, The Netherlands; Maastricht University Medical Center, Department of Cardiology, Maastricht, The Netherlands; Zuyderland Medical Center, Department of Cardiology, Heerlen, The Netherlands. Electronic address:

Background: N-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP), a marker for neurohumoral activation, has been associated with adverse outcome in patients with myocardial infarction. NT-proBNP levels may reflect extensive ischemia and microvascular damage, therefore we investigated the potential association between baseline NT-proBNP level and ST-resolution (STR), a marker of myocardial reperfusion, after primary percutaneous coronary intervention (pPCI).

Methods: we performed a post-hoc analysis of the On-TIME II trial (which randomized ST-elevation myocardial infarction (STEMI) patients to pre-hospital tirofiban administration vs placebo). Patients with measured NT-proBNP before angiography were included. Multivariate logistic-regression analyses was performed to investigate the association between baseline NTproBNP level and STR one hour after pPCI.

Results: Out of 984 STEMI patients, 918 (93.3%) had NT-proBNP values at baseline. Patients with STR <70% had higher NT-proBNP values compared to patients with complete STR (>70%) [Mean ±SD 375.2 ±1021.7 vs 1007.4 ±2842.3, Median (IQR) 111.7 (58.4-280.0) vs 168.0 (62.3-601.3), P <.001]. At multivariate logistic regression analysis, independent predictors associated with higher risk of poor myocardial reperfusion (STR <70%) were: NT-proBNP (OR 1.17, 95%CI 1.04-1.31, P = .009), diabetes mellitus (OR 1.87, 95%CI 1.14-3.07, P = .013), anterior infarct location (OR 2.74, 95% CI 2.00-3.77, P <.001), time to intervention (OR 1.06, 95%CI 1.01-1.11, P = .021), randomisation to placebo (OR 1.45, 95%CI 1.05-1.99, P = .022).

Conclusions: In STEMI patients, higher baseline NT-proBNP level was independently associate with higher risk of poor myocardial reperfusion, supporting the potential use of NT-proBNP as an early marker for risk stratification of myocardial reperfusion after pPCI in STEMI patients.
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http://dx.doi.org/10.1016/j.ahj.2020.12.017DOI Listing
March 2021

Antithrombotic therapy according to baseline bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention: applying the PRECISE-DAPT score in RE-DUAL PCI.

Eur Heart J Cardiovasc Pharmacother 2020 Dec 1. Epub 2020 Dec 1.

Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.

Aims: Patients with atrial fibrillation undergoing coronary intervention are at higher bleeding risk due to the concomitant need for oral anticoagulation and antiplatelet therapy. The RE-DUAL PCI trial demonstrated better safety with dual antithrombotic therapy (DAT: dabigatran 110 or 150 mg bid, clopidogrel or ticagrelor) compared to triple antithrombotic therapy (TAT: warfarin, clopidogrel or ticagrelor, and aspirin). We explored the impact of baseline bleeding risk based on the PRECISE-DAPT score for decision-making regarding DAT vs. TAT.

Methods And Results: A score ≥25 points qualified high bleeding-risk (HBR). Comparisons were made for the primary safety endpoint ISTH major or clinically relevant non-major bleeding, and the composite efficacy endpoint of death, thromboembolic events, or unplanned revascularization, analyzed by time-to-event analysis. PRECISE-DAPT was available in 2,336/2,725 patients, and 37.9% were HBR. Compared to TAT, DAT with dabigatran 110 mg reduced bleeding risk both in non-HBR (HR 0.42, 95%CI, 0.31-0.57) and HBR (HR 0.70, 95%CI, 0.52-0.94), with a greater magnitude of benefit among non-HBR (Pint=0.02). DAT with dabigatran 150 mg vs. TAT reduced bleeding in non-HBR (HR 0.60, 95%CI, 0.45-0.80), with a trend toward less benefit in HBR patients (HR 0.92, 95%CI, 0.63-1.34, Pint=0.08). Risk of ischaemic events was similar on DAT with dabigatran (both 110 and 150 mg) vs. TAT in non-HBR and HBR patients (Pint=0.45 and Pint=0.56, respectively).

Conclusions: PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications, and may help clinicians identifying the antithrombotic regimen intensity with the best benefit-risk ratio in an individual patient.
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http://dx.doi.org/10.1093/ehjcvp/pvaa135DOI Listing
December 2020

Oral Anticoagulants After Transcatheter Aortic Valve Replacement: Another Home Run for Direct Oral Anticoagulants?

JACC Cardiovasc Interv 2020 11;13(22):2598-2600

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.

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http://dx.doi.org/10.1016/j.jcin.2020.10.009DOI Listing
November 2020

Dual antithrombotic therapy with dabigatran in patients with atrial fibrillation after percutaneous coronary intervention for ST elevation myocardial infarction: results from the randomised RE-DUAL PCI trial.

EuroIntervention 2020 Nov 10. Epub 2020 Nov 10.

Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany.

Aims: To investigate the safety and efficacy of dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) vs warfarin triple therapy in patients with atrial fibrillation undergoing PCI for ST elevation myocardial infarction (STEMI).

Methods And Results: In RE-DUAL PCI, 305 patients with STEMI were randomised to dabigatran 110 mg (n=113 versus 106 warfarin) or 150 mg (n=86 versus 84 warfarin). Primary endpoint was time to first major or clinically relevant non-major bleeding event (MBE/CRNMBE). The thrombotic endpoint was a composite of death, thromboembolic events, or unplanned revascularisation. In STEMI patients, dabigatran 110 mg (HR 0.39, 95% CI 0.20-0.74) and 150 mg (0.43, 0.21-0.89) dual therapy reduced the risk of MBE/CRNMBE versus warfarin triple therapy (p interaction vs all other patients = 0.31 and 0.16). Risk of thrombotic events, for dabigatran 110 mg (HR 1.61, 95% CI: 0.85-3.08) and 150 mg (0.56, 0.20-1.51) had p interactions of 0.20 and 0.33, respectively. For net clinical benefit, HRs were 0.74 (95% CI 0.46-1.17) and 0.49 (0.27-0.91) for dabigatran 110 and 150 mg (p interaction = 0.80 and 0.12).

Conclusions: In patients after PCI for STEMI, dabigatran dual therapy had lower risks of bleeding events versus warfarin triple therapy with similar risks of thromboembolic events, supporting the use of dabigatran dual therapy even in patients with high thrombotic risk.
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http://dx.doi.org/10.4244/EIJ-D-20-00799DOI Listing
November 2020

Ticagrelor Versus Clopidogrel in Older Patients with NSTE-ACS Using Oral Anticoagulation: A Sub-Analysis of the POPular Age Trial.

J Clin Med 2020 Oct 12;9(10). Epub 2020 Oct 12.

Department of Cardiology, St. Antonius Hospital, 3435CM Nieuwegein, The Netherlands.

There are no randomised data on which antiplatelet agent to use in elderly patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and an indication for oral anticoagulation (OAC). The randomised POPular Age trial, in patients of 70 years or older with NSTE-ACS, showed a reduction in bleeding without increasing thrombotic events in patients using clopidogrel as compared to ticagrelor. In this sub-analysis of the POPular AGE trial, we compare clopidogrel with ticagrelor in patients with a need for oral anticoagulation. The follow-up duration was one year. The primary bleeding outcome was Platelet Inhibition and Patient Outcomes (PLATO) major and minor bleeding. The primary thrombotic outcome consisted of cardiovascular death, myocardial infarction and stroke. The primary net clinical benefit outcome was a composite of all-cause death, myocardial infarction, stroke, and PLATO major and minor bleeding. A total of 184/1011 (18.2%) patients on OAC were included in this subanalysis; 83 were randomized to clopidogrel and 101 to ticagrelor. The primary bleeding outcome was lower in the clopidogrel group (17/83, 20.9%) compared to the ticagrelor group (33/101, 33.5%; = 0.051), as was the thrombotic outcome (7/83, 8.4% vs. 19/101, 19.2%; = 0.035) and the primary net clinical benefit outcome (23/83, 27.7% vs. 49/101, 48.5%; = 0.003). In this subgroup of patients using OAC, clopidogrel reduced PLATO major and minor bleeding compared to ticagrelor without increasing thrombotic risk. This analysis therefore suggests that, in line with the POPular Age trial, clopidogrel is a better option than ticagrelor in NSTE-ACS patients ≥70 years using OAC.
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http://dx.doi.org/10.3390/jcm9103249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601891PMC
October 2020

Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on Acute Admissions at the Emergency and Cardiology Departments Across Europe.

Am J Med 2021 04 30;134(4):482-489. Epub 2020 Sep 30.

Department of Cardiology, Aarhus University Hospital, Denmark.

Purpose: We evaluated whether the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic was associated with changes in the pattern of acute cardiovascular admissions across European centers.

Methods: We set-up a multicenter, multinational, pan-European observational registry in 15 centers from 12 countries. All consecutive acute admissions to emergency departments and cardiology departments throughout a 1-month period during the COVID-19 outbreak were compared with an equivalent 1-month period in 2019. The acute admissions to cardiology departments were classified into 5 major categories: acute coronary syndrome, acute heart failure, arrhythmia, pulmonary embolism, and other.

Results: Data from 54,331 patients were collected and analyzed. Nine centers provided data on acute admissions to emergency departments comprising 50,384 patients: 20,226 in 2020 compared with 30,158 in 2019 (incidence rate ratio [IRR] with 95% confidence interval [95%CI]: 0.66 [0.58-0.76]). The risk of death at the emergency departments was higher in 2020 compared to 2019 (odds ratio [OR] with 95% CI: 4.1 [3.0-5.8], P < 0.0001). All 15 centers provided data on acute cardiology departments admissions: 3007 patients in 2020 and 4452 in 2019; IRR (95% CI): 0.68 (0.64-0.71). In 2020, there were fewer admissions with IRR (95% CI): acute coronary syndrome: 0.68 (0.63-0.73); acute heart failure: 0.65 (0.58-0.74); arrhythmia: 0.66 (0.60-0.72); and other: 0.68(0.62-0.76). We found a relatively higher percentage of pulmonary embolism admissions in 2020: odds ratio (95% CI): 1.5 (1.1-2.1), P = 0.02. Among patients with acute coronary syndrome, there were fewer admissions with unstable angina: 0.79 (0.66-0.94); non-ST segment elevation myocardial infarction: 0.56 (0.50-0.64); and ST-segment elevation myocardial infarction: 0.78 (0.68-0.89).

Conclusion: In the European centers during the COVID-19 outbreak, there were fewer acute cardiovascular admissions. Also, fewer patients were admitted to the emergency departments with 4 times higher death risk at the emergency departments.
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http://dx.doi.org/10.1016/j.amjmed.2020.08.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526639PMC
April 2021

Rationale and Design of the Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome (FORCE-ACS) Registry: Towards "Personalized Medicine" in Daily Clinical Practice.

J Clin Med 2020 Sep 30;9(10). Epub 2020 Sep 30.

Department of Cardiology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands.

Diagnostic and treatment strategies for acute coronary syndrome have improved dramatically over the past few decades, but mortality and recurrent myocardial infarction rates remain high. An aging population with increasing co-morbidities heralds new clinical challenges. Therefore, in order to evaluate and improve current treatment strategies, detailed information on clinical presentation, treatment and follow-up in real-world patients is needed. The Future Optimal Research and Care Evaluation in patients with Acute Coronary Syndrome (FORCE-ACS) registry (ClinicalTrials.gov Identifier: NCT03823547) is a multi-center, prospective real-world registry of patients admitted with (suspected) acute coronary syndrome. Both non-interventional and interventional cardiac centers in different regions of the Netherlands are currently participating. Patients are treated according to local protocols, enabling the evaluation of different diagnostic and treatment strategies used in daily practice. Data collection is performed using electronic medical records and quality-of-life questionnaires, which are sent 1, 12, 24 and 36 months after initial admission. Major end points are all-cause mortality, myocardial infarction, stent thrombosis, stroke, revascularization and all bleeding requiring medical attention. Invasive therapy, antithrombotic therapy including patient-tailored strategies, such as the use of risk scores, pharmacogenetic guided antiplatelet therapy and patient reported outcome measures are monitored. The FORCE-ACS registry provides insight into numerous aspects of the (quality of) care for acute coronary syndrome patients.
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http://dx.doi.org/10.3390/jcm9103173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601438PMC
September 2020

Microtransesophageal Echocardiographic Guidance during Percutaneous Interatrial Septal Closure without General Anaesthesia.

J Interv Cardiol 2020 7;2020:1462140. Epub 2020 Sep 7.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, Netherlands.

Objective: To study the safety and efficacy of microtransesophageal echocardiography (micro-TEE) and TEE during percutaneous atrial septal defect (ASD) and patent foramen ovale (PFO) closure.

Background: TEE has proven to be safe during ASD and PFO closure under general anaesthesia. Micro-TEE makes it possible to perform these procedures under local anaesthesia. We are the first to describe the safety and efficacy of micro-TEE for percutaneous closure.

Methods: All consecutive patients who underwent ASD and PFO closure between 2013 and 2018 were included. The periprocedural complications were registered. Residual shunts were diagnosed using transthoracic contrast echocardiography (TTCE). All data were compared between the use of TEE or micro-TEE within the ASD and PFO groups separately.

Results: In total, 82 patients underwent ASD closure, 46 patients (49.1 ± 15.0 years) with TEE and 36 patients (47.8 ± 12.1 years) using micro-TEE guidance. Median device diameter was, respectively, 26 mm (range 10-40 mm) and 27 mm (range 10-35 mm). PFO closure was performed in 120 patients, 55 patients (48.6 ± 9.2 years, median device diameter 25 mm, range 23-35 mm) with TEE and 65 patients (mean age 51.0 ± 11.8 years, median device diameter 27 mm, range 23-35 mm) using micro-TEE. There were no major periprocedural complications, especially no device embolizations within all groups. Six months after closure, there was no significant difference in left-to-right shunt after ASD closure and no significant difference in right-to-left shunt after PFO closure using TEE or micro-TEE.

Conclusion: Micro-TEE guidance without general anaesthesia during percutaneous ASD and PFO closure is as safe as TEE, without a significant difference in the residual shunt rate after closure.
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http://dx.doi.org/10.1155/2020/1462140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492935PMC
March 2021

Effect of *22 and Genetic Variants on Platelet Reactivity in Patients Treated with Clopidogrel and Lipid-Lowering Drugs Undergoing Elective Percutaneous Coronary Intervention.

Genes (Basel) 2020 09 11;11(9). Epub 2020 Sep 11.

Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.

This study aims to determine whether genetic variants that influence expression are associated with platelet reactivity in clopidogrel-treated patients undergoing elective percutaneous coronary intervention (PCI), and to evaluate the influence of statin/fibrate co-medication on these associations. A study cohort was used containing 1124 consecutive elective PCI patients in whom *22 and (G209A and A208G) SNPs were genotyped and the VerifyNow P2Y platelet reactivity test was performed. Minor allele frequencies were 0.4% for *22/*22, 6.8% for G209A AA, and 7.0% for A208G GG. *22 was not associated with platelet reactivity. The genetic variants were significantly associated with platelet reactivity (G209A AA: -24.6 PRU [-44.7, -4.6], = 0.016; A208G GG: -24.6 PRU [-44.3, -4.8], = 0.015). Validation of these results in two external cohorts, containing 716 and 882 patients, respectively, showed the same direction of effect, although not statistically significant. Subsequently, meta-analysis of all three cohorts showed statistical significance of both variants in statin/fibrate users ( = 0.04 for G209A and = 0.03 for A208G), with no difference in statin/fibrate non-users. In conclusion, G209A and A208G were associated with lower platelet reactivity in patients undergoing elective PCI who were treated with clopidogrel and statin/fibrate co-medication. Further research is necessary to confirm these findings.
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http://dx.doi.org/10.3390/genes11091068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564055PMC
September 2020

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

N Engl J Med 2020 10 30;383(15):1447-1457. Epub 2020 Aug 30.

From the Department of Cardiology, St. Antonius Hospital, Nieuwegein (J. Brouwer, V.J.N., J.P., D.R.P.P.C.P.Y., M.J.S., B.J.W.M.R., L.T., J.C.K., J.M.B.), the Department of Cardiology, Amsterdam University Medical Center, Amsterdam (R.D., J. Baan), the Department of Cardiology, Isala Hospital, Zwolle (R.S.H.), the Department of Cardiology, Maastricht University Medical Center (W.H., L.V., A.W.J.H.) and the Cardiovascular Research Institute Maastricht (A.W.J.H., J.M.B.), Maastricht, the Department of Cardiology, Medisch Spectrum Twente, Enschede (G.K.H.), the Department of Cardiology, Leiden University Medical Center, Leiden (F.K.), the Department of Cardiology, Haga Hospital, The Hague (C.E.S.), the Department of Cardiology, University Medical Center Groningen, Groningen (P.H.), Erasmus School of Health Policy and Management, Erasmus University, Rotterdam (F.W.F.T.), the Department of Cardiology, Zuyderland Medical Center, Heerlen (A.W.J.H.), and the Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht (P.R.S.) - all in the Netherlands; the Department of Cardiology, University Hospital Leuven, Leuven (C.L.F.D.), Cardiovascular Center Aalst, Onze Lieve Vrouwe Clinic (B.D.B.), and the Department of Cardiology, Algemeen Stedelijk Hospital Aalst (I.B.), Aalst, the Department of Cardiology, Sint-Jan Hospital, Brugge (J.A.S.V.D.H.), the Department of Cardiology, Hospital Oost-Limburg, Genk (B.F.), and the Department of Cardiology, Imelda Hospital, Bonheiden (J.R.) - all in Belgium; the Department of Cardiology, Institut National de Chirurgie Cardiaque et de Cardiologie Interventionnelle, Luxembourg, Luxembourg (P.F.); and the Department of Cardiology, University Hospital Královské Vinohrady and Third Medical Faculty, Charles University, Prague, Czech Republic (P.T.).

Background: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied.

Methods: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.

Results: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial.

Conclusions: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).
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http://dx.doi.org/10.1056/NEJMoa2017815DOI Listing
October 2020

Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial.

Circulation 2020 Nov 31;142(19):1799-1807. Epub 2020 Aug 31.

Department of Cardiology (L.M.W., P.W.A.J., J.P., D.R.P.P.C.P.Y., M.E.G., K.F.B., J.C.K., B.J.W.M.R., M.J.S., J.M.t.B.), St Antonius Hospital, Nieuwegein, The Netherlands.

Background: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG.

Methods: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death.

Results: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; =0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]).

Conclusions: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050749DOI Listing
November 2020

Reverse remodeling after percutaneous transluminal septal myocardial ablation in severe but asymptomatic LVOT obstruction (RASTA) study: Rationale and design of transcatheter septal reduction in asymptomatic patients with severe hypertrophic obstructive cardiomyopathy.

Catheter Cardiovasc Interv 2021 Feb 18;97(3):488-492. Epub 2020 Aug 18.

Department of Cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands.

Objectives: The aim of this study is to evaluate the impact of percutaneous transluminal septal myocardial ablation (PTSMA) on remodeling in asymptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) and severe left ventricular outflow tract (LVOT) obstruction.

Background: Symptoms justify invasive treatment in HOCM patients with LVOT obstruction. Adverse structural and functional changes (remodeling) in the heart occur preceding heart failure and sudden cardiac death. Early invasive treatment in asymptomatic patients may reverse adverse remodeling to the same extent as in symptomatic patients.

Methods: Reverse remodeling after PTSMA in severe but asymptomatic LVOT obstruction (RASTA) study is a prospective single-blind randomized trial (ClinicalTrials.gov number: NCT04230551). Ten asymptomatic HOCM patients with an exertional LVOT gradient ≥50 mmHg (or >30 mmHg in rest) are randomized 1:1 to PTSMA versus conservative therapy, in the absence of mitral valve disease or other indications for cardiac surgery. Five symptomatic (reference group) will undergo PTSMA according to the current guidelines.

Results: Remodeling is assessed using extensive cardiac imaging with transthoracic echocardiography and late gadolinium enhancement cardiac magnetic resonance at baseline and during follow-up at 1, 12, and 24 months. Extracellular volume fraction, global, and regional strain analysis, geometry, pressure gradients and changes in four-dimensional velocity mapping are primary parameters to study (reversal of) adverse remodeling.

Conclusions: The RASTA study gives insight in cardiac remodeling that may occur in asymptomatic patients after PTSMA. It will provide arguments whether to pursue (or not) a larger trial with clinical endpoints in asymptomatic HOCM patients with severe LVOT obstruction.
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http://dx.doi.org/10.1002/ccd.29178DOI Listing
February 2021

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

Circulation 2020 Aug 13;142(6):546-555. Epub 2020 Jul 13.

Department of Cardiology, Division Heart and Lungs (V.T., A.F.S., J.v.S., A.O.K., F.W.A.), UMC Utrecht, Utrecht University, the Netherlands.

Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.

Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.

Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; =28%; -heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.

Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.045526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493828PMC
August 2020

Can TAVR Be Effectively and Safely Performed Without Intraprocedural TEE?

Curr Cardiol Rep 2020 07 9;22(9):80. Epub 2020 Jul 9.

Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, 3435 Cm, Nieuwegein, The Netherlands.

Purpose Of Review: The TAVR procedure is a well-established therapy for patients with severe aortic stenosis at intermediate/high risk for surgery and a potential treatment for low-risk patients. It is much less invasive with short hospital stays and presents similar results compared with SAVR. Different "minimalist approach strategies" were proposed in order to obtain this performance. In these settings, transesophageal echocardiography (TEE) became less relevant for the TAVR procedure. The present review provides an update regarding the safety of TAVR without intraprocedural TEE.

Recent Findings: Transthoracic echocardiography and fluoroscopy are the primary imaging tools during TAVR. Several studies proved that TAVR under local anesthesia without TEE is as safe as that performed under TEE guidance. However, not all patients have a proper window for TTE, and particular cases with complex anatomy can benefit from TEE support during the intervention. Intraprocedural TEE no longer plays a crucial role in the TAVR procedure, but in some instances, it remains of great help to detect and avoid complications.
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http://dx.doi.org/10.1007/s11886-020-01344-8DOI Listing
July 2020

Dabigatran Dual Therapy vs Warfarin Triple Therapy Post-Percutaneous Coronary Intervention in Patients with Atrial Fibrillation With/Without a Proton Pump Inhibitor: A Pre-Specified Analysis of the RE-DUAL PCI Trial.

Drugs 2020 Jul;80(10):995-1005

Brigham and Women's Hospital and Heart and Vascular Center, and Harvard Medical School, Boston, MA, USA.

Background And Objective: In patients with atrial fibrillation following percutaneous coronary intervention, if a proton pump inhibitor is used, could that allow the use of warfarin triple therapy, or is there additional reduction in bleeding while using it with dual therapy?

Methods: The RE-DUAL PCI trial randomized 2725 patients with atrial fibrillation post-percutaneous coronary intervention to dabigatran dual therapy (110 or 150 mg twice daily, with clopidogrel or ticagrelor) or warfarin triple therapy (with clopidogrel or ticagrelor, and aspirin for 1-3 months). This prespecified subgroup analysis evaluated risks of a first major bleeding event or clinically relevant non-major bleeding event, all gastrointestinal bleeding, and a composite efficacy endpoint of all-cause mortality/thromboembolic event or unplanned revascularization according to baseline use of a proton pump inhibitor.

Results: Of 2678 analyzed patients, 1641 (61.3%) were receiving a proton pump inhibitor at baseline. Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy regardless of proton pump inhibitor use, with comparable risk of the composite efficacy endpoint (all interaction p values > 0.05). For gastrointestinal bleeding, no interaction was observed between study treatment and proton pump inhibitor use (interaction p values 0.84 and 0.62 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin triple therapy).

Conclusions: Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy, regardless of proton pump inhibitor use at baseline, in patients with atrial fibrillation who underwent percutaneous coronary intervention. Risk of the composite efficacy endpoint appeared to be similar for dabigatran dual therapy vs warfarin triple therapy in patients receiving/not receiving a proton pump inhibitor. CLINICALTRIALS.

Gov Unique Identifier: NCT02164864.
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http://dx.doi.org/10.1007/s40265-020-01323-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320045PMC
July 2020

Protamine in Patients Undergoing Transcatheter Aortic Valve Replacement: Why Not?

JACC Cardiovasc Interv 2020 06;13(12):1481-1483

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.

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http://dx.doi.org/10.1016/j.jcin.2020.04.056DOI Listing
June 2020

Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy.

BMC Cardiovasc Disord 2020 06 3;20(1):268. Epub 2020 Jun 3.

Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.

Background: To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD.

Methods: This prospective (April 2013-December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI.

Discussion: The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI.

Trial Registration: Trial registration name is "Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy" (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.
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http://dx.doi.org/10.1186/s12872-020-01558-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271437PMC
June 2020

Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium.

Clin Pharmacol Ther 2020 11 9;108(5):1067-1077. Epub 2020 Jul 9.

Department of Medicine and Program for Personalized and Genomic Medicine, University of Maryland, Baltimore, Maryland, USA.

Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate-induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 (P value = 1.67e-33). After correction for CYP2C19*2 no other single-nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1, CDC42BPA, and CTRAC1 showed genomewide significance (lowest P values: 1.07e-09, 4.53e-08, and 2.60e-10, respectively). CYP2C19*2 is the strongest genetic determinant of on-clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes.
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http://dx.doi.org/10.1002/cpt.1911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689744PMC
November 2020