Cost-effectiveness of a photopethysmographic procedure for screening for atrial fibrillation in 6 European countries.

BACKGROUND: Strokes cause an estimated annual health care burden of 170 billion euros across Europe. Atrial fibrillation is one of the major risk factors for stroke and increases the individual risk 4.2-fold. But prevention with anticoagulants may reduce this risk by 70%. Screening methods are employed to detect previously undetected atrial fibrillation. Screening studies in various European countries show a high degree of undetected atrial fibrillation. This study aims to assess the cost-effectiveness of systematic screening with a smartphone application, named Preventicus Heartbeats. It is a hands-on screening tool for use on smartphone to diagnose AF with high sensitivity and specificity. METHODS: A previously published model for calculating screening cost-effectiveness was extended to 6 European countries covering a wide range in terms of treatment costs and epidemiologic parameters. RESULTS: The use of screening lowers the cost per case in countries with comparatively high levels of health care costs (Switzerland: -€75; UK: -€7). Moderate higher costs per case were observed in 4 countries (Greece: €6; Netherlands: €15). Low levels of health care costs result in less or no potential for further cost reduction (Poland: €20; Serbia: €33). In all countries considered, the model showed an increase in effectiveness measures both in the number of strokes avoided and the quality adjusted life years. The number of strokes avoided per 1000 participants ranged from 2.52 (Switzerland) to 4.44 (Poland). Quality-adjusted life-years per case gained from screening ranged from 0.0105 (Switzerland) to 0.0187 (Poland). The screening procedure dominated in two countries (Switzerland, UK). For the remaining countries, the incremental cost effectiveness ratio ranged from €489/QALY (Greece) to €2548/QALY (Serbia). CONCLUSION: The model results showed a strong dependence of the results on the country-specific costs for stroke treatment. The use of the investigated screening method is close to cost-neutral or cost-reducing in the Western European countries and Greece. In countries with low price levels, higher cost increases due to AF screening are to be expected. Lower costs of anticoagulation, which are expected due to the upcoming patent expiry of direct anticoagulants, have a positive effect on the cost result.

Shockwave Coronary Intravascular Lithotripsy System for Heavily Calcified De Novo Lesions and the Need for a Cost-Effectiveness Analysis.

The optimal management for severely calcified coronary artery disease is multi-adjunctive. Different strategies with dedicated devices should be available in the cardiac catheterization laboratory with their selection depending on the nature of the calcific disease and its anatomical distribution. Shockwave Intravascular Lithotripsy (S-IVL) system offers a novel option for lesion preparation of heavily calcified plaques in coronary and peripheral vessels. S-IVL is based on the fundamental principles of lithotripsy, a technology that has been used to modify renal stones for over 30 years. Pulsatile mechanical energy is used to fragment selectively amorphous calcium, sparing soft tissue. S-IVL has the potential of more widespread adoption because of its proven safety, efficacy and operational simplicity, but cost-effectiveness of such advanced technology will need to be analyzed.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Assessment of absolute Tc-99m tetrofosmin retention in the myocardium as an index of myocardial blood flow and coronary flow reserve by gated-SPECT/CT: a feasibility study.

OBJECTIVE: Estimation of myocardial blood flow (MBF) and coronary flow reserve (CFR) by SPECT myocardial perfusion imaging (MPI) remains challenging. Our aim was to approximate MBF and CFR by quantifying the absolute Tc-99m tetrofosmin retention in the myocardium via gated-SPECT/CT MPI. METHODS: Tracer retention was calculated on the basis of the microsphere kinetic model and served as an index of MBF at stress and rest (sMBFi, rMBFi). CFR was given by the sMBFi/rMBFi ratio. A planar first-pass acquisition during dipyridamole stress and at rest provided the data for tracer input determination. The input was represented by the integral of a gamma variate fitted on the time-activity curve of the left ventricle. Gated-SPECT/CT was performed 1 h post tracer injection and myocardial activity was measured in attenuation-corrected transaxial slices by a threshold VOI. The input was also compensated for tissue attenuation by measuring the distance from the centre of the left ventricle to the body surface on fused SPECT/CT slices. Input and uptake results were adjusted for planar-SPECT counting geometry differences by the aid of a phantom experiment. Thirty-nine subjects with low probability of coronary artery disease (CAD), age lower than 75 years and normal MPI (control group) were compared with 57 patients with documented CAD (CAD group). RESULTS: CFR and sMBFi values of CAD patients (1.39 ± 0.37 and 1.42 ± 0.35 ml/min/g) were considerably lower (p < 0.0001) than controls (1.68 ± 0.25 and 1.72 ± 0.37 ml/min/g). Significant difference in CFR (p = 0.03) was also noted between CAD patients with normal MPI (1.48 ± 0.38) and controls. However, sMBFi managed to discriminate certain CAD subgroups (normal MPI/ischemia/scar/scar and ischemia) more efficiently than CFR. Maximum heart rate-blood pressure product (RPP) during stress was an independent predictor of sMBFi and CFR. The other independent CFR correlates were resting RPP and diabetes mellitus, while sMBFi was associated with age, sex, smoking, and stress perfusion defects. CONCLUSIONS: Despite the low myocardial extraction fraction of Tc-99m tetrofosmin, an approximation of MBF and CFR is feasible with gated-SPECT/CT MPI. These flow indices together were able to discriminate CAD patients from controls and stratify different patient subgroups.

Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction: the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial.

AIMS: Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone. METHODS AND RESULTS: The TOTAL trial (N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22) in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post-stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups. CONCLUSION: Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow.

Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with diabetes.

OBJECTIVE: It has been postulated that prasugrel might be the preferred treatment option in diabetes mellitus (DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to compare the pharmacodynamic action of ticagrelor versus prasugrel. RESEARCH DESIGN AND METHODS: In a prospective, single-center, single-blind, crossover study, 30 consecutive ACS patients with DM who had been pretreated with clopidogrel were randomized to either 90 mg ticagrelor twice daily or 10 mg prasugrel once daily with a 15-day treatment period. Platelet reactivity (PR) was assessed with the VerifyNow P2Y12 function assay, measured in P2Y12 reaction units (PRU). RESULTS: PR was significantly lower after ticagrelor (45.2 PRU [95% CI 27.4-63.1]) compared with prasugrel (80.8 PRU [63.0-98.7]), with a least squares mean difference of -35.6 PRU (-55.2 to -15.9, P = 0.001). High PR rate was 0% for ticagrelor and 3.3% for prasugrel (P = 1.0). CONCLUSIONS: In DM patients with ACS who had been pretreated with clopidogrel and who undergo PCI, ticagrelor achieves a significantly higher platelet inhibition than prasugrel. Both antiplatelet agents effectively treat high PR. The relevance of these findings to the clinical efficacy and safety of ticagrelor and prasugrel in DM patients needs further elucidation.

Facilitating assessment of QT interval duration during ventricular pacing.

AIMS: We aimed to facilitate the assessment of the QT interval duration during conventional right ventricular pacing (VP) by uncovering relationships with the underlying QT interval during intrinsic atrioventricular conduction (IC). METHODS AND RESULTS: The study patients (n = 122, age 68 ± 11 years) were dual-chamber device recipients with preserved IC and narrow QRS complexes. Patients were classified into either 'normal-QT' (n = 70) or 'prolonged-QT' (n = 52) group. Incremental atrial pacing rates were exercised to record serial QT/JT intervals over 5 min periods in IC mode and then in VP mode. Six different QT correction methods for heart rate were applied to assess the effect (i) of pacing mode (IC vs. VP) and (ii) of heart rate on the derived QT(c)/JT(c) intervals by mixed-effects linear models. Following VP, the uncorrected QT/JT intervals as well as the JTc intervals shortened (P < 0.001), whereas the QTc intervals prolonged (P < 0.001). In both patient groups, the Framingham and Nomogram methods demonstrated the optimal balance to assess QTc, with low heart rate dependence during VP and minimal interaction between pacing mode and heart rate. The Rautaharju formula provided excellent correction for the QT changes induced by VP, but the QTc interval responded differently to rate changes in IC vs. VP mode. Bazett's formula exaggerated QTc/JTc rate dependency during VP. CONCLUSION: The Framingham and Nomogram correction methods perform most reliably in assessing the underlying QT interval during IC from the ventricular paced QT interval.

Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction.

BACKGROUND: Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel. Direct pharmacodynamic comparison between them has not yet been reported in ST-segment-elevation myocardial infarction patients. METHODS AND RESULTS: In a prospective, single-center, single-blind study, 55 out of 117 (47%) screened consecutive ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention were randomized to either ticagrelor 180 mg loading followed by 90 mg bid, or prasugrel 60 mg loading followed by 10 mg od for 5 days. Platelet reactivity (PR) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0, 1, 2, 6, 24 hours, and 5 days postrandomization. The primary end point, PR with VerifyNow at hour 1, did not differ significantly between patients randomized to ticagrelor versus prasugrel (257.3 P2Y12 reaction unit [PRU], 95% CI 230.8-283.8 versus 231.3 PRU, 95% CI 205.3-257.4; P=0.2). PR did not differ at 2, 6, and 24 hours, although at day 5 it was lower with ticagrelor than prasugrel (25.6 PRU, 95% CI 12.3-38.9 versus 50.3 PRU, 95% CI 36.4-64.1; P=0.01). At hour 2, high on-treatment PR rates (cutoff 208 PRU) were 46.2% and 34.6% for ticagrelor and prasugrel, respectively, decreased significantly thereafter, whereas did not differ significantly between the 2 agents at all the time points of the study. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action. Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463163.

Optimal QT/JT interval assessment in patients with complete bundle branch block.

BACKGROUND: Prolonged ventricular repolarization duration confers increased risk for malignant ventricular arrhythmias. We sought to clarify the optimal method of QT/JT interval assessment in patients with complete bundle branch block (BBB). METHODS: Study patients (n = 71) were dual-chamber device recipients with baseline left or right BBB who preserved intrinsic ventricular activation during incremental atrial pacing. Patients were classified according to the presence or not of structural heart disease. The former group received chronic amiodarone therapy. QT and JT intervals were recorded at baseline heart rate of 51 ± 4 beats/min and during atrial pacing at 60, 80, and 100 beats/min. We used linear mixed-effects models to assess the effect of heart rate on the derived QTc and JTc values with the use of six different heart rate correction formulae. RESULTS: Heart rate had a significant effect on the QTc and the JTc intervals regardless of the correction formula used (P < 0.001 for all formulae). The formula of Hodges demonstrated the least variability in QTc and JTc measurements across the different heart rates in both patients groups without (F = 15.05 and F = 13.53, respectively) and with structural heart disease (F = 5.71 and F = 7.69, respectively), followed by the Nomogram and Framingham methods, whereas the uncorrected QT and JT intervals showed comparable heart rate-dependency. The application of Bazett's JTc and QTc led to the most pronounced interval variations in any case with BBB. CONCLUSIONS: The Hodges, Nomogram and Framingham correction methods provide best assessment of QT/JT intervals in BBB, whereas Bazett's formula exaggerates heart rate-dependency of ventricular repolarization intervals.

Preferred QT correction formula for the assessment of drug-induced QT interval prolongation.

INTRODUCTION: There is debate on the optimal QT correction method to determine the degree of the drug-induced QT interval prolongation in relation to heart rate (DeltaQTc). METHODS: Forty-one patients (71 +/- 10 years) without significant heart disease who had baseline normal QT interval with narrow QRS complexes and had been implanted with dual-chamber pacemakers were subsequently started on antiarrhythmic drug therapy. The QTc formulas of Bazett, Fridericia, Framingham, Hodges, and Nomogram were applied to assess the effect of heart rate (baseline, atrial pacing at 60 beats/min, 80 beats/min, and 100 beats/min) on the derived DeltaQTc (QTc before and during antiarrhythmic therapy). RESULTS: Drug treatment reduced the heart rate (P < 0.001) and increased the QT interval (P < 0.001). The heart rate increase shortened the QT interval (P < 0.001) and prolonged the QTc interval (P < 0.001) by the use of all correction formulas before and during antiarrhythmic therapy. All formulas gave at 60 beats/min similar DeltaQTc of 43 +/- 28 ms. At heart rates slower than 60 beats/min, the Bazett and Framingham methods provided the most underestimated DeltaQTc values (14 +/- 32 ms and 18 +/- 34 ms, respectively). At heart rates faster than 60 beats/min, the Bazett and Fridericia methods yielded the most overestimated DeltaQTc values, whereas the other 3 formulas gave similar DeltaQTc increases of 32 +/- 28 ms. CONCLUSIONS: Bazett's formula should be avoided to assess DeltaQTc at heart rates distant from 60 beats/min. The Hodges formula followed by the Nomogram method seem most appropriate in assessing DeltaQTc.