Long-term outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in ST-segment elevation myocardial infarction: 5-year follow-up of the BIOSTEMI randomised superiority trial.

BACKGROUND: Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain. METHODS: BIOSTEMI Extended Survival (BIOSTEMI ES) was an investigator-initiated, follow-up extension study of the BIOSTEMI prospective, multicentre, single-blind, randomised superiority trial that compared biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents in patients with STEMI undergoing primary percutaneous coronary intervention at ten hospitals in Switzerland. All individuals who had provided written informed consent for participation in the BIOSTEMI trial were eligible for this follow-up study. The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial re-infarction, or clinically indicated target lesion revascularisation, at 5 years. Superiority of biodegradable polymer sirolimus-eluting stents over durable polymer everolimus-eluting stents was declared if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0·975. Analyses were performed according to the intention-to-treat principle. The study was registered with ClinicalTrials.gov, NCT05484310. FINDINGS: Between April 26, 2016, and March 9, 2018, 1300 patients with STEMI (1622 lesions) were randomly allocated in a 1:1 ratio to treatment with biodegradable polymer sirolimus-eluting stents (649 patients, 816 lesions) or durable polymer everolimus-eluting stents (651 patients, 806 lesions). At 5 years, the primary composite endpoint of target lesion failure occurred in 50 (8%) patients treated with biodegradable polymer sirolimus-eluting stents and in 72 (11%) patients treated with durable polymer everolimus-eluting stents (difference of -3%; RR 0·70, 95% Bayesian credible interval 0·51-0·95; Bayesian posterior probability for superiority 0·988). INTERPRETATION: In patients undergoing primary percutaneous coronary intervention for STEMI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 5 years of follow-up. The difference was driven by a numerically lower risk for ischaemia-driven target lesion revascularisation. FUNDING: Biotronik.

Complex primary percutaneous coronary intervention with ultrathin-strut biodegradable versus thin-strut durable polymer drug-eluting stents in patients with ST-segment elevation myocardial infarction: A subgroup analysis from the BIOSTEMI randomized trial.

BACKGROUND: Ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) are superior to thin-strut durable polymer everolimus-eluting stents (DP-EES) with respect to target lesion failure (TLF) at 2 years among patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the impact of primary percutaneous coronary intervention (pPCI) complexity on long-term clinical outcomes with BP-SES versus DP-EES in STEMI patients. METHODS: We performed a post hoc subgroup analysis from the BIOSTEMI (NCT02579031) randomized trial, which included individual data from 407 STEMI patients enrolled in the BIOSCIENCE trial (NCT01443104). STEMI patients were randomly assigned to treatment with ultrathin-strut BP-SES or thin-strut DP-EES, and further categorized into those undergoing complex versus noncomplex pPCI. Complex pPCI was defined by the presence of ≥1 of the following criteria: 3 vessel treatment, ≥3 stents implanted, ≥3 lesions treated, bifurcation lesion with ≥2 stents implanted, total stent length ≥60 mm, and/or chronic total occlusion treatment. The primary endpoint was TLF, a composite of cardiac death, target-vessel myocardial reinfarction, or clinically indicated target lesion revascularization, within 2 years. RESULTS: Among a total of 1707 STEMI patients, 421 (24.7%) underwent complex pPCI. Baseline characteristics were similar between groups. At 2 years, TLF occurred in 14 patients (7.1%) treated with BP-SES and 25 patients (11.6%) treated with DP-EES (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.32-1.19; p = 0.15) in the complex pPCI group, and in 28 patients (4.4%) treated with BP-SES and 49 patients (8.2%) treated with DP-EES (HR: 0.54; 95% CI: 0.34-0.86; p = 0.008; p for interaction = 0.74) in the noncomplex pPCI group. Individual TLF components and stent thrombosis rates did not significantly differ between groups. CONCLUSION: In a post hoc subgroup analysis from the BIOSTEMI randomized trial, ultrathin-strut BP-SES were superior to thin-strut DP-EES with respect to TLF at 2 years among STEMI patients undergoing both complex and noncomplex pPCI.

Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (BIOSTEMI): a single-blind, prospective, randomised superiority trial.

BACKGROUND: Newer-generation drug-eluting stents that combine ultrathin strut metallic platforms with biodegradable polymers might facilitate vascular healing and improve clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) compared with contemporary thin strut second-generation drug-eluting stents. We did a randomised clinical trial to investigate the safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stents versus thin strut durable polymer everolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. METHODS: The BIOSTEMI trial was an investigator-initiated, multicentre, prospective, single-blind, randomised superiority trial at ten hospitals in Switzerland. Patients aged 18 years or older with acute STEMI who were referred for primary PCI were eligible to participate. Patients were randomly allocated (1:1) to either biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Central randomisation was done based on a computer-generated allocation sequence with variable block sizes of 2, 4, and 6, which was stratified by centre, diabetes status, and presence or absence of multivessel coronary artery disease, and concealed using a secure web-based system. Patients and treating physicians were aware of group allocations, whereas outcome assessors were masked to the allocated stent. The experimental stent (Orsiro; Biotronik; Bülach, Switzerland) consisted of an ultrathin strut cobalt-chromium metallic stent platform releasing sirolimus from a biodegradable polymer. The control stent (Xience Xpedition/Alpine; Abbott Vascular, Abbott Park, IL, USA) consisted of a thin strut cobalt-chromium stent platform that releases everolimus from a durable polymer. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial reinfarction (Q-wave and non-Q-wave), and clinically-indicated target lesion revascularisation, within 12 months of the index procedure. All analyses were done with the individual participant as the unit of analysis and according to the intention-to-treat principle. The trial was registered with ClinicalTrials.gov, number NCT02579031. FINDINGS: Between April 26, 2016, and March 9, 2018, we randomly assigned 1300 patients (1623 lesions) with acute myocardial infarction to treatment with biodegradable polymer sirolimus-eluting stents (649 patients and 816 lesions) or durable polymer everolimus-eluting stents (651 patients and 806 lesions). At 12 months, follow-up data were available for 614 (95%) patients treated with biodegradable polymer sirolimus-eluting stents and 626 (96%) patients treated with durable polymer everolimus-eluting stents. The primary composite endpoint of target lesion failure occurred in 25 (4%) of 649 patients treated with biodegradable polymer sirolimus-eluting stents and 36 (6%) of 651 patients treated with durable polymer everolimus-eluting stents (difference -1·6 percentage points; rate ratio 0·59, 95% Bayesian credibility interval 0·37-0·94; posterior probability of superiority 0·986). Cardiac death, target vessel myocardial reinfarction, clinically-indicated target lesion revascularisation, and definite stent thrombosis were similar between the two treatment groups in the 12 months of follow-up. INTERPRETATION: In patients with acute STEMI undergoing primary PCI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 1 year. This difference was driven by reduced ischaemia-driven target lesion revascularisation in patients treated with biodegradable polymer sirolimus-eluting stents compared with durable polymer everolimus-eluting stents. FUNDING: Biotronik.

Thermal biology mediates responses of amphibians and reptiles to habitat modification.

Human activities often replace native forests with warmer, modified habitats that represent novel thermal environments for biodiversity. Reducing biodiversity loss hinges upon identifying which species are most sensitive to the environmental conditions that result from habitat modification. Drawing on case studies and a meta-analysis, we examined whether observed and modelled thermal traits, including heat tolerances, variation in body temperatures, and evaporative water loss, explained variation in sensitivity of ectotherms to habitat modification. Low heat tolerances of lizards and amphibians and high evaporative water loss of amphibians were associated with increased sensitivity to habitat modification, often explaining more variation than non-thermal traits. Heat tolerances alone explained 24-66% (mean = 38%) of the variation in species responses, and these trends were largely consistent across geographic locations and spatial scales. As habitat modification alters local microclimates, the thermal biology of species will likely play a key role in the reassembly of terrestrial communities.

Tropical amphibians in shifting thermal landscapes under land-use and climate change.

Land-cover and climate change are both expected to alter species distributions and contribute to future biodiversity loss. However, the combined effects of land-cover and climate change on assemblages, especially at the landscape scale, remain understudied. Lowland tropical amphibians may be particularly susceptible to changes in land cover and climate warming because many species have narrow thermal safety margins resulting from air and body temperatures that are close to their critical thermal maxima (CTmax ). We examined how changing thermal landscapes may alter the area of thermally suitable habitat (TSH) for tropical amphibians. We measured microclimates in 6 land-cover types and CTmax of 16 frog species in lowland northeastern Costa Rica. We used a biophysical model to estimate core body temperatures of frogs exposed to habitat-specific microclimates while accounting for evaporative cooling and behavior. Thermally suitable habitat area was estimated as the portion of the landscape where species CTmax exceeded their habitat-specific maximum body temperatures. We projected changes in TSH area 80 years into the future as a function of land-cover change only, climate change only, and combinations of land-cover and climate-change scenarios representing low and moderate rates of change. Projected decreases in TSH area ranged from 16% under low emissions and reduced forest loss to 30% under moderate emissions and business-as-usual land-cover change. Under a moderate emissions scenario (A1B), climate change alone contributed to 1.7- to 4.5-fold greater losses in TSH area than land-cover change only, suggesting that future decreases in TSH from climate change may outpace structural habitat loss. Forest-restricted species had lower mean CTmax than species that occurred in altered habitats, indicating that thermal tolerances will likely shape assemblages in changing thermal landscapes. In the face of ongoing land-cover and climate change, it will be critical to consider changing thermal landscapes in strategies to conserve ectotherm species.

Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

BACKGROUND: Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. METHODS AND RESULTS: To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. CONCLUSIONS: In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166685.

Improved outcomes of elderly patients treated with drug-eluting versus bare metal stents in large coronary arteries: results from the BAsel Stent Kosten-Effektivitäts Trial PROspective Validation Examination randomized trial.

BACKGROUND: Drug-eluting stents (DES) improve outcomes in elderly patients with small coronary artery disease compared with bare-metal stents (BMS), but randomized data in elderly patients in need of large coronary stents are not available. METHODS: Planned secondary analysis of patients ≥75 years recruited to the "BASKET-PROVE" trial, in which 2,314 patients undergoing percutaneous coronary intervention for large (≥3.0 mm) native vessel disease were randomized 2:1 to DES (everolimus- vs sirolimus-eluting stents 1:1) versus BMS. All patients received 12 months of dual antiplatelet therapy. The primary end point was a composite of cardiac death or nonfatal myocardial infarction at 2 years. RESULTS: Comparison of DES versus BMS among 405 patients ≥75 years showed significantly lower rates of the primary end point for DES (5.0% vs 11.6%; hazard ration (HR) 0.64 [0.44-0.91]; P = .014). Rates of nonfatal myocardial infarction (1.2% vs 5.5%, hazard ration (HR) 0.44 [0.21-0.83]; P = .009), all-cause death (7.4% vs 14.4%; HR 0.7 [0.51-0.95]; P = .02), and target vessel revascularization (TVR) (2.3% vs 6.2%; HR 0.59 [0.34-0.99]; P = .046) were also lower, whereas stent thrombosis and bleeding rates were similar. In contrast, among patients <75 years (n = 1,909), the only significant benefit of DES was a reduced rate of TVR (4.0% vs 8.7%, HR 0.66 [0.55-0.80]; P < .0001). CONCLUSIONS: In patients ≥75 years requiring large (≥3.0 mm) coronary stents, use of DES was beneficial compared with BMS and reduced the rate of ischemic events, mortality, and TVR. These data suggest that DES should be preferred over BMS in elderly patients.

Evaluating connectivity for tropical amphibians using empirically derived resistance surfaces.

Agricultural expansion continues to drive forest loss in species-rich tropical systems and often disrupts movement and distributions of organisms. The ability of species to occupy and move through altered habitats likely depends on the level of contrast between natural forest and surrounding land uses. Connectivity models, such as circuit theory models, are widely used in conservation biology, and their primary input consists of resistance surfaces representing movement costs associated with landscape features. Cost values are most frequently determined by expert opinion, which may not capture relevant levels of contrast among features. We developed resistance surfaces using experiments that represent different local mechanisms hypothesized to affect connectivity for two Neotropical amphibian species. Response ratios were calculated to translate experimental results to cost values used in connectivity modeling. We used relative abundance data in three land-cover types to generate resistance surfaces for evaluating independent support of models derived from experiments. Finally, we analyzed agreement among movement pathways predicted for each species and among three commonly used connectivity measures: Euclidean, least cost, and resistance distances. Experiments showed that extreme microclimates associated with altered habitats significantly increased desiccation and mortality risk for both species. Resistances estimated from microclimate experiments were concordant with those from survey data for both species. For one focal species, resistance estimates derived from predator encounter rates were also highly correlated with abundance-derived resistances. There was generally low agreement among the three alternative distance measures, which underscores the importance of choosing connectivity models that are most appropriate for the study objectives. Overall, similarity among linkages modeled for each species was high, but decreased with declining forest cover. Our results highlight the value of experiments for drawing inferences about processes in resistance modeling, as well as the need to consider model differences and species-specific responses when developing strategies to maintain connectivity.

Severe multifocal coronary artery spasms after cessation of vasodilators in a patient with a spontaneous coronary artery dissection: a case report.

Background: Vasospastic angina (VSA) and spontaneous coronary artery dissection (SCAD) are challenging causes of non-atherosclerotic acute coronary syndromes (ACS). Here, we report a unique ACS case with coexisting VSA and SCAD, highlighting specific strategies in diagnosis and management of these poorly studied conditions. Case summary: A woman in her mid-60s with a history of suspected microvascular angina and no atherosclerosis in a previously performed coronary computed tomography angiography presented with worsening chest pain. Invasive coronary angiography revealed a focal SCAD with a resulting high-degree stenosis of the right coronary artery. Shortly after successful percutaneous coronary intervention with stent implantation and stopping her previous vasodilator therapy with nitroglycerine and molsidomine, the patient developed recurrent anterior non-ST-segment elevation myocardial infarction. Surprisingly, repeat coronary angiography revealed severe multifocal coronary artery spasms that were successfully treated with intracoronary nitroglycerine. Vasospastic angina was subsequently managed with diltiazem, molsidomine, and nitrates. Discussion: Our report underscores the challenges in diagnosing and managing SCAD and VSA in ACS. The possible interplay between SCAD and VSA highlights the need for careful vasodilator therapy management, as seen in our patient, where therapy discontinuation led to severe multifocal VSA. This emphasizes the need for a comprehensive approach for optimal outcomes in complex ACS cases.

Association of chocolate consumption with neurological and cardiovascular outcomes in atrial fibrillation: data from two Swiss atrial fibrillation cohort studies (Swiss-AF and BEAT-AF).

AIM: To assess the associations of chocolate consumption with neurocognitive function, brain lesions on magnetic resonance imaging (MRI), and cardiovascular outcome in patients with atrial fibrillation (AF). METHODS: We analysed data from patients of two prospective multicentre Swiss atrial fibrillation cohort studies (Swiss-AF) and (BEAT-AF). Assessments of MRI findings and neurocognitive function were performed only in the Swiss-AF population (in 1727 of 2415 patients [71.5%] with a complete data set), as patients enrolled in BEAT-AF were not systematically evaluated for these outcomes. Otherwise, the two cohorts had an equivalent set of clinical assessments. Clinical outcome analysis was performed in 3931 patients of both cohorts. Chocolate consumption was assessed by questionnaire. Patients were categorised as no/low chocolate consumption (No/Low-Ch) ≤1 servings/week, moderate chocolate consumption (Mod-Ch) >1-6 servings/week, and high chocolate consumption (High-Ch) >6 servings/week, respectively. Brain lesions were evaluated by MRI. Assessment of cognitive function was performed by neurocognitive functional testing and included global cognition measurement with a cognitive construct score. Cerebral MRI and cognition were evaluated at baseline. Cross-sectional associations between chocolate consumption and MRI findings were analysed by multivariate logistic regression models and associations with neurocognitive function by multivariate linear regression models. Clinical outcome events during follow-up were recorded and assessed by a clinical event committee. The associations between chocolate consumption and clinical outcomes were evaluated by Cox regression models. The median follow-up time was 6 years. RESULTS: Chocolate consumption was not associated with prevalence or volume of vascular brain lesions on MRI, nor major adverse cardiac events (ischaemic stroke, myocardial infarction, cardiovascular death). However, No/Low-Ch was independently associated with a lower cognitive construct score compared to Mod-Ch (No/Low-Ch vs. Mod-Ch: coeff. -0.05, 95% CI -0.10-0), whereas other neurocognitive function tests were not independently associated with chocolate consumption categories. In addition, there was a higher risk of heart failure hospitalisation (No/Low-Ch vs. Mod-Ch: HR 1.24, 95% CI 1.01-1.52) and of all-cause mortality (No/Low-Ch vs. Mod-Ch: HR 1.29, 95% CI 1.06-1.58) in No/Low-Ch compared to Mod-Ch. No significant associations with the evaluated outcomes were observed when High-Ch was compared to Mod-Ch. CONCLUSION: While chocolate consumption was not associated with MRI findings and major adverse cardiac events in an atrial fibrillation population, No/Low-Ch was associated with a lower cognitive construct score, higher risk of heart failure hospitalisation and increased all-cause mortality compared to Mod-Ch. CLINICALTRIALS: gov Identifier: NCT02105844.

Efficacy and Safety of Abbreviated Eptifibatide Treatment in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

The glycoprotein IIb/IIIa inhibitor eptifibatide, administered as bolus followed by infusion, is an adjunctive antithrombotic treatment during primary percutaneous coronary intervention (PCI) in selected patients with ST-segment elevation myocardial infarction (STEMI). Whether both bolus and infusion are necessary to improve outcomes is unknown. We hypothesized that primary PCI with eptifibatide bolus only is non-inferior to the conventional treatment (bolus and infusion) with regard to infarct size, while reducing bleeding complications. We analyzed 720 consecutive STEMI patients receiving eptifibatide bolus only or conventional treatment in an observational case-control study utilizing propensity score matching of clinical and intervention-specific confounders. Infarct size was estimated based on myocardial bound creatine kinase, creatine kinase (CK), and CK area under the curve values, with a prespecified non-inferiority margin of 20%. Major bleeding was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium classification. Eptifibatide bolus only was administered to 147 patients (20%), which were matched 1:1 to patients receiving conventional treatment. Based on peak myocardial bound creatine kinase, CK and CK area under the curve values, infarct size was -8.4% (95% CI [-31.2%, 14.4%]), -11.6% (95% CI [-33.5%, 10.3%]), and -13.9% (95% CI [-34.1%, 6.2%]) after eptifibatide bolus, respectively, reaching prespecified noninferiority compared with conventional treatment. Bolus treatment significantly reduced major bleeding complications (OR 0.48, 95% CI [0.30, 0.79]). In conclusion, eptifibatide given as abbreviated bolus only to selected STEMI patients who underwent primary PCI was noninferior regarding infarct size and resulted in less bleeding complications compared with conventional bolus and infusion treatment.

Multivessel percutaneous coronary intervention with thin-strut biodegradable versus durable polymer drug-eluting stents in ST-segment elevation myocardial infarction: A subgroup analysis of the BIOSTEMI randomized trial.

BACKGROUND: Randomized evidence comparing newer-generation drug-eluting stents for multivessel percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is limited. We sought to investigate clinical outcomes in STEMI patients undergoing multivessel PCI with thin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) versus durable polymer everolimus-eluting stents (DP-EES). METHODS: We performed a subgroup analysis of the BIOSTEMI (NCT02579031) randomized trial, which included individual patient data from STEMI patients enrolled into the BIOSCIENCE (NCT02579031) study. STEMI patients randomly allocated to BP-SES or DP-EES were divided into those undergoing multivessel versus culprit lesion-only PCI. The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial re-infarction or clinically indicated target lesion revascularization (TLR), within 24 months. RESULTS: Among 1707 STEMI patients, 145 patients underwent multivessel PCI. At 2 years, TLF occurred in 2 patients (2.8%) treated with BP-SES and 13 patients (18.7%) treated with DP-EES (hazard ratio [HR], 0.14; 95% confidence interval (CI), 0.03-0.61; p = 0.009) in the multivessel PCI group, and in 40 (5.3%) and 61 (8.2%) patients treated with BP-SES and DP-EES respectively (HR, 0.64; 95%CI, 0.43-0.96; p = 0.03; p for interaction = 0.050) in the culprit lesion-only PCI group. In the multivessel PCI group, the rates of clinically indicated TLR (0% vs. 12.4%) and target vessel myocardial re-infarction (0% vs. 4.6%) at 2 years were lower in patients treated with BP-SES compared with DP-EES. CONCLUSION: In a subgroup analysis of the BIOSTEMI trial, BP-SES were associated with lower 2-year TLF rates compared to DP-EES in STEMI patients undergoing multivessel PCI.

Biodegradable- Versus Durable-Polymer Drug-Eluting Stents for STEMI: Final 2-Year Outcomes of the BIOSTEMI Trial.

OBJECTIVES: The aim of this study was to investigate the safety and efficacy of biodegradable-polymer sirolimus-eluting stents (BP-SES) compared with durable-polymer everolimus-eluting stents (DP-EES) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Primary percutaneous coronary intervention (PCI) is an effective treatment for patients with STEMI, and long-term outcomes are determined by the safety and efficacy profile of the newest generation drug-eluting stents. METHODS: BIOSTEMI (A Comparison of an Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent for Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention) was an investigator-initiated, multicenter, assessor-blind, randomized superiority trial using Bayesian methods. Patients with STEMI undergoing primary PCI within 24 h of symptom onset were randomized in a 1:1 ratio to receive BP-SES (n = 649) or DP-EES (n = 651). The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial reinfarction, and clinically indicated target lesion revascularization (TLR) at 2 years. RESULTS: Between April 2016 and March 2018, 1,300 patients were included. Baseline characteristics were comparable between the 2 treatment groups. Follow-up through 2 years was complete in 1,221 patients (94%). At 2 years, TLF occurred in 33 patients (5.1%) treated with BP-SES and in 53 patients (8.1%) treated with DP-EES (rate ratio: 0.58; 95% Bayesian credible interval: 0.40 to 0.84; posterior probability of superiority = 0.998). The difference was driven by a lower incidence of clinically indicated TLR in patients treated with BP-SES compared with DP-EES (2.5% vs. 5.1%; rate ratio: 0.52; 95% Bayesian credible interval: 0.30 to 0.87; posterior probability of superiority = 0.993). There were no significant differences in rates of cardiac death, target vessel myocardial reinfarction, and definite stent thrombosis between the 2 treatment arms. CONCLUSIONS: In patients with STEMI undergoing primary PCI, BP-SES were superior to DP-EES with respect to TLF at 2 years. The difference was driven by lower rates of ischemia-driven TLR. (A Comparison of an Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent for Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention [BIOSTEMI]; NCT02579031).

Cardiovascular aspects of COVID-19.

Coronavirus disease 2019 (COVID-19) is primarily a pulmonary disease, but also affects the cardiovascular system in multiple ways. In this review, we will summarise and put into perspective findings and debates relating to the diverse aspects of cardiovascular involvement of COVID-19. We will review evidence for the role of the renin-angiotensin-aldosterone system (RAAS), the risk of pre-existing cardiovascular disease in COVID-19 susceptibility and course, and the mechanism of acute and long-term myocardial injury. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses membrane-bound angiotensin converting-enzyme-2 (ACE2) as a receptor for cell entry. ACE2 is part of an important counter-regulatory circuit antagonising the harmful effects of angiotensin II on lung and heart. Modulation of ACE2 may therefore affect disease susceptibility and disease course. However, observational clinical studies and one randomised trial have so far not yielded evidence for harmful or beneficial effects of blockers of the RAAS during COVID-19. Age, gender, and multi-morbidity all increase susceptibility to SARS-CoV-2. In contrast, pre-existing cardiovascular diseases do so only minimally, but they may aggravate the disease course. Direct SARS-CoV-2 infection of the heart tissue and myocytes is rare. Nevertheless, COVID-19 may lead to myocarditis-like acute cardiac injury, characterised by myocardial oedema, but lacking extensive myocyte loss and lymphocytic infiltration. Independent of this, increases in cardiac biomarkers (troponin, N-terminal pro-brain natriuretic peptide, D-dimer) are frequent, especially in the phase of severe systemic inflammation and acute respiratory distress syndrome, and quantitatively associated with poor outcome. The pulmonary infection may result initially in right ventricular dysfunction, but in cases with severe systemic infection hypoxia, hyperinflammation and cytokine storm heart failure may eventually ensue. Unlike other infections and inflammatory states, COVID-19 does not appear to trigger acute coronary syndromes. In children, even mild COVID-19 can induce a multisystem inflammatory syndrome with Kawasaki-like symptoms frequently accompanied by cardiogenic shock.

Differences in presentation and clinical outcomes between left or right bundle branch block and ST segment elevation in patients with acute myocardial infarction.

BACKGROUND: In patients with acute myocardial infarction, the presence of a left bundle branch block or right bundle branch block may be associated with worse prognosis compared to isolated ST segment elevation. However, specificities in clinical presentation and outcomes of acute myocardial infarction patients with left bundle branch block or right bundle branch block are poorly characterized. METHODS: We analysed acute myocardial infarction patients with left bundle branch block (n=880), right bundle branch block (n=732) or ST segment elevation without bundle branch block (n=15,852) included in the Acute Myocardial Infarction in Switzerland-Plus registry between 2008-2019. RESULTS: Acute myocardial infarction patients with bundle branch block were older and had more pre-existing cardiovascular conditions compared to ST segment elevation. Pulmonary oedema and cardiogenic shock were most frequent in patients with left bundle branch block (18.8% vs 12.0% for right bundle branch block and 7.9% for ST segment elevation, p<0.001). Acute myocardial infarction patients with bundle branch block had more three-vessel (40.6% vs 25.3%, p<0.001 vs ST segment elevation) and left main disease (5.6% vs 2.0%, p<0.001 vs ST segment elevation). Major adverse cardiac and cerebrovascular events, a composite of reinfarction, stroke/transient ischaemic attack, and death during hospitalization, were highest in acute myocardial infarction patients with left bundle branch block (13.9% vs 9.9% for right bundle branch block and 6.7% for ST segment elevation, p<0.05), which was driven by hospital mortality. After multivariate adjustment, however, mortality was similar in patients with left bundle branch block and lower in patients with right bundle branch block, respectively, when compared to ST segment elevation. Mortality was only increased when a right bundle branch block with concomitant STE was present (odds ratio 1.77, 95% confidence interval 1.19-2.64, p<0.01 vs ST segment elevation). CONCLUSIONS: Compared to ST segment elevation, an isolated bundle branch block reflects high-risk clinical characteristics but does not independently determine increased hospital mortality in acute myocardial infarction.

Gender differences in patient and system delay for primary percutaneous coronary intervention: current trends in a Swiss ST-segment elevation myocardial infarction population.

BACKGROUND: Women with ST-segment elevation myocardial infarction (STEMI) experience greater delays for percutaneous coronary intervention-facilitated reperfusion than men. Whether women and men benefit equally from current strategies to reduce ischaemic time and whether there are gender differences in factors determining delays is unclear. METHODS: Patient delay (symptom onset to first medical contact) and system delay (first medical contact to percutaneous coronary intervention-facilitated reperfusion) were compared between women ( n=967) and men ( n=3393) in a Swiss STEMI treatment network. Trends from 2000 to 2016 were analysed, with additional comparisons between three time periods (2000-2005, 2006-2011 and 2012-2016). Factors predicting delays and hospital mortality were determined by multivariate regression modelling. RESULTS: Female gender was independently associated with greater patient delay ( P=0.02 vs. men), accounting for a 12% greater total ischaemic time among women in 2012-2016 (median 215 vs. 192 minutes, P<0.001 vs. men). From 2000-2005 to 2012-2016, median system delay was reduced by 18 and 25 minutes in women and men, respectively ( P<0.0001 for trend, P=n.s. for gender difference). Total occlusion of the culprit artery, stent thrombosis, a Killip class of 3 or greater, and presentation during off-hours predicted delays in men, but not in women. A Killip class of 3 or greater and age, but not gender or delays, were independently associated with hospital mortality. CONCLUSIONS: STEMI-related ischaemic time in women remains greater than in men due to persistently greater patient delays. In contrast to men, clinical signs of ongoing chest discomfort do not predict delays in women, suggesting that female STEMI patients are less likely to attribute symptoms to a condition requiring urgent treatment.

Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II.

BACKGROUND: Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking. OBJECTIVES: To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation. METHODS: Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed. RESULTS: Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase. CONCLUSIONS: In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions.

Screening For Pulmonary Hypertension With Multidetector Computed Tomography Among Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Aim: To assess the accuracy of multi-detector computed tomography (MDCT) derived pulmonary vessel measurements in predicting pulmonary hypertension (PH) among patients with severe symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Background: PH is common among patients with severe AS undergoing TAVI and is associated with adverse outcomes. MDCT is the imaging modality of choice to assess anatomical dimensions among patients selected for TAVI. Methods: One hundred and thirty-nine patients with severe AS undergoing TAVI with both CT scans and right heart catheterizations (RHC) were included. CT diameters of the main pulmonary artery (MPA), right (RPA) and left (LPA), and ascending aorta (AA) were measured. The relationship between CT measurements and PA pressures assessing using RHC was tested with linear regression. Results: The CT derived ratio of the diameter of the MPA to the diameter of the AA (PA/AAratio) correlated best with mean PA pressure (R2 = 0.48) and PA systolic pressure (R2 = 0.50). Receiver operating characteristic curve analysis showed that the PA/AAratio is a moderate predictor of PH (AUC 0.74, 95% CI 0.65-0.83, p < 0.0001) and that the optimal cut off point is 0.80 (sensitivity 56%, specificity 88%, positive predictive value 95.5%, negative predictive value 30.6% for PH). Conclusions: Elderly patients with severe AS and PA/AAratio values ≥ 0.80 on MDCT are more likely to have PH but PH cannot be reliably excluded among such patients with lower PA/AAratio values.