Transcatheter Aortic Valve Implantation in Low-Risk Tricuspid or Bicuspid Aortic Stenosis: The NOTION-2 Trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become the first choice to treat older patients with severe symptomatic aortic stenosis (AS). This study aimed to compare TAVI with surgery in low-risk patients ≤ 75 years of age, including both tricuspid and bicuspid AS. METHODS: The NOTION-2 trial enrolled and 1:1 randomized low-risk patients aged ≤ 75 years with severe symptomatic AS to TAVI or surgery. The primary endpoint was a composite of all-cause mortality, stroke or rehospitalization (related to the procedure, valve or heart failure) at 12 months. RESULTS: A total of 370 patients were enrolled with a mean age of 71.1 years and a median Society of Thoracic Surgeons risk score of 1.1%. A total of 100 patients had bicuspid AS. The 1-year incidence of the primary endpoint was 10.2% in the TAVI group and 7.1% in the surgery group (absolute risk difference 3.1%; 95% confidence interval [CI], -2.7% to 8.8%; hazard ratio (HR) 1.4, 95% CI: 0.7 to 2.9; p=0.3). Patients with TAVI, when compared to surgery, had lower risk of major bleeding and new-onset atrial fibrillation and higher risk of non-disabling stroke, permanent pacemaker implantation and moderate-or-greater paravalvular regurgitation. The risk of the primary composite endpoint was 8.7% and 8.3% in patients with tricuspid AS (HR 1.0, 95% CI: 0.5 to 2.3) and 14.3% and 3.9% in patients with bicuspid AS (HR 3.8, 95% CI: 0.8 to 18.5) treated with TAVI or surgery, respectively (P for interaction=0.1). CONCLUSIONS: Among low-risk patients aged ≤ 75 years with severe symptomatic AS, the rate of the composite of death, stroke, or rehospitalization at one year was similar between TAVI and surgery. TAVI outcomes in young bicuspid AS patients warrant caution and should be further investigated. (NOTION-2, ClinicalTrials.gov, NCT02825134).

Association between pre-operative prolonged corrected QT interval and all-cause mortality after non-cardiac surgery.

BACKGROUND: Prolonged corrected QT interval (QTc) has been linked to risk of arrhythmias and mortality in the general population. Pre-operative electrocardiography is often obtained for patient-and procedural cardiovascular risk assessment. The aim of this study was to investigate the association of pre-operative QTc and all-cause mortality in a non-cardiac surgical cohort. METHODS: A retrospective study of all patients over 18 years undergoing non-cardiac surgery at Landspitali-the National University Hospital in Iceland between 2 January 2005 to 31 December 2015, with follow-up through 20 May 2016. Patients were separated into five categories according to their pre-operative QTc interval ≤ 379, 380-439 (reference group), 440-479, 480-519 and ≥520 ms. Primary outcome was long-term mortality and secondary outcome was 30-day mortality. RESULTS: A total of 10,209 surgeries for 10,209 individuals were included. The median follow-up for mortality was 2691 days (interquartile range [IQR] 1620-3705 days). Patients with longer QTc interval had a higher comorbidity burden, were more likely to undergo emergency surgery and were often prescribed cardiac medications. After adjustment for confounding variables, the hazard ratio (HR) for long-term mortality compared with reference (QTc 380-439 ms) was 0.85 [CI: 0.66-1.09] for QTc ≤379, 1.08 [CI: 0.99-1.17] for QTc 440-479 ms, 1.26 [CI: 1.10-1.43] for QTc between 480 and 519 ms and 0.97 [CI: 0.78-1.21] for QTc ≥520 ms. When compared with reference, only patients with QTc interval between 480 and 519 ms had higher odds ratio for 30-day mortality as odds ratio for other groups were following; 1.12 [CI: 0.18-3.8] for ≤379 ms, 1.03 [CI: 0.70-1.51] for QTc 440-479 ms, 1.64 [CI: 1.02-2.60] for QTc 480-519 ms and 0.98 [0.44-2.06] for QTc ≥520 ms. CONCLUSION: Pre-operative QTc between 480 and 519 ms is associated with both higher long-term and 30-day mortality after non-cardiac surgery. The results suggest that this could reflect an underlying cardiovascular risk.

Long-term survival of Icelandic women following acute myocardial infarction.

Objective. To evaluate the impact of sex on treatment and survival after acute myocardial infarction (AMI) in Iceland. Methods. A retrospective, nationwide cohort study of patients with STEMI (2008-2018) and NSTEMI (2013-2018) and obstructive coronary artery disease. Patient and procedural information were obtained from a registry and electronic health records. Survival was estimated with Kaplan-Meier method and Cox regression analysis used to identify risk factors for long-term mortality. Excess mortality from the AMI episode was estimated by comparing the survival with age- and sex-matched population in Iceland at 30-day interval. Results. A total of 1345 STEMI-patients (24% women) and 1249 NSTEMI-patients (24% women) were evaluated. Women with STEMI (mean age: 71 ± 11 vs. 67 ± 12) and NSTEMI (mean age: 69 ± 13 vs. 62 ± 12) were older and less likely to have previous cardiovascular disease. There was neither sex difference in the extent of coronary artery disease nor treatment. Although crude one-year post-STEMI survival was lower for women (88.7% vs. 93.4%, p = .006), female sex was not an independent risk factor after adjusting for age and co-morbidities after STEMI and was protective for NSTEMI (HR 0.67, 95% CI: 0.46-0.97). There was excess 30-day mortality in both STEMI and NSTEMI for women compared with sex-, age- and inclusion year-matched Icelandic population, but thereafter the mortality rate was similar. Conclusion. Women and men with AMI in Iceland receive comparable treatment including revascularization and long-term survival appears similar. Prognosis after NSTEMI is better in women, whereas higher early mortality after STEMI may be caused by delays in presentation and diagnosis.

[Acute myocardial infarction in young adults: incidence, risk factors and prognosis].

INTRODUCTION: The incidence of acute myocardial infarction (AMI) might not be decreasing as much among young adults as in the general population in recent years. The goal of our study was to explore incidence, risk factors and prognosis of AMI among young patients in Iceland. MATERIAL AND METHODS: This was a retrospective case control study. The data was obtained from the SCAAR-SWEDEHEART database, medical records from Landspitali University Hospital and the death register from the Directorate of Health. The epidemiology of women ≤55 years and men ≤50 years diagnosed with AMI (STEMI/NSTEMI) in Iceland in 2014-2020 was compared with older patients. RESULTS: Of all the cases (2852), 344 patients (12%) were young. No change was demonstrated in the incidence of AMI in the young patients during the study period. The proportion of STEMI was higher among young patients (52% vs. 35%, p<0.001). Smoking (50% vs. 26%, p<0.001) and obesity (BMI>30 kg/m2)(47% vs. 36%, p<0.01) were more prevalent in younger patiens compared to the older. Older patients were more likely to die in the year following the AMI, both from all-cause (7% vs. 3%, p<0.05) and cardiovascular mortality (7% vs. 3%, p<0.05). A difference in recurrent AMI between the young and older patients was not demonstrated (2% vs. 3%, p=0.3). CONCLUSION: During the research period, a change in the incidence of AMI among young patients, was not demonstrated. Younger patients with AMI have different risk factors than older patients, they have lower mortality rate but the same risk of recurrent AMI.

[Effects of the COVID-19 pandemic and associated non-pharmaceutical interventions on diagnosis of myocardial infarction and selected infections in Iceland 2020].

INTRODUCTON: Nonpharmaceutical interventions to contain the spread of COVID-19 infections in Iceland in 2020 were successful, but the effects of these measures on incidence and diagnosis of other diseases is unknown. The aim of this study was to evaluate the impact of the COVID-19 pandemic on the diagnosis of myocardial infarction (MI) and selected infections with different transmission routes. MATERIALS AND METHODS: Health records of individuals 18 years or older who were admitted to Landspitali University Hospital (LUH) in 2016-2020 with pneumonia or MI were extracted from the hospital registry. We acquired data from the clinical laboratories regarding diagnostic testing for Chlamydia trachomatis, influenza, HIV and blood cultures positive for Enterobacterales species. Standardized incidence ratio (SIR) for 2020 was calculated with 95% confidence intervals (95%CI) and compared to 2016-2019. RESULTS: Discharge diagnoses due to pneumonia decreased by 31% in 2020, excluding COVID-19 pneumonia (SIR 0.69 (95%CI 0.64-0.75)). Discharge diagnoses of MI decreased by 18% (SIR 0.82 (95%CI 0.75-0.90)), and emergency cardiac catheterizations due to acute coronary syndrome by 23% (SIR 0.77 (95%CI 0.71-0.83)), while there was a 15% increase in blood stream infections for Enterobacterales species (SIR 1.15 (95%CI 1.04-1.28)). Testing for Chlamydia trachomatis decreased by 14.8% and positive tests decreased by 16.3%. Tests for HIV were reduced by 10.9%, while samples positive for influenza decreased by 23.6% despite doubling of tests being performed. CONCLUSION: The number of pneumonia cases of other causes than COVID-19 requiring admission dropped by a quarter in 2020. MI, chlamydia and influensa diagnoses decreased notably. These results likely reflect a true decrease, probably due to altered behaviour during the pandemic.

[Advances in lung cancer diagnosis and treatment - a review].

Lung cancer is the second and third most common cancer in Iceland for females and males, respectively. Although the incidence is declining, lung cancer still has the highest mortality of all cancers in Iceland. Symptoms of lung cancer can be specific and localized to the lungs, but more commonly they are unspecific and result in significant diagnostic delay. Therefore, majority of lung cancer patients are diagnosed with non-localized disease. In recent years, major developments have been made in the diagnosis and treatment of lung cancer. Positive emission scanning (PET) and both transbroncial (EBUS) or transesophageal ultrasound (EUS) biopsy techniques have resulted in improved mediastinal staging of the disease and minimal invasive video-assisted thoracic surgery (VATS) has lowered postoperative complications and shortened hospital stay. Technical developments in radiotherapy have benefitted those patients who are not candidates for curative surgery. Finally, and most importantly, recent advances in targeted chemotherapeutics and development of immunomodulating agents have made individual tailoring of treatment possible. Recent screening-trials with low-dose computed tomography show promising results in lowering mortality. This evidence-based review focuses on the most important developments in the diagnosis and treatment of lung cancer, and includes Icelandic studies in the field.

[Management and revascularization of diabetics with coronary artery disease in Iceland].

BACKGROUND: The incidence of diabetes is growing, and diabetics have increased risk of atherosclerosis and diffuse coronary artery disease (CAD). Our aim was to assess the revascularization treatment of diabetics with CAD in Iceland from 2010-2020, changes in management and long-term survival of patients. METHODS: All patients in Iceland with diabetes and CAD on cardiac catheterization 2010-2020 were included in this retrospective, population-based study. We analyzed data from the SCAAR/SWEDEHEART database: patients' background information, findings of cardiac catheterization, planned treatment and results. The Kaplan-Meier method was used to estimate long-term survival and Cox-regression-analysis to adjust for predictor variables. RESULTS: Of 1905 cases (1485 patients), 1230 (65%) underwent PCI, 274 (14%) CABG and 401 (21%) had medical therapy only. The age distribution differed: The PCI group had the widest age bracket, the CABG group the narrowest, and the medical therapy group had the highest mean age. Most patients with STEMI or cardiogenic shock underwent PCI, while most patients with concomitant heart-valve disease underwent CABG. The proportion of patients undergoing CABG increased with more diffuse CAD. 41% of patients with left main- and three-vessel disease underwent CABG while only 2% of those with single-vessel disease. From 2010-2020 the proportion of patients that underwent PCI increased from 49% to 72%. There was no difference in survival between the PCI and CABG groups (p=1.00). CONCLUSION: Three quarters of patients with diabetes and obstructive CAD are now treated with PCI. The PCI and CABG groups had overall equal survival but the groups had different characteristics.

[Management of patients with left main stem stenosis in Iceland 2010-2020: PCI or CABG].

INTRODUCTION: Coronary artery bypass surgery (CABG) has been standard treatment for patients with left main coronary artery disease (LMCAD) but percutaneous coronary intervention (PCI) can be a good alternative. Our aim was to evaluate revascularization of LMCAD-patients in Iceland and treatment changes in recent years. We also assessed the impact of patient background factors on treatment choice and long-term survival. METHODS: This retrospective, population-based registry-study analyzed data from the SCAAR-SWEDEHEART database. Patients with significant LMCAD on coronary angiography in Iceland 2010-2020, without previous history of CABG or contraindication for surgery were enrolled. The Kaplan-Meier method was used to study long-term survival and COX-regression analysis to adjust for predictor variables. FINDINGS: Of 702 LMCAD patients, 195 were treated with PCI, 460 with CABG and 47 with medical therapy. The widest age-range was in the PCI group and the mean age was highest in the medical therapy group. Patients with LMCAD and concomitant three vessel disease or heart valve disese were mostly treated with CABG (76.1% and 84.4%). The majority of patients with LMCAD only were treated with PCI, as well as patients presenting with STEMI or in cardiogenic shock (67.1% and 70.0%). The proportion of patients treated with PCI increased from 19.8% in 2010-2015 to 42.7% in 2016-2020. There was no significant difference in survival between the PCI and CABG-groups (p=0.41). CONCLUSIONS: In patients with LMCAD the main factors determining treatment choice are age, anatomical complexity and acuteness. There has been a significant increase in LMCAD patients treated with PCI.

[Impact of renal dysfunction on early outcomes of coronary artery bypass grafting surgery].

INTRODUCTION: Impaired renal function as seen in chronic kidney disease (CKD) is a known risk factor for coronary artery diseases and has been linked to inferior outcome after myocardial revascularization. Studies on the outcome of coronary bypass grafting (CABG) in CKD-patients are scarce. We aimed to study this subgroup of patients following CABG in a well defined whole-nation cohort, focusing on short term complications and 30 day mortality. MATERIALS AND METHODS: A retrospective study on 2300 consecutive patients that underwent CABG at Landspítali University Hospital 2001-2020. Patients were divided into four groups according to preoperative estimated glomerular filtration rate (GFR), and the groups compared. GFR 45-59 mL/mín/1.73m2, GFR 30-44 mL/mín/1.73m2, GFR <30 mL/mín/1.73m2 and controls with normal GFR (≥60 mL/mín/1.73m2). Clinical information was gathered from medical records and logistic regression used to estimate risk factors of 30-day mortality. RESULTS: Altogether 429 (18.7%) patients had impaired kidney function; these patients being more than six years older, having more cardiac symptoms and a higher mean EuroSCORE II (5.0 vs. 1.9, p<0.001) compared to controls. Furthermore, their left ventricular ejection fraction was also lower, their median hospital stay extended by two days and major short-term complications more common, as was 30 day mortality (24.4% vs. 1.4%, p<0.001). In multivariate analysis advanced age, ejection fraction <30% and GFR <30 mL/min/1.73m2 were independent predictors of higher 30-day mortality (OR=10.4; 95% CI: 3.98-25.46). CONCLUSIONS: Patients with impaired renal function are older and more often have severe coronary artery disease. Early complications and 30-day mortality were much higher in these patients compared to controls and advanced renal failure and the strongest predictor of 30-day mortality.

Acute gastrointestinal bleeding among patients on antiplatelet and anticoagulant therapy after percutaneous coronary intervention.

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy and some require additional anticoagulation. We aimed to investigate the incidence of acute gastrointestinal bleeding (AGIB) among PCI patients receiving antiplatelet and anticoagulant therapy. METHODS: A population-based study that included all patients undergoing PCI during 2008-2016 in Iceland. Data from the Icelandic Medicines Registry were obtained on all outpatient prescriptions 1 year after first PCI. Patients receiving single or dual-antiplatelet therapy with or without anticoagulation cotherapy were analyzed. Rehospitalization for AGIB and endoscopic data were obtained within the 12-month follow-up period. RESULTS: A total of 5166 patients (male 75%) underwent PCI during the study period. The incidence of AGIB was 1% (54/5166) per year. The mean age among non-bleeders 65 (±11) years was lower than among bleeders 69 (±9) years (p = .002). The proportion of acute upper GIB (AUGIB) was 56%, whereas lower GIB occurred in 44%. Overall, 41% with AUGIB had PPIs compared to 39% of non-bleeders (NS). The incidence of AGIB among patients on single antiplatelet therapy combined with an anticoagulant was 2.5% compared to 0.9% among those on single antiplatelet treatment alone (p = .028). The number needed to harm (NNH) for treatment with single antiplatelet therapy and anticoagulant therapy compared to single antiplatelet therapy was 62 but no deaths related to AGIB. CONCLUSIONS: The 1-year incidence of AGIB was low with no mortality. Bleeding risk was found to be higher among patients on single antiplatelet therapy combined with anticoagulant therapy compared to patients on single antiplatelet therapy alone.

[Indications and outcomes of TAVI (transcatheter aortic valve implantation) in Iceland].

INTRODUCTION: Surgical aortic valve replacement (SAVR) has been the standard of treatment for aortic stenosis but transcatheter aortic valve implantation (TAVI) is increasingly used as treatment in Iceland and elsewhere. Our objective was to assess the outcome of TAVI in Iceland, focusing on indications, complications and survival. MATERIAL AND METHODS: This retrospective study included all TAVI-procedures performed in Iceland between January 2012 and June 2020. Patient characteristics, outcome and complications were registered, and overall estimated survival compared to an age and sex matched Icelandic reference-population. The mean follow-up was 2.4 years. RESULTS: Altogether 189 TAVI procedures (mean age 83±6 years, 41.8% females), were performed, all with a self-expanding biological valve. Most patients (81.5%) had symptoms of severe heart failure (NYHA-class III-IV) and median EuroSCORE-II was 4.9 (range: 0.9-32). Echocardiography pre-TAVI showed a mean aortic-valve area of 0.67 cm2 and a max aortic-valve gradient of 78 mmHg. One out of four patients (26.5%) needed permanent pacemaker implantation following TAVI. Other complications were mostly vascular-related (13.8%) but cardiac cardiac temponade and stroke occurred in 3.2 and 2.6% of cases, respectively and severe paravalvular aortic valve regurgitation in 0.5% cases. Thirty-day mortality was 1.6% (n=3) with one-year survival of 93.5% (95% CI: 89.8-97.3). Finally long-term survival survival of TAVI-patients was similar to the matched reference population (p=0.23). CONCLUSIONS: The outcome of TAVI-procedures in Iceland is good, especially regarding 30-day mortality and long-term survival that was comparable to a reference population. Incidence of major complications was also low.

[Cardiac Lipoma - Case presentation].

Cardiac lipomas are very rare benign tumors of the heart. They are usually asymptomatic and are often an incidental finding on cardiac imaging. This case report involves an 82-year-old female with a history of diabetes admitted because of poor glycemic control. An echocardiogram requested because of arrhythmias and heart failure revealed a tumor in the right atrium. Computed tomographic and ultrasound appearances were consistent with a lipoma and demonstrated a large mass in the right atrium, causing a significant stenosis of the superior vena cava but no clinical symptoms or signs of superior vena cava syndrome.

Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI.

BACKGROUND: The instantaneous wave-free ratio (iFR) is an index used to assess the severity of coronary-artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events. METHODS: We conducted a multicenter, randomized, controlled, open-label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary-artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 12 months after the procedure. RESULTS: A primary end-point event occurred in 68 of 1012 patients (6.7%) in the iFR group and in 61 of 1007 (6.1%) in the FFR group (difference in event rates, 0.7 percentage points; 95% confidence interval [CI], -1.5 to 2.8; P=0.007 for noninferiority; hazard ratio, 1.12; 95% CI, 0.79 to 1.58; P=0.53); the upper limit of the 95% confidence interval for the difference in event rates fell within the prespecified noninferiority margin of 3.2 percentage points. The results were similar among major subgroups. The rates of myocardial infarction, target-lesion revascularization, restenosis, and stent thrombosis did not differ significantly between the two groups. A significantly higher proportion of patients in the FFR group than in the iFR group reported chest discomfort during the procedure. CONCLUSIONS: Among patients with stable angina or an acute coronary syndrome, an iFR-guided revascularization strategy was noninferior to an FFR-guided revascularization strategy with respect to the rate of major adverse cardiac events at 12 months. (Funded by Philips Volcano; iFR SWEDEHEART ClinicalTrials.gov number, NCT02166736 .).

Instantaneous Wave-Free Ratio versus Fractional Flow Reserve guided intervention (iFR-SWEDEHEART): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial.

BACKGROUND: Instantaneous wave-free ratio (iFR) is a new hemodynamic resting index for assessment of coronary artery stenosis severity. iFR uses high frequency sampling to calculate a gradient across a coronary lesion during a period of diastole. The index has been tested against fractional flow reserve (FFR) and found to have an overall classification agreement of 80% to 85%. Whether the level of disagreement is clinically relevant is unknown. Clinical outcome data on iFR are scarce. This study is a registry-based randomized clinical trial, which is a novel strategy using health quality registries as on-line platforms for randomization, case record forms, and follow-up. DESIGN/METHODS: iFR-SWEDEHEART is a multicenter, prospective, randomized, controlled, clinical open-label clinical trial. Two thousand patients with stable angina or acute coronary syndrome and an indication for physiology-guided assessment of one or more coronary stenoses will be randomized 1:1 to either iFR- or FFR-guided intervention. The randomization will be conducted online in the Swedish web-based system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART) registry. The trial has a non-inferiority design, with a primary combined end point of all-cause death, non-fatal myocardial infarction, and unplanned revascularization at 12 months. End points will be identified through national registries and undergo central blind adjudication to ensure data quality. DISCUSSION: The iFR-SWEDEHEART trial is an registry-based randomized clinical trial evaluating the safety and efficacy of the diagnostic method iFR compared to FFR.

Cohort Profile: the European Unified Registries On Heart care Evaluation and Randomised Trials (EuroHeart) - Acute Coronary Syndrome and Percutaneous Coronary Intervention.

AIMS: The European Unified Registries On Heart care Evaluation And Randomized Trials (EuroHeart) aims to improve the quality of care and clinical outcomes for patients with cardiovascular disease. The collaboration of acute coronary syndrome/percutaneous coronary intervention (ACS/PCI) registries is operational in seven vanguard European Society of Cardiology member countries. METHODS AND RESULTS: Adults admitted to hospitals with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are included, and individual patient-level data collected and aligned according to the internationally agreed EuroHeart data standards for ACS/PCI. The registries provide up to 155 variables spanning patient demographics and clinical characteristics, in-hospital care, in-hospital outcomes, and discharge medications. After performing statistical analyses on patient data, participating countries transfer aggregated data to EuroHeart for international reporting.Between 1st January 2022 and 31st December 2022, 40 021 admissions (STEMI 46.7%, NSTEMI 53.3%) were recorded from 192 hospitals in the seven vanguard countries: Estonia, Hungary, Iceland, Portugal, Romania, Singapore, and Sweden. The mean age for the cohort was 67.9 (standard deviation 12.6) years, and it included 12 628 (31.6%) women. CONCLUSION: The EuroHeart collaboration of ACS/PCI registries prospectively collects and analyses individual data for ACS and PCI at a national level, after which aggregated results are transferred to the EuroHeart Data Science Centre. The collaboration will expand to other countries and provide continuous insights into the provision of clinical care and outcomes for patients with ACS and undergoing PCI. It will serve as a unique international platform for quality improvement, observational research, and registry-based clinical trials.

A retrospective study on adherence to secondary prevention medications after coronary bypass surgery.

OBJECTIVES: We assessed adherence to statins, beta-blockers and renin-angiotensin system (RAS) inhibitors after coronary artery bypass graft surgery and factors associated with non-adherence. METHODS: This nationwide retrospective cohort study included all individuals undergoing coronary artery bypass surgery from 22 May 2007 to 20 December 2018, at Landspitali-the National University Hospital (n = 1536). Data on dispensed prescriptions were retrieved from the National Prescription Medicine Registry. Adherence was estimated by the proportion of days covered up to 2 years after hospital discharge, with cut-offs for strict adherence and non-adherence at over 80% and under 50%, respectively. Multivariable logistic regression was used to assess variables associated with non-adherence. RESULTS: Criteria for strict adherence were met by 39.2%, 36.9% and 30.1% of patients for statins, beta-blockers and RAS inhibitors, respectively. Non-adherence criteria were met for 14.4%, 25.9% and 43.6% of patients for statins, beta-blockers and RAS inhibitors, respectively. High Hospital Frailty Risk Score Class (statins: odds ratio (OR) 2.29, confidence interval (CI) 1.02-4.86; RAS inhibitors: OR 2.06, CI 1.04-4.04), concomitant aortic valve replacement (statins: OR 1.64, CI 1.11-2.38; RAS inhibitors: OR 1.78, CI 1.26-2.52) and a new prescription for a medication class following surgery (statins: OR 2.87, CI 2.06-4.01; beta-blockers: OR 1.70, CI 1.32-2.18; RAS inhibitors: OR 6.95, CI 5.27-9.25) were associated with non-adherence. CONCLUSIONS: Non-adherence to medical therapy after coronary artery bypass surgery is common. Patients with a higher burden of frailty and patients naive to the medical treatment of coronary artery disease should be a target group for efforts to increase medication adherence.

5-Year Outcomes of PCI Guided by Measurement of Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve.

BACKGROUND: Instantaneous wave-free ratio (iFR) is a coronary physiology index used to assess the severity of coronary artery stenosis to guide revascularization. iFR has previously demonstrated noninferior short-term outcome compared to fractional flow reserve (FFR), but data on longer-term outcome have been lacking. OBJECTIVES: The purpose of this study was to investigate the prespecified 5-year follow-up of the primary composite outcome of all-cause mortality, myocardial infarction, and unplanned revascularization of the iFR-SWEDEHEART trial comparing iFR vs FFR in patients with chronic and acute coronary syndromes. METHODS: iFR-SWEDEHEART was a multicenter, controlled, open-label, registry-based randomized clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2,037 patients were randomized to undergo revascularization guided by iFR or FFR. RESULTS: No patients were lost to follow-up. At 5 years, the rate of the primary composite endpoint was 21.5% in the iFR group and 19.9% in the FFR group (HR: 1.09; 95% CI: 0.90-1.33). The rates of all-cause death (9.4% vs 7.9%; HR: 1.20; 95% CI: 0.89-1.62), nonfatal myocardial infarction (5.7% vs 5.8%; HR: 1.00; 95% CI: 0.70-1.44), and unplanned revascularization (11.6% vs 11.3%; HR: 1.02; 95% CI: 0.79-1.32) were also not different between the 2 groups. The outcomes were consistent across prespecified subgroups. CONCLUSIONS: In patients with chronic or acute coronary syndromes, an iFR-guided revascularization strategy was associated with no difference in the 5-year composite outcome of death, myocardial infarction, and unplanned revascularization compared with an FFR-guided revascularization strategy. (Evaluation of iFR vs FFR in Stable Angina or Acute Coronary Syndrome [iFR SWEDEHEART]; NCT02166736).

Instantaneous wave-free ratio compared with fractional flow reserve in PCI: A cost-minimization analysis.

BACKGROUND: Coronary physiology is a routine diagnostic tool when assessing whether coronary revascularization is indicated. The iFR-SWEDEHEART trial demonstrated similar clinical outcomes when using instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) to guide revascularization. The objective of this analysis was to assess a cost-minimization analysis of iFR-guided compared with FFR-guided revascularization. METHODS: In this cost-minimization analysis we used a decision-tree model from a healthcare perspective with a time-horizon of one year to estimate the cost difference between iFR and FFR in a Nordic setting and a United States (US) setting. Treatment pathways and health care utilizations were constructed from the iFR-SWEDEHEART trial. Unit cost for revascularization and myocardial infarction in the Nordic setting and US setting were derived from the Nordic diagnosis-related group versus Medicare cost data. Unit cost of intravenous adenosine administration and cost per stent placed were based on the average costs from the enrolled centers in the iFR-SWEDEHEART trial. Deterministic and probabilistic sensitivity analyses were carried out to test the robustness of the result. RESULTS: The cost-minimization analysis demonstrated a cost saving per patient of $681 (95% CI: $641 - $723) in the Nordic setting and $1024 (95% CI: $934 - $1114) in the US setting, when using iFR-guided compared with FFR-guided revascularization. The results were not sensitive to changes in uncertain parameters or assumptions. CONCLUSIONS: IFR-guided revascularization is associated with significant savings in cost compared with FFR-guided revascularization.

Genetic variants associated with platelet count are predictive of human disease and physiological markers.

Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease.

Final analysis of a 14-year long-term follow-up study of the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in women from four nordic countries.

BACKGROUND: The quadrivalent human papillomavirus (qHPV) vaccine prevented vaccine HPV type-related infection and disease in young women in the 4-year FUTURE II efficacy study (NCT00092534). We report long-term effectiveness and immunogenicity at the end of 14 years of follow-up after enrollment in FUTURE II. METHODS: Young women (16-23 years of age) from Denmark, Iceland, Norway, and Sweden who received three qHPV vaccine doses during the randomized, double-blind, placebo-controlled FUTURE II base study were followed for effectiveness for an additional ≥10 years through national registries. Tissue samples including but not limited to those collected during organized cervical cancer screening programs were obtained from regional biobanks to be adjudicated for histopathology diagnosis and tested for HPV DNA. The observed incidence of HPV16/18-related high-grade cervical dysplasia (primary outcome) was compared with recent historical background incidence rates in an unvaccinated population. Serum was collected at years 9 and 14 to assess antibody responses. FINDINGS: No cases of HPV16/18-related high-grade cervical dysplasia were observed in the per-protocol effectiveness population (N = 2121; 24,099·0 person-years of follow-up) during the entire study. Vaccine effectiveness of 100% (95% CI 94·7-100) was demonstrated for ≥12 years, with a trend toward continued protection through 14 years post-vaccination. Seropositivity rates at study conclusion were >90% (HPV6/11/16) and 52% (HPV18) using competitive Luminex immunoassay, and >90% (all four HPV types) using the more sensitive IgG Luminex immunoassay. INTERPRETATION: Vaccination of young women with qHPV vaccine offers durable protection against HPV16/18-related high-grade cervical dysplasia for ≥12 years, with a trend toward continued protection through 14 years post-vaccination, and induces sustained HPV6/11/16/18 antibody responses for up to 14 years post-vaccination. There was no evidence of waning immunity, suggesting no need for a booster dose during that period. FUNDING: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.