The role of remnant cholesterol in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Remnant cholesterol (RC) is the cholesterol content within triglyceride rich lipoproteins. It promotes atherosclerotic cardiovascular disease beyond low density lipoprotein cholesterol (LDL-C). The prognostic role of RC in patients with ST-segment elevation myocardial infarction (STEMI) is unknown. We aimed to estimate RC-related risk beyond LDL-C in patients with STEMI. METHODS AND RESULTS: A total of 6602 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) from 1999 to 2016 were included. RC was calculated as total cholesterol minus LDL-C minus high-density lipoprotein cholesterol. Adjusted Cox models were used to estimate the association between continuous RC levels and all-cause mortality, cardiovascular death, ischemic stroke, and recurrent myocardial infarction (MI) at long-term (median follow-up of 6.0 years). Besides, discordance analyses were applied to examine the risk of the discordantly high RC (RC percentile rank minus LDL-C percentile rank> 10 units) compared to the discordantly low RC (LDL-C percentile rank minus RC percentile rank> 10 units). The concordance was defined as the percentile rank difference between RC and LDL-C ≤ 10 units. The median age of patients was 63 years [interquartile range (IQR) 54-72] and 74.8% were men. There were 2441, 1651, and 2510 patients in the discordantly low RC group, concordant group, and discordantly high RC group. All outcomes in the discordantly high RC group were higher than the other groups and the event rate of all-cause mortality in this group was 31.87%. In the unadjusted analysis, the discordantly high RC was associated with increased all-cause mortality [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.63-2.04] and increased cardiovascular death (HR 1.79, 95% CI 1.55-2.06) compared to the discordantly low RC. In an adjusted model RC was associated with higher all-cause mortality (HR 1.14, 95% CI 1.07-1.22). The discordantly high RC was associated with increased all-cause mortality (adjusted HR 1.55, 95% CI 1.37-1.75) and increased cardiovascular death (adjusted HR 1.47, 95% CI 1.25-1.72) compared to the discordantly low RC. There were no associations between RC and ischemic stroke or recurrent MI. CONCLUSIONS: In patients with STEMI treated with primary PCI, elevated RC levels beyond LDL-C and discordantly high RC were independently associated with increased all-cause mortality.

In patients with STEMI treated with primary PCI, elevated RC levels beyond LDL-C were independently associated with increased all-cause mortality. About 38% of patients with STEMI present discordantly high RC which is associated with elevated all-cause mortality and cardiovascular death.RC as a continuous variable is associated with higher all-cause mortality.

Prevalence and Impact of Frailty in Patients ≥70 Years Old with Acute Coronary Syndrome Referred for Coronary Angiography.

INTRODUCTION: Elderly patients with acute coronary syndrome (ACS) have a higher risk of adverse cardiovascular events and may be frail but are underrepresented in clinical trials. Previous studies have proposed that frailty assessment is a better tool than chronological age, in assessing older patients' biological age, and may exceed conventional risk scores in predicting the prognosis. Therefore, we wanted to investigate the prevalence and impact on 12-month outcomes of frailty in patients ≥70 years with ACS referred for coronary angiography (CAG). METHODS: Patients ≥70 years with ACS referred for CAG underwent frailty scoring with the clinical frailty scale (CFS). Patients were divided into three groups depending on their CFS: robust (1-3), vulnerable (4), and frail (5-9) and followed for 12 months. RESULTS: Of 455 patients, 69 (15%) patients were frail, 79 (17%) were vulnerable, and 307 (68%) were robust. Frail patients were older (frail: 80.9 ± 5.7 years, vulnerable: 78.5 ± 5.5 years, and robust: 76.6 ± 4.9 years, p < 0.001) and less often treated with percutaneous coronary intervention (frail: 56.5%, vulnerable: 53.2%, and robust: 68.6%, p = 0.014). 12-month mortality was higher among frail patients (frail: 24.6%, vulnerable: 21.8%, and robust: 6.2%, p < 0.001). Frailty was associated with a higher mortality after adjustment for age, sex, comorbidities, the Global Registry of Acute Coronary Events (GRACE) score, and revascularisation (HR 2.67, 95% CI 1.30-5.50, p = 0.008). There was no difference between GRACE and CFS in predicting 12-month mortality (p = 0.893). CONCLUSIONS: Fifteen percent of patients ≥70 years old with ACS referred for CAG are frail. Frail patients have significantly higher 12-month mortality. GRACE and CFS are similar in predicting 12-month mortality.

High Lipoprotein(a) May Explain One-Quarter of Clinical Familial Hypercholesterolemia Diagnoses in Danish Lipid Clinics.

CONTEXT: Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH). OBJECTIVE: We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH. METHODS: Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a). RESULTS: We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a). CONCLUSION: Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.

Brain Health After COVID-19, Pneumonia, Myocardial Infarction, or Critical Illness.

Importance: Brain health is most likely compromised after hospitalization for COVID-19; however, long-term prospective investigations with matched control cohorts and face-to-face assessments are lacking. Objective: To assess whether long-term cognitive, psychiatric, or neurological complications among patients hospitalized for COVID-19 differ from those among patients hospitalized for other medical conditions of similar severity and from healthy controls. Design, Setting, and Participants: This prospective cohort study with matched controls was conducted at 2 academic hospitals in Copenhagen, Denmark. The case cohort comprised patients with COVID-19 hospitalized between March 1, 2020, and March 31, 2021. Control cohorts consisted of patients hospitalized for pneumonia, myocardial infarction, or non-COVID-19 intensive care-requiring illness between March 1, 2020, and June 30, 2021, and healthy age- and sex-matched individuals. The follow-up period was 18 months; participants were evaluated between November 1, 2021, and February 28, 2023. Exposures: Hospitalization for COVID-19. Main Outcomes and Measures: The primary outcome was overall cognition, assessed by the Screen for Cognitive Impairment in Psychiatry (SCIP) and the Montreal Cognitive Assessment (MoCA). Secondary outcomes were executive function, anxiety, depressive symptoms, and neurological deficits. Results: The study included 345 participants, including 120 patients with COVID-19 (mean [SD] age, 60.8 [14.4] years; 70 men [58.3%]), 125 hospitalized controls (mean [SD] age, 66.0 [12.0] years; 73 men [58.4%]), and 100 healthy controls (mean [SD] age, 62.9 [15.3] years; 46 men [46.0%]). Patients with COVID-19 had worse cognitive status than healthy controls (estimated mean SCIP score, 59.0 [95% CI, 56.9-61.2] vs 68.8 [95% CI, 66.2-71.5]; estimated mean MoCA score, 26.5 [95% CI, 26.0-27.0] vs 28.2 [95% CI, 27.8-28.6]), but not hospitalized controls (mean SCIP score, 61.6 [95% CI, 59.1-64.1]; mean MoCA score, 27.2 [95% CI, 26.8-27.7]). Patients with COVID-19 also performed worse than healthy controls during all other psychiatric and neurological assessments. However, except for executive dysfunction (Trail Making Test Part B; relative mean difference, 1.15 [95% CI, 1.01-1.31]), the brain health of patients with COVID-19 was not more impaired than among hospitalized control patients. These results remained consistent across various sensitivity analyses. Conclusions and Relevance: This prospective cohort study suggests that post-COVID-19 brain health was impaired but, overall, no more than the brain health of patients from 3 non-COVID-19 cohorts of comparable disease severity. Long-term associations with brain health might not be specific to COVID-19 but associated with overall illness severity and hospitalization. This information is important for putting understandable concerns about brain health after COVID-19 into perspective.

Pre-hospital pulse glucocorticoid therapy in patients with ST-segment elevation myocardial infarction transferred for primary percutaneous coronary intervention: a randomized controlled trial (PULSE-MI).

BACKGROUND: Inflammation in ST-segment elevation myocardial infarction (STEMI) is an important contributor to both acute myocardial ischemia and reperfusion injury after primary percutaneous coronary intervention (PCI). Methylprednisolone is a glucocorticoid with potent anti-inflammatory properties with an acute effect and is used as an effective and safe treatment of a wide range of acute diseases. The trial aims to investigate the cardioprotective effects of pulse-dose methylprednisolone administered in the pre-hospital setting in patients with STEMI transferred for primary PCI. METHODS: This trial is a randomized, blinded, placebo-controlled prospective clinical phase II trial. Inclusion will continue until 378 patients with STEMI have been evaluated for the primary endpoint. Patients will be randomized 1:1 to a bolus of 250 mg methylprednisolone intravenous or matching placebo over a period of 5 min in the pre-hospital setting. All patients with STEMI transferred for primary PCI at Rigshospitalet, Copenhagen University Hospital, Denmark, will be screened for eligibility. The main eligibility criteria are age ≥ 18 years, acute onset of chest pain with < 12 h duration, STEMI on electrocardiogram, no known allergy to glucocorticoids or no previous coronary artery bypass grafting, previous acute myocardial infarction in assumed culprit, or a history with previous maniac/psychotic episodes. Primary outcome is final infarct size measured by late gadolinium enhancement on cardiac magnetic resonance (CMR) 3 months after STEMI. Secondary outcomes comprise key CMR efficacy parameters, clinical endpoints at 3 months, the peak of cardiac biomarkers, and safety. DISCUSSION: We hypothesize that pulse-dose methylprednisolone administrated in the pre-hospital setting decreases inflammation and thus reduces final infarct size in patients with STEMI treated with primary PCI. TRIAL REGISTRATION: EU-CT number: 2022-500762-10-00; Submitted May 5, 2022. CLINICALTRIALS: gov Identifier: NCT05462730; Submitted July 7, 2022, first posted July 18, 2022.

Kinetics of cardiac troponin and other biomarkers in patients with ST elevation myocardial infarction.

Objective: To examine changes in concentration, time-to-peak and the ensuing half-life of cardiac biomarkers in patients with myocardial infarction. Methods: Blood sampling was performed every third hour within 24 h after percutaneous coronary intervention (PCI) on a cohort of patients with ST elevation myocardial infarction. Cardiac troponin (cTn) was measured by the Dimension Vista, Vitros, Atellica, and Alinity high-sensitivity (hs) cTnI assays, and the Elecsys hs-cTnT assay. Further, creatine kinase (CK), myoglobin, creatine kinase MB (CKMB) and other biomarkers were analyzed. Results: A total of 36 patients completed blood sampling (median age 60 years, IQR 56.4-66.5 years; seven women, 19.4%). Hs-cTnI measured by the Vitros assay was the first hs-cTn to peak at 9.1 h (95%-CI 6.2-10.1) after PCI and 11.7 h (95%-CI 10.4-14.8) after symptoms onset. There were no notable differences between hs-cTn assays in regard to time-to-peak. Also, Vitros hs-cTnI reached the highest median ratio of concentration to upper reference level of nearly 2,000. The median half-life from peak concentration ranged from 7.6 h for myoglobin (CI 6.8-8.6) to 17.8 h for CK (CI 6.8-8.6). For hs-cTn assays the median T½ ranged from 12.4 h for the Vista hs-cTnI assay (95%-CI 11.0-14.1 h) to 17.3 h for the Elecsys hs-cTnT (95%-CI 14.9-20.8 h). Conclusions: This study updates knowledge on the kinetics of cardiac biomarkers in current clinical use. There was no notable difference in trajectories, time-to-peak or half-life between hs-cTn assays.

Troponin dependent 30-day mortality in patients with acute pulmonary embolism.

BACKGROUND: Troponin concentrations above upper reference are associated with increased mortality in patients with pulmonary embolism (PE). We aimed to assess whether risk of 30-day mortality increases in a dose-response relationship with concentration of troponin. METHODS: Using Danish national registries, we identified patients ≥ 18 years of age hospitalized with first-time PE between 2013 and 2018 and available troponin measurements - 1/+1 day from admission. Patients were stratified into quintiles by increasing troponin concentration. Risk of 30-day mortality was assessed performing cumulative mortality curves and Cox regression model comparing the troponin quintiles. RESULTS: We identified 5,639 PE patients of which 3,278 (58%) had a troponin concentration above upper reference. These patients were older (74 years), 50% male and with heavier comorbidity compared to patients with non-elevated troponin. We found increasing 30-day mortality with increasing troponin concentration (1% in 1st quintile (95% CI 0.5-1.5%), 2% in 2nd quintile (95% CI 1-2.5%), 8% in 3rd quintile (95% CI 5-9%), 11% in 4th quintile (95% CI 9-13%) and 15% in 5th quintile (95% CI 13-16%), confirmed in a Cox model comparing 1st quintile with 2nd quintile (HR 1.09; 95% CI 0.58-2.02), 3rd quintile (HR 3.68; 95% CI 2.20-6.15), 4th quintile (HR 5.51; 95% CI 3.34-9.10) and 5th quintile (HR 8.09; 95% CI 4.95-13.23). CONCLUSION: 30-day mortality was strongly associated with troponin concentration useful for improving risk stratification, treatment strategies and outcomes in PE patients.

Genetic testing increases the likelihood of a diagnosis of familial hypercholesterolaemia among people referred to lipid clinics: Danish national study.

BACKGROUND AND AIMS: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH. METHODS: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice. RESULTS: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant. CONCLUSIONS: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.

Neuropsychiatric and Cognitive Outcomes in Patients 6 Months After COVID-19 Requiring Hospitalization Compared With Matched Control Patients Hospitalized for Non-COVID-19 Illness.

Importance: Prolonged neuropsychiatric and cognitive symptoms are increasingly reported in patients after COVID-19, but studies with well-matched controls are lacking. Objective: To investigate cognitive impairment, neuropsychiatric diagnoses, and symptoms in survivors of COVID-19 compared with patients hospitalized for non-COVID-19 illness. Design, Setting, and Participants: This prospective case-control study from a tertiary referral hospital in Copenhagen, Denmark, conducted between July 2020 and July 2021, followed up hospitalized COVID-19 survivors and control patients hospitalized for non-COVID-19 illness, matched for age, sex, and intensive care unit (ICU) status 6 months after symptom onset. Exposures: Hospitalization for COVID-19. Main Outcomes and Measures: Participants were investigated with the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semi-structured interview for subjective symptoms. Primary outcomes were total MoCA score and new onset of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses, subjective symptoms, and neurologic examination results. All outcomes were adjusted for age, sex, ICU admission, admission length, and days of follow-up. Secondary outcomes were adjusted for multiple testing. Results: A total of 85 COVID-19 survivors (36 [42%] women; mean [SD] age 56.8 [14] years) after hospitalization and 61 matched control patients with non-COVID-19 illness (27 [44%] women, mean age 59.4 years [SD, 13]) were enrolled. Cognitive status measured by total geometric mean MoCA scores at 6-month follow-up was lower (P = .01) among COVID-19 survivors (26.7; 95% CI, 26.2-27.1) than control patients (27.5; 95% CI, 27.0-27.9). The cognitive status improved substantially (P = .004), from 19.2 (95% CI, 15.2-23.2) at discharge to 26.1 (95% CI, 23.1-29.1) for 15 patients with COVID-19 with MoCA evaluations from hospital discharge. A total of 16 of 85 patients with COVID-19 (19%) and 12 of 61 control patients (20%) had a new-onset psychiatric diagnosis at 6-month follow-up, which was not significantly different (odds ratio, 0.93; 95% CI, 0.39-2.27; P = .87). In fully adjusted models, secondary outcomes were not significantly different, except anosmia, which was more common after COVID-19 (odds ratio, 4.56; 95% CI, 1.52-17.42; P = .006); but no longer when adjusting for multiple testing. Conclusions and Relevance: In this prospective case-control study, cognitive status at 6 months was worse among survivors of COVID-19, but the overall burden of neuropsychiatric and neurologic signs and symptoms among survivors of COVID-19 requiring hospitalization was comparable with the burden observed among matched survivors hospitalized for non-COVID-19 causes.

Echolucent Carotid Plaques Becomes More Echogenic over Time - A 3D Ultrasound Study.

BACKGROUND: Despite the presence of only a few established risk factors, some patients will experience atherosclerotic events. Therefore, methods for improved risk stratification for atherosclerotic events are wanted. We aimed to detect changes in carotid artery atherosclerotic plaque volume and echogenicity over time in patients with an acute thromboembolic event and in patients with chronic atherosclerotic disease, both treated with statin, using a novel 3D ultrasound system. METHODS: We included two cohorts of patients; 70 patients, naïve to statin treatment, admitted with acute, first-time myocardial infarction (aMI), and 69 patients who had been on statin treatment for a minimum of 6 months with chronic peripheral arterial disease (cPAD). 3D ultrasound examination was performed at baseline and after 3 and 12 months. Plaque volume was quantified in 3D ultrasound plaque acquisitions, and echogenicity was assessed using grayscale median (GSM) and normalized with adventitia as reference. RESULTS: The aMI group had darker plaques than the cPAD group at baseline (mean GSM: 60.98, standard deviation (SD): 24.09 vs. 71.75, SD: 21.55; P = 0.006), 3 months (63.64, SD: 20.47 vs. 73.44, SD: 20.46; P = 0.006) and at 12 months follow-up (59.25, SD: 18.07 vs. 71.02, SD: 22.31; P = 0.004). The differences were not significant after adjusting for traditional risk factors. Dividing both groups by the median GSM, the darkest half of the aMI group's had an increase in GSM mainly within the first 3 months (10.49, CI 95%: 2.45 to 18.53; P = 0.012) and hereafter remained unchanged at 12 months follow-up (-0.53, CI 95%: -7.28 to 6.22, P = 0.875). In the darkest cPAD group GSM also increased within 3 months (8.14, CI 95%: 1.85-14.32, P = 0.012) and hereafter stabilized till 12 months (-2.54, CI 95%: -9.62 to 4.53, P = 0.475). Plaque volume did not change in the aMI group from baseline (median: 55.41 mm3, interquartile range (IQR): 24.24-84.31) to 12 months (58.67 mm3, IQR: 31.81-93.51) (P = 0.220) whereas there was a small decrease in the cPAD group from baseline (71.63 mm3, IQR: 40.12-135.61) to 12 months (67.73 mm3, IQR: 31.00-122.38) (P = 0.026). CONCLUSIONS: Echolucent carotid plaque, assessed with the novel 3D matrix ultrasound system, had increasing GSM within 3 months period, indicating stabilization of the more vulnerable plaques in aMI and cPAD patients. Plaque volume decreased over 12 months follow-up in a long-term statin-treated patient with cPAD, but not during the first 12 months statin therapy in patients with aMI.

Long-term Risk of Death and Hospitalization in Patients With Heart Failure and Takotsubo Syndrome: Insights From a Nationwide Cohort.

BACKGROUND: Data concerning the long-term risk of heart failure (HF) in patients with takotsubo syndrome (TTS) are sparse. We compared the rates of death and hospitalization due to HF with matched individuals from the background population and patients with ST-segment elevation myocardial infarction (STEMI). METHODS: In this nationwide observational cohort study, all patients with first-time TTS (2011-2018) who were alive at discharge were identified by using data from Danish nationwide registries. These were matched for age and sex with individuals from the background population (1:4 matching) and with patients with STEMI who were alive at discharge (1:3 matching). RESULTS: A total of 881 patients with TTS who were alive at discharge were identified (median age 70 years; 89.4% men). During a mean follow-up of 2.9 years, the incidence rates of death, HF hospitalization, and TTS recurrence in survivors of TTS were 6.9, 0.9 and 1.1 events per 100 person-years. The corresponding absolute 3-year risks were 9.3%, 1.8% and 2.5%, respectively. Survivors of TTS had higher associated rates of death compared with the background population (hazard ratio [HR] 2.05 [95% CI, 1.62-2.60]) and survivors of STEMI (HR 1.69 [1.34-2.13]). Similarly, survivors of TTS had higher associated rates of hospitalization due to HF compared with the background population (HR 4.24 [1.88-9.53]), but lower rates compared with survivors of STEMI (HR 0.34 [0.20-0.56]). Propensity-score matched analyses yielded similar results. CONCLUSIONS: Survivors of TTS had significantly higher associated mortality rates than the background population and survivors of STEMI. Survivors of TTS had lower HF hospitalization rates than survivors of STEMI, but the rates were higher than those of the background population.

Amiodarone attenuates cardiac Rubidium-82 in consecutive PET/CT scans in a rodent model.

BACKGROUND: Risk stratification and diagnosis using Rubidium-82 (82Rb) positron emission tomography (PET) is a routine clinical approach in coronary artery disease (CAD). Various drugs are used to treat CAD; however, whether any of them change the uptake of 82Rb in the heart has not been investigated. The aim of this study is to determine whether drugs used in treatment of CAD affect the uptake of 82Rb in the heart in healthy rats. METHODS: Seventy-seven Sprague-Dawley rats were included in the cross-sectional study. All rats underwent baseline 82Rb PET/CT and divided into eleven groups treated with different drugs. One group was control group (no treatment), eight groups were treated with monotherapy (amiodarone, acetylsalicylic acid (ASA), clopidogrel, ticagrelor, atorvastatin, enalapril, amlodipine, metoprolol succinate), and two groups were treated with polypharmacy (ASA, ticagrelor, atorvastatin, amlodipine or ASA, clopidogrel, atorvastatin, amlodipine). Once a day, they were administered pharmacological therapy through oral gavage, and on day seven, follow-up scanned with 82Rb PET/CT. RESULTS: In the control group without pharmacological treatment, no difference in the standard uptake value (SUV) ratio between heart and muscle from baseline to follow-up (5.8 vs 7.0, P = .3) was found. The group treated with amiodarone had a significantly reduced SUV ratio from baseline to follow-up (5.8 vs 5.1, P = .008). All other drugs investigated had no difference in SUV ratio from baseline to follow-up. CONCLUSION: In this study, we showed that drugs normally used to treat CAD do not affect the uptake of 82Rb. However, amiodarone result in a significantly lowered 82Rb uptake, compared to control. This information about amiodarone would probably not change the size assessment of a myocardial perfusion defect in a clinical setting. However, it could change the kinetic parameters when assessing absolute myocardial blood flow in patients treated with amiodarone.

Comparison of Effect of Ischemic Postconditioning on Cardiovascular Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention With Versus Without Thrombectomy.

In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy.

Pulmonary embolism: Age specific temporal trends in incidence and mortality in Denmark 1999-2018.

BACKGROUND: Through the last two decades the prevention, diagnosis and treatment of pulmonary embolism (PE) has evolved along with demographic changes. The influence of these current transformations is important in the assessment of the future burden of PE. We aimed to describe age specific temporal trends in incidence of first-time PE and subsequent mortality. METHODS: We identified patients ≥18 years of age with a first-time in-hospital diagnosis of PE in Danish national registers. By dividing patients into seven age groups (18-34, 35-44, 45-54, 55-65, 65-74, 75-84, >85 years), age specific incidence and 1-year mortality rates were calculated for four different calendar periods between 1999 and 2018. RESULTS: From 1999 to 2018 65,478 patients with a first-time PE were identified. PE incidence per 100,000 person years increased during the study period in all age-groups (18-34 years: 10 to 18, 35-44 years: 18 to 35, 45-54: 26 to 63, 55-64 years: 42 to 123, 65-74 years: 92 to 229, 75-84 years: 166 to 383 and >85 years: 155 to 417), ptrend <0.0001 for all. During the study period 1-year mortality rate decreased from 4 to 2 per 10 person years in patients aged 65-74 years and this trend was found in all age groups (ptrend = 0.0001 for all). CONCLUSION: Despite a decreasing mortality rate, incidence rate of PE increased in Denmark across all age groups from 1999 to 2018, reflecting improved sensitivity of diagnostic methods and changes in the burden of comorbid conditions, all together warranting a continuing need for early prevention of PE.

Importance of Risk Assessment in Timing of Invasive Coronary Evaluation and Treatment of Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome: Insights From the VERDICT Trial.

Background The optimal timing of invasive examination and treatment of high-risk patients with non-ST-segment-elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard-care invasive coronary angiography on the risk of all-cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non-ST-segment-elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48-72 hours) invasive strategy. The primary outcome of the present study was all-cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow-up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16-3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63-1.10]) (Pinteraction=0.006). Conclusions In patients with non-ST-segment-elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high-risk and low-risk patients with non-ST-segment-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02061891.

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Room for improvement: initiation of lipid-lowering treatment and achievement of lipid target levels-a Danish registry-based study.

AIMS: Prevention of adverse outcomes in individuals with high cholesterol levels may be improved by intensified lipid-lowering treatment (LLT). We studied whether treatment goals of low-density lipoprotein cholesterol (LDL-C) were reached within 1 year from baseline (defined as first LDL-C measurement) in a Danish population. METHODS AND RESULTS: Danish registries were used to identify all persons in the Northern Region of Denmark who had LDL-C measured between 1997 and 2012 and who were naïve to LLT. Patients were categorized in LDL-C <5 or ≥5 mmol/L and further subdivided into low, high, and very high predicted cardiovascular (CV) risk as suggested by European guidelines for risk stratification. Initiation of LLT and lipid target levels were assessed after 1 year (3.0, 2.5, and 1.8 mmol/L, respectively). In this study, we examined the intensity of LLT and whether treatment goals were reached. More patients with LDL-C ≥5 mmol/L, regardless of the CV risk, initiated LLT compared with patients who had a very high CV risk and LDL-C <5 mmol/L. In total, 37.7% (n = 32 581) of all patients with a follow-up LDL-C, and 25.1% (n = 3229) of patients with LDL-C ≥5 mmol/L, had achieved their target levels after 1 year. Only 45.2% (n = 4545) of the LDL-C ≥5 mmol/L high-risk patients with a follow-up LDL-C had started LLT 12 months after baseline. CONCLUSION: Less than half of patients presenting with an LDL-C ≥5 mmol/L start LLT within 1 year, representing a missed opportunity for both primary and secondary prevention of CV disease.