PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation.

BACKGROUND: The benefit of percutaneous coronary intervention (PCI) in patients with stable coronary artery disease and severe aortic stenosis who are undergoing transcatheter aortic-valve implantation (TAVI) remains unclear. METHODS: In an international trial, we randomly assigned, in a 1:1 ratio, patients with severe symptomatic aortic stenosis and at least one coronary-artery stenosis with a fractional flow reserve of 0.80 or less or a diameter stenosis of at least 90% either to undergo PCI or to receive conservative treatment, with all patients also undergoing TAVI. The primary end point was a major adverse cardiac event, defined as a composite of death from any cause, myocardial infarction, or urgent revascularization. Safety, including bleeding events and procedural complications, was assessed. RESULTS: A total of 455 patients underwent randomization: 227 to the PCI group and 228 to the conservative-treatment group. The median age of the patients was 82 years (interquartile range, 78 to 85), and the median Society of Thoracic Surgeons-Procedural Risk of Mortality score (on a scale from 0 to 100%, with higher scores indicating a greater risk of death within 30 days after the procedure) was 3% (interquartile range, 2 to 4). At a median follow-up of 2 years (interquartile range, 1 to 4), a major adverse cardiac event (primary end point) had occurred in 60 patients (26%) in the PCI group and in 81 (36%) in the conservative-treatment group (hazard ratio, 0.71; 95% confidence interval [CI], 0.51 to 0.99; P = 0.04). A bleeding event occurred in 64 patients (28%) in the PCI group and in 45 (20%) in the conservative-treatment group (hazard ratio, 1.51; 95% CI, 1.03 to 2.22). In the PCI group, 7 patients (3%) had PCI procedure-related complications. CONCLUSIONS: Among patients with coronary artery disease who were undergoing TAVI, PCI was associated with a lower risk of a composite of death from any cause, myocardial infarction, or urgent revascularization at a median follow-up of 2 years than conservative treatment. (Funded by Boston Scientific and the Danish Heart Foundation; NOTION-3 ClinicalTrials.gov number, NCT03058627.).

Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans.

BACKGROUND: Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans. METHODS: Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays. RESULTS: Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0-6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180-679 mL) autologous plasma, the concentration of cTn in participants' blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8-168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7-295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0-44.9) to 52.7 mL/min (95% CI, 42.2-57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2-95.0). CONCLUSIONS: This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury.

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.

Overcoming professional barriers encountered by women in interventional cardiology: an EAPCI statement.

Despite the increasing proportion of female medical and nursing students, there is still a significant under-representation of women working as healthcare providers in interventional cardiology, with very few of them reaching senior leadership, academic positions, or acting principal investigators, as well as actively involved in company advisory boards. In this position paper, we will describe the current status of women working in interventional cardiology across Europe. We will also provide an overview of the most relevant determinants of the under-representation of women at each stage of the interventional cardiology career path and offer practical suggestions for overcoming these challenges.

In vivo molecular imaging of cardiac angiogenesis in persons with and without type 2 diabetes: A cross-sectional 68 Ga-RGD-PET study.

AIMS: To assess cardiac angiogenesis in type 2 diabetes by positron emission tomography (PET) tracer [68 Ga]Ga-NODAGA-E[(cRGDyK)]2 (68 Ga-RGD) imaging. METHODS: Cross-sectional study including 20 persons with type 2 diabetes and 10 non-diabetic controls (CONs). Primary prespecified outcome was difference in cardiac angiogenesis (cardiac 68 Ga-RGD mean target-to-background ratio [TBRmean ]) between type 2 diabetes and CONs. Secondary outcome was to investigate associations between cardiac angiogenesis and kidney function and other risk factors. RESULTS: Participants with type 2 diabetes had a mean ± SD age of 61 ± 9 years, 30% were women, median (IQR) diabetes duration of 11 (6-19) years and 3 (15%) had a history of cardiovascular disease. The CONs had comparable age and sex distribution to the participants with type 2 diabetes, and none had a history of coronary artery disease. Myocardial flow reserve was lower in type 2 diabetes (2.7 ± 0.6) compared with CONs (3.4 ± 1.2) ( p  = 0.03) and coronary artery calcium score was higher (562 [142-905] vs. 1 [0-150] p  = 0.04). Cardiac 68 Ga-RGD TBRmean was similar in participants with type 2 diabetes (0.89 ± 0.09) and CONs (0.89 ± 0.10) ( p  = 0.92). Cardiac 68 Ga-RGD TBRmean was not associated with estimated glomerular filtration rate, urine albumin creatinine ratio, cardiovascular disease, coronary artery calcium score or baroreflex sensitivity, neither in pooled analyses nor in type 2 diabetes. CONCLUSIONS: Cardiac angiogenesis, evaluated with 68 Ga-RGD PET, was similar in type 2 diabetes and CONs. Cardiac angiogenesis was not associated with kidney function or other risk markers in pooled analyses or in analyses restricted to type 2 diabetes.

Myocardial creep and cardiorespiratory motion correction improves diagnostic accuracy of Rubidium-82 cardiac positron emission tomography.

AIM: To evaluate the feasibility of retrospectively detecting and correcting periodical (cardiac and respiratory motion) and non-periodical shifts of the myocardial position (myocardial creep) using only the acquired Rubidium-82 positron emission tomography raw (listmode) data. METHODS: This study comprised 25 healthy participants (median age = 23 years) who underwent repeat rest/adenosine stress Rubidium-82 myocardial perfusion imaging (MPI) and 53 patients (median age = 64 years) considered for revascularization who underwent a single MPI session. All subjects were evaluated for myocardial creep during MPI by assessing the myocardial position every 200 ms. A proposed motion correction protocol, including corrections for cardiorespiratory and creep motion (3xMC), was compared to a guideline-recommended protocol (StandardRecon). For the volunteers, we report test-retest repeatability using standard error of measurements (SEM). For the patient cohort, we evaluated the area under the receiver operating curve (AUC) for both stress and ischemic total perfusion deficits (sTPD and iTPD, respectively) using myocardial ischemia defined as fractional flow reserve values < 0.8 in the relevant coronary segment as the gold standard. RESULTS: Test-retest repeatability was significantly improved following corrections for myocardial creep (SEM; sTPD: StandardRecon = 2.2, 3xMC = 1.8; iTPD: StandardRecon = 1.6, 3xMC = 1.2). AUC analysis of the ROC curves revealed significant improvements for iTPD measurements following 3xMC [sTPD: StandardRecon = 0.88, 3xMC = 0.92 (P = .21); iTPD: StandardRecon = 0.88, 3xMC = 0.95 (P = .039)]. CONCLUSION: 3xMC has the potential to improve the diagnostic accuracy of myocardial MPI obtained from positron emission tomography. Therefore, its use should be considered both in clinical routine and large-scale multicenter studies.

Long-term prognostic outcomes and implication of oral anticoagulants in patients with new-onset atrial fibrillation following st-segment elevation myocardial infarction.

BACKGROUND: New-onset atrial fibrillation (NEW-AF) following ST-segment elevation myocardial infarction (STEMI) is a common complication, but the true prognostic impact of NEW-AF is unknown. Additionally, the optimal treatment of NEW-AF among patients with STEMI is warranted. METHODS: A large cohort of consecutive patients with STEMI treated with percutaneous coronary intervention were identified using the Eastern Danish Heart Registry from 1999-2016. Medication and end points were retrieved from Danish nationwide registries. NEW-AF was defined as a diagnosis of AF within 30 days following STEMI. Patients without a history of AF and alive after 30 days after discharge were included. Incidence rates were calculated and multivariate analyses performed to determine the association between NEW-AF and long-term mortality, incidence of ischemic stroke, re-MI, and bleeding leading to hospitalization, and the comparative effectiveness of OAC therapy on these outcomes. RESULTS: Of 7944 patients with STEMI, 296 (3.7%) developed NEW-AF. NEW-AF was associated with increased long-term mortality (adjusted HR 1.48, 95% CI 1.20-1.82, P<.001) and risk of bleeding leading to hospitalization (adjusted HR 1.36, 95% CI 1.00-1.85, P=.050), and non-significant increased risk of ischemic stroke (adjusted HR 1.45, 95% CI 0.96-2.19, P=.08) and re-MI (adjusted HR 1.14, 95% CI 0.86-1.52, P=.35) with a median follow-up of 5.8 years. In NEW-AF patients, 38% received OAC therapy, which was associated with reduced long-term mortality (adjusted HR 0.69, 95% CI 0.47-1.00, P=.049). CONCLUSIONS: NEW-AF following STEMI is associated with increased long-term mortality. Treatment with OAC therapy in NEW-AF patients is associated with reduced long-term mortality.

Non-invasive assessment of temporal changes in myocardial microvascular function in persons with type 2 diabetes and healthy controls.

BACKGROUND: Cardiac Rubidium-82 (82 Rb) positron emission tomography/computed tomography (PET/CT) provides a measure of the myocardial blood flow and the myocardial flow reserve, which reflects the function of both large epicardial arteries and the myocardial microcirculation. Knowledge on changes in the myocardial microvascular function over time is lacking. METHODS: In this cohort study, we recruited 60 persons with type 2 diabetes and 30 non-diabetic controls, in 2013; all free of overt cardiovascular disease. All underwent a cardiac 82 Rb PET/CT scan. In 2019, all survivors (n = 82) were invited for a repeated cardiac 82 Rb PET/CT scan using the same protocol, and 29 with type 2 diabetes and 19 controls participated. RESULTS: Median duration between visits was 6.2 years (IQR: 6.1-6.3). In the total cohort, the mean age was 66.4 years (SD: 9.3) and 33% were females. The myocardial flow reserve was lower in persons with type 2 diabetes compared to controls (p = 0.002) but there was no temporal change in the myocardial flow reserve in participants with type 2 diabetes: mean change: -0.22 (95% CI: -0.47 to 0.02) nor in controls: -0.12 (-0.49 to 0.25) or when comparing type 2 diabetes to controls: mean difference: -0.10 (95% CI: -0.52 to 0.31). The temporal reduction in stress-induced myocardial blood flow did not differ within the groups but was more pronounced in type 2 diabetes compared to controls: mean difference: -0.30 (95% CI: -0.55 to -0.04). CONCLUSION: The myocardial microvascular function was impaired in persons with type 2 diabetes compared to controls but did not change significantly in either of the groups when evaluated over 6 years.

The benefit of complete revascularization after primary PCI for STEMI is attenuated by increasing age: Results from the DANAMI-3-PRIMULTI randomized study.

OBJECTIVES: To ascertain the effect of age on outcomes after culprit-only and complete revascularization after Primary PCI (PPCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: The numbers of older patients being treated with PPCI are increasing. The optimal management of nonculprit stenoses in such patients is unclear. METHODS: We conducted an analysis of patients aged ≥75 years randomized in the DANAMI-3-PRIMULTI study to either culprit-only or complete FFR-guided revascularization. The primary endpoint was a composite of all-cause mortality, nonfatal reinfarction, and ischaemia-driven revascularization of lesions in noninfarct-related arteries after a median of 27 months of follow-up. RESULTS: One hundred and ten of six hundred and twenty seven patients in the DANAMI-3-PRIMULTI trial were aged ≥75 years. These patients were more likely female (p < .001), hypertensive (p < .001), had lower hemoglobin levels (p < .001), and higher serum creatinine levels (p < .001) than the younger patients in the trial. Other than less use of drug-eluting stents (96.6 versus 88.0%: p = .02), there were no significant differences in procedural technique and success between patients aged <75 years and those ≥75 years of age. There was no significant difference in the incidence of the primary endpoint in patients ≥75 years randomized to culprit-only or FFR-guided complete revascularization (HR 1.49 [95% CI 0.57-4.65]; log-rank p = .19; p for interaction versus patients <75 years <.001). There was a significant interaction between age as a continuous variable, treatment assignment, and the primary outcome (p < .001); beyond the age of about 75 years, there may be no prognostic advantage to complete revascularization. CONCLUSIONS: In patients ≥75 years, after treatment of the culprit lesion in STEMI, there is no significant prognostic benefit to prophylactic complete revascularization of nonculprit stenoses. Pending further study, data would support a symptom-guided approach to further invasive treatment.

Interventional treatment of acute myocardial infarction-related cardiogenic shock.

PURPOSE OF REVIEW: Acute revascularization is with some evidence the only intervention proven to improve the prognosis in myocardial infarction-related cardiogenic shock but several interventions are continuously being investigated in order to increase survival among these patients. In this review, several aspects related to the interventional treatment of cardiogenic shock are discussed chronologically from symptom debut to leaving the cardiac catheterization laboratory. RECENT FINDINGS: In the randomized CULPRIT-SHOCK trial, a culprit-only revascularization strategy was reported superior to immediate complete revascularization among patients with multivessel disease. Recent large-scale observational data underline the marked prognostic importance of time from medical contact to revascularization in acute myocardial infarction-related cardiogenic shock. Moreover, studies suggest a potential beneficial effect of a transradial vascular access as well as early initialization of mechanical circulatory support in carefully selected patients. This, however, needs further validation. SUMMARY: Acute revascularization remains a crucial part of the initial management of acute myocardial infarction-related cardiogenic shock. Among cardiogenic shock patients presenting with multivessel disease, a culprit-only approach should be the routine strategy. Time to revascularization plays a crucial role in the setting of cardiogenic shock, why prehospital optimization and triaging may be the most important factors in order to improve prognosis in AMI-related cardiogenic shock.

Association of Body Mass Index with Mortality in Patients with Cardiogenic Shock following Acute Myocardial Infarction: A Contemporary Danish Cohort Analysis.

AIMS: The obesity paradox suggests a better prognosis in overweight or obese patients with heart failure and acute myocardial infarction (AMI) than patients with normal weight. Few studies have investigated the association between BMI and mortality in patients with AMI complicated by cardiogenic shock (AMICS). The aim of this study was to evaluate the association between BMI and 30-day mortality in patients with AMICS. METHODS AND RESULTS: A retrospective study of 1,716 patients with AMICS treated at 2 tertiary centers in south-eastern Denmark between 2010 and 2017. Patients undergoing revascularization and who were admitted to the intensive care unit were included (n = 1,216). BMI was available in 1,017 patients (83.6%). Patients were divided according to the WHO classification as normal weight BMI <24.9 kg/m2 (n = 453), overweight BMI 25-29.9 kg/m2 (n = 391), obese class 1 BMI 30-34.9 kg/m2 (n = 131), and obese class 2 + 3 BMI >35 kg/m2 (n = 42). Differences in baseline characteristics, in-hospital treatment, and the primary outcome of all-cause mortality at 30 days were examined. Obese patients had more comorbidities such as diabetes, hypertension, and dyslipidemia than patients with normal weight. Need for renal replacement therapy was higher among obese patients (normal weight, 19% vs. obese class 2 + 3, 35%, p = 0.02); otherwise, no difference in management was found. No difference in 30-day mortality was observed between groups (normal weight 44%, overweight 38%, obese class 1 41%, and obese class 2 + 3 45% at 30 days; ns). CONCLUSIONS: Thirty-day mortality in patients with AMICS was not associated with the BMI category. Thus, evidence of an "obesity paradox" was not observed in this contemporary cohort of patients with AMICS in Denmark.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study.

BACKGROUND: Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. METHODS: This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan-Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. RESULTS: A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow-Pittsburgh Cerebral Performance Categories 1-2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18-1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03-1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12-1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16-1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52-0.76). CONCLUSIONS: A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

Diagnostic performance of a new ECG algorithm for reducing false positive cases in patients suspected acute coronary syndrome.

BACKGROUND: Early and correct diagnosis of ST-segment elevation myocardial infarction (STEMI) is crucial for providing timely reperfusion therapy. Patients with ischemic symptoms presenting with ST-segment elevation on the electrocardiogram (ECG) are preferably transported directly to a catheterization laboratory (Cath-lab) for primary percutaneous coronary intervention (PPCI). However, the ECG often contains confounding factors making the STEMI diagnosis challenging leading to false positive Cath-lab activation. The objective of this study was to test the performance of a standard automated algorithm against an additional high specificity setting developed for reducing the false positive STEMI calls. METHODS: We included consecutive patients with an available digital prehospital ECG triaged directly to Cath-lab for acute coronary angiography between 2009 and 2012. An adjudicated discharge diagnosis of STEMI or no myocardial infarction (no-MI) was assigned for each patient. The new automatic algorithm contains a feature to reduce false positive STEMI interpretation. The STEMI performance with the standard setting (STD) and the high specificity setting (HiSpec) was tested against the adjudicated discharge diagnosis in a retrospective manner. RESULTS: In total, 2256 patients with an available digital prehospital ECG (mean age 63 ± 13 years, male gender 71%) were included in the analysis. The discharge diagnosis of STEMI was assigned in 1885 (84%) patients. The STD identified 165 true negative and 1457 true positive (206 false positive and 428 false negative) cases (77.3%, 44.5%, 87.6% and 17.3% for sensitivity, specificity, PPV and NPV, respectively). The HiSpec identified 191 true negative and 1316 true positive (180 false positive and 569 false negative) cases (69.8%, 51.5%, 88.0% and 25.1% for sensitivity, specificity, PPV and NPV, respectively). From STD to HiSpec, false positive cases were reduced by 26 (12,6%), but false negative results were increased by 33%. CONCLUSIONS: Implementing an automated ECG algorithm with a high specificity setting was able to reduce the number of false positive STEMI cases. However, the predictive values for both positive and negative STEMI identification were moderate in this highly selected STEMI population. Finally, due the reduced sensitivity/increased false negatives, a negative AMI statement should not be solely based on the automated ECG statement.

Validation of the all-comers design: Results of the TARGET-AC substudy.

BACKGROUND: Results of clinical trials are often criticized by low inclusion rate and potential sampling bias in patient recruitment. The aim of this validation registry is to evaluate how far an all-comers design in the context of clinical research can ensure the representation of the true all-comers population. METHODS: This validation registry is a prospective international multicentre registry, conducted at 10 out of the total 21 centers, participating in TARGET-AC (registered under NCT02520180). During a predefined four-week period data were recorded prospectively on all PCIs performed in the participating centers, whether or not patients were enrolled in TARGET-AC. Data were collected on patient demographics, angiographic lesion- and procedural characteristics. For patients who were not enrolled in the study, operators were asked to declare the reason for not enrolling the patient, using a single-choice questionnaire. RESULTS: A total of 131 patients were enrolled in the TARGET-AC study during the investigated period (ER group), standing as 20% (range 4% and 54%) of all eligible cases per protocol. In the ER group more patients presented with stable angina (61% vs. 43%, respectively; P < .001). Whereas ST-elevation infarction was less common (5% vs. 26%, respectively; P < .001), there was no difference in non-ST elevation acute coronary syndrome (32% vs. 27%, respectively; P = .248). Risk factors and comorbidities did not show any difference between the ER and the non-enrolled (NER) groups, except for greater rate of significant valvular disease in the NER group (12% vs 19%, respectively; P = .037). The NER group presented more thrombotic stenoses than the ER group (20% vs 12%, respectively; P = .040). No difference was found in any other investigated angiographic parameters, like target vessels, bifurcation lesion, severe calcification or chronic total occlusions. Admission during regular working hours and availability of study nurse were associated with markedly higher recruitment rate. CONCLUSION: Results suggest that TARGET AC was outbalanced for stable patients over primary PCIs as compared to real world. However in terms of risk factors and comorbidities the trial managed to represent the collective of real world clinical practice. Fairly representative cases were included at an average inclusion-to-eligible rate of 20%.

Relation of cardiac adipose tissue to coronary calcification and myocardial microvascular function in type 1 and type 2 diabetes.

BACKGROUND: Cardiac adipose tissue may have local paracrine effects on epicardial arteries and the underlying myocardium, promoting calcification and affecting myocardial microcirculation. We explored whether the total amount of cardiac adipose tissue was associated with coronary artery calcium score (CAC) and myocardial flow reserve in persons with type 1 or type 2 diabetes and healthy controls. METHODS: We studied three groups: (1) 30 controls, (2) 60 persons with type 1 diabetes and (3) 60 persons with type 2 diabetes. The three groups were matched for sex and age. The three groups derived from retrospective analysis of two clinical studies. All underwent cardiac 82Rb positron emission tomography/computed tomography (PET/CT) scanning. Cardiac adipose tissue volume (the sum of epicardial and pericardial fat), CAC, and myocardial flow reserve (ratio of pharmacological stress flow and rest flow) were evaluated using semiautomatic software. We applied linear regression to assess the association between cardiac adipose tissue, CAC and myocardial flow reserve. RESULTS: Mean (SD) cardiac adipose tissue volume was 99 (61) mL in the control group, 106 (78) mL in the type 1 diabetes group and 228 (97) mL in the type 2 diabetes group. Cardiac adipose tissue was positively associated with body mass index in all three groups (p ≤ 0.02). In the controls, cardiac adipose tissue was positively associated with CAC score (p = 0.008) and negatively associated with myocardial flow reserve (p = 0.005). However, cardiac adipose tissue was not associated with CAC or myocardial flow reserve in the groups including persons with type 1 or type 2 diabetes (p ≥ 0.50). CONCLUSIONS: In contrast to what was found in healthy controls, we could not establish a relation between cardiac adipose tissue and coronary calcification or myocardial microvascular function in person with type 1 or type 2 diabetes. The role of cardiac adipose tissue in cardiovascular disease in diabetes remains unclear.

Biomarkers in patients with Takotsubo cardiomyopathy compared to patients with acute anterior ST-elevation myocardial infarction.

Background: Takotsubo cardiomyopathy (TTC) is a syndrome of acute non-coronary heart failure with similar symptoms and electrocardiograms to acute anterior ST-elevation myocardial infarction (STEMI). Little is known about the pathophysiology of TTC. We assessed admission plasma concentrations of biomarkers reflecting neuroendocrine response (copeptin, mid-regional-pro-adrenomedullin, pro-atrial-natriuretic-peptide, soluble thrombomodulin (sTM), syndecan-1) and inflammation (suppression-of-tumorigenicity 2 (ST2), high-sensitive C-reactive-protein) in TTC patients and compared to patients with acute anterior STEMI.Materials and methods: Twenty TTC patients were matched with 40 STEMI patients by age, gender and left ventricular ejection fraction. Blood was sampled upon hospital admission immediately before acute coronary angiography.Results: The groups had similar comorbidities. TTC patients had higher plasma concentrations of sTM: 7.94 (5.89;9.61) vs. 6.42 (5.50;7.82)ng/ml, p = 0.04 and ST2 (53 (32;157) vs. 45 (31;55)ng/ml, p = 0.008) and higher heart rate: 101 ([Formula: see text]33) vs. 76([Formula: see text]14)bpm, p = 0.0001, but lower concentrations of copeptin (10.4 (7.6;39) vs. 92.3 (13;197)pmol/l, p < 0.05) and troponin T (348 (98;759) vs. 1190 (261;4105)ng/l, p = 0.04).Conclusion: TTC patients had higher plasma concentrations of sTM and ST2, higher heart rate and lower copeptin and troponin T concentrations compared to acute anterior STEMI patients. This study contributes to the hypothesis that TTC patients have endothelial cell damage and are hemodynamically more stable than patients with acute anterior STEMI on admission.

Mortality in cardiogenic shock is stronger associated to clinical factors than contemporary biomarkers reflecting neurohormonal stress and inflammatory activation.

PURPOSE: To validate the IABP-SHOCK II risk score in a Danish cohort and assess the association between the IABP-SHOCK II risk score and admission concentration of biomarkers reflecting neurohormonal - (Copeptin, Pro-atrial natriuretic peptide (proANP), Mid-regional pro-adrenomedullin (MRproADM)) and inflammatory (ST2) activation in patients with CS complicating ST segment elevation myocardial infarction (STEMI). METHODS: A total of 137 consecutive patients admitted with STEMI and CS at two tertiary heart centres were stratified according to the IABP-SHOCK II risk score (0-2; 3/4; 5-9), and had blood sampled upon admission. RESULTS: Plasma concentrations of Copeptin (median (pmol/L) score 0-2: 313; score 3/4: 682; score 5-9: 632 p < 0.0001), proANP (pmol/L) (1459; 2225; 2876 p = 0.0009) and MRproADM (nmol/L) (0.86; 1.2; 1.4 p = 0.04) were significantly associated with the risk score, whereas ST2 (ng/mL) was not (44; 60; 45 p = 0.23). The IABP-SHOCK II risk score predicted 30-day mortality (score 0-2: 22%; score 4/3: 51%; score 5-9: 72%, area under the curve (AUC): 0.73, plogrank < 0.0001), while the tested biomarkers did not (AUC: 0.51

Degree of ST-segment elevation in patients with STEMI reflects the acute ischemic burden and the salvage potential.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is clinically diagnosed by significant ST-segment elevation (STE) in the electrocardiogram (ECG). The importance of the sum of significant ST-segment elevation (∑STE) before primary percutaneous coronary intervention (PPCI) - considered an indicator of the degree of ischemia - is sparse. We evaluated the association of ∑STE before PPCI with respect to area at risk, infarct size and myocardial salvage. METHODS: A total of 503 patients with STEMI and available cardiac magnetic resonance (CMR) were included. CMR was performed at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 92 (IQR, 88-96). The ECG before PPCI with the most prominent STE was used for analysis. RESULTS: ∑STE divided into quartiles were progressive linearly associated with area at risk (p < 0.001), final infarct size (p < 0.001) and extent of microvascular obstruction (p < 0.001) and inverse linearly associated with final myocardial salvage (p < 0.001). Similar results were found for linear regression analyses. However, ∑STE was not associated with final myocardial salvage in patients with pre-PCI TIMI (thrombolysis in myocardial infarction) flow 0/1 (p = 0.24) in contrast to patients with pre-PCI TIMI flow 2/3 (p ≤ 0.001). CONCLUSION: In patients with STEMI presenting within 12 h of symptom onset, the degree of STE in the ECG before PPCI is a marker of the extent of myocardium at risk that in turn affects the infarct size in patients with pre-PCI TIMI flow 0/1, whereas the degree of STE in patients with pre-PCI TIMI flow 2/3 is a marker of the extent of the myocardium at risk as well as myocardial salvage - both affecting the myocardial damage.

Early Q-wave morphology in prediction of reperfusion success in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention - A cardiac magnetic resonance imaging study.

BACKGROUND: Pathological Q-wave (QW) in the electrocardiogram (ECG) before primary percutaneous coronary intervention (primary PCI) is a strong prognostic marker in patients with ST-segment elevation myocardial infarction (STEMI). However, current binary QW criteria are either not clinically applicable or have a lack of diagnostic performance. Accordingly, we evaluated the association between duration, depth and area of QW and markers of the effect of reperfusion (reperfusion success). METHODS: A total of 516 patients with their first STEMI had obtained an ECG before primary PCI and an acute cardiac magnetic resonance imaging (CMR) at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 92 (IQR, 89-96). The largest measurable QW in ECG was used for analysis of duration, depth and area of QW (QW morphology). The QW morphology was evaluated as a continuous variable in linear regression models and as a variable divided in four equally large groups. RESULTS: The QW morphology as four equally large groups was significantly associated with all CMR endpoints (p ≤ 0.001) and showed a linear relationship (p ≤ 0.001) with final infarct size (for QW duration, ß = 0.47; QW depth, ß = 0.41 and QW area, ß = 0.39), final infarct transmurality (for QW duration, ß = 0.36; QW depth, ß = 0.26 and QW area, ß = 0.23) and final myocardial salvage index (for QW duration, ß = -0.34; QW depth, ß = -0.26 and QW area, ß = -0.24). CONCLUSION: Although modest, the QW morphology in STEMI patients showed significant linear association with markers of reperfusion success. Hence, it is suggested that the term pathological is not used as a dichotomous parameter in patients with STEMI but rather evaluated on the basis of extent.