Pre-Hospital Decision Process and Prognosis in Men and Women with Coronary Heart Disease

The overall aim of this thesis was to describe experiences, strategies and actions in the prehospital phase among patients with a first acute myocardial infarction and to examine long-term trends in survival among patients with coronary heart disease. The thesis consists of two qualitative and two quantitative studies. Interviews were conducted with 21 men and 17 women, experiencing symptoms from a first acute myocardial infarction (AMI) and analyzed with Grounded Theory. Two national prospective cohort studies were performed by using the Swedish Inpatient register (IPR). From this, prognosis for 37,276 adult patients 18 years who underwent a first coronary artery bypass (CABG) 1987-2006 could be estimated. During the decision process, various spectra of bodily changes were described in both men and women, sometimes over an extended period before submission to hospital. Intermittent, vague and insidious symptoms caused confusion about how to act. Vague symptoms sometimes experienced by the men did not match their preconception of typical symptoms in a myocardial infarction. To come to an understanding they compared with their past experiences which led to an awareness of the abnormality, the severity and the need for contact medical attention. The women usually attributed their symptoms to harmless conditions and struggled to continue with their responsibilities in their daily lives. Intensified symptoms made the women unable to perform their daily task and they could no longer maintain earlier explanations for their discomfort which contributed to an understanding for the need of professional help. Sometimes, when men and women sought medical attention for their discomfort, and had no objective signs of an AMI they were dismissed, with no diagnosis, which caused a hesitation to contact medical care once again. This emphasizes that health care professionals have to pay more attention to the patient’s narrative. In the quantitative part of the thesis younger men with a first AMI had a 2 to 4-fold risk for mortality compared to men in the same age in the general population while women had a 6 to 14-fold risk during the last study period (2002-2006). Survival increased during the study period in men. In women there was a favorable trend in survival until the last period 2002-2006 but survival then reverted to that in the second period (1992-1996) in the last period. Men and women ≥55 years surviving the first 30 days after CABG (coronary artery bypass grafting) showed a lower mortality risk than those in the general population and showed a decreasing trend in mortality during the study period. Women below the age of 55 showed no significant improvement in survival and had a 4-fold risk for mortality compared to women in the same age in the general population. Men <55 displayed improved survival, which was higher than that for men in the general population

Cardiac troponins and growth-differentiation factor-15 (GDF-15) for prediction of angiographic coronary artery disease in chest pain patients without myocardial injury

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Grieg Foundation and Western Norway Regional Health Authority. Background There is a growing evidence that patients with angiographic signs of coronary artery disease should receive preventive therapy to reduce the risk of future adverse cardiac events. Purpose Evaluate whether cardiac troponin T and I (cTnT and cTnI) concentrations within the range from the limit of detection of the assay to the 99th percentile or GDF-15 may help identify patients with angiographic evidence of coronary artery disease (CAD). Methods A subgroup of 550 patients from the WESTCOR study with both cTnT and cTnI concentrations ≤99th percentile was evaluated with coronary computed tomography angiography (CCTA). CAD was defined as ≥10% narrowing of lumen of any coronary artery on CT angiogram or too high calcium score for anatomy to be evaluated. Overall diagnostic accuracy of cTnT, cTnI and GDF-15 and their combination were evaluated calculating the area under the receiver-operating characteristics curve (ROC-AUC). cTn analysis were performed using high-sensitivity assays from Roche Diagnostics (cTnT, limit of detection of 5 ng/L and gender-neutral 99th percentile of 14 ng/L) and Abbott Diagnostics (cTnI, limit of detection 1.6 ng/L and 99th percentile 16 ng/L for women and 34 ng/L for men). GDF-15 analyses were performed using the GDF-15 assay on Cobas e801 (Roche Diagnostics). Results A total of 53.5 percent (294 of 550 patients) had angiographic coronary disease. The risk of having CAD was significantly higher in patients with cTnT between 5 ng/ml and the gender-neutral 99th percentile compared to very low levels of cTnT &amp;lt;5 ng/ml, 65.7% (95% CI: 60-71%) vs 38.1% (95% CI: 32-44%, p-value for difference &amp;lt;0.001). Similar numbers for cTnI between 2 ng/ml and the gender-specific 99th percentile compared to very low levels &amp;lt;2 ng/ml was 62.9% (95% CI: 57-69%) vs 43.2% (95% CI: 37-49%, p-value for difference &amp;lt;0.001). The odds ratio for CAD if cTnT was ≥5 ng/ml or cTnI ≥2 compared to very low levels was 3.1 (2.1-4.4) for cTnT and 2.2 (1.6-3.1) for cTnI. For GDF-15, the risk of having CAD was lower in patients with low values &amp;lt;1200 ng/L (49.7%, 95% CI: 45-54%) compared to patients with higher concentrations &amp;gt;1200 ng/L (75.9%, 95% CI: 66-86%, p-value for difference &amp;lt;0.001). The accuracy of cTnT was significantly higher than for cTnI for identifying CAD (AUC 0.67, 95% CI 0.63-0.71 vs. 0.61, 95% CI 0.58-0.66, p-value for difference &amp;lt;0.01), and borderline higher than for GDF-15 (AUC 0.62, p-value for difference 0.067). Adding GDF-15 to cTn did not increase diagnostic performance of cTnT (AUC 0.67 vs. 0.68, p-value for difference 0.56) or cTnI (AUC 0.61 vs. 0.63, p-value for difference 0.23). Conclusion Overall diagnostic performance of cTnT is superior to cTnI in identifying patients without angiographic evidence of CAD. Adding GDF-15 does not increase overall diagnostic performance. Legend: Figure 1. Receiver-operating characteristics curve of cTnT, cTnI and GDF-15 for the identification of CAD (≥10% lumen reduction). </jats:sec

Novel low-delta value troponin algorithms have good precision for rule-out of NSTE-ACS

Abstract Background Rapid rule-out algorithms for non-ST-elevation infarction (NSTEMI) may be beneficial for logistics in the emergency room. Current algorithms are designed to rule-out NSTEMI, but do not differentiate between unstable angina (UAP) in need of revascularization and non-cardiac chest pain patients (NCCP) who could be discharged. Recent improvements in analytical precision of high sensitivity troponin (cTn) assays allow for trialing algorithms with very small delta values. Purpose Could the use of lower delta values produce rule-out algorithms for NSTE-ACS with a false negative rate of ≤5%, and a sufficient high rule-out rate of patients with NCCP. Method 927 patients with suspected NSTE-ACS were consecutively included. Serum samples were collected at 0, 3 and 8–12 hours. The final diagnosis was adjudicated by two independent cardiologists based on all clinical data including routine cTnT. The 0- and 3-hour samples were additionally measured for cTnIand cTnI from Singulex Clarity System (cTnI(sgx)). The diagnostic performance to rule-out NSTE-ACS was compared between one low-delta value algorithm from each assay (cTnT, cTnI and cTnT). Results The prevalence of NSTEMI was 13.4%, UAP 11.4% and NCCP 60%. Median age was 63 years, 60% males. Fig. 1 shows baseline and 3-hour delta cTn values for the UAP and NCCP patients for the three different assays. The baseline cTn value differed significantly between UAP and NCCP for all assays, p value &amp;lt;0.001. The novel low-delta cTnT algorithm (Table 1) ruled out 8 NSTE-ACS patients (3.5%), the cTnI algorithm and cTnI (sgx) algorithm ruled out 11 (4.8%) and 12 (5.2%) patients with NSTE-ACS, respectively. Moreover, the cTnT algorithm allocated 35.3% of the NCCP patients to discharge. Respective numbers for the cTnI(sgx) and cTnI algorithm were 30.6% and 33.5%. Comparing the ROC curves, the cTnT algorithm had significantly higher AUC compared to the cTnI(sgx) algorithm (p value =0.005, DeLong test). Conclusion The low-delta value algorithms correctly ruled in ≥95% of the NSTE-ACS patients whilst &amp;gt;30% of NCCP patients were ruled out. The cTnT algorithm had the best performance with a significant higher AUC compared to the cTnI(sgx) algorithm. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Western Norway Regional Health Authority, Haukeland and Stavanger University hospital </jats:sec

P860Adding clinical risk scores to troponin-based rule-out algorithms improves identification of patients at high risk for coronary revascularization within 6 weeks: the WESTCOR study

Abstract Background The ESC 0/3-h and High-STEACS study algorithms using high-sensitive troponin assays have proven effective in ruling out NSTEMI, but the safety of out-of-hospital follow-up of ruled out patients is disputable. Clinical risk scores may help to identify patients who develop major adverse cardiac events (MACE) defined as NSTEMI, death or coronary lesions in need of acute or elective revascularization within six weeks after admittance. Purpose Assess the ability of the ESC and High-STEACS study algorithms alone and in combination with clinical risk scores to identify MACE in unselected patients presenting with chest pain. Methods 985 patients (mean 63 years, 61% male) with suspected NSTE-ACS were consecutively included from Sept. 2015 to Feb. 2017. Serum samples were collected at 0, 3 and 8–12 hours and hs-cTnT and hs-cTnI were measured. The final diagnosis was adjudicated by two independent cardiologists. The troponin-based algorithms where compared to nine clinical risk scores, HEART, CARE, GRACE, T-MACS, TIMI, EDACS, sEDACS, Goldman and Geleijnse. Results The prevalence of NSTEMI during index hospitalization was 13%. The ESC 0/3-h and High-STEACS algorithms missed 3 events of NSTEMI with excellent NPV of 99.5 and 99.6. Rule-out patients with normal ECGs, GRACE score &lt;140 and no residual pain had a prevalence of MACE within 6 weeks of 9% using both algorithms. The most frequent event was non-acute revascularization due to unstable angina pectoris. Three of ten clinical risk scores had higher accuracy than the ESC 0/3-h algorithm for identification of MACE: HEART (AUC 0.84), CARE (AUC 0.79) and T-MACS (AUC 0.76). Combining the ESC 0/3-h rule-out algorithm and HEART≤3 had the best AUC of 0.85, missing only 12 (3%) MACE. Troponin-based algorithms and HEART True pos. True neg. False pos. False neg. NPV PPV Sens. Spes. Prop. low-risk AUC Troponin-based algorithms, endpoint NSTEMI ESC 0/3h TnT 118 628 196 3 99.5 37.6 97.5 76.2 66.8 0.87 High-STEACS TnI 118 715 109 3 99.6 52.0 97.5 86.8 76.0 0.92 Troponin-based algorithms, endpoint MACE ESC 0/3h TnT 143 577 171 54 91.4 45.5 72.6 77.1 66.8 0.75 High-STEACS TnI 130 651 97 67 90.7 57.3 66.0 87.0 76.0 0.77 Troponin-based algorithms combined with HEART score, endpoint MACE ESC 0/3h HEART 3 185 414 334 12 97.2 35.7 94.1 55.4 44.6 0.85 High-STEACS HEART 3 186 411 337 11 97.4 35.6 94.7 55.0 44.7 0.85 Causes of MACE Conclusion The ESC 0/3-h and High-STEACS algorithms identify almost all patients with low risk of NSTEMI, who are candidates for none or out-of-hospital follow-up. However, 9% of ruled out patients have MACE within 6 weeks. The combination of ESC algorithm and clinical risk scores markedly reduce the number of ruled out patients with MACE. </jats:sec