Fractional flow reserve derived from coronary CT angiography in stable coronary disease: a new standard in non-invasive testing?

Fractional flow reserve (FFR) measured during invasive coronary angiography is the gold standard for lesion-specific decisions on coronary revascularization in patients with stable coronary artery disease (CAD). Current guidelines recommend non-invasive functional or anatomic testing as a gatekeeper to the catheterization laboratory. However, the "holy grail" in non-invasive testing of CAD is to establish a single test that quantifies both coronary lesion severity and the associated ischemia. Most evidence to date of such a test is based on the addition of computational analysis of FFR to the anatomic information obtained from standard-acquired coronary CTA data sets at rest (FFRCT). This review summarizes the clinical evidence for the use of FFRCT in stable CAD in context to the diagnostic performance of other non-invasive testing modalities. Key Points • The process of selecting appropriate patients for invasive coronary angiography is inadequate • Invasive fractional flow reserve is the standard for assessing coronary lesion-specific ischemia • Fractional flow reserve may be derived from standard coronary CT angiography (FFR CT ) • FFR CT provides high diagnostic performance in stable coronary artery disease.

The relation between coronary artery calcification in asymptomatic subjects and both traditional risk factors and living in the city centre: a DanRisk substudy.

OBJECTIVE: To evaluate the association between the risk factor for living in the city centre as a surrogate for air pollution and the presence of coronary artery calcification (CAC) in a population of asymptomatic Danish subjects. DESIGN AND SUBJECTS: A random sample of 1825 men and women of either 50 or 60 years of age were invited to take part in a screening project designed to assess risk factors for cardiovascular disease (CVD). Noncontrast cardiac computed tomography was performed on all subjects, and their Agatston scores were calculated to evaluate the presence of subclinical coronary atherosclerosis. The relationship between CAC and several demographic and clinical parameters was evaluated using multivariate logistic regression. RESULTS: A total of 1225 individuals participated in the study, of whom 250 (20%) were living in the centres of major Danish cities. Gender and age showed the greatest association with the presence of CAC: the odds ratio (OR) for men compared with women was 3.2 [95% confidence interval (CI) 2.5-4.2; P < 0.0001], and the OR for subjects aged 60 versus those aged 50 years was 2.2 (95% CI 1.7-2.8; P < 0.0001). Other variables independently associated with the presence of CAC were diabetes and smoking with ORs of 2.0 (95% CI 1.1-3.5; P = 0.03) and 1.9 (95% CI 1.4-2.5, P < 0.0001), respectively. The adjusted OR for subjects living in city centres compared to those living outside was 1.8 (95% CI 1.3-2.4; P = 0.0003). CONCLUSION: Both conventional risk factors for CVD and living in a city centre are independently associated with the presence of CAC in asymptomatic middle-aged subjects.

Coronary dual source multi detector computed tomography in patients suspected of coronary artery disease: prevalence of incidental extra-cardiac findings.

OBJECTIVES: (1) To establish the prevalence of incidental extra-cardiac findings (ECFs) in coronary multi detector computed tomography (CCT) performed in a large, homogeneous cohort of patients suspected of coronary artery disease (CAD). (2) To examine whether any association can be established between ECFs and pretest risk as determined by conventional risk factors for CAD, the Diamond-Forrester risk model or coronary artery calcium scores. (3) To assess cost related to extra-cardiac examinations. DESIGN: Retrospective study of consecutive patients who had CCT performed. A large field of view was recreated from the non-enhanced CT scan and evaluated by a radiologist for incidental ECFs. SUBJECTS: Patients with chest pain referred to CTA by a cardiologist. RESULTS: In 1383 patients a total of 481 ECFs were indentified, 378 minor (meaning no follow-up was needed) and 103 major ECFs (ECF followed up clinically and/or with additional imaging), in a total of 393 (28%) patients. 85 (6%) patients had one major ECF and 9 (0.7%) patients had two major ECFs. In 19 (4 cases of malignancy) patients the major ECF had therapeutic consequences. Significant positive associations were found between age and smoking, respectively and the presence of ECFs. The cost estimate of saving one life from malignant disease based on ECF examinations is 40,190€. CONCLUSION: Incidental extra-cardiac findings are common, sometimes revealing serious, even malignant disease. Diagnostic follow-up of major ECFs seems to be cost-effective in a Danish clinical setting. We recommend investigating a large field of view for incidental ECFs following CCT.

Long term risk stratification of patients with acute coronary syndromes: characteristics of troponin T testing and continuous ST segment monitoring.

OBJECTIVE: To examine the long term prognostic characteristics of troponin T testing and continuous multi-lead ST segment monitoring in combination with clinical and 12 lead ECG risk indicators in patients with acute coronary syndromes (ACS). PATIENTS AND DESIGN: Patients with suspected ACS (n = 213) were studied. Troponin T was analysed in blood samples collected during the first 12 hours after admission. Continuous vectorcardiography ST segment monitoring was performed for 24 hours and the number of ST vector magnitude episodes was registered. Patients were followed up for a median of 28 months. The end point was a composite of cardiac death and acute myocardial infarction. RESULTS: Thirty eight (18%) patients reached the composite end point. The median (interquartile range) time from study inclusion to the time of the composite end point was longer for patients predicted to be at risk by troponin T testing (n = 27) than for those predicted to be at risk by ST segment monitoring (n = 20) (8.4 (0.2-15) months v 0.3 (0.1-4.3) months, p = 0.04). Significant univariate predictors of the composite end point were age > or = 65 years, diabetes, previous myocardial infarction, congestive heart failure, use of beta blockers or diuretics at admission, 12 lead ECG ST segment depression at admission, troponin T concentration > or = 0.10 microg/l, and > or = 1 ST vector magnitude episodes. Age > or = 65 years, previous myocardial infarction, and troponin T concentration > or = 0.10 microg/l provided independent prognostic information after multivariate analysis of potential risk variables. The prognostic value of transient ischaemic episodes in ACS seems to be confined to the short term. CONCLUSIONS: Both biochemical and continuous ECG markers reflect an increased risk for patients with ACS; however, the methods exhibit different temporal risk characteristics.

Are we underestimating the full potential of early thrombolytic treatment in patients with acute myocardial infarction?

Use of the Boersma curve in order to describe the beneficial effect of thrombolytic treatment at different treatment delays seems questionable, because the curve may underestimate the favourable prognostic effects of early thrombolysis in patients with acute myocardial infarction

Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease.

AIM: Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD. METHODS AND RESULTS: Three hundred and twenty patients were randomized to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor, or unfractionated heparin. There were no significant differences between the treatment groups in fibrinogen or C-reactive protein levels. Overall, the fibrinogen levels were significantly increased in the first 24-96 h and still elevated at 30 days. The C-reactive protein levels showed a more pronounced increase during the first 24-96 h, but then markedly decreased over 30 days. Troponin-positive compared to troponin-negative patients had higher fibrinogen and C-reactive protein levels up to 96 h, although there was an increase compared to pre-treatment levels in both groups. A high fibrinogen level (pre-treatment top tertile) was associated with an increased rate of death or myocardial (re-)infarction at 30 days, 13% vs 5.6%, P=0.03, and increased long-term mortality. A high C-reactive protein level was related to increased 30-day mortality, 4% vs 0%, P=0.01. CONCLUSION: Myocardial cell injury was related to a high degree of inflammation, only some of which is an acutephase response due to tissue damage. The rise in fibrinogen was sustained, which might reflect low grade inflammation with long-term risk of thrombosis. The transient elevation of C-reactive protein levels might indicate a propensity to a pronounced inflammatory response and is associated with increased mortality.

Telemedicine used for remote prehospital diagnosing in patients suspected of acute myocardial infarction.

INTRODUCTION: In patients with acute myocardial infarction (AMI), considerable time elapses from symptom onset until initiation of thrombolytic therapy or primary percutaneous coronary intervention. Prehospital diagnosing can reduce time delays, and remote diagnosing using telemedicine may be appropriate in areas and countries where ambulances are not staffed with physicians. OBJECTIVES: To evaluate whether it was technically feasible for physicians at a remote university hospital to diagnose ST-segment-elevation-AMI (AMI(STelev)) in patients suspected of AMI, who were transported by ambulances to a local hospital. To determine associated prehospital delays and in-hospital treatment delays. METHODS: Patients carried in telemetry equipped ambulances had 12-lead electrocardiograms (ECGs) acquired as soon as possible. En route to the local hospital the ECGs were transmitted to a remote university hospital, by use of the GSM-system. The physician on call at the university hospital interviewed the patients, who were provided with cellular phone headsets, and alerted the local hospital if signs of AMI(STelev), bundle-branch-block-AMI or malignant arrhythmia were detected. Patients transported by traditional ambulances were included in a prospective control group. RESULTS: In 214 (86%) of 250 patients prehospital diagnosing was successful. Geographically related transmission problems were the primary reason for failure. Ninety-eight per cent of transmitted electrocardiograms and obtained history takings were technically acceptable for diagnostic purposes. Door-to-needle times were shorter amongst patients with AMI(STelev) who were subjected to prehospital diagnosing (n = 13) as compared with patients transported by traditional ambulances (n = 14) (38 vs. 81 min) (P = 0.004). CONCLUSIONS: It was technically feasible to use telemedicine for remote prehospital diagnosing of patients suspected of AMI. Patients subjected to prehospital diagnosing had shorter door-to-needle times compared with a prospective control group.

Positional changes of spatial QRS- and ST-segment variables in normal subjects: implications for continuous vectorcardiography monitoring during myocardial ischemia.

Electrocardiographic QRS- and ST-segment changes are to be expected during changes in body posture. We prospectively analyzed the influence of changes in body position on continuous vectorcardiography monitoring of QRS-vector difference (QRS-VD) and ST change-vector magnitude (STC-VM) according to the currently used criteria of myocardial ischemia in 21 normal subjects. Fifteen (71%) and 6 (29%) subjects had significant positional QRS-VD and STC-VM changes, respectively. Vectorcardiography changes were most frequent and pronounced in the left lateral position. An alternative to the existing criterion of ischemia is proposed to improve the specificity of STC-VM. Subjects with positional QRS-VD changes had higher mean STC-VM values as compared with those without such changes. Otherwise no characteristics among those with positional vectorcardiography changes could be identified. There was no statistically significant association between positional QRS-VD and STC-VM changes (R = .13, P = .57). We conclude that the clinical use of QRS-VD in its present form for continuous vectorcardiography monitoring of myocardial ischemia seems to be of limited practical value, because of the presence of frequent "pseudo-ischemic" changes. STC-VM seems to have a significant potential of continuous vectorcardiography monitoring. However, an indicator of body position change or even an algorithm enabling on-line correction for positional vectorcardiography changes seems to be essential to improve the accuracy of this technique in identifying myocardial ischemia.

A technical approach for optimizing surveillance of patients with unstable coronary syndromes: continuous vectorcardiography ischemic monitoring.

Continuous vectorcardiography ischemic monitoring (VCG) is a noninvasive technique which has contributed much to our understanding of the dynamics of acute coronary syndromes. For risk assessment of patients with unstable angina pectoris or non-Q-wave myocardial infarction, VCG shows important prognostic power which is further enhanced by its combination with the measurement of highly sensitive and specific biochemical markers of myocardial injury. VCG surveillance after revascularization therapy of Q-wave myocardial infarction is widely accepted because of its potential of assessing vessel patency, of estimating infarct size, and of revealing residual myocardial ischemia. Valuable prognostic information is available in real time with VCG, and treatment strategies may be based upon more reliable grounds. In this survey, the VCG technique is presented together with the most frequently used vectorcardiographic variables. Further, the use of the method for risk stratification of patients with unstable coronary syndromes is also described.

Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study Group.

BACKGROUND: This study was designed to assess the efficacy and safety of intravenous dofetilide in acute termination of atrial fibrillation (AF) and flutter (AFL). Dofetilide, an investigational class III antiarrhythmic agent, selectively inhibits the rapid component of the delayed rectifier potassium current, thus prolonging the effective refractory period and duration of the action potential. Dofetilide can be administered intravenously and has a rapid onset of electrophysiologic action. METHODS AND RESULTS: Ninety-six patients with AF (n = 79) or AFL (n = 17) with a median arrhythmia duration of 62 days (range 1 to 180) were randomized to placebo (n = 30) or 8 micrograms/kg IV dofetilide (n = 66) over 30 minutes. Conversion was defined as termination of the atrial arrhythmia within 3 hours from the start of infusion. The conversion rate was 30.3% after dofetilide and 3.3% after placebo (P <.006). Conversion rate was higher in AFL than in AF: 64% versus 24% (P =. 012). In nonconverters, there was no statistically significant difference between the change in heart rate among the dofetilide-treated compared with the placebo-treated patients (P =. 42). Torsade de pointes ventricular tachycardia developed in 2 patients (3%). In both patients, drug infusion was discontinued before the event because of prolongation of the QT interval. CONCLUSIONS: Intravenous dofetilide is effective in acute termination of AF and AFL of medium duration, with a particularly high efficacy rate in AFL. A small but serious risk of proarrhythmia must be anticipated.

Temporal and positional variability of the ST segment during continuous vectorcardiography monitoring in healthy subjects.

Continuous vectorcardiography ST-segment monitoring (cVST) is a well-established method in the diagnosis and risk evaluation of patients with acute myocardial ischemia. Previous investigations have demonstrated that electrocardiographic ST-segment changes are to be expected, during both repeated measurements and changes in body position. We prospectively analyzed the influence of spontaneous temporal variation (technical and biological noise) and changes in body position on the ST segment (ST-vector magnitude [ST-VM]) during cVST of 21 healthy human subjects. The 95% expectancy range of the spontaneous intraindividual ST-VM variation was found to be +/-8 microV for the error of measurement, and +/-14 and +/-24 microV during 24-hour and day-to-day cVST measurements, respectively. Positional ST-segment changes in the orthogonal leads were frequent, especially in leads X and Z, and in the left lateral position. Positional orthogonal ST-segment changes resulted in significant ST-VM changes in two of seven subjects. It is concluded that the low spontaneous temporal ST-VM variation must be considered as good reproducibility. Moreover, the present findings support currently used ST-VM ischemia criteria. However, the impact of positional changes on ST-VM seems to be of importance (with the possibility of false-positive results) and should be taken into account during cVST.

Admission risk assessment by cardiac troponin T in unstable coronary artery disease: additional prognostic information from continuous ST segment monitoring. TRIM study group. Thrombin Inhibition in Myocardial Ischemia.

OBJECTIVES: We investigated whether the addition of 24 h of continuous vectorcardiography ST segment monitoring (cVST) for an early (within 24 h of the latest episode of angina) determination of cardiac troponin T (cTnT) could provide additional prognostic information in patients with unstable coronary artery disease (UCAD), i.e., unstable angina and non-Q wave myocardial infarction. BACKGROUND: Determination of cTnT at admission and cVST are individually reported to be valuable techniques for the risk assessment of patients with UCAD. METHODS: Two hundred and thirty-two patients suspected of UCAD were studied. Patients were followed for 30 days, and the occurrence of cardiac death or acute myocardial infarction (AMI) were registered. RESULTS: One ST segment episode or more (relative risk [RR] 7.43, p = 0.012), a cTnT level > or = 0.20 microg/liter (RR 3.85, p = 0.036) or prestudy medication with calcium antagonists (RR 3.31, p = 0.041) were found to carry independent prognostic information after multivariate analysis of potential risk variables. By combining a cTnT determination and subsequent cVST for 24 h, subgroups of patients at high (25.8%) (n = 31), intermediate (3.1%) (n = 65) and low risk (1.7%) (n = 117) of death or AMI could be identified. CONCLUSIONS: Twenty-four hours of cVST provides additional prognostic information to that of an early cTnT determination in patients suspected of having UCAD. The combination of biochemical and electrocardiographic methods provides powerful and accurate risk stratification in UCAD.