Stephanie Lehrke

Determinants of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque

Objective To understand the determinants of troponin release in patients with stable coronary artery disease (CAD) by comparing high sensitive troponin T (hsTnT) levels with computed tomography angiography (CTA) characteristics of atherosclerotic plaque. Methods hsTnT was determined in 124 consecutive patients with stable angina, who underwent clinically indicated 256-slice CTA for suspected CAD. CTA was used to assess (1) coronary calcification; (2) stenosis severity; (3) non-calcified plaque volume; (4) plaque composition (soft or mixed, described as ‘non-calcified’ versus calcified) and (5) the presence of vascular remodeling in areas of non-calcified plaque. Results All CT scans were performed without adverse events, and diagnostic image quality was achieved in 1830/1848 available coronary segments (99.0%). In 29/124 patients, hsTnT was ≥14 pg/ml (range 14.0–34.4). Weak, albeit significant, correlations were found between hsTnT and calcium scoring (r=0.45, p<0.001), while a stronger correlation was found between hsTnT and the total non-calcified plaque burden (r=0.79, p<0.001). Patients with non-calcified plaque (n=44) yielded significantly higher hsTnT values than those with normal vessels (n=46) or those with only calcified lesions (n=26), (12.6±5.2 vs 8.3±2.6 and 8.8±3.0 pg/ml, respectively, p<0.001). Furthermore, those with remodeled non-calcified plaque (n=8) showed even higher hsTnT values of 26.3±6.5 pg/ml than all other groups (p<0.001). This allowed the identification of patients with remodeled non-calcified plaque by hsTnT with high accuracy (area under the curve=0.90, SE=0.07, 95% CI 0.84 to 0.95). Conclusions Chronic clinically silent rupture of non-calcified plaque with subsequent microembolisation may be a potential source of troponin elevation. In light of recent imaging studies, in which patients with positively remodeled non-calcified plaque were shown to be at high risk for developing acute coronary syndromes, hsTnT may serve as a biomarker for such ‘vulnerable’ coronary lesions even in presumably stable CAD.

Use of cardiovascular magnetic resonance for risk stratification in chronic heart failure: prognostic value of late gadolinium enhancement in patients with non-ischaemic dilated cardiomyopathy

Objective Owing to its variable clinical course, risk stratification is of paramount importance in non-ischaemic dilated cardiomyopathy (DCM). The goal of this study was to investigate the long-term prognostic significance of late gadolinium enhancement (LGE) as detected by contrast-enhanced cardiovascular magnetic resonance (CE-CMR) in patients with DCM. Design Observational cohort study. Setting University hospital. Patients 184 consecutive patients with DCM. Measurements CE-CMR was performed on a 1.5 T clinical scanner. Presence, extent and patterns of LGE were determined by two independent observers. Outcome measures Patients were followed for the composite end point of cardiac death, hospitalisation for decompensated heart failure, or appropriate implantable cardioverter defibrillator discharge for a mean±SEM of 685±30 days. Results LGE was detected in 72/184 patients (39%) and was associated with a lower left ventricular (LV) ejection fraction (31% (20.9–42.2%) vs 44% (33.1–50.9%), p<0.001), higher LV end-diastolic volume index (133 (116–161) ml/m2 vs 109 (92.7–137.6) ml/m2, p<0.001) and higher LV mass (80 (67.1–94.8) g/m2 vs 65.8 (55.2–82.9) g/m2, p<0.001). Patients in whom LGE was present were more likely to experience the composite end point (15/72 vs 6/112, p=0.002). Receiver operating characteristic curve analysis revealed a LGE of >4.4% of LV mass as optimal discriminator for the composite end point. When entered into multivariate Cox regression analysis, LGE retained its independent predictive value, yielding an associated HR of 3.4 (95% CI 1.26 to 9). Conclusion The presence of LGE in this large DCM patient cohort is associated with pronounced LV remodelling, functional impairment and an adverse outcome. Further research is necessary to determine whether these findings will aid the clinical management of DCM patients.

Assessment of disease severity and outcome in patients with systemic light-chain amyloidosis by the high-sensitivity troponin T assay

Cardiac biomarkers provide prognostic information in light-chain amyloidosis (AL). Thus, a novel high-sensitivity cardiac troponin T (hs-TnT) assay may improve risk stratification. hs-TnT was assessed in 163 patients. Blood levels were higher with cardiac than renal or other organ involvement and were related to the severity of cardiac involvement. Increased sensitivity was not associated with survival benefit. Forty-seven patients died during follow-up (22.3 ± 1.0 months). Nonsurvivors had higher hs-TnT than survivors. Outcome was worse if hs-TnT more than or equal to 50 ng/L and best less than 3 ng/L. Survival of patients with hs-TnT 3 to 14 ng/L did not differ from patients with moderately increased hs-TnT (14-50 ng/L), but was worse if interventricular septum was more than or equal to 15 mm. Discrimination according to the Mayo staging system was only achieved by the use of the hs-TnT assay, but not by the fourth-generation troponin T assay. Multivariate analysis revealed hs-TnT, NT-proBNP, and left ventricular impairment as independent risk factors for survival. hs-TnT and NT-proBNP predicted survival, even after exclusion of patients with impaired renal function. Plasma levels of the hs-TnT assay are associated with the clinical, morphologic, and functional severity of cardiac AL amyloidosis and could provide useful information for clinicians on cardiac involvement and outcome.

Assessment of myocardial deformation with cardiac magnetic resonance strain imaging improves risk stratification in patients with dilated cardiomyopathy.

AIMS To investigate the prognostic impact of left-ventricular (LV) cardiac magnetic resonance (CMR) deformation imaging in patients with non-ischaemic dilated cardiomyopathy (DCM) compared with late-gadolinium enhancement (LGE) quantification and LV ejection fraction (EF). METHODS AND RESULTS A total of 210 subjects with DCM were examined prospectively with standard CMR including measurement of LGE for quantification of myocardial fibrosis and feature tracking strain imaging for assessment of LV deformation. The predefined primary endpoint, a combination of cardiac death, heart transplantation, and aborted sudden cardiac death, occurred in 26 subjects during the median follow-up period of 5.3 years. LV radial, circumferential, and longitudinal strains were significantly associated with outcome. Using separate multivariate analysis models, global longitudinal strain (average of peak negative strain values) and mean longitudinal strain (negative peak of the mean curve of all segments) were independent prognostic parameters surpassing the value of global and mean LV radial and circumferential strain, as well as NT-proBNP, EF, and LGE mass. A global longitudinal strain greater than -12.5% predicted outcome even in patients with EF < 35% (P < 0.01) and in those with presence of LGE (P < 0.001). Mean longitudinal strain was further investigated using a clinical model with predefined cut-offs (EF < 35%, presence of LGE, NYHA class, mean longitudinal strain greater than -10%). Mean longitudinal strain exhibited an independent prognostic value surpassing that provided by NYHA, EF, and LGE (HR = 5.4, P < 0.01). CONCLUSION LV longitudinal strain assessed with CMR is an independent predictor of survival in DCM and offers incremental information for risk stratification beyond clinical parameters, biomarker, and standard CMR.

Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene

BackgroundMutations in MYBPC3 encoding myosin binding protein C belong to the most frequent causes of hypertrophic cardiomyopathy (HCM) and may also lead to dilated cardiomyopathy (DCM). MYBPC3 mutations initially were considered to cause a benign form of HCM. The aim of this study was to examine the clinical outcome of patients and their relatives with 18 different MYBPC3 mutations.Methods87 patients with HCM and 71 patients with DCM were screened for MYBPC3 mutations by denaturing gradient gel electrophoresis and sequencing. Close relatives of mutation carriers were genotyped for the respective mutation. Relatives with mutation were then evaluated by echocardiography and magnetic resonance imaging. A detailed family history regarding adverse clinical events was recorded.ResultsIn 16 HCM (18.4%) and two DCM (2.8%) index patients a mutation was detected. Seven mutations were novel. Mutation carriers exhibited no additional mutations in genes MYH7, TNNT2, TNNI3, ACTC and TPM1. Including relatives of twelve families, a total number of 42 mutation carriers was identified of which eleven (26.2%) had at least one adverse event. Considering the twelve families and six single patients with mutations, 45 individuals with cardiomyopathy and nine with borderline phenotype were identified. Among the 45 patients, 23 (51.1%) suffered from an adverse event. In eleven patients of seven families an unexplained sudden death was reported at the age between 13 and 67 years. Stroke or a transient ischemic attack occurred in six patients of five families. At least one adverse event occurred in eleven of twelve families.ConclusionMYBPC3 mutations can be associated with cardiac events such as progressive heart failure, stroke and sudden death even at younger age. Therefore, patients with MYBPC3 mutations require thorough clinical risk assessment.

Strain-Encoded CMR for the Detection of Inducible Ischemia During Intermediate Stress

OBJECTIVES This study sought to evaluate the diagnostic accuracy of strain-encoded cardiac magnetic resonance (SENC) for the detection of inducible ischemia during intermediate stress. BACKGROUND High-dose dobutamine stress cardiac magnetic resonance (DS-CMR) is a well-established modality for the noninvasive detection of coronary artery disease (CAD). However, the assessment of cine scans relies on the visual interpretation of wall motion, which is subjective, and modalities that can objectively and quantitatively assess the time course of myocardial strain response during stress are lacking. METHODS Stress-induced ischemia was assessed by wall motion analysis and by SENC in 80 patients with suspected or known CAD and in 18 healthy volunteers who underwent DS-CMR in a clinical 1.5-T scanner. Quantitative coronary angiography was used as the standard reference for the presence of CAD (> or =50% diameter stenosis). RESULTS On a patient level, 46 of 80 patients (58%) had CAD, including 20 with single-vessel, 18 with 2-vessel, and 8 with 3-vessel disease. During peak stress, SENC correctly detected ischemia in 45 versus 38 of 46 patients with CAD (7 additional correct findings for SENC), yielding significantly higher sensitivity than cine (98% vs. 83%, p < 0.05). No patients were correctly diagnosed by cine and missed by SENC. During intermediate stress, SENC showed diagnostic value similar to that provided by cine imaging only during peak dobutamine stress (sensitivity of 76% vs. 83%, specificity of 88% vs. 91%, and accuracy of 81% vs. 86%; p = NS for all). Quantification analysis demonstrated that strain rate response is a highly sensitive marker for the detection of inducible ischemia (area under the curve = 0.96; SE = 0.01; 95% confidence interval: 0.93 to 0.99) that precedes the development of inducible wall motion abnormalities and already significantly decreases with moderate 40% to 60% coronary lesions. CONCLUSIONS Using SENC, CAD can be detected during intermediate stress with similar accuracy to that provided by cine only during peak stress. By this approach, patient safety may be improved during diagnostic procedures within lower time spent (Strain-Encoded Cardiac Magnetic Resonance Imaging for Dobutamine Stress Testing; NCT00758654).

Risk Stratification in Patients With Inferior Acute Myocardial Infarction Treated by Percutaneous Coronary Interventions The Role of Admission Troponin T

BackgroundCardiac troponin T (cTnT) elevations on admission indicate a high-risk subgroup of patients with ST-segment elevation acute myocardial infarction (AMI). This finding has been attributed to less effective reperfusion after thrombolytic therapy. The aim of this study was to determine the role of admission cTnT on the efficacy of percutaneous coronary interventions (PCIs) in inferior AMI. Methods and ResultsOne hundred fifty-nine consecutive patients with inferior ST-segment AMI were enrolled and followed up for a mean of 448 days. Patients were stratified by cTnT on admission. A cTnT ≥0.1 &mgr;g/L was found in 58% of patients. These patients had longer time intervals from onset of symptoms to therapy (P <0.001) and higher 30-day (10.8% versus 1.5%, P =0.027) and long-term (17.2% versus 4.5%, P =0.023) cardiac mortalities. Rates of the combined end point of death, nonfatal reinfarction, and need for repeated target vessel revascularization procedures were not different in cTnT groups (log rank, 0.69;P =0.41). PCI was attempted in 93.3% of cTnT-positive and 98.5% cTnT-negative patients (P =0.24) but was less frequently successful in patients with cTnT ≥0.1 &mgr;g/L (77.9% versus 96.9%, P <0.001). Coronary stenting reduced 30-day and long-term cardiac mortality, particularly among cTnT-positive patients. In a multivariate analysis, cTnT indicated an ≈5-fold-higher risk (adjusted OR, 4.6; 95% CI, 0.79 to 27.11;P =0.089) and was a strong albeit not independent risk predictor. ConclusionsIn inferior AMI, a positive admission cTnT is associated with lower success rates of direct PCI and higher rates of cardiac events over the short and long term. These patients benefit from coronary stenting.

Strain-Encoded Cardiac Magnetic Resonance for the Evaluation of Chronic Allograft Vasculopathy in Transplant Recipients

The aim of our study was to investigate the ability of Strain‐Encoded magnetic resonance imaging (MRI) to detect cardiac allograft vasculopathy (CAV) in heart transplantation (HTx)‐recipients. In consecutive subjects (n = 69), who underwent cardiac catheterization, MRI was performed for quantification of myocardial strain and perfusion reserve. Based on angiographic findings subjects were classified: group A including patients with normal vessels; group B, patients with stenosis <50%; and group C, patients with severe CAV (stenosis ≥ 50%). Significant correlations were observed between myocardial perfusion reserve with peak systolic strain (r =−0.53, p < 0.001) and with mean diastolic strain rate (r = 0.82, p < 0.001). Peak systolic strain and strain rate were significantly reduced only in group C, while mean diastolic strain rate and myocardial perfusion reserve were already reduced in group B and A. Myocardial perfusion reserve and mean diastolic strain rate had higher accuracy for the detection of CAV (AUC = 0.95, 95% CI = 0.87–0.99 and AUC = 0.93, 95% CI = 0.84–0.98, respectively) and followed peak systolic strain and strain rate (AUC = 0.80, 95% CI = 0.69–0.89 and AUC = 0.78, 95% CI = 0.67–0.87, respectively). Besides the quantification of myocardial perfusion, the estimation of the diastolic strain rate is a useful parameter for CAV assessment. In combination with the clinical evaluation, these parameters may be effective tools for the routine surveillance of HTx‐recipients.

Image quality and radiation dose in 256-slice cardiac computed tomography: Comparison of prospective versus retrospective image acquisition protocols

PURPOSE To assess coronary artery image quality and patient radiation exposure in patients who underwent clinically indicated 256-slice CTA. METHODS Consecutive patients (n=193) underwent 256-slice CTA, using (1) retrospective gating without radiation dose modulation, (2) retrospective gating with radiation dose modulation and (3) prospective gating. Image quality was determined by consensus of two experienced observers using a 5-grade scale. The effective dose was calculated. RESULTS In all patients, CTA was performed without adverse events. Retrospective CTA was assessed in 39 patients with and 39 without dose modulation, while 115 patients underwent prospective CTA. Heart rate was related to image quality with all protocols (r=0.46, p<0.001). Up to a heart rate of 75 bpm no significant difference in overall image quality was observed for all three protocols, while no significant differences could be observed between retrospective CTA with and without dose modulation for any segments or heart rates. Prospective and retrospective CTA with dose modulation showed radiation savings of ∼75 % and ∼30 %, respectively compared to retrospective CTA without dose modulation (p<0.001). CONCLUSIONS In patients with heart rates up to 75 bpm prospective CTA should be the first choice acquisition protocol. For heart rates >75 bpm, retrospective CTA with dose modulation should be considered.

Tirofiban optimizes platelet inhibition for immediate percutaneous coronary intervention in high-risk acute coronary syndromes

It was the aim of this study to compare the efficacy of early platelet inhibition by 600 mg clopidogrel and acetylsalicylic acid (ASA) to a triple therapy including a glycoprotein IIb-IIIa receptor blocker. Immediate percutaneous coronary intervention (PCI) is recommended for high-risk acute coronary syndromes. In this setting the efficacy of platelet inhibition is unknown. One hundred patients were randomized to receive ASA and 600 mg clopidogrel, or additional open-label tirofiban (bolus of 10 microg/kg body weight followed by continued infusion of 0.15 microg/kg body weight per minute) as soon as non-ST-segment elevation myocardial infarction was diagnosed. The primary endpoint was the reduction of infarct size determined by post-interventional increases of cardiac troponin T (cTnT). Secondary endpoints included platelet function measured by optical and impedance aggregometry using ADP (5 and 20 microM) and collagen (1 microg/ml) as platelet agonists. Tirofiban maximized platelet inhibition (p < 0.0001) immediately and was associated with significantly lower post-interventional cTnT concentrations (p = 0.0352). In the dual platelet inhibition arm, clopidogrel was not effective in 69% of patients at the time of coronary intervention, and still in 47%, if pre-treatment time was >120 minutes. The frequency of cardiovascular (death, myocardial infarction, revascularization) and bleeding events was comparable. Platelet aggregation is not adequately inhibited in cTnT-positive patients in the setting of immediate PCI with very short pre-treatment times. Only tirofiban provided consistent and effective inhibition of platelet aggregation at the time of immediate or very early invasive therapy.