Britta Goldmann

Prehospital testing for troponin T in patients with suspected acute myocardial infarction

BACKGROUND Cardiac troponin T (TnT) is a highly sensitive and specific marker for myocardial damage and can be detected early after myocardial injury. Our hypothesis was to use TnT as an objective marker to verify acute myocardial infarction before hospital admission. METHODS AND RESULTS We evaluated the sensitivity of a rapid qualitative assay for serum TnT for the detection of acute myocardial infarction in the ambulance and assessed the predictive value of a positive prehospital TnT test for death and myocardial infarction during 6-months of follow-up. The study, conducted in an urban area, included 158 consecutive patients with suspected acute myocardial infarction (93 men aged 69 +/- 13 years). A myocardial infarction was confirmed in 40 and excluded in 118 patients. The prehospital TnT test was positive in 11 patients, of whom 7 had acute myocardial infarction. Fifty-three patients had a positive test result at hospital admission, with evidence of myocardial infarction in 39 of them. The sensitivity to acute myocardial infarction was 18% for the prehospital and 98% for the in-hospital test with 78% and 88% specificity, respectively. During follow-up, patients with a positive prehospital TnT test result had cardiac events more often (9 of 11) than patients with a negative result (26 of 147; P <.0001). CONCLUSIONS In areas with short transport times to the patient the rapid TnT test performed at the point of care identified only a minority of the patients with acute myocardial infarction. A positive prehospital TnT test result seems to be an objective marker for a worse outcome in patients presenting with suspected acute myocardial infarction.

Troponin: an important prognostic marker and risk-stratification tool in non-ST-segment elevation acute coronary syndromes.

Over the past decade, there has been a progressive evolution of cardiac marker testing in patients with acute coronary syndromes (ACS). This has not only resulted in a dramatic shift in how we view the diagnosis of myocardial infarction (MI), but it has also extended the role of cardiac marker testing into risk stratification and guidance of treatment decisions. By the year 2000, the development of highly sensitive and cardiac-specific troponin assays had resulted in a consensus change in the definition of MI, placing increased emphasis on cardiac-marker testing with troponins as the new gold standard. Furthermore, and perhaps more importantly, the role of the troponins as superior markers of subsequent cardiac risk in ACS patients became firmly established. Most recently, the supportive role of these markers in identifying patients with ACS who may derive particular benefit from potent anti-thrombotic and anti-platelet therapy or early invasive treatment strategies has been demonstrated. This paper will review the evolution of these important roles of troponin testing for risk stratification in ACS.

Neutrophil activation precedes myocardial injury in patients with acute myocardial infarction

Myeloperoxidase (MPO), a heme protein abundantly expressed and secreted by polymorphonuclear neutrophils (PMN), has emerged as a critical mediator in coronary atherosclerosis. Retrospective analyses have suggested that free plasma levels of MPO predict adverse outcome in patients with low troponin T (TnT) levels who subsequently experience myocardial injury. The aim of this study was to evaluate the time course of MPO plasma levels in the early stages of acute myocardial infarction (AMI). Of 155 consecutive patients hospitalized for acute coronary syndromes, 38 presenting within 2 h of the onset of symptoms and subsequently diagnosed for AMI were included in the study. Serial blood samples taken between 1 and 24 h after the onset of chest pain were analyzed for MPO, TnT, creatine kinase MB, myoglobin, and high sensitive C-reactive protein. Fifty patients with angiographically proven but stable coronary artery disease (CAD) served as controls. In contrast to all other investigated markers, MPO was markedly elevated within 2 h of symptom onset in patients with AMI. Heparin, which is known to increase MPO plasma levels in patients with stable CAD, had no effect on MPO plasma levels in AMI patients. High levels of MPO plasma levels at the time of admission and the rapid peak of free plasma MPO levels after the onset of symptoms suggests that PMN activation is an early event in AMI and potentially precedes myocardial injury.

Aetiology of mitral regurgitation differentially affects 2-year adverse outcomes after MitraClip therapy in high-risk patients.

To assess, and identify predictors of, 2‐year adverse outcomes of surgical high‐risk patients after successful MitraClip therapy (MC), differentiated by the aetiology of mitral regurgitation (MR).

Diagnostic value of MPO plasma levels in patients admitted for suspected myocardial infarction

BACKGROUND Besides its well-established role in atherosclerosis, myeloperoxidase (MPO) has gained attention as a prognostic indicator in cardiovascular disease. Previous studies assessed MPO retrospectively and at a single time point. The current study aimed to evaluate the prognostic information of MPO prospectively and in consecutive measurements in patients presenting with chest pain. METHODS MPO plasma levels were determined in 274 consecutive chest pain patients admitted to the emergency room. RESULTS A total of 100 patients (36.5%) were finally diagnosed for acute myocardial infarction (AMI). Patients with AMI had significantly higher MPO levels than patients without AMI. Importantly, MPO levels were elevated in patients finally diagnosed for AMI even when troponin I (TNI) was negative (cutoff: 0.032 ng/ml). Overall, MPO yielded a negative predictive value (NPV) of 85.5% (95% confidence interval (CI): 82.6-88.4) and a sensitivity for diagnosing AMI of 80.0% (95% CI: 75.8-84.2) compared to a NPV of 91.7% (95% CI: 89.5-94.0) and a sensitivity of 85.9% (95% CI: 82.3-89.5) for TNI. For patients with a symptom onset of ≤ 2 h the sensitivity of MPO increased to 95.8% (95% CI: 93.7-97.9) whereas the sensitivity of TNI dropped to 50.0% (95% CI: 44.8-55.2). The negative predictive value of MPO for this group of patients was 95.6% (95% CI: 94.0-97.3) compared to 73.3% (95% CI: 69.8-76.9) for TNI. DISCUSSION The current data underscore the role of MPO as diagnostic marker in acute coronary disease; however the additive information derived from MPO is restricted to patients presenting in the early phase of symptom onset.

Total serum transforming growth factor-β1 is elevated in the entire spectrum of genetic aortic syndromes.

Total serum transforming growth factor‐beta 1 (tsTGF‐β1) is increased in patients with Marfan syndrome (MFS), but it has not been assessed in thoracic aortic aneurysm and dissection (TAAD), Loeys‐Dietz syndrome (LDS), and bicuspid aortic valve disease (BAVD).

Three-Year Clinical Outcome After 2nd-Generation Cryoballoon-Based Pulmonary Vein Isolation for the Treatment of Paroxysmal and Persistent Atrial Fibrillation : A 2-Center Experience

BACKGROUND Pulmonary vein isolation (PVI) using the 2nd-generation cryoballoon (CB2) for the treatment of atrial fibrillation (AF) has demonstrated encouraging acute and mid-term results. However, follow-up data on outcomes beyond 1 year are sparse. We investigated the 3-year outcome after PVI using the CB2.Methods and Results:100 patients with paroxysmal (PAF, 70/100 [70%] patients) or persistent AF (pAF, 30/100 [30%] patients) underwent CB2-based PVI in 2 experienced centers in Germany. Freeze-cycle duration was 240 s. After successful PVI a bonus freeze-cycle of the same duration was applied in the first 71 patients but was omitted in the following 29 patients. Phrenic nerve palsy occurred in 3 patients (3%); 2 patients were lost to follow-up. After a median follow-up of 38 (29-50) months, 59/98 (60.2%) patients remained in stable sinus rhythm (PAF: 48/70 (69%), pAF: 11/28 (39%) P=0.0084). In 32/39 (77%) patients with arrhythmia recurrence, a second ablation procedure using radiofrequency energy was conducted. Persistent PVI was noted in 76/125 (61%) PVs. After a mean of 1.37±0.6 procedures and a median follow-up of 35 (25-39) months, 77/98 (78.6%) patients remained in stable sinus rhythm (PAF: 56/70 (80%), pAF: 20/28 (71%), P=0.0276). CONCLUSIONS CB2-based PVI resulted in a 60.2% single-procedure and a 78.6% multiple-procedure success rate after 3 years. Repeat procedures demonstrated a high rate of durable PVI.

Gender-specific diagnostic performance of a new high-sensitivity cardiac troponin I assay for detection of acute myocardial infarction

Background: The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date. Methods: The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction. The troponin I concentration was determined on admission (0 hours) and 3 hours later. The diagnostic algorithm incorporated troponin I elevation above the gender-specific 99th percentile as well as predefined relative or absolute 3-hour changes in the troponin I concentration (delta). Results: The diagnostic criterion of troponin I above the 99th percentile resulted in a negative predictive value of 98.0% and 98.2% in men and women, respectively. For rule-in of non-ST-segment elevation myocardial infarction, the use of absolute deltas yielded higher positive predictive values and sensitivities compared to relative deltas. With detection rates of about 85% and 82% in men and women, respectively, non-ST-segment elevation myocardial infarction was diagnosed with a positive predictive value close to 84% in men and 80% in women. Conclusions: The investigational troponin I assay provides an excellent non-ST-segment elevation myocardial infarction rule out. With gender-specific differences, the application of absolute changes in troponin concentration was superior to relative changes to rule in patients with non-ST-segment elevation myocardial infarction.

Liberation of vessel-adherent myeloperoxidase reflects plaque burden in patients with stable coronary artery disease

OBJECTIVE Myeloperoxidase (MPO) has emerged as an important pathophysiological determinant of inflammatory vascular artery disease. It is appreciated that vessel immobilized, rather than circulating, MPO is critical for the progression of atherosclerotic lesions. The objective of this study was to investigate whether vessel-immobilized MPO is associated with the extent of coronary plaque burden. METHODS MPO plasma levels were determined by ELISA before and after heparin-release of vessel-bound MPO, to study the relation between vascular MPO deposition and densitometrically assessed coronary plaque burden in 77 patients with stable coronary artery disease. RESULTS Patients with a low increase in MPO plasma levels upon heparinization had a significantly smaller total plaque area and volume (12.1[IR:6.2-19.4]mm(2) vs. 19.8[IR:11.3-31.5]mm(2), p < 0.01; 27.8[IR:12.3-44.8]mm(3) vs. 55.2[IR:24.2-87.5]mm(3), p < 0.05). Multivariable linear regression revealed that ΔMPO was independently associated with plaque area, and that ΔMPO increased with the number of affected vessels. Selective sampling confirmed the predominant role of coronary MPO deposition. CONCLUSION Our data demonstrate that heparin-induced mobilization of vessel-bound MPO is closely linked to coronary plaque burden and thus further corroborate the evidence for the intimate involvement of this enzyme in vascular pathophysiology, as well as the importance of inflammation in atherosclerosis.

Risikostratifizierung des akuten Koronarsyndroms

Hintergrund: Der Begriff “akutes Koronarsyndrom” umfasst die akuten, lebensbedrohlichen Phasen der koronaren Herzerkrankung. Konventionelle Kriterien wie klinische Beschwerden, EKG-Veränderungen und CK-MB-Bestimmungen reichen in der Regel nicht aus, um die Patienten ohne ST-Strecken-Hebung sicher zu evaluieren. Troponinbestimmung: Anhand serieller Bestimmungen von kardialem Troponin T oder Troponin I gelingt es, innerhalb eines Zeitraums von etwa 6 Stunden die Patienten mit klinisch instabiler Angina herauszufiltern, die “minimale Myokardzellschäden” haben, welche der herkömmlichen Laborroutine entgehen. Diese Patienten haben ein dem klassischen Infarktpatienten vergleichbares Risiko hinsichtlich kardialer Ereignisse wie Myokardinfarkt und Tod. Ist der Troponinwert nicht erhöht, liegt das kardiale Risiko unter 1%. Schlussfolgerung: Zwar schließt ein fehlender Troponinnachweis das Vorliegen einer koronaren Herzerkrankung nicht aus, jedoch müssen vorrangig die Patienten mit erhöhtem Risiko frühzeitig stationär aufgenommen und behandelt werden. Bei diesen Patienten haben sich vor allem potente, antithrombotische Substanzen, wie zum Beispiel die Glykoprotein-IIb/IIIa-Rezeptorantagonisten, bewährt, die ohne oder begleitend mit einer Koronarintervention verabreicht wurden.Background: The spectrum of symptoms of patients with active ischemic heart disease ranges from silent ischemia to acute myocardial infarction and the extent of myocardial damage from reversible myocardial injury to extensive necrosis. The term “acute coronary syndrome” comprises this continuum. In particular the evaluation of patients without ST-segment elvalation is difficult, for clinical symptoms, ECG criteria and CK-MB measurements appear insufficient for appropriate risk stratification. Troponin Measurement: Serial measurements of either troponin T or I reliably detect minor myocardial damage in those patients, who are known to be at a higher risk for adverse cardiac events comparable to the risk of patients with acute myocardial infarction. Hence determination of troponins allow superior risk stratification contributing to early triage and therapeutic decision making. Without elevation of troponins the cardiac risk for death or myocardial infarction will not exceed 1 %. Conclusion: Patients with elevated troponins should be early hospitalized and further evaluated in order to begin efficacious therapy as soon as possible. These patients represent a high-risk subgroup of patients clinically classified as unstable angina, who might benefit from potential antithrombotic treatment such as low-molecular weight heparin or glycoprotein IIb/IIIa antagonists without or with revascularization strategies.