Wolfgang Kuebler

Diagnostic efficiency of troponin T measurements in acute myocardial infarction.

BackgroundThe present study was designed to evaluate the effliciency of a newly developed troponin T enzyme immunoassay for the detection of acute myocardial infarction. Methods and ResultsThe study comprised 388 patients admitted with chest pain and suspected myocardial infarction and 101 patients with skeletal muscle damage and additional suspected myocardial cell damage. Troponin T was elevated to more than twice the analytical sensitivity of the assay (0.5 μg/l) in all patients with non-Q wave (range, 1.2-5 μg/l) and Q wave infarction (range, 3-220 μg/l). Troponin T appeared in serum as early as 3 hours after onset of pain in 50% of the patients and remained elevated in all patients for more than 130 hours, revealing release kinetics of both free cytosolic and structurally bound molecules. The diagnostic efficiency of troponin T was superior to that of creatine kinase-MB (98% versus 97%) and remained at 98% until 5.5 days after admission, if patients with unstable angina were excluded from analysis. In the 79 patients with unstable angina, troponin T was elevated (range, 0.55-3.1 μg/l) in at least one blood sample from each of 37 patients (56%). Circulating troponin T was correlated to the presence of reversible ST segment or T wave changes on the electrocardiogram (p<0.005) and to the frequency of in-hospital complications. In the 101 patients with skeletal muscle damage and suspected additional cardiac muscle damage, troponin T was the most useful test; its efficiency was 89% or 94% (depending on the discriminator value used) as compared with 63% for creatine kinase-MB. ConclusionsThus, the data of the study indicate that the newly developed troponin T test improves the efficiency of serodiagnostic tools for the detection of myocardial cell necrosis as compared with conventionally used cardiac enzymes. (Circulation 1991;83:902–912)

Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction

In a previous study on the diagnostic efficiency of troponin T measurements in patients with suspected acute myocardial infarction (AMI), the authors found a high variability of troponin T serum concentration changes on day 1 in patients with AMI who underwent thrombolytic treatment. Therefore, the aims of the present study were to investigate the intracellular compartmentation of troponin T and to analyze the effects of AMI reperfusion on the appearance kinetics of cardiac troponin T in serum. Cardiac troponin T was measured with a newly developed bideterminant sandwich assay using cardiospecific, affinity-purified polyclonal antibodies and peroxidase-labeled monoclonal antibody. An unbound cytosolic troponin T pool was found in ultracentrifuged homogenates of myocardial tissue of different species ranging from 0.013 to 0.036 mg/g wet weight. The soluble troponin T molecule had electrophoretic properties identical to troponin T compartmented in the myofibrils. The clinical study group comprised 57 patients with AMI undergoing thrombolytic treatment. Blood flow to the infarct zone and point of time of reperfusion were tested by immediate and late angiography. The appearance of troponin T in serum on day 1 after the onset of AMI depended strongly on reperfusion and on duration of ischemia before reperfusion. Thus, in patients with early reperfused AMI, a marked peak in troponin T serum concentrations was found at 14 hours after the onset of pain. This early troponin T peak was absent in patients with AMI reperfusion occurring greater than 5.5 hours after the onset of pain and in patients with nonreperfused AMI. By contrast, the kinetics of troponin T release after the first day after AMI were unaffected by reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of Doppler echocardiographic mitral inflow patterns: implications for risk stratification in patients with chronic congestive heart failure

OBJECTIVES This prospective study tested whether transmitral flow patterns add incremental value to peak oxygen consumption (VO2) in determining the prognosis of patients with chronic congestive heart failure (CHF) and systolic dysfunction. BACKGROUND Peak VO2 is an objective marker of functional capacity and is routinely used as a criterion to identify heart transplant candidates. Diastolic dysfunction limits functional capacity, but its prognostic importance relative to that of peak VO2 is unknown. METHODS Peak VO2 and mitral inflow velocities were prospectively measured in 311 consecutive patients (mean age 54 years, 84% male) with impaired left ventricular function (ejection fraction <40%; 88 patients with ischemic and 223 with dilated cardiomyopathy) who were evaluated for heart transplant candidacy. RESULTS During a mean follow-up period of 512 +/- 314 days, 65 patients died and 43 patients underwent heart transplantation. Diastolic filling patterns, peak VO2 and left ventricular end-diastolic diameters were independent predictors of cardiac mortality. In patients with peak VO2 < or = 14 ml/min per kg body weight, the outcome was markedly poorer in the presence of restrictive filling patterns as compared with their absence (two-year survival rate 52% vs. 80%). Similarly, despite peak VO2 levels >14 ml/min per kg, the outcome was less favorable in the presence of restrictive filling patterns (two-year survival rate 80% vs. 94%). A risk-stratification model based on the identified independent noninvasive predictors separated groups into those with high (93%), intermediate (65%) and low (39%) two-year survival rates. CONCLUSIONS Transmitral flow patterns add incremental value to peak VO2 in determining the prognosis of patients with CHF and impaired systolic function.

Ventricular oversensing: A study of 101 patients implanted with dual chamber defibrillators and two different lead systems

WERETKA, S., et al. : Ventricular Oversensing: A Study of 101 Patients Implanted with Dual Chamber Defibrillators and Two Different Lead Systems. Modern dual chamber ICD systems are able to overcome various sensing problems. However, improvement of their performance is still required. The aim of this study was to assess the sensing function in 101 consecutive patients (84 men, 17 women; mean age 63 ± 12 years; mean follow‐up 24 ± 4 months) implanted with dual chamber defibrillators and integrated (IB) or dedicated bipolar (DB) lead systems. Follow‐up data were analyzed for the presence of ventricular oversensing. Oversensing occurred in 25 (25%) patients, significantly more frequent in patients implanted with IB compared to DB lead systems (21/52 vs 4/49, P = 0.0002). Patients with cardiomyopathies (CMs) were more prone to sensing malfunctions than patients with no CM (12/30 vs 13/71, P = 0.04). T wave oversensing (n = 14), respirophasic ventricular oversensing (n = 4), and P wave oversensing (n = 6) were the most common pitfalls of ventricular sensing. P wave oversensing was unique to the IB lead system. CT scans performed in these patients disclosed the position of the RV coil to be proximal to the tricuspid area. Four patients received inappropriate ICD shocks due to oversensing. In all but two patients who received lead revision, oversensing was resolved by noninvasive means. In conclusion: (1) ventricular oversensing is a common problem occurring in up to 25% of patients with dual chamber ICDs; (2) P wave oversensing is a ventricular sensing problem affecting function of 11% of dual chamber devices with IB lead systems; (3) IB leads are significantly more susceptible to T wave and P wave oversensing than DB leads; and (4) patients with cardiomyopathies are more prone to oversensing than patients with other heart diseases. (PACE 2003; 26[Pt. I]:65–70)

Determination of left ventricular filling parameters by pulsed Doppler echocardiography: a noninvasive method to predict high filling pressures in patients with coronary artery disease

This study investigated the influence of left ventricular end-diastolic filling pressure (LVEDP) on instantaneous transmitral inflow velocities as assessed by pulsed Doppler echocardiography. The study was performed in 87 consecutive patients with coronary artery disease (12 women, 65 men, mean age 58 +/- 8 years, range 37 to 78 years) in whom Doppler tracings of mitral inflow velocities were recorded 24 hours before diagnostic cardiac catheterization. The ratio of early-to-late diastolic velocity integrals was significantly correlated with LVEDP (r = 0.35, SD = 0.77, p less than 0.001). In addition, in a comparison patients with LVEDP greater than or equal to 20 mm Hg to those with LVEDP less than 20 mm Hg, peak early filling velocity (R) was significantly higher, peak late filling velocity (A) was lower, and hence R/A and area under the early filling curve/area under the late diastolic filling curve (E/L) ratios were significantly higher in patients with markedly elevated filling pressures (LVEDP 20 mm Hg: R = 41 +/- 12, A = 56 +/- 16, R/A = 0.75 +/- 0.23, E/L = 1.0 +/- 0.4, n = 54, and LVEDP greater than or equal to 20 mm Hg: R = 49 +/- 18, A = 46 +/- 12, R/A = 1.23 +/- 0.9, E/L = 1.94 +/- 1.2, n = 34. An E/L ratio greater than or equal to 1.4 showed a sensitivity of 59%, a specificity of 83%, a positive predictive accuracy of 69%, and a negative predicting accuracy of 76% in detecting patients with markedly elevated LVEDP.(ABSTRACT TRUNCATED AT 250 WORDS)

A unified functional/anatomic substrate for circus movement atrial flutter: Activation and refractory patterns in the canine right atrial enlargement model☆

OBJECTIVES This study was designed to test the concept of a functional/anatomic interaction in a canine model of reentry based on right atrial enlargement and to elucidate the electrophysiologic basis for functional conduction block. BACKGROUND The monotonic feature of atrial flutter suggests a uniform substrate for the arrhythmia. Atrial flutter in the sterile pericarditis model is due to single-loop circus movement around a functional or a functional/anatomic obstacle near the atrioventricular (AV) ring. Sustained circus movement requires a critical interaction of a functional arc of block, a natural obstacle, the AV ring and a zone of slow conduction. The location of the inferior vena cava predisposes the lower right atrium to single-loop reentry. METHODS In 11 dogs with right atrial enlargement, 127 bipolar epicardial electrograms were obtained during atrial flutter. For correlation of activation and refractory maps, the effective refractory period under each electrode was determined using the extrastimulus technique. RESULTS Atrial flutter was due to single-loop reentry around functional arcs of block near the AV ring (n = 2) or around functional/anatomic obstacles (n = 8) involving the inferior vena cava. A slow zone was located between the arc and the AV ring and between the inferior vena cava and AV ring, respectively. During initiation, the arc joined the AV ring, forcing activation to proceed around the free end of the arc before breaking through the arc near the AV ring. Arrhythmia termination required the arc of block to rejoin the AV ring. Inducibility of sustained atrial flutter was associated with a marked spatial dispersion of refractoriness. The configuration of the functional arc of block was critically dependent on the spatial pattern of refractoriness. CONCLUSIONS Atrial flutter requires a similar functional or functional/anatomic substrate independent of the underlying etiology. The spatial distribution of refractoriness in enlarged canine atria provides an adequate substrate for the development of functional conduction block.

Multisite pacing for prevention of atrial tachyarrhythmias: potential mechanisms ☆

OBJECTIVES To determine the effects of single-, dual-, triple- and quadruple-site atrial pacing on atrial activation and refractoriness in normal canine hearts. BACKGROUND Multisite pacing has been suggested to be superior to single-site pacing for prevention of atrial tachyarrhythmias. However, the underlying electrophysiological mechanisms are undetermined at the moment, as is the rationale for the selection of pacing locations and the number of pacing sites. METHODS In 13 normal beagle dogs, an epicardial multielectrode (128 bipoles) and a multiplexer mapping system were used to reconstruct epicardial atrial activation patterns obtained during simultaneous stimulation from up to four electrodes located in the high and low right and left atrium, respectively. For all pacing modes (single-, dual-, triple- and quadruple-site pacing), total activation times and local effective refractory periods at eight randomly selected sites as well as local recovery intervals were determined. In a subgroup of five dogs, total epicardial activation times were also obtained during single-site septal stimulation (septal group). RESULTS Activation times and local recovery intervals were minimized by triple-site stimulation, whereas a fourth site did not produce further shortening. Septal stimulation produced epicardial activation times comparable to quadruple-site stimulation. Local refractory periods and their dispersion always remained unaffected. Functional conduction blocks apparent during single-site were found to resolve during multisite stimulation. CONCLUSIONS Multisite pacing can prevent functional conduction blocks by multidirectional excitation and a reduction in total activation time. Triple-site and, possibly, septal pacing modes are expected to be most efficient because both minimize total activation times and maximize the multidirectionality of excitation. In spite of unaffected local refractory periods, the shortening of local recovery intervals might homogenize atrial repolarization and, thus, contribute to the preventive effects of multisite pacing.

Circus movement atrial flutter in the canine sterile pericarditis model. Relation of characteristics of the surface electrocardiogram and conduction properties of the reentrant pathway.

OBJECTIVES This study was designed to elucidate the basis for the electrocardiographic (ECG) appearance of atrial flutter in the canine sterile pericarditis model. BACKGROUND During atrial flutter, the surface ECG may show typical F waves or isolated P waves of any polarity. METHODS Electrocardiographic leads II, III and aVF and epicardial atrial activation maps constructed from 127 simultaneously recorded bipolar electrograms were compared in 20 dogs with sterile pericarditis and inducible atrial flutter. RESULTS In 10 dogs with F wave atrial flutter, single loop reentry occurred around combined functional/anatomic obstacles that included one or both caval veins and a vertically oriented arc of functional conduction block. In 10 dogs with P wave atrial flutter, a merely functional (n = 4) or combined (n = 6) obstacle involving any atrial vessel and more vertically (n = 5) or more horizontally (n = 5) oriented arcs of block was present. The isoelectric interval between P waves corresponded to the conduction time within the slow zone of the reentrant circuit (96 +/- 27 vs. 100 +/- 24 ms, mean +/- SD). Slow conduction accounted for 65 +/- 8% of the cycle length in P wave atrial flutter, but for only 29 +/- 7% in F wave atrial flutter (p < 0.05). Slow conduction was usually associated with activation of fewer than five epicardial electrodes per 10-ms isochronal interval, reflecting only a small amount of atrial tissue. The polarity of P or F waves was determined by the direction of the major wave front activating the most electrodes per 10-ms isochronal interval, irrespective of whether the right or the left atrium was activated. CONCLUSIONS The F waves result from reentrant activation at a relatively constant speed around a vertically oriented functional/anatomic obstacle involving one or both caval veins. The P waves occur when the circuit contains a marked area of slow conduction.

Efficacy of intravenous prourokinase and a combination of prourokinase and urokinase in acute myocardial infarction

Fifty-four patients with Q-wave acute myocardial infarction (AMI) were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (prourokinase). To determine the optimal treatment regimen, prourokinase was applied in 3 different ways: group I received a bolus of 7.5 mg and a subsequent infusion of 40.5 mg over 60 minutes. Patency of the infarct artery was observed in 7 patients (50%) at the end of the infusion time. One hour after the end of the infusion the fibrinogen level had decreased to 87 +/- 12% of the preinfusion level; the plasminogen and alpha-2 antiplasmin levels to 61 +/- 13% and 59 +/- 34%, respectively. In group II prourokinase was administered as a 7.5 mg bolus followed by 66.5 mg over 60 minutes. Eleven patients (55%) had patent infarct-related coronary arteries and fibrinogen, plasminogen and alpha-2 antiplasmin levels had decreased to 58 +/- 29%, 38 +/- 18% and 21 +/- 14%, respectively. Group III was treated with a bolus of 3.7 mg prourokinase and 250,000 IU urokinase followed by 44.3 mg prourokinase, resulting in a patency rate of 65% (13 patients). Fibrinogen, plasminogen and alpha-2 antiplasmin levels decreased to 76 +/- 15%, 67 +/- 15% and 47 +/- 29%, respectively. Fibrin-specific thrombolysis can be achieved with glycosylated prourokinase. At higher dosages considerable systemic activation of the fibrinolytic system with little enhancement of the observed therapeutic effect occurred. The combination of prourokinase and urokinase yielded a higher patency rate than either dosage of prourokinase alone, although the difference was not statistically significant in this pilot trial.

Effects of the IKr-Blocking Agent Dofetilide and of the IKs-Blocking Agent Chromanol 293b on Regional Disparity of Left Ventricular Repolarization in the Intact Canine Heart

Recent in vitro studies have described regional differences of ion current expression and function, possibly accounting for reduced homogeneity of repolarization in the heart. In 11 intact canine hearts regional disparity of repolarization was determined at baseline and after administration of the IKr blocking agent dofetilide (30 &mgr;g/kg) and the IKs-blocking agent chromanol 293b (10 mg/kg). Effective refractory periods (ERPs) were determined through up to 10 needle electrodes inserted into basal, midwall and apical regions of the left ventricular wall using the extrastimulus technique (cycle length [CL] 300 and 850 ms). At baseline (CL of 850 ms), ERPs were significantly longer in epicardial muscle layers of the apex compared to the base. In deeper muscle layers regional differences of ERPs were not detectable. Administration of dofetilide increased apico-basal disparity of repolarization, due to a more marked increase of ERPs in the apex than in the base. In contrast, homogeneous ERPs were evident along the apico-basal axis after administration of chromanol 293b. Transmural dispersion of refractoriness could not be observed in any region at baseline, or after drug-administration. In the intact canine heart, apico-basal disparity of repolarization varies between individual muscle layers. Dependent on their current specificity, antiarrhythmic agents may enhance or diminish regional disparity of repolarization.