Cardiac troponin T concentrations above the 99th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy.

OBJECTIVE: A recently developed immunoassay for high-sensitivity measurement of cardiac troponin T (hsTnT) allows measurement at the 99th percentile for a normal population with an assay imprecision <10%. It is unclear whether such a low cutpoint (14 ng/L) is helpful for long-term risk stratification of patients with an acute coronary syndrome (ACS) undergoing routine early invasive strategy. PATIENTS AND MAIN OUTCOME MEASURES: Consecutive patients with ACS admitted to a chest pain unit were studied. The usefulness of hsTnT for early diagnosis of myocardial infarction (MI) and prediction of all-cause death or death/MI over a median of 271 days following presentation was compared against the fourth generation cTnT at the 99th percentile cutpoint. RESULTS: Of 1,384 patients with ACS enrolled, 47.8% had non-ST-segment elevation MI (NSTEMI), 26.4% unstable angina, 21.8% STEMI and 4% had non-ACS. Adjusted risk for all-cause death [adjusted HR 8.26 (95%CI: 1.13-66.33), p = 0.038] and death/MI [adjusted HR 2.71 (95% CI: 1.15-6.38), p = 0.023] were significantly higher with hsTnT above the 99th percentile. In particular, among patients with a standard fourth generation cTnT result below the 99th percentile cutoff (0.01 ng/mL), hsTnT improved risk assessment. Mortality risk associated with an elevated hsTnT was present across the spectrum of ACS, as well as in conditions with hsTnT elevations not related to ACS. CONCLUSION: hsTnT at the 99th percentile cutoff is useful for the diagnostic evaluation of patients with ACS, and provides strong and independent predictive power for adverse long-term outcomes even after early invasive strategy.

Far-field R wave oversensing in a dual chamber arrhythmia management device: predisposing factors and practical implications.

Initial experience with the Medtronic Jewel 7250, the ICD designed to detect and treat ventricular and supraventricular tachyarrhythmias, is very promising. Its effectiveness, however, depends on sensing performance, which has not yet been systematically examined. The aim of the study was to determine the incidence of, predisposing factors for, and practical implications of far-field R wave oversensing (FFRWOS) in this dual chamber ICD. During a total follow-up of 797 months in 48 patients who had the Jewel 7250, follow-up strip charts, 12-channel Holter recordings and, in particular cases, Holter recordings with intracardiac markers were analyzed for the presence of FFRWOS. FFRWOS was documented in ten (21.3%) patients. Compared to other lead locations, the right atrial appendage lead position was most frequently associated with FFRWOS (7/27 vs 3/21, P < 0.05). Patients with FFRWOS had significantly more treated and nontreated atrial episodes, many of which were judged to have been detected inappropriately. In one case, inappropriate atrial antitachycardia pacing due to R wave oversensing triggered sustained ventricular tachycardia, terminated eventually with a high energy shock. In dual chamber ICDs, FFRWOS may represent a frequent phenomenon possibly leading to serious consequences. For atrial leads, a lateral atrial wall position seems to be preferable. In most cases, FFRWOS can be eliminated by optimization of atrial sensing parameters. Given the possibility of ventricular proarrhythmia with atrial pacing therapy, the capability of ventricular backup defibrillation in respective devices is at least reassuring.

[Predictive value of frequency, duration and rate of ventricular salvos in ambulatory ECG for inducibility of sustained ventricular tachycardia]. / Prädiktiver Wert der Frequenz, der Dauer und der Häufigkeit ventrikulärer Salven im Langzeit-EKG für die Induzierbarkeit anhaltender Kammertachykardien.

Identification of high risk patients with coronary artery disease (CAD) prone to sudden cardiac death still remains a difficult issue. In 211 patients with CAD diagnosed by coronary angiography and documented non-sustained ventricular tachycardia (NSVT), programmed ventricular stimulation (PVS) was performed. NSVTs documented during Holter monitoring were analysed concerning frequency, duration and rate. To relate those parameters to the inducibility of sustained monomorphic ventricular tachycardias (MVT) during PVS, the total population was divided in different groups; patients with 1, 2-5 or > 5 salvos within 24 h; patients having salvos with a rate of > or = 150/min or < 150/min; patients with 3-5, 6-10 or > 10 consecutive extra beats. It could be demonstrated that in patients with CAD and NSVTs, induction of MVTs during PVS is more likely if the rate of the spontaneously occurring NSVT is > or = 150/min (22.1 vs 8.9%; p = 0.042). In contrast, there is apparently no correlation between the duration and incidence of NSVTs and the prevalence of MVTs during PVS. Multivariate analysis revealed the rate of documented NSVTs (odds ratio 2.98, p = 0.0314) and a decrease of left ventricular ejection fraction (odds ratio 1.69; p = 0.0013) as independent risk factors for the inducibility of MVTs. Conclusions CAD patients with fast salvos (> or = 150 beats/min) and reduced left ventricular ejection fraction are more likely to reveal inducible MVT during PVS and should, therefore, preferably be subjected to invasive risk stratification. The number of salvos per day and the number of consecutive beats, on the other hand, do not seem to be of relevant predictive value.

T-wave alternans in LQTS: repolarization-rate dynamics from digital 12-lead Holter data.

T-wave alternans (TWA) is a harbinger of ventricular vulnerability and an important prognostic indicator for torsade de pointes and likely sudden death in patients with LQTS. We analyzed the occurrence of TWA in 18 patients with LQTS (7 males, 11 females, ages ranging from 6 months to 32 years--median 8.4 years). Analysis was performed with software to investigate dynamics of cycle length mediated repolarization changes. Digital Holter ECG analysis revealed macroscopic, true TWA in 3 of 18 patients. TWA showed a variable morphological expression. One patient had continuous changes of T wave polarity, but not on a periodic beat-to-beat basis. Onsets of macroscopic TWA were preceded by long/short cycle length sequences and tachycardic rates above 130 to 140 bpm. Impact of ventricular premature beats on TWA onset was insignificant. Two of the identified patients with TWA had sudden cardiac death during follow-up (one refused PM therapy). At present, TWA cannot be detected automatically from Holter ECGs and therefore may be missed, despite the potential danger for the individuals. The observation that predominantly high beat rates and not beat rate changes, per se, triggered episodes of TWA renders difficult general therapeutic recommendations for the identified patients at risk.

Electrocardiographic measures of repolarization revisited: why? what? how?

Ventricular repolarization continues to be an enigma to clinical cardiologists and cardiac electrophysiologists. On the one hand, a century of experience has documented an association between abnormal T-wave morphology, QT prolongation and dispersion, T-wave alternans, and nonspecific ST-T waves with arrhythmia risk or negative prognostic outcome. On the other hand, recent advances in molecular electrophysiology have definitively implicated abnormal function and structure of cardiac ion channels associated with repolarization as primary arrhythmogenic mechanisms in long QT syndrome, Brugada's Syndrome, and idiopathic ventricular fibrillation and ventricular tachycardia. In spite of this extensive clinical experience and newly established mechanistic knowledge, robust measurements of repolarization and sensitive algorithms for reliable assessment of risk and prediction of arrhythmia occurrence have remained elusive. New insights into electrocardiographic waveform that reflect and capture the underlying spatial and dynamic characteristics of repolarization offer opportunity to devise clinical indices of repolarization that might be more predictive of risk or outcome than those currently used. Experimental and model data show evidence that the location and size of repolarization lesions may be deduced from T waveform. The changes of repolarization induced by altered activation sequence, and cycle length mediated alterations to repolarization offer additional means to assess the magnitude and significance of such lesions that are linked to increased arrhythmogenic risk. This article explores indices of repolarization that are sensitive to repolarization and its change and that provide opportunity to better characterize and assess repolarization for risk stratification.

Rate and time dependent effects of D-sotalol on the monophasic action potential after sudden increase of the heart rate.

Experimental and clinical data suggests that almost all Class III antiarrhythmic agents diminish their ability to prolong cardiac repolarization at fast heart rates. However, only limited data exists about the time course of efficacy decay of Class III agents after sudden increase of the heart rate. In the present study, we assessed both rate and time dependent changes of the efficacy of d-sotalol in higher stimulation frequencies following an abrupt increase in heart rate. This might imitate the situation seen in the development of paroxysmal tachycardias. Monophasic action potentials were recorded from the right ventricular apex during sinus rhythm and constant stimulation with the paced cycle length (PCL) of 550 ms, 400 ms, and 330 ms in the baseline and 20 minutes after intravenous administration of d-sotalol (2.5 mg/kg) in seven patients with documented life-threatening ventricular tachyarrhythmias. D-sotalol significantly prolonged monophasic action potential duration at different steady-state heart rates (sinus rhythm: 21.1% +/- 3.6%; PCL 550 ms: 16.6% +/- 4.3%, 400 ms: 11.2% +/- 2.7%, 330 ms: 5.8% +/- 2.1%). The prolongation is significantly shorter in higher steady-state pacing, confirming a pronounced reverse-use dependent decrease of the efficacy of d-sotalol at faster stimulation frequencies. After the abrupt increase in heart rate, the beat-to-beat adaptation of the postdrug action potential prolongation exhibits only slight reverse-use dependent shortening. The decrease of the efficacy of d-sotalol is insignificant for the first 20 consecutive beats at the stimulation frequency of the PCL of 400 msec (from 16.6% at PCL of 550 ms to 14.6% at the 20th beat of the PCL of 400 ms), and for the first ten consecutive beats at the stimulation frequency of the PCL of 330 ms (from 16.8% at PCL of 550 ms to 12.3% at the 10th beat of the PCL of 330 ms). This slow decay of action potential prolongation after an abrupt increase in heart rate might contribute to the antiarrhythmic action of d-sotalol in cardiac tachyarrhythmias.

Ventricular arrhythmias in dilated cardiomyopathy.

Although prognosis of dilated cardiomyopathy (DCM) has improved due to advances in diagnosis and therapy, still too many sudden cardiac deaths occur in DCM. Spontaneous ventricular ectopy is a very common finding in patients with DCM, but the prognostic significance of Holter monitoring remains controversial. Other noninvasive methods, e.g., late potentials and QT dispersion, have not yet contributed to the evaluation of prognosis for arrhythmogenic events in DCM. Programmed ventricular stimulation has been repeatedly used to stratify long-term prognosis, yet satisfactory data are still missing as many deaths occur in patients without inducible arrhythmias. Several prognostic studies are still in progress, and preliminary data for the use of ICDs already appear to be promising. In patients with poor left ventricular function and ICDs in situ, prognosis is determined by progression of heart failure. Heart transplantation may be the ultimate therapeutic instrument for end-stage heart failure patients. For patients with advanced DCM and increased risk for malignant arrhythmias who are unsuitable for orthotopic heart transplantation, the combined therapy with an ICD and dynamic cardiomyoplasty may be an alternative treatment.

[New aspects of defibrillator therapy]. / Neue Aspekte der Defibrillatortherapie.

The implantable cardioverter defibrillator is currently a therapy of first choice in patients with malignant therapy refractory ventricular arrhythmias. The occurrence of malignant ventricular tachycardia cannot be suppressed by the defibrillator but is treated using antitachycardia pacing, cardioversion or defibrillation. During recent years, electrodes, defibrillation shockforms and device size were continuously optimized. The development of transvenous lead systems resulted in significant reduction of perioperative mortality and morbidity. With the availability of biphasic shockforms and single-lead unipolar devices marked reduction of defibrillation thresholds were achieved and transvenous lead systems without subcutaneous could be implanted. Improvements in device technology lead to smaller devices which can be implanted subpectorally even using local anaesthesia. But there is still enormous potential to develop an ideal antiarrhythmic device. One of the most significant problems of the defibrillator therapy represents the delivery of inappropriate shocks due to supraventricular tachyarrhythmias and sinustachycardia. To solve this problem different approaches are currently developed. Extension in memory allows to store several data logs and intracardiac electrograms for individual adapted adjustment of the therapy. Intracardiac electrogram width measurement for discrimination between ventricular and supraventricular arrhythmias is currently evaluated. Dual-chamber arrhythmia discrimination algorithms of an integrated dual-chamber pacemaker and defibrillator are clinically studied. Hemodynamic sensors for determining the severity of the arrhythmia are currently under experimental evaluation. The combination of latissimus dorsi dynamic cardiomyoplasty and ICD therapy may improve survival in patients with severely depressed left ventricular function and malignant ventricular arrhythmias. Several randomized prospective trials are currently in progress potentially expanding the use of the ICD in patients at risk for sudden cardiac death. The high costs of defibrillator therapy is still a limitation for its use, but higher production figures and advancing technology could reduce the system prize.

Electrophysiological mechanisms of action of ethmozine that explain its antiarrhythmic efficacy in the late stage of experimental myocardial infarction in dogs.

The effects of intravenous ethmozine (3 mg.kg-1) on electrophysiological parameters of ischaemically damaged myocardium and induced ventricular tachyarrhythmias were studied by programmed stimulation in 17 conscious dogs with 4 to 8 day-old ligation of the left anterior descending coronary artery. Ethmozine showed a beneficial effect on sustained ventricular tachycardia by suppressing its inducibility in five of 14 animals or by slowing its rate in six of 14 animals. Ethmozine prolonged the ventricular effective refractory period in normal and infarcted myocardium, and impaired depressed conduction in ischaemically damaged tissue. The latter was indicated by significant lengthening of late potentials recorded from the infarction zone. The QT interval was only slightly increased with ethmozine. Our findings indicate an antiarrhythmic action of ethmozine in the late stage of myocardial infarction. Major mechanisms accounting for its efficacy may predominantly be associated with marked depression of slow conduction in the infarction zone, as well as with prolongation of ventricular refractoriness without significant changes of ventricular repolarization.

[The implantable cardioverter/defibrillator (ICD). Developments up to the present time and future perspectives]. / Der implantierbare Kardioverter/Defibrillator (ICD). Entwicklung bis heute und Zukunftsperspektiven.

The implantable cardioverter/defibrillator is gaining increasing significance in the therapy of life-threatening ventricular arrhythmias. Independently, the team of Mirowski and the team of Schuder started to develop experimental automatic implantable defibrillators in the seventies. In 1980, the first human implant of an automatic defibrillator was done by Levi Watkins together with the team of Mirowski in Baltimore, USA. Since 1989 implantable cardioverter/defibrillators exhibit multiple functions among which are high energy defibrillation therapy, low energy cardioversion, antitachycardia pacing, permanent and post therapy antibradycardia pacing, diagnostic counters, and device status parameters. This offers a markedly improved technical device to the patients. Evaluation of the patient's diagnostic counters provide a detailed overview about the patient's arrhythmia history and information for optimizing antitachycardia pacing therapy and additional antiarrhythmic drug therapy. The availability of non-thoractomy transvenous lead systems and biphasic shock forms allows the insertion of the device without open chest surgery and even without subcutaneous leads resulting in low mortality rates and an exclusively transvenous system. Single-lead unipolar devices are currently investigated in clinical trials. Future development of atrial sensing lead systems may further reduce inappropriate shock therapy triggered by sinus tachycardia or atrial tachyarrhythmias, e.g. atrial fibrillation, and may be used for dual chamber stimulation. Hemodynamic sensors for determining the severity of the arrhythmia are currently under experimental evaluation. Possible prognostic indications of ICD therapy in patients without a history of malignant arrhythmias are currently studied in several prospective trials. All new directions hold promise to expand and improve the use of ICDs in patients at risk for sudden cardiac death.

Cardiac late potentials for diagnosis in heart disease.

In recent years abundant information has been obtained about the relationship of heart disease and cardiac late potentials. Non-invasive recordings of ventricular late potentials are useful in risk stratification of various clinical conditions, in particular, in patients following myocardial infarction. Here a close correlation has been established between cardiac late potentials and spontaneous or induced sustained ventricular tachycardias using programmed electrical stimulation. Cardiac late potentials also appear to be associated with arrhythmic events in patients with cardiomyopathies, and following unsuccessful antitachycardia surgery. Furthermore, recording of abnormal late potentials are associated both with acute rejection after cardiac transplantation and unsuccessful thrombolytic therapy after myocardial infarction. Interestingly, antiarrhythmic drugs have no clear effect on cardiac late potentials.

Electrophysiological mechanisms of action of the levorotatory isomer of sotalol in a canine infarct model of inducible ventricular tachycardia: comparison with the beta-1 receptor antagonist bisoprolol.

To evaluate the antiarrhythmic efficacy of l-sotalol and bisoprolol on inducible ventricular arrhythmias, conscious dogs with 4- to 8-day-old myocardial infarction were studied by programmed electrical stimulation. Direct recordings from infarcted and adjacent normal subepicardium were made using a specially designed composite electrode. From 18 dogs developing sustained ventricular tachycardia (sVT) during control stimulation, l-sotalol (1.5 mg/kg i.v.) prevented reinducibility of sVT in 10 animals, while in seven other animals it significantly reduced the rate of tachycardia. Bisoprolol (0.2 mg/kg i.v.), tested in a separate group of 10 dogs susceptible to sVT, was mostly ineffective in preventing or slowing the tachycardia. Both agents significantly prolonged conduction time and refractoriness within the atrioventricular conduction system, and decreased heart rate. However, while l-sotalol lengthened ventricular refractoriness and QT interval, bisoprolol exerted only a minor effect on these parameters. Neither of the drugs affected conduction in normal and infarcted myocardium, as indicated by almost unchanged QRS complex width and duration of ventricular late potentials, respectively. The results indicate that acute beta-blockade is ineffective against sVT induced during the subacute stage of myocardial infarction. The antiarrhythmic efficacy of l-sotalol may predominantly be related to its prolonging effect on ventricular refractoriness, supporting the concept of pure class III action.

Advances in follow-up techniques for implantable defibrillators.

The complexity of newer implantable defibrillators has made device follow-up increasingly more intricate. Extensive data-logging capacity provides specific information on recorded events, which facilitates more accurate determination of patient arrhythmias. This helps the clinician judge whether the device is detecting and treating arrhythmias appropriately, or whether false sensing of external signals or supraventricular rhythms is occurring. There is also a record of the efficacy of delivered therapy from the device that helps in optimizing subsequent programming. Programming itself has become much more complicated, with multiple independently programmable therapy zones, each with numerous available therapeutic modalities. In addition, defibrillator status information has been improved. Accurate battery voltage measurements give a reasonable estimate of remaining device life, and pace/sense and shock lead impedances can be measured to provide information on total system integrity. Together, these advances allow more specific programming of the device to the individual patient's condition but require increasing experience and expertise of the physician.

Acute efficacy and chronic follow-up of patients with non-thoracotomy third generation implantable defibrillators.

Non-thoracotomy implantation of implantable cardioverter defibrillators (ICDs) has simplified the process of device insertion, promising to decrease associated procedural complications while providing sudden death protection at least equal to epicardial systems. This study presents the acute and chronic results of 110 patients who underwent attempted non-thoracotomy ICD implantation with the Medtronic Transvene lead system and PCD model 7217 or 7219. Of the 110 patients attempted, 100 (91%) had the system successfully implanted without the need for an epicardial patch. One patient died 1 week postoperatively of septic shock related to the implantation (0.9% perioperative mortality). During follow-up of 16 +/- 11 months, 45% of the patients had an event detected as ventricular tachycardia; 26% of these detections were felt clinically to be due to supraventricular rhythms. Of the remainder, 87% were successfully treated with the first VT therapy, and 98% were terminated by the final therapy; 66% of the patients had at least one episode of ventricular fibrillation, of which 5% were felt to be inappropriate detections; 85% of the appropriate episodes were successfully treated with the first VF therapy, and all were converted by the final therapy. Total mortality at 6, 12, and 24 months was 3%, 11%, and 19% respectively. Only one patient had sudden cardiac death, occurring at 13 months postimplant. Overall, the non-thoracotomy lead system for this ICD displayed infrequent implant complications and proved to be reliable at terminating arrhythmias and maintaining a low rate of sudden cardiac death in this high risk population.

[Arrhythmogenic right ventricular disease]. / Die arrhythmogene rechtsventrikuläre Erkrankung.

In patients with arrhythmogenic right ventricular disease (ARVD), life threatening ventricular tachyarrhythmias and sudden cardiac death mostly occur in adolescence, or in young adults before the age of 40. In the right ventricle, progressive fibrolipomatous replacement of the ventricular myocardium is pathognomonic. In severe cases progressive congestive right heart failure can develop although mild forms are extremely difficult to recognized. In most cases the disease can be diagnosed only by elaborate investigation. Right ventricular cineangiography, myocardial biopsy, MRI, and electrophysiological investigation are the most important diagnostic procedures. If the disease is diagnosed in an early stage the risk of life-threatening arrhythmias can be reduced by carefully selected antiarrhythmic therapy.

Effects of prenylamine and AQ-A 39 on reentrant ventricular arrhythmias induced during the late myocardial infarction period in conscious dogs.

The effects of prenylamine (PNL) and AQ-A 39 on sustained ventricular tachycardia (SVT) were studied by programmed stimulation in conscious dogs 4-10 days after ligation of the left anterior descending (LAD) coronary artery. In 8 of 16 dogs developing SVT in the control, PNL (3 mg/kg intravenously, i.v.) suppressed inducibility of SVT and slowed the rate of tachycardia in 6 other animals. In a separate group of 10 dogs with inducible SVT, AQ-A 39 (4 mg/kg i.v.) abolished elicitation of tachycardia in 3 dogs and decreased its rate in 6 other dogs. Neither drug affected normal conduction significantly, but PNL impaired slow conduction in the infarct zone, as indicated by prolongation of late potential. Both agents increased the effective refractory period (ERP) of infarcted and normal ventricular myocardium and prolonged the corrected QT interval. PNL and AQ-A 39 exert notable efficacy in preventing infarcted heart from severe ventricular arrhythmias. Prolongation of ventricular refractoriness and repolarization, as well as decreased slow conduction in ischemically damaged myocardium, are major mechanisms accounting for the effectiveness of these drugs against ventricular arrhythmias.

[Ventricular tachyarrhythmia in acute and chronic myocardial ischemia: non-drug therapy and evaluation of outcome]. / Ventrikuläre Tachyarrhythmie bei akuter und chronischer Myokardischämie: Nichtmedikamentöse Therapie und ihre Erfolgsbeurteilung.

In recent years new methods of non-pharmacological therapy of ventricular tachyarrhythmias have gained increasing importance. The development of implantable defibrillators and increasing experience with catheter ablation techniques represent important alternatives to pharmacological antiarrhythmic therapy which is presently employed only in a subgroup of patients with life-threatening tachyarrhythmias and coronary heart disease.