Stefan Osswald

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy

BACKGROUND The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitäts Trial (BASKET)

BACKGROUND No prospective trial-based data are available for incremental cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in unselected patients, as treated in everyday practice. METHODS The Basel stent cost-effectiveness trial (BASKET) included 826 consecutive patients treated with angioplasty and stenting for 1281 de-novo lesions, irrespective of indication for angioplasty. Patients were randomised to one of two DES (Cypher, n=264; Taxus, n=281) or to a cobalt-chromium-based BMS (Vision, n=281) and followed up for 6 months for occurrence of major adverse cardiac events and costs. Analysis was by intention-to-treat. The primary endpoint was cost-effectiveness after 6 months, with effectiveness defined as reduction of major adverse cardiac events. FINDINGS Cardiac death, myocardial infarction, or target vessel revascularisation occurred in 39 of 544 (7.2%) patients with DES and 34 of 280 (12.1%) with BMS (odds ratio 0.56, 95% CI 0.35-0.91; p=0.02), without significant differences between the two DES. Total costs at 6 months were higher with DES (mean 10,544, SD 6849) than with BMS (9639, 9067; p<0.0001); higher stent costs of DES were not compensated for by lower follow-up costs. Incremental cost-effectiveness ratio of DES compared with BMS to avoid one major event was 18,311, and costs per quality-adjusted life-year gained were more than 50 000. Subgroup analyses showed that DES were more cost-effective for elderly patients in specific high-risk groups. INTERPRETATION In a real-world setting, use of DES in all patients is less cost effective than in studies with selected patients. Use of these stents could be restricted to patients in high-risk groups.

Utility of Absolute and Relative Changes in Cardiac Troponin Concentrations in the Early Diagnosis of Acute Myocardial Infarction

Background— Current guidelines for the diagnosis of acute myocardial infarction (AMI), among other criteria, also require a rise and/or fall in cardiac troponin (cTn) levels. It is unknown whether absolute or relative changes in cTn have higher diagnostic accuracy and should therefore be preferred. Methods and Results— In a prospective, observational, multicenter study, we analyzed the diagnostic accuracy of absolute (&Dgr;) and relative (&Dgr;%) changes in cTn in 836 patients presenting to the emergency department with symptoms suggestive of AMI. Blood samples for the determination of high-sensitive cTn T and cTn I ultra were collected at presentation and after 1 and 2 hours in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists. The area under the receiver operating characteristic curve for diagnosing AMI was significantly higher for 2-hour absolute (&Dgr;) versus 2-hour relative (&Dgr;%) cTn changes (area under the receiver operating characteristic curve [95% confidence interval], high-sensitivity cTn T: 0.95 [0.92 to 0.98] versus 0.76 [0.70 to 0.83], P<0.001; cTn I ultra: 0.95 [0.91 to 0.99] versus 0.72 [0.66 to 0.79], P<0.001). The receiver operating characteristic curve–derived cutoff value for 2-hour absolute (&Dgr;) change was 0.007 &mgr;g/L for high-sensitivity cTn T and 0.020 &mgr;g/L for cTn I ultra (both cutoff levels are half of the 99th percentile of the respective cTn assay). Absolute changes were superior to relative changes in patients with both low and elevated baseline cTn levels. Conclusions— Absolute changes of cTn levels have a significantly higher diagnostic accuracy for AMI than relative changes, and seem therefore to be the preferred criteria to distinguish AMI from other causes of cTn elevations. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Treatment of ventricular tachycardia by transcatheter radiofrequency ablation in patients with ischemic heart disease.

BACKGROUND Recurrent sustained ventricular tachycardia (VT) is not responsive to antiarrhythmic drugs in the majority of patients, who therefore need therapy with nonpharmacological methods. We evaluated prospectively the feasibility, safety, and efficacy of transcatheter radiofrequency (RF) ablation of VT in 21 selected patients with ischemic heart disease and VT. METHODS AND RESULTS Twenty-one patients with ischemic heart disease and recurrent, drug-refractory VT documented by 12-lead ECG were selected who had sufficient hemodynamic tolerance of VT to undergo transcatheter mapping. Documented clinical VT was reproduced by programmed cardiac stimulation (PCS), and the site of origin was localized by a combination of techniques, including pace mapping, activation-sequence mapping, recordings of middiastolic potentials, and application of resetting and entrainment principles. RF current at 55 V was applied (3.8 +/- 3.1 applications per patient) for as long as 30 seconds at a time to target sites. Twenty-four distinct clinical VTs (mean cycle length, 445 +/- 52 milliseconds) were mapped and ablated in 21 patients. In 17 of 21 patients (81%), the procedure was acutely successful, and the target clinical VT could no longer be induced by PCS after the procedure, whereas in 4 patients, clinical VT remained inducible. By contrast, VTs with shorter cycle length and different QRS morphology than the ablated VT could still be induced by PCS in 12 of 21 patients. One patient died in intractable congestive heart failure 10 days after the procedure, and the remaining 20 are alive at the end of the follow-up period. The majority of the patients continued to be treated with at least one additional mode of antiarrhythmic therapy; 12 patients were still taking antiarrhythmic drugs, and 9 patients received an implantable cardioverter/defibrillator. During a mean follow-up period of 13.2 +/- 5.0 months, 9 of 20 patients (45%) had recurrent VT. In 4 patients, the recurrent VT was different than the previously ablated one. Clinical VT recurred in all 4 patients in whom RF ablation had been acutely unsuccessful. Four patients with recurrent VT underwent repeat RF ablation procedures that were acutely successful and had no further recurrence. CONCLUSION Transcatheter RF ablation is feasible but has only moderately high efficacy in a small, selected group of patients with ischemic heart disease and drug-refractory, highly frequent, hemodynamically tolerated, sustained VT. In the majority of the patients, this treatment technique is palliative rather than definitive, and many of the patients continue to require other methods of antiarrhythmic therapy.

Limitations and Late Complications of Third-Generation Automatic Cardioverter-Defibrillators

BACKGROUND This study examines the limitations and complex management problems associated with the use of tiered-therapy, implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS The study group comprises the first 154 patients undergoing implantation of tiered-therapy ICDs at our institution. Pulse generators from three different manufacturers were used. In 39 patients, a complete nonthoracotomy lead system was used. The perioperative mortality was 1.3%. Of these 154 patients, 37% experienced late postoperative problems. Twenty-one patients required system revision within 36.5 months (mean, 8.57 +/- 11.3) of surgery. Reasons for revision were spurious shocks due to electrode fractures (3) or electrode adapter malfunction (2), inadequate signal from endocardial rate-sensing electrodes (3), superior vena cava or right ventricular coil migration (5), failure to correct tachyarrhythmias due to a postimplant rise in defibrillation threshold (5), or pulse generator failure (3). One of these patients required system removal for infection after revision of an endocardial lead. A further 32 patients received inappropriate shocks for atrial fibrillation with a rapid ventricular response or sinus tachycardia. Two of these patients also received shocks for ventricular tachycardia initiated by antitachycardia pacing triggered by atrial fibrillation. Ventricular pacing for bradycardia was associated with inappropriate shocks due to excessive autogain in 2 patients. CONCLUSIONS Despite the major diagnostic and therapeutic advantages of tiered-therapy ICDs, a significant proportion of patients continue to experience hardware-related complications or receive inappropriate shocks.

Necessity for Surgical Revision of Defibrillator Leads Implanted Long-Term Causes and Management

Background— Defibrillator lead malfunction is a potential long-term complication in patients with an implantable cardioverter-defibrillator (ICD). The aim of this study was to determine the incidence and causes of lead malfunction necessitating surgical revision and to evaluate 2 approaches to treat lead malfunction. Methods and Results— We included 1317 consecutive patients with an ICD implanted at 3 European centers between 1993 and 2004. The types and causes of lead malfunction were recorded. If the integrity of the high-voltage part of the lead could be ascertained, an additional pace/sense lead was implanted. Otherwise, the patients received a new ICD lead. Of the 1317 patients, 38 experienced lead malfunction requiring surgical revision and 315 died during a median follow-up of 6.4 years. At 5 years, the cumulative incidence was 2.5% (95% confidence interval, 1.5 to 3.6). Lead malfunction resulted in inappropriate ICD therapies in 76% of the cases. Implantation of a pace/sense lead was feasible in 63%. Both lead revision strategies were similar with regard to lead malfunction recurrence (P=0.8). However, the cumulative incidence of recurrence was high (20% at 5 years; 95% confidence interval, 1.7 to 37.7). Conclusions— ICD lead malfunction necessitating surgical revision becomes a clinically relevant problem in 2.5% of ICD recipients within 5 years. In selected cases, simple implantation of an additional pace/sense lead is feasible. Regardless of the chosen approach, the incidence of recurrent ICD lead-related problems after lead revision is 8-fold higher in this population.

High-Sensitivity Cardiac Troponin in the Distinction of Acute Myocardial Infarction From Acute Cardiac Noncoronary Artery Disease

Background— We hypothesized that high-sensitivity cardiac troponin (hs-cTn) and its early change are useful in distinguishing acute myocardial infarction (AMI) from acute cardiac noncoronary artery disease. Methods and Results— In a prospective, international multicenter study, hs-cTn was measured with 3 assays (hs-cTnT, Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI Siemens) in a blinded fashion at presentation and serially thereafter in 887 unselected patients with acute chest pain. Accuracy of the combination of presentation values with serial changes was compared against a final diagnosis adjudicated by 2 independent cardiologists. AMI was the adjudicated final diagnosis in 127 patients (15%); cardiac noncoronary artery disease, in 124 (14%). Patients with AMI had higher median presentation values of hs-cTnT (0.113 &mgr;g/L [interquartile range, 0.049–0.246 &mgr;g/L] versus 0.012 &mgr;g/L [interquartile range, 0.006–0.034 &mgr;g/L]; P<0.001) and higher absolute changes in hs-cTnT in the first hour (0.019 &mgr;g/L [interquartile range, 0.007–0.067 &mgr;g/L] versus 0.001 &mgr;g/L [interquartile range, 0–0.003 &mgr;g/L]; P<0.001) than patients with cardiac noncoronary artery disease. Similar findings were obtained with the hs-cTnI assays. Adding changes of hs-cTn in the first hour to its presentation value yielded a diagnostic accuracy for AMI as quantified by the area under the receiver-operating characteristics curve of 0.94 for hs-cTnT (0.92 for both hs-cTnI assays). Algorithms using ST-elevation, presentation values, and changes in hs-cTn in the first hour accurately separated patients with AMI and those with cardiac noncoronary artery disease. These findings were confirmed when the final diagnosis was readjudicated with the use of hs-cTnT values and validated in an independent validation cohort. Conclusion— The combined use of hs-cTn at presentation and its early absolute change excellently discriminates between patients with AMI and those with cardiac noncoronary artery disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin

BACKGROUND We examined whether undetectable levels of high-sensitivity cardiac Troponin (hs-cTn) can be used to rule out acute myocardial infarction (AMI) with a single blood draw at presentation to the emergency department (ED). METHODS AND RESULTS In a prospective multicenter study we used 4 different hs-cTn assays (hs-cTnT Roche, and hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting with acute chest pain. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs-cTnT levels. Mean follow up was 24 months. Among 2072 consecutive patients with available hs-cTnT levels, 21% had an adjudicated diagnosis of AMI. Among AMI patients, 98.2% had initially detectable levels of hs-cTnT (sensitivity 98.2%, 95%CI 96.3%-99.2%, negative predictive value (NPV) 98.6%, 95%CI 97.0%-99.3%). Undetectable levels of hs-cTnT ruled out AMI in 26.5% of patients at presentation. The NPV was similar with the three hs-cTnI assays: among 1180 consecutive patients with available hs-cTnI (Siemens), the NPV was 98.8%; among 1151 consecutive patients with available hs-cTnI (Beckman Coulter), the NPV was 99.2%; among 1567 consecutive patients with available hs-cTnI (Abbott), the NPV was 100.0%. The percentage of patients with undetectable levels of hs-cTnI was similar among the three hs-cTnI assays and ranged from 11.4% to 13.9%. CONCLUSIONS Undetectable levels of hs-cTn at presentation have a very high NPV and seem to allow the simple and rapid rule out of AMI. This criteria applies to much more patients with hs-TnT as compared to the investigated hs-cTnI assays.

Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay

Background: We aimed to prospectively validate a novel 1-hour algorithm using high-sensitivity cardiac troponin T measurement for early rule-out and rule-in of acute myocardial infarction (MI). Methods: In a multicentre study, we enrolled 1320 patients presenting to the emergency department with suspected acute MI. The high-sensitivity cardiac troponin T 1-hour algorithm, incorporating baseline values as well as absolute changes within the first hour, was validated against the final diagnosis. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data and serial measurements of high-sensitivity cardiac troponin T levels. Results: Acute MI was the final diagnosis in 17.3% of patients. With application of the high-sensitivity cardiac troponin T 1-hour algorithm, 786 (59.5%) patients were classified as “rule-out,” 216 (16.4%) were classified as “rule-in” and 318 (24.1%) were classified to the “observational zone.” The sensitivity and the negative predictive value for acute MI in the rule-out zone were 99.6% (95% confidence interval [CI] 97.6%–99.9%) and 99.9% (95% CI 99.3%–100%), respectively. The specificity and the positive predictive value for acute MI in the rule-in zone were 95.7% (95% CI 94.3%–96.8%) and 78.2% (95% CI 72.1%–83.6%), respectively. The 1-hour algorithm provided higher negative and positive predictive values than the standard interpretation of highsensitivity cardiac troponin T using a single cut-off level (both p < 0.05). Cumulative 30-day mortality was 0.0%, 1.6% and 1.9% in patients classified in the rule-out, observational and rule-in groups, respectively (p = 0.001). Interpretation: This rapid strategy incorporating high-sensitivity cardiac troponin T baseline values and absolute changes within the first hour substantially accelerated the management of suspected acute MI by allowing safe rule-out as well as accurate rule-in of acute MI in 3 out of 4 patients. Trial registration: ClinicalTrials.gov, NCT00470587

Death Without Prior Appropriate Implantable Cardioverter-Defibrillator Therapy A Competing Risk Study

Background— Implantable cardioverter-defibrillators (ICDs) improve survival in selected patients with left ventricular systolic dysfunction in randomized trials. Competing death without prior appropriate ICD therapy might preclude benefit from ICD implantation in a less selected routine-care population. Methods and Results— We selected all patients with ischemic or dilated cardiomyopathy with an ICD implanted for primary or secondary prevention from a single-center prospective registry between 1994 and 2006. The end point was time to first appropriate ICD therapy/confirmed ventricular fibrillation or death without prior appropriate ICD therapy. We analyzed cumulative incidence functions and used competing risk regression to study predictors of appropriate ICD therapy or prior death. In 442 patients, 73 deaths occurred during a median follow-up of 3.6 years (maximum, 12.7 years). The cumulative incidence of first appropriate ICD therapy until year 7 was 52%, whereas 11% died without prior ICD therapy. The cumulative incidence of appropriate ICD therapy for ventricular fibrillation was 13%, whereas 23% died without prior therapy for ventricular fibrillation. Appropriate ICD therapy was twice as likely in secondary prevention compared with primary prevention, whereas death rates before ICD therapy were similar in both groups. Diuretic use for heart failure compared with nonuse predicted a 4-fold-increased risk of death prior to ICD therapy, although the incidence of appropriate ICD therapy was similar in both groups. Conclusion— In a contemporary ICD population, the risk of death without prior appropriate ICD therapy is substantial, especially in patients with advanced heart failure.