Evidence regarding clinical use of microvolt T-wave alternans [Accuracy of microvolt T-wave alternans testing]

Background: Microvolt T-wave alternans (MTWA) testing in many studies has proven to be a highly accurate predictor of ventricular tachyarrhythmic events (VTEs) in patients with risk factors for sudden cardiac death (SCD) but without a prior history of sustained VTEs (primary prevention patients). In some recent studies involving primary prevention patients with prophylactically implanted cardioverter-defibrillators (ICDs), MTWA has not performed as well. Objective: This study examined the hypothesis that MTWA is an accurate predictor of VTEs in primary prevention patients without implanted ICDs, but not of appropriate ICD therapy in such patients with implanted ICDs. Methods: This study identified prospective clinical trials evaluating MTWA measured using the spectral analytic method in primary prevention populations and analyzed studies in which: (1) few patients had implanted ICDs and as a result none or a small fraction (≤15%) of the reported end point VTEs were appropriate ICD therapies (low ICD group), or (2) many of the patients had implanted ICDs and the majority of the reported end point VTEs were appropriate ICD therapies (high ICD group). Results: In the low ICD group comprising 3,682 patients, the hazard ratio associated with a nonnegative versus negative MTWA test was 13.6 (95% confidence interval [CI] 8.5 to 30.4) and the annual event rate among the MTWA-negative patients was 0.3% (95% CI: 0.1% to 0.5%). In contrast, in the high ICD group comprising 2,234 patients, the hazard ratio was only 1.6 (95% CI: 1.2 to 2.1) and the annual event rate among the MTWA-negative patients was elevated to 5.4% (95% CI: 4.1% to 6.7%). In support of these findings, we analyzed published data from the Multicenter Automatic Defibrillator Trial II (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trials and determined that in those trials only 32% of patients who received appropriate ICD therapy averted an SCD. Conclusion: This study found that MTWA testing using the spectral analytic method provides an accurate means of predicting VTEs in primary prevention patients without implanted ICDs; in particular, the event rate is very low among such patients with a negative MTWA test. In prospective trials of ICD therapy, the number of patients receiving appropriate ICD therapy greatly exceeds the number of patients who avert SCD as a result of ICD therapy. In trials involving patients with implanted ICDs, these excess appropriate ICD therapies seem to distribute randomly between MTWA-negative and MTWA-nonnegative patients, obscuring the predictive accuracy of MTWA for SCD. Appropriate ICD therapy is an unreliable surrogate end point for SCD

A view from the Bridge: agreement between the SF-6D utility algorithm and the Health utilities Index

BACKGROUND: The SF-6D is a new health state classification and utility scoring system based on 6 dimensions (‘6D’) of the Short Form 36, and permits a ‘‘bridging’’ transformation between SF-36 responses and utilities. The Health Utilities Index, mark 3 (HUI3) is a valid and reliable multi-attribute health utility scale that is widely used. We assessed within-subject agreement between SF-6D utilities and those from HUI3. METHODS: Patients at increased risk of sudden cardiac death and participating in a randomized trial of implantable defibrillator therapy completed both instruments at baseline. Score distributions were inspected by scatterplot and histogram and mean score differences compared by paired t-test. Pearson correlation was computed between instrument scores and also between dimension scores within instruments. Between-instrument agreement was by intra-class correlation coefficient (ICC). RESULTS: SF-6D and HUI3 forms were available from 246 patients. Mean scores for HUI3 and SF-6D were 0.61 (95% CI 0.60–0.63) and 0.58 (95% CI 0.54–0.62) respectively; a difference of 0.03 (p50.03). Score intervals for HUI3 and SF-6D were (-0.21 to 1.0) and (0.30–0.95). Correlation between the instrument scores was 0.58 (95% CI 0.48–0.68) and agreement by ICC was 0.42 (95% CI 0.31–0.52). Correlations between dimensions of SF-6D were higher than for HUI3. CONCLUSIONS: Our study casts doubt on the whether utilities and QALYs estimated via SF-6D are comparable with those from HUI3. Utility differences may be due to differences in underlying concepts of health being measured, or different measurement approaches, or both. No gold standard exists for utility measurement and the SF-6D is a valuable addition that permits SF-36 data to be transformed into utilities to estimate QALYs. The challenge is developing a better understanding as to why these classification-based utility instruments differ so markedly in their distributions and point estimates of derived utilities

Wide QRS Tachycardia with Atrioventricular Dissociation and an HV Interval of 60 msec

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73193/1/j.1540-8167.1997.tb00814.x.pd

Effects of Rivaroxaban on Biomarkers of Coagulation and Inflammation: A Post Hoc Analysis of the X-VeRT Trial.

Introduction  This X-VeRT (eXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in patients with nonvalvular aTrial fibrillation scheduled for cardioversion) substudy evaluated the effects of treatment with rivaroxaban or a vitamin-K antagonist (VKA) on levels of biomarkers of coagulation (D-dimer, thrombin-antithrombin III complex [TAT] and prothrombin fragment [F1.2]) and inflammation (high sensitivity C-reactive protein [hs-CRP] and high-sensitivity interleukin-6 [hs-IL-6]) in patients with atrial fibrillation (AF) who were scheduled for cardioversion and had not received adequate anticoagulation at baseline (defined as, in the 21 days before randomization: no oral anticoagulant; international normalized ratio <2.0 with VKA treatment; or <80% compliance with non-VKA oral anticoagulant treatment). Methods  Samples for biomarker analysis were taken at baseline ( n  = 958) and treatment completion (42 days after cardioversion; n  = 918). The influence of clinical characteristics on baseline biomarker levels and the effect of treatment on changes in biomarker levels were evaluated using linear and logistic models. Results  Baseline levels of some biomarkers were significantly associated with type of AF (D-dimer and hs-IL-6) and with history of congestive heart failure (hs-CRP, D-dimer, and hs-IL-6). Rivaroxaban and VKA treatments were associated with reductions from baseline in levels of D-dimer (-32.3 and -37.6%, respectively), TAT (-28.0 and -23.1%, respectively), hs-CRP (-12.5 and -17.9%, respectively), and hs-IL-6 (-9.2 and -9.8%, respectively). F1.2 levels were reduced from baseline in patients receiving a VKA (-53.0%) but not in those receiving rivaroxaban (2.7%). Conclusion  Anticoagulation with rivaroxaban reduced levels of key inflammation and coagulation biomarkers to a similar extent as VKAs, with the exception of F1.2. Further investigation to confirm the value of these biomarkers in patients with AF is merited

„Effekte eines 8-wöchigen propriozeptiven neuromuskulären Faszikulationsdehnprogramms auf die Länge der Wadenmuskulatur und die Vorfußbelastung bei semiprofessionellen Fußballern“

Eine verkürzte Wadenmuskulatur wird als Ursache für eine Vielzahl an Pathologien erachtet. Durch die Verkürzung der Muskelsehneneinheit des Musculus triceps surae und der Achillessehne kommt es zu einer eingeschränkten Dorsalextension des Fußes und das dadurch reduzierte Bewegungsausmaß im oberen Sprunggelenk führt zu Schmerzen und degenerativen Veränderungen im Bereich der Achillessehne (Achillodynie), am Achillessehnenansatz (Ansatztendinose, posteriorer Fersensporn, Plantarfasziits) und dem Vorfuß (Metatarsalgie). Der pathoanatomische Zusammenhang einer verkürzten Wadenmuskulatur und der Metatarsalgie beruht auf einer chronisch erhöhten Vorfußbelastung. Die kausal orientierte Therapie der Beschwerden besteht in einer Verlängerung der Muskel-Sehnen-Strecke. Da sich bisher vorwiegend auf die Therapie von ausgeprägten Verkürzungen mit sichtbarer Spitzfußstellung konzentriert wurde, lag der therapeutische Fokus folglich auch vermehrt auf der operativen Verlängerung der Muskelsehneneinheit. Dadurch lässt sich auch das Übergewicht an Studien bezüglich operativer Ansätze und derer Ergebnisse erklären. Die konservative Herangehensweise einer Verlängerung der Wadenmuskulatur in Form von Dehnprogrammen und deren Auswirkungen auf die Vorfußbelastung ist bisher unzureichend untersucht worden. Die vorliegende Studie untersucht die Auswirkungen eines gezielten achtwöchigen Wadendehnungsprogramms auf Veränderungen des Bewegungsausmaßes im oberen Sprunggelenk und der Vorfußbelastung. Eine Interventionsgruppe (n= 22) und eine Kontrollgruppe (n= 19) wurden zweimalig mit einem zeitlichen Abstand von acht Wochen untersucht. Während die Interventionsgruppe für acht Wochen einem gezielten Wadendehnungsprogramm folgt, führt die Kontrollgruppe die etablierten Dehnroutinen unverändert fort. Das prä- und postinterventionelle Bewegungsausmaß im oberen Sprunggelenk wird mit Hilfe des Silfverskiöld Tests quantifiziert. Der Test gibt zudem Rückschlüsse, ob es sich um eine isolierte Verkürzung des M. gastrocnemius oder eine komplexe Verkürzung des gesamten M. triceps surae handelt. Die Vorfußbelastung wird mittels dynamischer Pedobarographie, dem subjektiven Schmerzempfinden und der Vorfußbeschwielung gemessen. Ergänzt werden die Erkenntnisse, durch die im Zuge eines Sprungtests ermittelten funktionellen Parameter Sprunghöhe, Bodenkontaktzeit und Reaktivitätsindex. Als Dehntechnik wurde das Propriozeptive Neuromuskuläre Faszkulationsdehnen gewählt, da dieser Technik die größte Wirkung auf Veränderungen des Bewegungsausmaßes attestiert wird. Als Studienpopulation wurden Fußballspieler gewählt, da bei ihnen aufgrund der ungleichmäßigen funktionellen Beanspruchung der Beinmuskulatur in der Regel eine Verkürzung der Wadenmuskulatur, die mit einer krankheitswertig gesteigerten Vorfußbelastung einhergeht, vorliegt. Die Ergebnisse der Studie zeigen, dass die Dehnintervention zu einer Vergrößerung der ROM im OSG führt. In der Interventionsgruppe konnte eine durchschnittliche Zunahme des Bewegungsausmaßes im oberen Sprunggelenk von durchschnittlich 0,75° auf der rechten Seite und 2° auf der linken Seite beobachtet werden. Dem gegenüber steht eine durchschnittliche Abnahme des Bewegungsausmaßes in der Kontrollegruppe von 2,5° auf der rechten Seite und 1,5° auf der linken Seite. Die eindeutige Vergrößerung der ROM führt jedoch nicht zu den erwarteten Veränderungen der Parameter, die die Vorfußbelastung quantifizieren. Auch auf die funktionellen Parameter des Sprungtests hat die Zunahme der Beweglichkeit im oberen Sprunggelenk keine eindeutig positiven Auswirkungen. Aufgrund der Messwerte der vorliegenden Untersuchung kann die These, dass eine Dehnintervention zu einer Reduktion der Vorfußbelastung führt, nicht bestätigt werden. Die Ergebnisse widersprechen dem allgemeinen Verständnis der Auswirkungen einer verlängerten Wadenmuskulatur auf die Vorfußbelastung. Aufgrund der vorliegenden Daten bedarf es mehr Studien, die den Zusammenhang des Bewegungsausmaßes im oberen Sprunggelenk und dynamischen plantaren Belastungsprofilen untersuchen, um ein besseres Verständnis für mögliche Zusammenhänge zu bieten und gegebenenfalls bisher nicht verstandene Mechanismen aufzudecken

Evidence regarding clinical use of microvolt T-wave alternans

Background: Microvolt T-wave alternans (MTWA) testing in many studies has proven to be a highly accurate predictor of ventricular tachyarrhythmic events (VTEs) in patients with risk factors for sudden cardiac death (SCD) but without a prior history of sustained VTEs (primary prevention patients). In some recent studies involving primary prevention patients with prophylactically implanted cardioverter-defibrillators (ICDs), MTWA has not performed as well. Objective: This study examined the hypothesis that MTWA is an accurate predictor of VTEs in primary prevention patients without implanted ICDs, but not of appropriate ICD therapy in such patients with implanted ICDs. Methods: This study identified prospective clinical trials evaluating MTWA measured using the spectral analytic method in primary prevention populations and analyzed studies in which: (1) few patients had implanted ICDs and as a result none or a small fraction (≤15%) of the reported end point VTEs were appropriate ICD therapies (low ICD group), or (2) many of the patients had implanted ICDs and the majority of the reported end point VTEs were appropriate ICD therapies (high ICD group). Results: In the low ICD group comprising 3,682 patients, the hazard ratio associated with a nonnegative versus negative MTWA test was 13.6 (95% confidence interval [CI] 8.5 to 30.4) and the annual event rate among the MTWA-negative patients was 0.3% (95% CI: 0.1% to 0.5%). In contrast, in the high ICD group comprising 2,234 patients, the hazard ratio was only 1.6 (95% CI: 1.2 to 2.1) and the annual event rate among the MTWA-negative patients was elevated to 5.4% (95% CI: 4.1% to 6.7%). In support of these findings, we analyzed published data from the Multicenter Automatic Defibrillator Trial II (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trials and determined that in those trials only 32% of patients who received appropriate ICD therapy averted an SCD. Conclusion: This study found that MTWA testing using the spectral analytic method provides an accurate means of predicting VTEs in primary prevention patients without implanted ICDs; in particular, the event rate is very low among such patients with a negative MTWA test. In prospective trials of ICD therapy, the number of patients receiving appropriate ICD therapy greatly exceeds the number of patients who avert SCD as a result of ICD therapy. In trials involving patients with implanted ICDs, these excess appropriate ICD therapies seem to distribute randomly between MTWA-negative and MTWA-nonnegative patients, obscuring the predictive accuracy of MTWA for SCD. Appropriate ICD therapy is an unreliable surrogate end point for SCD