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Biomedical subjects

Georg Schmidt

Publications and source records attributed to Georg Schmidt.

At least 19 recordsLinked to original sources
PubMed2006

Effects of circumferential or segmental pulmonary vein ablation for paroxysmal atrial fibrillation on cardiac autonomic function.

BACKGROUND: Circumferential and segmental pulmonary vein ablations are two established treatment strategies for ablation of atrial fibrillation. Both techniques require the application of radiofrequency current at anatomical sites that are close to autonomic ganglia. However, the effects of current pulmonary vein ablation techniques on cardiac autonomic function are unknown. OBJECTIVE: The purpose of this study was to analyze the short- and long-term effects of circumferential and segmental pulmonary vein ablation on cardiac autonomic function. METHODS: One hundred patients with highly symptomatic atrial fibrillation were randomly assigned to undergo either circumferential or segmental pulmonary vein ablation. Holter recordings were recorded at baseline and at regular intervals for up to 1 year after ablation. Autonomic function was assessed by deceleration capacity and acceleration capacity of heart rate as well as by standard measures of heart rate variability. RESULTS: In the circumferential pulmonary vein ablation group, deceleration capacity and acceleration capacity decreased highly significantly from 5.7 +/- 2.1 ms and -8.0 +/- 1.9 ms at baseline to 3.3 +/- 1.8 ms and -5.5 +/- 2.3 ms directly after ablation, respectively (P<.00001). Impairment of deceleration capacity and acceleration capacity was present up to 1 year after ablation. In the segmental pulmonary vein ablation group, deceleration capacity and acceleration capacity decreased from 5.8 +/- 2.0 ms and -7.8 +/- 1.6 ms at baseline to 3.4 +/- 1.2 ms and -6.0 +/- 2.4 ms directly after ablation (P<.00001), respectively. However, deceleration capacity and acceleration capacity returned to baseline values within 1 month. CONCLUSIONS: Circumferential and segmental pulmonary vein ablations induce an immediate decrease of autonomic function. However, while this decrease is only transient with segmental pulmonary vein ablation, it persists with circumferential pulmonary vein ablation for at least 1 year.

Aged↗
PubMed2006

Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study.

BACKGROUND: Decreased vagal activity after myocardial infarction results in reduced heart-rate variability and increased risk of death. To distinguish between vagal and sympathetic factors that affect heart-rate variability, we used a signal-processing algorithm to separately characterise deceleration and acceleration of heart rate. We postulated that diminished deceleration-related modulation of heart rate is an important prognostic marker. Our prospective hypotheses were that deceleration capacity is a better predictor of risk than left-ventricular ejection fraction (LVEF) and standard deviation of normal-to-normal intervals (SDNN). METHODS: We quantified heart rate deceleration capacity by assessing 24-h Holter recordings from a post-infarction cohort in Munich (n=1455). We blindly validated the prognostic power of deceleration capacity in post-infarction populations in London, UK (n=656), and Oulu, Finland (n=600). We tested our hypotheses by assessment of the area under the receiver-operator characteristics curve (AUC). FINDINGS: During a median follow-up of 24 months, 70 people died in the Munich cohort and 66 in the London cohort. The Oulu cohort was followed-up for 38 months and 77 people died. In the London cohort, mean AUC of deceleration capacity was 0.80 (SD 0.03) compared with 0.67 (0.04) for LVEF and 0.69 (0.04) for SDNN. In the Oulu cohort, mean AUC of deceleration capacity was 0.74 (0.03) compared with 0.60 (0.04) for LVEF and 0.64 (0.03) for SDNN (p<0.0001 for all comparisons). Stratification by dichotomised deceleration capacity was especially powerful in patients with preserved LVEF (p<0.0001 in all cohorts). INTERPRETATION: Impaired heart rate deceleration capacity is a powerful predictor of mortality after myocardial infarction and is more accurate than LVEF and the conventional measures of heart-rate variability.

Aged↗
PubMed2006

Turbulence dynamics: an independent predictor of late mortality after acute myocardial infarction.

INTRODUCTION: The prognostic value of heart rate turbulence for predicting mortality after acute myocardial infarction is well established. This study investigates a new measure of heart rate turbulence, termed turbulence dynamics, which quantifies the relationship between turbulence slope and underlying heart rate (HR(VPC)). METHODS: Six hundred eight patients participating in the European Myocardial Infarction Amiodarone Trial had > or =25 ventricular premature complexes/24 h. During a follow-up period of 21 months (median), 120 patients died. Turbulence dynamics was assessed as the slope of the regression line between turbulence slope and HR(VPC). Survival analyses included age, history of previous myocardial infarction, presence of diabetes mellitus, mean normal-to-normal interval, heart rate variability index, presence of non-sustained ventricular tachycardia, left ventricular ejection fraction, turbulence onset and turbulence slope. All risk predictors were dichotomized at pre-defined cut-off points, turbulence dynamics was dichotomized at the median. Primary endpoint of the study was death of any cause. RESULTS: In most patients, turbulence slope was inversely correlated to HR(VPC). Univariately, turbulence dynamics was the second strongest risk predictor of mortality (relative risk 2.4 (95% confidence interval 1.6-3.6), p<0.001). Multivariately, turbulence dynamics was the third strongest risk predictor (1.7 (1.1-2.7, p<0.01)). CONCLUSION: In the patient population studied, turbulence dynamics was an independent predictor of mortality. The results indicate that in addition to the overall level of autonomic function the loss of autonomic adaptability contributes to prognosis.

Acute Disease↗
PubMed2006

Impaired cardiac autonomic nervous activity predicts sudden cardiac death in patients with operated and unoperated congenital cardiac disease.

OBJECTIVES: Sudden cardiac death is a leading cause of mortality in patients with congenital cardiac disease after surgical correction and is potentially preventable. The identification of patients at risk is therefore of major interest. We sought to assess the prognostic value of impaired cardiac autonomic nervous activity in patients with congenital cardiac disease. METHODS: Forty-three consecutive patients with congenital cardiac disease were included in this prospective study. Parameters of heart rate turbulence and heart rate variability were calculated from Holter electrocardiograms. In addition, serum brain natriuretic peptide levels were measured. A combined end point of sudden cardiac death or nearly missed sudden cardiac death was used. RESULTS: During a mean follow up of 27 +/- 12.7 months, 5 patients died, and another 2 were successfully resuscitated. On univariate analysis, both brain natriuretic peptide levels and parameters of heart rate variability and heart rate turbulence were associated with impaired prognosis. On multivariate analysis, pathologic heart rate turbulence was found to be the strongest independent risk stratifier (hazard ratio, 61.5; P < .001). CONCLUSIONS: Impaired cardiac autonomic nervous activity is associated with an increased risk of sudden cardiac death in congenital cardiac disease. Our results suggest that heart rate turbulence might be superior to established markers of cardiac autonomic dysfunction, such as heart rate variability. The combined use of heart rate turbulence, heart rate variability, and markers of neurohormonal activation, such as brain natriuretic peptide, might further improve the prognostic value.

Adult↗
PubMed2006

Modified recombinant allergens for safer immunotherapy.

Molecular cloning and recombinant production of allergens offered new perspectives for the increasing problem of allergies. A variety of preparations are being developed aiming to increase safety and improve efficacy of specific immunotherapy. Recombinant-based approaches are mostly focused on genetic modification of allergens to produce molecules with reduced allergenic activity and conserved antigenicity, i.e. hypoallergens. Studies dealing with genetic modifications of allergen genes reported the production of site-directed mutants, deletion mutants, allergen fragments and oligomers, and allergen chimeras. An alternative to genetic engineering is the chemical modification of pure recombinant allergens. It has been shown that allergens modified with immunostimulatory DNA sequences (allergen-ISS conjugates), which masks IgE epitopes and adds a desirable Th1-inducing character to the allergen molecule. Other chemical modifications include oligomerization by aldehydes (allergoids) and maleylation, which seems to target allergens to particular antigen presenting cells. Several of these modified allergen preparations have been already evaluated for their safety in clinical provocation studies. So far, clinical trials showed the efficacy and safety of immunotherapy with an Amb a 1-ISS conjugate for ragweed pollen-allergic patients. In addition, a preparation consisting of hypoallergenic fragments of Bet v 1 was evaluated for immunotherapy of birch pollen-allergic patients. In parallel, several animal studies have now demonstrated the potential of genetic immunization for allergy treatment in the future.

Allergens↗
PubMed2005

Frequency of sudden cardiac death among acute myocardial infarction survivors with optimized medical and revascularization therapy.

The epidemiologic pattern of sudden cardiac death (SCD) may have changed in the modern treatment era of patients after an acute myocardial infarction (AMI). We evaluated the effect of optimized medical and revascularization therapy on the incidence of SCD after an AMI. A total of 2,130 consecutive patients (mean age 59 +/- 10 years) with an AMI from 2 European centers (Germany and Finland) was included in the study. In this population, 1,004 patients (47%) were treated with an optimized medical and revascularization strategy (defined as treatment with revascularization, beta blockers, aspirin, statins, and angiotensin-converting enzyme inhibitors). Nonoptimized treatment, defined as a lack of any optimized treatment, was received by 1,126 patients (53%). During the mean follow-up of 2.9 +/- 1.3 years, the incidence of SCD was very low among patients who received optimized treatment (1.2%, annual incidence 0.4%) compared with those who did not (3.6%, annual incidence 1.4%, p <0.01). The treatment strategy that had the greatest effect on differences in the SCD rate was revascularization therapy, with the hazard ratio of SCD being 2.1 (95% confidence interval 1.2 to 3.7, p <0.01) for SCD among nonrevascularized patients. Nonoptimized treatment was more often received by older patients, women, diabetic patients, and those with depressed left ventricular function. In conclusion, the incidence of SCD is low in the modern treatment era of patients after an AMI. Coronary revascularization seems to have a great effect on altered the epidemiologic pattern of SCD.

Adrenergic beta-Antagonists↗
PubMed2005

QRS duration and late mortality in unselected post-infarction patients of the revascularization era.

AIMS: To assess the association of prolonged QRS duration and late mortality in unselected post-infarction patients of the revascularization era. METHODS AND RESULTS: A total of 1455 survivors of acute myocardial infarction (MI) in sinus rhythm and under 76 years of age were enrolled. Ninety eight percent of the patients received reperfusion/revascularization therapy (90% percutaneous coronary intervention). After revascularization, prolonged QRS duration (>or=120 ms) was present in 87 patients (6.0%). Additional risk factors studied were age (>or=65 years), presence of diabetes mellitus, history of previous MI, mean heart rate (>75 b.p.m.), heart rate variability index (<or=20 U), arrhythmia on Holter, left ventricular ejection fraction (LVEF<or=30%), and heart rate turbulence (HRT). Primary endpoint was total mortality. During a follow-up period of 22+/-5 months, 70 patients died. On multivariable analysis, prolonged QRS duration showed the highest association with total mortality (hazard ratio 4.0; CI 2.3-6.9) followed by HRT Category 2 (3.8; 2.0-7.3) and LVEF<or=30% (3.1; 1.7-5.6). The association of prolonged QRS duration and late mortality was particularly strong in patients with LVEF<or=30% (5.0; 1.8-14.1). On multivariable analysis of secondary endpoints, prolonged QRS duration was significantly associated with cardiac mortality (3.9; 1.9-7.8), but not with sudden death and serious arrhythmic events. CONCLUSION: In the revascularization era, incidence of prolonged QRS duration is reduced. However, prolonged QRS duration is still highly correlated with increased late mortality.

Aged↗
PubMed2005

Characteristics of heart beat intervals and prediction of death.

OBJECTIVE: To assess the value for improving risk stratification of measures, unadjusted and adjusted for heart rate, of heart rate variability (HRV) and heart rate turbulence (HRT) based on 2- to 24-h ambulatory electrocardiographic recordings; and to relate this to the decision to use an implantable cardiac defibrillator (ICD) and the attendant consequences on effectiveness and cost-effectiveness. BACKGROUND: Risk stratification for high risk or low risk of lethal ventricular arrhythmic events, and hence for a decision about defibrillator implant, most commonly utilizes the left ventricular ejection fraction (LVEF). Electrocardiographic (ECG) approaches include 24-h ambulatory ECG recordings, with counts of ventricular premature contractions (VPCs), measures of heart rate variability (HRV), and heart rate turbulence (HRT). HRT has two components: turbulence onset (TO) and turbulence slope (TS). METHODS AND RESULTS: We evaluated the qualifying ambulatory ECG recordings from 744 patients in the active treatment arms of the Cardiac Arrhythmia Suppression Trial (CAST). Beat characteristics, VPC counts, normal-to-normal beat intervals, and time-domain measures of HRV and HRT were calculated. Tachograms were rescaled to a heart rate of 75 and the resulting "normalized" measures evaluated as risk predictors for death, compared to unnormalized measures. Measures based on 2-h ECGs were also evaluated as risk predictors. The most powerful univariate predictor of survival was the normalized turbulence slope. The best multivariate prediction model had six components: history of angina, hypertension, diabetes, and absence of post-myocardial infarction revascularization, the log of LVEF, normalized TS, HR, and an interaction term of HR and normalized TS. Gains in effectiveness from use of this model cost between $0 and $4000 per year of life saved. CONCLUSIONS: Turbulence slope substantially exceeded other ECG-based measures in improving prediction of subsequent death in models which included LVEF, and other clinical parameters. Use of this model would improve the effectiveness and cost-effectiveness of the ICD.

Arrhythmias, Cardiac↗
PubMed2005

Prediction of sudden cardiac death after acute myocardial infarction: role of Holter monitoring in the modern treatment era.

AIMS: Current treatment may have changed the risk profiles of survivors of acute myocardial infarction (AMI). We evaluated the utility of Holter-based risk variables in the prediction of sudden cardiac death (SCD) among survivors of AMI treated with modern therapy. METHODS AND RESULTS: A total of 2130 AMI patients (mean age 59 +/- 10 years) were included. The patients were treated with modern therapeutic strategies, for example, 94% were on beta-blocking therapy and 70% underwent coronary revascularization. Various risk parameters from Holter monitoring were analysed. During a median follow-up of 1012 days (interquartile range: 750-1416 days), cardiac mortality was 113/2130, including 52 SCDs. All Holter variables predicted the occurrence of SCD (P<0.01), but only reduced post-ectopic turbulence slope (TS) (P<0.001) and non-sustained ventricular tachycardia (P<0.01) remained as marked SCD predictors after adjustment for age, diabetes, and ejection fraction (EF). In a subgroup analysis, none of the Holter variables predicted SCD among those with an EF < or = 0.35, but many variables predicted SCD among those with an EF >0.35, particularly TS (hazard ratio 5.9; 95% CI 2.9-11.7, P<0.001). CONCLUSION: Among the post-AMI patients treated according to the current guidelines, the incidence of SCD is low. Various Holter variables still predict the occurrence of SCD, particularly among the patients with preserved left ventricular function.

Death, Sudden, Cardiac↗
PubMed2005

Reduced prognostic power of ventricular late potentials in post-infarction patients of the reperfusion era.

AIMS: To test the prognostic value of ventricular late potentials (LPs) in a large cohort of post-infarction patients in the modern reperfusion era. METHODS AND RESULTS: 1800 consecutive survivors of acute myocardial infarction in sinus rhythm and under 76 years of age were enrolled. Many (99%) of the patients received reperfusion/revascularization therapy (91% percutaneous coronary intervention) and up-to-date pharmacological treatment (99% aspirin, 93% beta-blockers, 90% ACE-inhibitors, and 85% statins). LPs were calculated in 968 patients and found to be present in 90 (9.3%). The primary endpoint was the composite of cardiac death and serious arrhythmic events. The secondary endpoint was the composite of sudden cardiac death and serious arrhythmic events. During follow-up (median 34 months), 26 patients reached the primary endpoint. The presence of LPs was not significantly associated with the primary endpoint in univariable or multivariable analysis. In contrast, low (< or = 30%) left ventricular ejection fraction (hazard ratio 9.6, 95% confidence interval 4.1-22.4), heart rate turbulence category 2 (7.5, 2.4-23.9) and category 1 (5.3, 1.9-14.9) were significant predictors in both univariable and multivariable analysis. CONCLUSION: Ventricular LPs are of limited use for risk stratification in unselected post-infarction patients in the modern reperfusion era.

Aged↗
PubMed2005

Esophageal cancer surgery in heart transplant patients.

We herein report about 2 heart transplant patients undergoing surgical resection for esophageal cancer. Both were long-term survivors after orthotopic heart transplantation for dilated cardiomyopathy. One patient underwent a transthoracic esophagectomy and gastric pull-up for an early squamous cell carcinoma of the infracarinal esophagus. The second patient underwent a resection of the cervical esophagus and interposition of a free jejunal segment after neoadjuvant radiochemotherapy for a locally advanced squamous cell carcinoma in the cervical esophagus.

Aged↗
PubMed2005

Heart rate turbulence and left ventricular ejection fraction in Chagas disease.

AIMS: Chagas disease patients often present premature ventricular complexes (PVCs), depression of left ventricular ejection fraction (LVEF) and autonomic dysfunction, which is generally evaluated by heart rate variability (HRV) analysis. As frequent PVCs may complicate HRV computation, we measured heart rate turbulence (HRT) and evaluated the correlation between ejection fraction and HRT or HRV in Chagas disease. METHODS: We studied 30 patients (47+/-11 years, 20 men) with Chagas cardiomyopathy and left ventricular dilatation who underwent clinical evaluation, ejection fraction (EF: 45+/-14%) determination and 24-h Holter monitoring (median PVC=1781). In all patients, the standard deviation of normal RR intervals (SDNN), the square root of the mean square differences of successive RR intervals (RMSSD) and values of turbulence onset (TO) and turbulence slope (TS) were calculated. RESULTS: HRT indices were independent of mean RR interval and presented high correlation with EF: TO (-0.11+/-0.01%, r=-0.60, P<0.001) and TS (5.8+/-3.7 ms/RR-interval, r=0.73, P<0.001). Of HRV parameters, only SDNN, corrected for mean RR interval, showed a weak but not significant correlation with EF (r=0.41). The comparison of HRT/EF and HRV/EF correlation coefficients, indicated the presence of a significant difference (P=0.017). CONCLUSIONS: HRT indices appear to correlate better with EF than SDNN in Chagas disease. Thus, an analysis based on heart rate transient adaptation seems to perform better than HRV in detecting the autonomic alterations that parallel left ventricular dysfunction in Chagas disease patients. The high number of PVCs observed in these patients further support the use of HRT methodology.

Adult↗
PubMed2005

Heart rate turbulence: a new predictor for risk of sudden cardiac death.

Initial acceleration and a subsequent deceleration of sinus rhythm following a ventricular ectopic beat with a compensatory pause has been termed heart rate turbulence (HRT). The changes in sinus rhythm are thought to be mediated by a baroreflex response to the lower stroke volume of the ectopic beat. HRT is vagally mediated and abolished by atropine, whereas beta-blockers have no effect. HRT has been shown to be an independent and powerful predictor of mortality after myocardial infarction. In patients on beta-blockers, it scores better than left ventricular ejection fraction (LVEF) in its predictive value. Two common measures of HRT are turbulence onset and turbulence slope. When both these measures are abnormal, it is as powerful a predictor of mortality as LVEF. HRT correlates with other indices of cardiac autonomic functions like baroreflex sensitivity and heart rate variability. A composite autonomic index including all these three has been shown to be a powerful predictor of mortality. In patients undergoing direct percutaneous intervention for myocardial infarction, HRT improves in those attaining successful reperfusion. Abnormal values for HRT have been noted in patients with dilated cardiomyopathy and Chagas disease. Diabetic and elderly individuals are more likely to have blunted HRT. HRT cannot be measured in patients lacking ventricular ectopic beats and in patients presenting with atrial fibrillation.

Arrhythmias, Cardiac↗
PubMed2004

Presence of sympathetically denervated but viable myocardium and its electrophysiologic correlates after early revascularised, acute myocardial infarction.

AIMS: After acute myocardial infarction (AMI), regional denervation exceeding the scar area has been described. We sought to define the electrophysiologic correlates of denervated, but viable, myocardium by combining scintigraphic imaging with extensive electrocardiographic evaluation in AMI patients treated with early reperfusion therapy. METHODS AND RESULTS: Within 14 days after AMI, 67 consecutive patients underwent radionuclide imaging of myocardial resting perfusion using (201)thallium and of presynaptic sympathetic innervation using (123)I-metaiodobenzylguanidine (MIBG). The mean left ventricular ejection fraction was 58+/-15%. Electrophysiologic studies included evaluation of ventricular repolarisation (resting ECG), depolarisation (signal-averaged ECG), and 24-h Holter monitoring. The perfusion defect, innervation defect, and perfusion/innervation mismatch size of the left ventricle were 14+/-15%, 39+/-22%, and 26+/-16%, respectively. Mismatch was present in 60/67 patients (90%) and correlated with prolonged repolarisation defined by QTc interval (r = 0.40; P < 0.001), and with indexes of delayed depolarisation from signal-averaged ECG (r = -0.32; P = 0.014). Other electrophysiologic parameters did not correlate. During follow-up (4.3+/-1 years) event rates were low, with two cardiac deaths and no severe ventricular arrhythmia causing hospitalisation. CONCLUSIONS: After early reperfusion for myocardial infarction, viable but denervated myocardium is frequent and correlates with slow depolarisation and repolarisation. However, in patients with small infarct size and preserved left ventricular function, these findings seem to have little influence on outcome.

3-Iodobenzylguanidine↗
PubMed2004

Heart rate turbulence: a 5-year review.

April 2004 marks the fifth anniversary of the first heart rate turbulence (HRT) publication, which demonstrated the usefulness of HRT in predicting cardiac death in postmyocardial infarction patients. Since then, HRT has been shown to predict prognosis of patients with dilated cardiomyopathy and of patients with heart failure of mixed etiology. HRT also has been shown to be predictive even in the current lower-mortality era of acute revascularization therapy for myocardial infarction. We discuss the latest criteria for obtaining reliable measurements of HRT, review factors that influence HRT values, and consider recent clinical studies.

Autonomic Nervous System↗
PubMed2004

Structural relationships between measures based on heart beat intervals: potential for improved risk assessment.

Decreased left ventricular ejection fraction is the most commonly used risk factor for identification of patients at high-risk for lethal ventricular arrhythmic events. Twenty-four-hour electrocardiographic (ECG) approaches to risk stratification include: counts of ventricular premature contractions (VPCs), measures of heart rate variability (HRV), and heart rate turbulence (HRT) which has two components, turbulence onset and turbulence slope (TS). Refinement of these ECG risk stratifiers could enhance their clinical utility. We explored the structural relationships between heart rate (HR) and HRV and HRT measures. Our goal was to separate out the component of these measures due to the underlying average heart rate (HR), thus potentially reducing the variability of the measures and increasing their power to stratify risk. We proposed re-scaling tachograms of heart-beat intervals so that the re-scaled tachogram has a HR of 75 (or equivalently an average interval of 800 ms) and calculating HRV and HRT from the rescaled time series. We also explored the relationship between the number of VPCs and HRT. We showed that TS is structurally related to the number of VPCs (and hence to the length of the ECG recording). We proposed an adjusted TS that is independent of the number of VPCs. We also addressed the ability of shorter ECG recording to estimate HRV and HRT measures. We evaluated standard and rescaled HRV and HRT measures using qualifying ambulatory ECG recordings from 744 patients in the Cardiac Arrhythmia Suppression Trial. We found that measures based on the rescaled tachogram had reduced variance (20% to 40%). Correlations between measures were also substantially reduced. We also found substantial circadian effects on some, but not all HRV indices, not explained by the circadian pattern in HR and possibly pointing to additional measures for risk prediction. In conclusion, we found that adjusting for HR and the number of VPCs in heart-beat related ambulatory ECG measures has the potential to significantly improve the power of these measures to risk stratify cardiac patients.

Algorithms↗