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Biomedical subjects

Stefan Osswald

Publications and source records attributed to Stefan Osswald.

At least 19 recordsLinked to original sources

Unusual VDD-pacing.

The case of an 80-year-old woman who underwent permanent VDD-pacemaker implantation for recurrent syncope in the presence of second-degree type 2 AV-block is reported. During follow-up, low atrial sensing with AV-synchrony of only 58-73% was noted. Four years after the pacemaker implantation, the patient was hospitalized for non-cardiac reasons and the chest radiograph showed displacement of the atrial dipole into the right ventricular outflow tract (RVOT). It is hypothesized that AV-synchrony was maintained by left atrial sensing due to the anatomic proximity of the RVOT to the left atrial appendage.

Aged, 80 and over↗

Atrial fibrillation: estimated excess rate of stroke due to lacking adherence to guidelines.

QUESTIONS UNDER STUDY: Many patients with atrial fibrillation (AF), risk factors for stroke and no obvious contraindications do not receive oral anticoagulation. Estimations of the increased rate of stroke due to neglected anticoagulation, particularly in an elderly, non-selected population, are unknown. METHODS: Consecutive patients with paroxysmal or permanent atrial fibrillation admitted to the medical or surgical department of our hospital for any reason were studied. Risk factors for stroke and contraindications for anticoagulation were recorded. Estimations of the increased rate of cerebrovascular events due to neglected anticoagulation were based on data of a large meta-analysis. Patients were further stratified into different age and risk groups. RESULTS: 484 patients with a mean age of 75 (12) years were studied, 45% were female. 237 patients had no oral anticoagulation at hospital discharge, despite guideline recommendations. Contraindications for anticoagulation were found in 85 (36%) of these patients, resulting in 152 patients with neglected anticoagulation (31% of all patients with AF). We estimated that, if all those patients would have been treated according to guidelines, 7.4 strokes per year could be prevented in the study population. The estimated rate of preventable events was 4.9%/year (7.4/152). CONCLUSIONS: With better adherence to guidelines for oral anticoagulation in patients with atrial fibrillation and risk factors for stroke, a significant number of strokes could be prevented.

Administration, Oral↗

Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents.

OBJECTIVES: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. BACKGROUND: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. METHODS: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivitäts Trial). The primary focus of this observation was cardiac death/MI. RESULTS: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. CONCLUSIONS: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis.

Aged↗

Cardiac resynchronization therapy in chronic heart failure.

Cardiac resynchronisation therapy (CRT) has emerged as a treatment option for patients with severe, drug-refractory heart failure and signs of intraventricular dyssynchrony. In clinical trials CRT reduced the overall mortality, improved symptoms, exercise tolerance, and left ventricular function, as compared with optimised medical therapy alone. One of the challenging fields in patient selection for CRT is to identify the 20-30% of heart failure patients with bundle branch block that will not respond to this novel therapy. Other fields of uncertainty, such as CRT in patients with atrial fibrillation or chronic right ventricular stimulation as well as the role of a back-up defibrillator will be discussed.

Atrial Fibrillation↗

Early clinical experience with CardioCard - a credit card-sized electronic patient record.

QUESTIONS UNDER STUDY: CardioCard is a CDROM of credit card size containing medical information on cardiac patients. Patient data acquired during hospital stay are stored in PDF format and secured by a password known to patients only. In a consecutive series of patients, we assessed acceptance and utility of this new information medium. METHODS AND RESULTS: A questionnaire was sent to all patients who had received CardioCard over a one-year period. The questionnaire was returned by 392 patients (73%). 44% of patients had the card with them all the time. The majority of patients (73%) considered the CardioCard useful (8% not useful, 19% no statement) and most (78%) would even agree to bear additional costs. Only 5% worried about data security. In contrast, 44% would be concerned of data transmission via internet. During an observation period of 6 (SD 3) months, data were accessed by 27% of patients and 12% of their physicians. The proportion of card users was lower among older patients: < or = 50 years (y), 39%; 51.60 y, 38%; 61.70 y, 26%; >70 y, 16% and particularly among older women: 61.70 y, 9%; >70 y, 5%. Technical problems during data access occurred in 34%, mostly due to incorrect handling. CONCLUSIONS: A majority of patients considered CardioCard as useful and safe. Lack of hardware equipment or insufficient computer knowledge, but not safety issues were the most important limitations. As patients expressed concerns regarding protection of privacy if data were accessible via internet, this would remain a strong limiting factor for online use.

Adult↗

Ventricular tachycardia in an ice-hockey player after a blunt chest trauma.

A case of a professional ice-hockey with a blunt chest trauma is presented. A year after the first cardiac evaluation, he experienced sustained ventricular tachycardia after another slight chest trauma. An implantable cardioverter-defibrillator was implanted. The pathophysiological background of tachycardias after a blunt chest trauma and its management are discussed.

Adult↗

Prophylactic implantable cardioverter defibrillator therapy in dilated cardiomyopathy: impact of left ventricular function.

BACKGROUND: The value of an implantable cardioverter defibrillator (ICD) for primary prevention in dilated cardiomyopathy (DCM) is unclear, as randomized trials could not show a survival benefit compared to drug therapy. It has not been investigated if patients with a very poor left ventricular function (LVEF) could profit from an ICD. METHODS: Consecutive patients with DCM who received an ICD between December 1996 and November 2003 were included in this analysis. Patients were divided in group A (secondary prevention) and group B (primary prevention). Both groups were stratified in subgroups with left ventricular ejection fraction (LVEF) below and above 20%. RESULTS: Fifty eight patients were included (male 50, age 56.4+/-12.7 years). Follow-up was 34+/-19 months. There was no difference regarding death (18% vs. 11%), but significant differences (p value <0.05) regarding any adverse events (55% vs. 22%), any ICD intervention (48% vs. 17%) and ICD interventions for life-threatening arrhythmias (27% vs. 0%) between group A and B. LVEF was not predictive for events in group A, whereas in group B only patients with a LVEF <20% had events (p value 0.02). Over time there was an increase of the LVEF of more than 15% determined by echocardiography in 36% of patients, significantly more often in group B. CONCLUSIONS: Indication for primary prevention with an ICD in DCM should be made with caution. Larger studies are needed to determine if patients with LVEF of <20% might benefit from an ICD.

Adult↗

A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation.

OBJECTIVE: Brugada syndrome (BS) is an inherited electrical cardiac disorder characterized by right bundle branch block pattern and ST segment elevation in leads V1 to V3 on surface electrocardiogram that can potentially lead to malignant ventricular tachycardia and sudden cardiac death. About 20% of patients have mutations in the only so far identified gene, SCN5A, which encodes the alpha-subunit of the human cardiac voltage-dependent sodium channel (hNa(v)1.5). Fever has been shown to unmask or trigger the BS phenotype, but the associated molecular and the biophysical mechanisms are still poorly understood. We report on the identification and biophysical characterization of a novel heterozygous missense mutation in SCN5A, F1344S, in a 42-year-old male patient showing the BS phenotype leading to ventricular fibrillation during fever. METHODS: The mutation was reproduced in vitro using site-directed mutagenesis and characterized using the patch clamp technique in the whole-cell configuration. RESULTS: The biophysical characterization of the channels carrying the F1344S mutation revealed a 10 mV mid-point shift of the G/V curve toward more positive voltages during activation. Raising the temperature to 40.5 degrees C further shifted the mid-point activation by 18 mV and significantly changed the slope factor in Na(v)1.5/F1344S mutant channels from -6.49 to -10.27 mV. CONCLUSIONS: Our findings indicate for the first time that the shift in activation and change in the slope factor at a higher temperature mimicking fever could reduce sodium currents' amplitude and trigger the manifestation of the BS phenotype.

Action Potentials↗

Value of repeated cardiac magnetic resonance imaging in patients with suspected arrhythmogenic right ventricular cardiomyopathy.

AIM: Diagnosis of early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC) with minimal structural abnormalities is challenging. The purpose of this study was to assess the value of repeated cardiac magnetic resonance imaging (CMR) in patients referred for right ventricular arrhythmias and clinical suspicion of ARVC. METHODS AND RESULTS: Prospective follow-up study of 18 patients (8 females) studied with CMR for suspected ARVC. Patients with implanted defibrillators (ICD) were excluded. Mean follow-up was 37 +/- 16 (12-59) months. Patients were assigned to 2 categories (ARVC likely or ARVC unlikely) according to a CMR-score based on right ventricular abnormalities. Clinical follow-up revealed no disease progression in 17 patients (94%). In 1 patient, an ICD was implanted because of disease progression. Of 9 patients with initial findings suggestive of ARVC, follow-up CMR remained positive in 3 and was diagnosed as normal in 6, mainly due to the inability to confirm the presence of fatty infiltrates at follow-up (5 of 6 patients). Initially, 9 patients had a normal CMR and 8 of those remained normal during follow-up. CONCLUSION: Repeated CMR after an average follow-up of 3 years was normal in 6 of 9 patients with clinical findings consistent with early stages of ARVC at the time of baseline CMR. Thus, CMR diagnosis of early stage ARVC is difficult and should be made with caution.

Arrhythmogenic Right Ventricular Dysplasia↗

Influence of revascularization on long-term outcome in patients > or =75 years of age with diabetes mellitus and angina pectoris.

Little is known about the effect of revascularization in patients > or =75 years of age with symptomatic coronary artery disease (CAD) and diabetes mellitus (DM) for whom periprocedural risk and overall mortality are increased. Therefore, we examined the 301 patients of the Trial of Invasive versus Medical therapy in the Elderly with symptomatic CAD (TIME) with special regard to diabetic status. Patients were randomized to an invasive versus optimized medical strategy. The median follow-up was 4.1 years (range 0.1 to 6.9). Patients with DM (n = 69) had a greater incidence of hypertension (73% vs 58%, p = 0.03), > or =2 risk factors (93% vs 46%, p <0.01), previous heart failure (22% vs 12%, p = 0.04), and previous myocardial infarction (59% vs 43%, p = 0.02), and a lower left ventricular ejection fraction (48% vs 54%, p = 0.02) than did patients without DM. Mortality was greater in patients with DM than in those without DM (41% vs 25%, p = 0.01; adjusted hazard ratio 1.86, p = 0.01). Revascularization improved the overall survival rate from 61% (no revascularization) to 79% (p <0.01; adjusted hazard ratio 1.68, p = 0.03), an effect similarly observed in patients with and without DM. The event-free survival rate was 11% in nonrevascularized patients with DM compared with 40% in nonrevascularized patients without DM and 41% and 53% in revascularized patients with and without DM, respectively (p <0.01). Angina severity and antianginal drug use were similar for patients with and without DM, but those with DM performed worse in daily activities and physical functioning. In conclusion, elderly diabetic patients with chronic angina have a worse outcome than those with DM but benefit similarly from revascularization regarding symptom relief and long-term outcome. However, physical functioning related to daily activities is reduced in those with DM and may need special attention.

Age Factors↗

An electrocardiogram-based algorithm to detect loss of left ventricular capture during cardiac resynchronization therapy.

BACKGROUND: Loss of left ventricular capture in patients with cardiac resynchronization devices may account for worsening heart failure and can be difficult to diagnose without a programmer. OBJECTIVE: To determine whether distinct morphologic changes on the surface electrocardiogram indicate loss of left ventricular capture. DESIGN: After analysis of the R-S spike ratio in the 12-lead electrocardiogram during right ventricular and biventricular pacing in 10 patients, an algorithm to detect loss of left ventricular capture was developed. SETTING: University hospital. PATIENTS: 54 patients with a cardiac resynchronization device and underlying left bundle-branch block. MEASUREMENTS: Leads V1 and I of a 12-lead electrocardiogram were assessed after biventricular pacing was confirmed and after the device was programmed to right ventricular pacing only (simulating loss of left ventricular capture). RESULTS: The sensitivity of the algorithm to correctly identify loss of left ventricular capture was 94% (95% CI, 88.2% to 97.7%), and the specificity was 93% (CI, 86.3% to 95.8%). The likelihood ratio of a positive test result was 12.8 (CI, 6.443 to 23.310), and the likelihood ratio of a negative test result was 0.06 (CI, 0.024 to 0.137). LIMITATIONS: The algorithm was tested in patients in whom the right ventricular electrode was placed in the apex of the right ventricle only. CONCLUSION: Presence of biventricular capture--the prerequisite for successful cardiac resynchronization therapy--and loss of left ventricular capture can be accurately detected by an algorithm based on analysis of the R-S ratio on leads V1 and I of the surface electrocardiogram.

Algorithms↗

Methadone-induced Torsade de pointes tachycardias.

Methadone is a synthetic opioid frequently used in drug maintenance programs for heroin addicts. It prolongs the QT-interval and is mainly metabolized by the isoenzyme CYP3A4 of the hepatic cytochrome-P450-system, which is used by numerous other QT-prolonging agents. Its most severe side effect is the development of life-threatening Torsade de pointes ventricular tachycardia in the setting of a prolonged QT-interval. Since drug addicts are prone to concomitant medical conditions requiring additional medication as well as to continued abuse of cocaine, they are at higher risk for developing this major complication of methadone therapy. Before subjecting patients on methadone to other drugs, the QT-interval should be determined and it should be ascertained whether the new agent has the property to prolong the QT-interval or is metabolised by the cytochrome-P450 system.

Adult↗

Right atrial pacing impairs cardiac function during resynchronization therapy: acute effects of DDD pacing compared to VDD pacing.

OBJECTIVES: We aimed to compare the hemodynamic effects of right-atrial-paced (DDD) and right-atrial-sensed (VDD) biventricular paced rhythm on cardiac resynchronization therapy (CRT). BACKGROUND: Cardiac resynchronization therapy improves hemodynamics in patients with severe heart failure and left ventricular (LV) dyssynchrony. However, the impact of active right atrial pacing on resynchronization therapy is unknown. METHODS: Seventeen CRT patients were studied 10 months (range: 1 to 46 months) after implantation. At baseline, the programmed atrioventricular delay was optimized by timing LV contraction properly at the end of atrial contraction. In both modes the acute hemodynamic effects were assessed by multiple Doppler echocardiographic parameters. RESULTS: Compared to DDD pacing, VDD pacing resulted in much better improvement of intraventricular dyssynchrony assessed by the septal-to-posterior wall motion delay (VDD 106 +/- 83 ms vs. DDD 145 +/- 95 ms; p = 0.001), whereas the interventricular mechanical delay (difference between onset of pulmonary and aortic outflow) did not differ (VDD 20 +/- 21 ms vs. DDD 18 +/- 17 ms; p = NS). Furthermore, VDD pacing significantly prolonged the rate-corrected LV filling period (VDD 458 +/- 123 ms vs. DDD 371 +/- 94 ms; p = 0.0001) and improved the myocardial performance index (VDD 0.60 +/- 0.18 vs. DDD 0.71 +/- 0.23; p < 0.01). CONCLUSIONS: Our findings suggest that avoidance of right atrial pacing results in a higher degree of LV resynchronization, in a substantial prolongation of the LV filling period, and in an improved myocardial performance. Thus, the VDD mode seems to be superior to the DDD mode in CRT patients.

Atrial Fibrillation↗

A novel nonsense mutation in the SCN5A gene leads to Brugada syndrome and a silent gene mutation carrier state.

BACKGROUND: Brugada syndrome (BS) is an electrical cardiac disorder with a right bundle branch block and ST segment elevation in leads V1 to V3 on surface electrocardiograms (ECGs), and is a syndrome that may lead to sudden cardiac death. PURPOSE: The aim of the present study was to screen for mutations in the SCN5A gene in a family with BS, and to characterize the consequences of the mutation on channel function. RESULTS: A heterozygous nonsense SCN5A mutation (W822X) was identified in the index patient. The mutation was confirmed in the patient's asymptomatic 16-year-old brother and 48-year-old father. The mutation was absent in the index patient's sister and mother. The ECG of the index patient showed a BS type 2 ECG phenotype, which converted into a type 1 ECG phenotype in the presence of flecainide. The ECG of the patient's brother was not typical for BS, but ajmaline treatment unmasked a type 1 ECG phenotype. The ECG of the asymptomatic father was normal at baseline and in the presence of ajmaline. No Na+ currents could be measured in tsA201 cells transfected with W822X mutant channels. Heterozygote expression showed a nearly 50% reduction in Na+ current amplitude with no significant alterations of biophysical properties, indicating a loss of functional Na+ channels, obviously without any dominant-negative activity on wild type channels. CONCLUSIONS: The haploinsufficiency of the Nav1.5 protein is the plausible explanation for the clinical BS phenotype in this family. Because the heterozygous W822X mutation theoretically leads to channel expression at one-half of the normal level, the authors suggest that a modifier gene may influence or rescue the phenotype in the asymptomatic family members.

Adolescent↗

Cardiac resynchronization in severe heart failure and left bundle branch block: a single center experience.

OBJECTIVE: To assess the feasibility and longterm outcome of cardiac resynchronization therapy (CRT) in patients with impaired left ventricular function (LVEF <35%), left bundle branch block (QRS >120 ms) and dyspnoea NYHA 0 III at a single centre. METHODS AND RESULTS: Forty-seven patients were referred for implantation of a CRT device. In only 4 patients (9%) the device could not be implanted due to technical problems during the procedure. In the remaining 43 patients (65 +/- 10 years; 7 female) a CRT device was implanted. Follow-up time was 12 +/- 10 months. Twenty-one patients had dilated cardiomyopathy (DCM) and 22 patients had coronary artery disease (CAD). NYHA functional class improved from 3.0 +/- 1.4 to 2.5 +/- 0.7 (p <0.0001), accompanied by an improvement of LVEF [median 20% (range 15-25) vs 32% (range 20-40); p <0.0001]. A significant reduction of hospitalisation time for heart failure was found when the year before and the year after device implantation [18 days (range 5-27) vs 1 day (range 0-3); p <0.0001] were compared. Twelve (28%) patients, 9 with CAD, and 3 with DCM died. Two CAD patients and all patients with DCM who died had a combined CRT device with implantable cardioverter/defibrillator. CONCLUSION: In patients with severely impaired LVEF and wide QRS due to LBBB, CRT is feasible and safe. It improved dyspnoea and LVEF and reduced hospitalisation stays for heart failure during long-term follow-up.

Aged↗

Risks and benefits of optimised medical and revascularisation therapy in elderly patients with angina--on-treatment analysis of the TIME trial.

AIM: To assess treatment effects of optimised medical therapy and PCI or CABG surgery on one-year outcome in patients 75 years old with chronic angina. METHODS AND RESULTS: On-treatment analysis of the TIME data: all re-vascularised patients (REVASC n=174: 112 randomised to revascularisation and 62 to drugs with late revascularisation) were compared to all patients on continued drug therapy (MED n=127: 86 randomised to drugs and 41 to revascularisation only). Baseline characteristics of both groups were similar (age 80 +/- 4 years). Risk of death at one year (adjusted hazard ratio (HR)=1.31; 95%-CI: 0.58-2.99; P=0.52) and of death/infarction (adjusted hazard RATIO=1.77; 95%-CI 0.91-3.41; P=0.09) were comparable between REVASC and MED patients. Furthermore, the risk of death within 30 days was even slightly lower among REVASC patients (unadjusted hazard RATIO=0.73; 95%-CI: 0.21-2.53; P=0.98). Overall, REVASC patients had greater improvements in symptoms and well-being than MED patients (P<0.01). Surgical patients had similar mortality rates as angioplasty patients, but they also had greater symptomatic improvements (P<0.01). CONCLUSION: Treated medically, elderly patients with chronic angina have a similarly high 30-day and one-year mortality as patients of the same age being re-vascularised; however, they can expect lower improvements in symptoms and well being.

Aged↗