[Sleep-disordered breathing and cardiac resynchronization therapy]. / Schlafbezogene Atmungsstörungen und kardiale Resynchronisationstherapie.

Patients with progressive heart failure often suffer from sleep-disordered breathing (SDB). Upon receiving cardiac resynchronization therapy (CRT), there is an improvement of cardiac function and central sleep apnea syndrome (CSA) with Cheyne-Stokes respiration; however, effects of CRT on obstructive sleep apnea syndrome seemed to be without clinical relevance. Likewise, additional atrial overdrive pacing did not improve CRT effects relevantly in CSA patients. During CRT, there is an improvement in sleep parameters, sleep quality by reduction of depressive syndromes, and in long-term survival. Therefore, all patients with chronic heart failure and indication for CRT should be monitored regarding SDB before and after CRT device implantation.

[Modern angiographic diagnostic techniques in the catheter laboratory]. / Moderne Techniken der angiographischen Diagnostik im Katheterlabor.

Even at the beginning of the twenty-first century angiography still is the gold standard for imaging coronary arteries. Many limitations of this technique have facilitated advancements, such as quantitative coronary angiography and 3-dimensional reconstruction. The use of intravascular ultrasound has enabled a transmural in vivo imaging of the coronary arteries while creating cross-sectional images of the vessel wall. This led to a better evaluation of vascular plaques and the surrounding structures of the vessel. Optical coherence tomography is a new modality based on infrared light, which provides intraluminal and extraluminal imaging of vessels with a resolution of 10-20 µm, which is better than intravascular ultrasound (IVUS). However even this modern diagnostic tool is limited in the assessment of the relevance of an epicardial stenosis. Evaluation of the fractional flow reserve is a pathophysiological test, which measures the pressure before and after an epicardial stenosis and is able to assess the functional condition of a vessel with a high sensitivity and specificity. The so-called C-arm computed tomography (CACT; DynaCT Cardiac; Siemens, Erlangen, Germany) is a new application of an intraprocedural technique based on rotation of an x-ray source around a patient. It is able to generate information similar to that created by conventional computed tomography (CT) scans and offers the possibility to significantly enhance angiographic diagnostic modalities.

Influence of age on pain perception in acute myocardial ischemia: a possible cause for delayed treatment in elderly patients.

BACKGROUND: Elderly patients tend to seek later for medical help during myocardial infarction. This may be caused by impaired pain perception with ageing. The aim of our study was to prospectively evaluate age-dependent differences in pain perception during temporary induced coronary ischemia. METHODS: In 102 patients (68 male, age 68±11 years) undergoing percutaneous coronary intervention, ischemia was induced by balloon inflation for up to 120 s. Time to onset of perceived pain, pain characteristics and pain severity (0=no pain, 100=worst pain possible) was registered. This was repeated twice to evaluate ischemic preconditioning. A 12 lead ECG-tracing was simultaneously recorded. Patients were divided by their median age into 2 groups with comparable demographics: ≤69 years (group 1) and >69 years (group 2). RESULTS: Group 1 patients demonstrated earlier onset of pain (most apparent during the second inflation: 31±15 s vs. 46±26 s; p<0.001), and greater pain severity (inflation #1: 64±21 vs. 51±25 [p=0.017]; #2: 66±23 vs.52±27 [p=0.008]; #3: 63±23 vs. 54±24 [p=0.085]). ST-changes did not differ (0.24±0.10 vs. 0.20±0.14, [p=0.18]; 0.27±0.17 vs. 0.20±0.14, [p=0.11]; 0.19±0.13 vs. 0.16±0.09; [p=0.32]). Time from occlusion to onset of ECG changes did not differ between the groups, but increased with repetitive inflations (inflation #1: 29±11 s vs. 29±11 s; #2: 31±14 vs. 33±11; #3: 39±21 vs. 40±15 s [increase p=0.017; p<0.001]). CONCLUSION: These data suggest that the perception of pain from myocardial ischemia in the elderly is significantly less severe and delayed compared to younger patients.

[Dronedarone: the new antiarrythmic agent?]. / Dronedarone: Das neue Antiarrhythmikum?

Dronedarone is recommended as the successor drug to amiodarone because a faster onset of effects and less side effects are to be expected. This review describes the pharmacological properties of this multi-channel blocker and summarizes the results from recent studies proving successful antiarrhythmic therapy using dronedarone in patients with atrial fibrillation.

[Are neurohumoral parameters predictive for the efficacy of cardiac resynchronization therapy? The role of natriuretic peptides]. / Sind neurohumorale Blutparameter wegweisend für die Effizienz der kardialen Resynchronisationstherapie? Die Rolle der natriuretischen Peptide.

During recent years, heart failure has been recognized as a complex disease involving both hemodynamic abnormalities caused by reduced contractile forces and neurohormonal changes characterized by an increase in sympathetic tone and an activation of the renin-angiotensin-aldosterone system as well as the endothelial pathways. Neurohumoral factors represent the natural response of the individual to heart failure. Among them natriuretic peptides, i. e., brain natriuretic peptide (BNP) and amino-terminal pro BNP (Nt-proBNP) release have recently been shown to be a reliable and rapid marker for diagnosis, optimization of pharmacological treatment and risk stratification in heart failure patients. This article summarizes important aspects of the release of natriuretic peptides as a guide for diagnosis, therapy and prognosis of patients with heart failure and cardiac resynchronization therapy.

Home Monitoring in an ICD patient with incessant ventricular tachycardia.

Due to the increasing number of patients and complexity of modern tachycardia devices, efficient therapy surveillance as offered by Home Monitoring (HM) is of increasing importance. We report of an ICD patient with incessant ventricular tachycardia, in whom immediate arrhythmia transmission by HM permitted hospitalization and change of medication without time delay.

Brain natriuretic peptide release in cardiac surgery patients.

Brain natriuretic peptide (BNP) release is a marker of increased myocardial wall tension, which is elevated in patients with disturbed left ventricular function. As it is increasingly being used as a reliable marker for diagnosis, optimization of pharmacological treatment, and risk stratification, BNP measurement might be also relevant for patients undergoing cardiac surgery. Measured BNP levels can be used to predict postoperative complications and the risk of further cardiac events. Preoperative BNP levels support the decision for the timing of aortic valve replacement in asymptomatic severe aortic stenosis. An increase in BNP levels early predicts allograft rejection after cardiac transplantation or ineffective cardiac resynchronization therapy. Moreover, BNP levels can be used to differentiate between cardiac and non-cardiac reasons for acute dyspnea in the management of surgical patients. Finally, the application of recombinant human BNP seems to improve recovery after cardiac surgical procedures. Thus, BNP can be a helpful tool for monitoring and treating patients before, during, and after cardiac surgery to predict and improve the effectiveness of therapy and reduce hospitalization and costs.

[Improved identification of suitable patients for cardiac resynchronization therapy by transthoracic echocardiography]. / Verbesserte Identifizierung geeigneter Kandidaten für die kardiale Resynchronisationstherapie mittels transthorakaler Echokardiographie.

Transthoracic echocardiography provides numerous options for the evaluation and quantification of contractile cardiac asynchrony in patients with advanced heart failure. Important information on the presence of asynchrony can be obtained already during a standard routine examination with conventional techniques (2D, M-mode and Doppler). Newer techniques such as tissue Doppler imaging and real-time 3D-echocardiography enable us to better quantify the degree of asynchrony. The following article describes the echocardiographic features of asynchrony and algorithms for the improved identification of suitable patients for cardiac resynchronization therapy.

[Value of cardiac multislice spiral CT for the assessment of degenerative aortic stenosis: comparison with echocardiography]. / Wertigkeit der kardialen Mehrschicht-Spiral-CT zur Beurteilung der degenerativen Aortenklappenstenose: Vergleich zur Echokardiographie.

OBJECTIVE: To non-invasively assess the severity of aortic valve stenosis (AS) by the determination of aortic valve calcification (AVC) using multislice spiral computed tomography (MSCT). MATERIALS AND METHODS: Forty-one consecutive patients (17 male, 24 female, mean age 71.0 +/- 7.9 years) with a history of AS and an aortic valve area < or = 2 cm (2) underwent retrospectively ECG-gated 4-slice MSCT and echocardiography. The AVCs were quantitatively assessed using the score described by Agatston as well as by calculating the calcium mass. The echocardiographically determined aortic valve area (AVA) and the severity of AS according to the ACC/AHA guidelines were compared to the degree of aortic valve calcifications. Pearson's correlation coefficient, cut-off values, kappa test and F-test with post hoc Bonferroni t-tests were calculated. RESULTS: Calcium scores were significantly higher in patients with severe AS, when compared to mild or moderate AS (p < 0.001). In patients suffering from severe AS, the mean Agatston score was 4125.5 +/- 1168.9 (calcium mass 904.1 +/- 263.3) while in patients with moderate and mild AS the corresponding values were 1596.3 +/- 987.0 (319.1 +/- 208.3) and 785.9 +/- 390.1 (149.1 +/- 90.2), respectively. Pearson's correlation coefficients were r = - 0.75 for the Agatston score and r = - 0.72 for the calcium mass. There was a moderate agreement between severity of AS according to the ACC/AHA guidelines and the degree of AS determined from AVC scores with kappa = 0.6091 and kappa = 0.6985, respectively. CONCLUSION: Severe AS may be differentiated from moderate or mild AS using cardiac MSCT. Extensive calcifications of the aortic valve presenting with an Agatston-Score > or = 2824 (calcium mass > or = 611) indicate a severe AS and should be taken as an indication for further diagnostic workup.

Quantitative and qualitative assessment of left ventricular volume with ECG-gated multislice spiral CT: value of different image reconstruction algorithms in comparison to MRI.

PURPOSE: To assess the value of different image reconstruction algorithms for assessment of the left ventricular function using retrospectively ECG-gated multislice spiral computed tomography (MSCT) of the heart. MATERIAL AND METHODS: MSCT and cine magnetic resonance (MR) imaging of the heart were performed in 15 patients. For MSCT, standard and multisegmental image reconstruction with improved temporal resolution were used. Standardized multiplanar reformats in the short axis and long axis views were reconstructed from MSCT data. End-systolic (ESV) and end-diastolic volume (EDV), stroke volume (SV), ejection fraction (EF) and myocardial mass (MM) were calculated. Left ventricular wall motion was assessed qualitatively. RESULTS: MSCT was in acceptable agreement with MR imaging for quantification of the ventricular function. According to the Bland-Altman approach the mean differences for the left ventricular volumes (ESV, EDV, SV) ranged from -9.6 ml to 3.1 ml with standard image reconstruction and from -0.6 ml to 1.9 ml utilizing multisegmental image reconstruction with limits of agreement ranging from -26.6 ml to 12.5 ml and -15.6 ml to 15.0 ml, respectively. Applying the multisegmental image reconstruction algorithm, a significantly improved agreement with the MR data was found for EDV, SV and EF. For wall motion analysis, standard image reconstruction showed a significant difference to MR imaging with a correspondence in 83.75% of the 240 assessed segments, while multisegmental image reconstruction agreed with MR imaging in 92.5% of the segments. CONCLUSION: Multisegmental image reconstruction improves the quantitative assessment of left ventricular function when compared to standard image reconstruction. Multisegmental image reconstruction allows qualitative wall motion analysis.

Value of 3D-volume rendering in the assessment of coronary arteries with retrospectively ECG-gated multislice spiral CT.

PURPOSE: To assess the diagnostic value and measurement precision of 3D volume rendering technique (3D-VRT) from retrospectively ECG-gated multislice spiral CT (MSCT) data sets for imaging of the coronary arteries. MATERIAL AND METHODS: In 35 patients, retrospectively ECG-gated MSCT of the heart using a four detector row MSCT scanner with a standardized examination protocol was performed as well as quantitative X-ray coronary angiography (QCA). The MSCT data was assessed on segmental basis using 3D-VRT exclusively. The coronary artery diameters were measured at the origin of each main coronary branch and 1 cm, 3 cm and 5 cm distally. The minimum, maximum and mean diameters were determined from MSCT angiography and compared to QCA. RESULTS: A total of 353 of 525 (67.2%) coronary artery segments were assessable by MSCT angiography. The proximal segments were more often assessable when compared to the distal segments. Stenoses were detected with a sensitivity of 82.6% and a specificity of 92.8%. According to the Bland-Altman method the mean differences between QCA and MSCT ranged from -0.55 to 1.07 mm with limits of agreement from -2.2 mm to -2.7 mm. CONCLUSION: When compared to QCA, the ability of 3D-VRT to quantitatively assess coronary artery diameters and coronary artery stenoses is insufficient for clinical purposes.

[Quantification of cardiac function with multislice spiral CT using retrospective EKG-gating: comparison with MRI]. / Quantifizierung der Herzfunktion in der Mehrschicht Spiral CT mit retrospektivem EKG-Gating: Vergleich zur Kernspintomographie.

PURPOSE: To quantify left ventricular function derived from retrospectively ECG-gated multislice spiral CT (MSCT) data sets in comparison to MRI. MATERIALS AND METHODS: In 16 patients (14 males, 2 females, mean age 56.8 +/- 11.5 years), retrospectively ECG-gated MSCT angiography of the coronary arteries and breath-hold steady state free precession cine MRI were performed. From MSCT data-sets, 20 axial image series were reconstructed every 5 % of the RR interval. Multiplanar images were reformatted in the short axis orientation from axial images. End-systolic and end-diastolic images were selected. From these images end-systolic volume (ESV), end-diastolic volume (EDV) and stroke volume (SV) as well as the ejection fraction (EF) and myocardial mass (MM) were determined using the Simpson's method and compared with MRI. Furthermore, image quality was assessed for both imaging modalities using a four point grading scale. RESULTS: All parameters were found to have an excellent correlation between MSCT and MRI data (Pearson's correlation coefficient 0.95 - 0.99), without clinically relevant differences between both modalities. On average, the difference between both methods was 0.5 ml for ESV, 0.8 ml for EDV, 1.3 ml for SV, 0.9 % for EF and 2.3 g for MM. Image quality was slightly better for MRI (1.5 +/- 0.65) than for MSCT (1.64 +/- 0.74). CONCLUSION: Retrospectively ECG-gated MSCT angiography can not only visualize the coronary arteries but also enables precise quantification of the left ventricular function from the same MSCT data set.

Steroid-eluting and fractally coated electrodes in children with high pacing thresholds.

High pacing thresholds in epicardially implanted leads are a frequent issue in children after cardiac surgery. In 2 infants, repeated revisions of non-steroid-eluting leads were necessary. To avoid further frequent replacements, two epicardial ventricular leads, one steroid-eluting and an additional fractally coated electrode as a pacing "backup" were connected to the atrial and ventricular outlet of a DDD pacemaker, allowing a comparison between two both electrodes. Showing no differences in long-term measurements, both electrodes seem to provide a comparably high level of safety.

[A differentiated approach to the diagnosis of pulmonary embolism and deep venous thrombosis using multi-slice CT]. / Abklärung von Lungenembolie und venöser Thromboembolie mittels Mehrschicht-Spiral CT.

PURPOSE: To establish a differentiated protocol for multi-slice CT (MSCT) examinations in cases of clinically suspected pulmonary embolism (PE) using pulmonary CT-angiography (CTA) and indirect CT-phlebography (CTP). MATERIALS AND METHODS: 161 patients with suspected PE were examined using an MSCT (SOMATOM Volume Zoom; Siemens, Forchheim, Germany). After intravenous administration of 120 ml of contrast material, a thin collimation chest-CT scan was performed (120 kV, 100 mAs, collimation: 4 x 1 mm). If PE was present, or previous examinations and clinical signs suggested deep venous thrombosis (DVT), a CTP was subsequently completed. CTPs were performed using a 4 x 5 mm protocol (120 kV, 170 mAs). Venous phase scanning, starting from the pelvic crest, was completed in the popliteal fossa three minutes after contrast material injection. In 73 extremities, CTP were compared to the results of ultrasound, phlebography and autopsy. Scan ranges were documented in all patients. Cumulative doses were calculated for male and female subgroups. RESULTS: 62 patients in our series suffered from PE and in 47 of these patients deep venous thrombosis was seen additionally. Of the 99 patients without PE, 47 also received indirect CTP. CTP confirmed the suspicion and extent of DVT in 8 patients. Only in 2 of 39 patients (5.1 %) was previously unknown DVT found, despite the exclusion of PE. Regarding DVT, sensitivity was 94.3 % and specificity was 92.1 % for indirect CTP. Cumulative chest CT doses averaged 3.3 mSv for males and 4.2 mSv for females, the calculated CTP dosage was 9.3 mSv (according to ICRP 60). CONCLUSIONS: The examination protocol presented is suitable for clinical usage in patients with suspected PE. If PE is confirmed, indirect CTP is justified, so that detailed information of the venous system can be obtained. However, the relatively high radiation dosage of an additional CTP requires a strict indication regiment in patients with a negative CTA.

[The influence of motion artifacts conditioned by reconstruction, on the coronary calcium score in multislice spiral CT]. / Der Einfluss rekonstruktionsbedingter Bewegungsartefakte auf den koronaren Kalziumscore bei der Mehrschicht-Spiral-CT.

UNLABELLED: The influence of motion artifacts conditioned by reconstruction, on the coronary calcium score in multislice spiral CT. PURPOSE: A major problem of the quantification of coronary calcifications is a high variability of the coronary calcium score between recurrent examinations and different observers. Aim of our study is to evaluate the influence of different RR-intervals on the coronary calcium score utilizing retrospectively gated Multislice Spiral CT (MSCT) data sets. MATERIALS AND METHOD: 50 consecutive patients underwent MSCT examination (Somatom Volume Zoom, Siemens, Forchheim, G) utilizing a standardized scan protocol (4 x 2.5 mm collimation, 3 mm increment, tube current 133 mAs, tube voltage 120 kV). Retrospectively gated image reconstruction was performed every 10 % of the RR interval. Coronary calcification was evaluated by the Agatston score. Coronary risk assessment was performed in all patients with image reconstruction beginning at 80 % of the RR interval. The reconstruction intervals with the least motion artifacts were identified and chosen as reference for a reevaluation of the coronary risk. The results of different reconstruction times were compared. RESULTS: The mean calcium score was 551.6. The calcium score varied between 512.2 (90 %) and 571.7 (70 %), depending on the image reconstruction interval. Compared to the mean calcium score a new classification of the coronary risk was necessary in 7/50 of the patients at 80 % reconstruction interval, and in 2/50 of the patients at 50 % of the RR interval, respectively. CONCLUSION: Movement of the coronary arteries at different image reconstruction intervals has an important influence on the coronary calcium score. Based on our data, we propose image reconstruction at 50 % of the RR interval for evaluation of the coronary calcium score by MSCT.

Alternative forms of the human thioredoxin mRNA: identification and characterization.

Thioredoxin (TRX) is an ubiquitous and relatively conserved oxidoreductant enzyme which is involved in a multitude of redox reactions through the formation of reversible disulfide bonds. A recent report indicates the presence of novel isoforms of TRX proteins isolated from MP6 cell lines [Rosén et al., Int. Immunol. 7 (1995) 625-633]. In these isoforms, as evidenced from amino acid sequencing, several Lys residues of the wild-type sequence were replaced by Arg. Although the human genome contains several (isoformic) copies of the TRX gene, only one appears to be transcriptionally active [Kaghad et al., Gene, 140 (1994) 273-278]. As we characterized the isoforms of TRX mRNAs, we found that several MP6 TRX cDNA clones were devoid of the characteristic poly(A) tail. In order to increase the efficiency of isolating mRNAs without the poly(A) tail, we developed a novel procedure for exclusive capturing of a specific mRNA by magnetic beads coated with biotinylated antisense oligodeoxyribonucleotide. Using this method on MP6 cell total RNA, we isolated an additional truncated version of the TRX mRNA. This latter form does not produce any variant TRX enzyme, as an inframe stop codon truncates the product. This isoform was also present in mRNAs isolated from human placenta, leucocyte cells and Molt4 cells, the latter two being the progenitors of MP6 cells. From a thorough analysis of the sequence of the truncated TRX mRNA, we conclude that this variant originated from an event of altered splicing, as consensus splice sites were present in the normal TRX cDNA at precise positions.

Cloning and sequence of a cDNA encoding a novel hybrid proline-rich protein associated with cytokinin-induced haustoria formation in Cuscuta reflexa.

A complete cDNA encoding a novel hybrid Pro-rich protein (HyPRP) was identified by differentially screening 3 x 10(4) recombinant plaques of a Cuscuta reflexa cytokinin-induced haustorial cDNA library constructed in lambda gt10. The nucleotide (nt) sequence consists of: (i) a 424-bp 5'-non coding region having five start codons (ATGs) and three upstream open reading frames (uORFs); (ii) an ORF of 987 bp with coding potential for a 329-amino-acid (aa) protein of M(r) 35,203 with a hydrophobic N-terminal region including a stretch of nine consecutive Phe followed by a Pro-rich sequence and a Cys-rich hydrophobic C terminus; and (iii) a 178-bp 3'-UTR (untranslated region). Comparison of the predicted aa sequence with the NBRF and SWISSPROT databases and with a recent report of an embryo-specific protein of maize [Jose-Estanyol et al., Plant Cell 4 (1992) 413-423] showed it to be similar to the class of HyPRPs encoded by genes preferentially expressed in young tomato fruits, maize embryos and in vitro-cultured carrot embryos. Northern analysis revealed an approx. 1.8-kb mRNA of this gene expressed in the subapical region of the C. reflexa vine which exhibited maximum sensitivity to cytokinin in haustorial induction.

Calicheamicin gamma 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifically.

Calicheamicin gamma 1I is a recently discovered diyne-ene--containing antitumor antibiotic with considerable potency against murine tumors. In vitro, this drug interacts with double-helical DNA in the minor groove and causes site-specific double-stranded cleavage. It is proposed that the observed cleavage specificity is a result of a unique fit of the drug and DNA followed by the generation of a nondiffusible 1,4-dehydrobenzene--diradical species that initiates oxidative strand scission by hydrogen abstraction on the deoxyribose ring. The ability of calicheamicin gamma 1I to cause double-strand cuts at very low concentrations may account for its potent antitumor activity.

Molecular genetics of Red biosynthesis in Streptomyces.

We have studied the molecular biology of undecylprodigiosin (Red) biosynthesis by Streptomyces coelicolor as a model system for understanding the genetic regulation of antibiotic biosynthesis. A collection of new red mutants was obtained using a directed screen. Regions of DNA involved in the transcriptional regulation of red gene expression were also isolated.