Effect of concomitant Renal DeNervation and cardiac ablation on Atrial Fibrillation recurrence - RDN+AF study.

BACKGROUND: Renal denervation (RDN) can reduce cardiac sympathetic activity maintained by arterial hypertension (aHT). Its potential antiarrhythmic effect on rhythm outcome in patients with multi-drug resistant aHT undergoing catheter ablation for atrial fibrillation (AF) is unclear. METHODS: The RDN+AF study was a prospective, randomized, two-center trial. Patients with paroxysmal or persistent AF and uncontrolled aHT (mean systolic 24-h ambulatory BP > 135 mmHg) despite taking at least three antihypertensive drugs were enrolled. Patients were 1:2 randomized to either RDN+AF ablation or AF-only ablation. Primary endpoint was freedom from any AF episode > 2 min at 12 months assessed by implantable loop recorder (ILR) or 7d-holter electrocardiogram. Secondary endpoints included rhythm outcome at 24 months, blood pressure control, periprocedural complications, and renovascular safety. RESULTS: The study randomized 61 patients (mean age 65 ± 9 years, 53% men). At 12 months, RDN+AF patients tended to have a greater decrease in ambulatory BPs but did not reach statistical significance. No differences in rhythm outcome were observed. Freedom from AF recurrence in the RDN+AF and AF-only group measured 61% versus 53% p = .622 at 12 months and 39% versus 47% p = .927 at 24 months, respectively. Periprocedural complications occurred in 9/61 patients (15%). No patient died. CONCLUSION: Among patients with multidrug-resistant aHT and paroxysmal or persistent AF, concomitant RDN+AF ablation was not associated with better blood pressure control or rhythm outcome in comparison to AF-only ablation and medical therapy.

The short term influence of right ventricular pacing burden on echocardiographic and spiroergometric parameters in patients with preserved left ventricular ejection fraction.

BACKGROUND: The incidence of worsened clinical outcome due to high right ventricular (RV) pacing burden in patients with preserved left ventricular function remains controversial. OBJECTIVE: To investigate the impact of RV pacing on several echocardiographic and spiroergometric parameters. METHODS: In 60 pacemaker patients with preserved left ventricular ejection fraction (LVEF) serial echocardiographies and spiroergometries were performed over a time course of 12 months. Additionally, in 48 patients retrospective echocardiographic analyses of the LV- and RV function were carried out up to 24 months after pacemaker implantation. RESULTS: The patients were divided into two groups: The high RV pacing burden group (hRVP: ≥ 40%) and the low RV pacing group (lRVP < 40%) according to the definitions in previous randomized MOST and DAVID trials. After a period of 12-month pacemaker therapy no changes to left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), LVEF, E/A-ratio; E/E'-ratio and tricuspid annular plane systolic excursion (TAPSE) could be revealed, independently of the RV pacing burden. Additionally, after 24-month long term follow-up there were no differences in LVEF and TAPSE in both groups. Accordingly, no relevant changes of peak exercise capacity, ventilatory anaerobic threshold or maximal oxygen consumption could be demonstrated independently of the RV pacing. CONCLUSIONS: In pacemaker patients with preserved LVEF the burden of RV pacing has no adverse influence on several echocardiographic and spiroergometric surrogate parameters of pacemaker-induced cardiomyopathy after a follow-up of 12 to 24 month. Despite this, screening for pacemaker induced cardiomyopathy should be performed especially in the presence of new heart failure symptoms.

Left atrial phasic transport function closely correlates with fibrotic and arrhythmogenic atrial tissue degeneration in atrial fibrillation patients: cardiac magnetic resonance feature tracking and voltage mapping.

AIMS: To characterize the association of phasic left atrial (LA) transport function and LA fibrosis guided by multimodality imaging containing cardiac magnetic resonance imaging (CMR) feature tracking and bipolar voltage mapping. METHODS AND RESULTS: Consecutive patients presenting for first-time ablation of atrial fibrillation (AF) were prospectively enrolled. Each patient underwent CMR prior to the ablation procedure. LA phasic indexed volumes (LA-Vi) and emptying fractions (LA-EF) were calculated and CMR feature tracking guided LA wall motion analysis was performed. LA bipolar voltage mapping was carried out in sinus rhythm to find areas of low voltage as a surrogate for fibrosis and arrhythmogenesis. One hundred and sixty-eight patients were enrolled. Low-voltage areas (LVAs) were present in 70 patients (42%). Contrary to LA volume, CMR based LA-EF [odds ratio (OR) 0.88, 95% confidence interval (CI) 0.80-0.96, P = 0.005] and LA booster pump strain rate (SR) (OR 0.98, 95% CI 0.97-0.99, P = 0.001) significantly predicted presence and extent of LVA in multivariate logistic regression analysis for patients scanned in SR. In receiver operating characteristic analysis, LA-EF <40% carried a sensitivity of 83% and specificity of 76% (area under the curve 0.8; 95% CI 0.71-0.89) to predict presence of LVA. For patients scanned in AF only minimal LA-Vi on CMR (OR: 1.06; 95% CI: 1.02-1.10; P = 0.002) predicted presence of LVA. CONCLUSION: For patients scanned in SR LA-EF and LA booster pump SR are closely linked to the presence and extent of LA LVA.

Electrophysiological findings during atrial fibrillation reablation: Extending from pulmonary vein reconnection to sequential bipolar voltage map information.

BACKGROUND: Left atrial substrate modification targeting low voltage zones (LVZ) is an ablation strategy that-in addition to pulmonary vein (PV) isolation-tries to eliminate arrhythmogenic mechanisms harbored in such tissue. Electrophysiological findings at reablation include (a) PV reconnection, (b) reconnection over previous substrate ablation, and (c) de-novo LVZ. OBJECTIVE: To study, prevalence and contribution of these arrhythmogenic electrophysiological entities in patients with atrial fibrillation (AF) recurrences. METHODS: Consecutive patients with highly symptomatic AF undergoing index and reablation were included (n = 113). In all patients' PV reconnection, reconnection over previous substrate ablation and spontaneous de-novo LVZ were quantitatively assessed and integrated into an individual reablation strategy. Follow-up was based on continuous device monitoring. RESULTS: At re-do procedure, 45 out of 113 (39.8%) patients showed PV reconnection as the only electrophysiological abnormality. Reconduction over previous lines was the only electrophysiological abnormality in 8 out of 113 (7.1%) patients. Spontaneous de-novo LVZ was the only electrophysiological abnormality in 12 out of 113 (10.6%) patients. Combined findings of PV reconnection, line reconduction, and/or spontaneous de-novo LVZ were seen in 40 out of 113 (35.4%) patients. No detectable electrophysiological abnormality was observed in 8 out of 113 (7.1%) patients. In univariate analysis, none of the tested electrophysiological characteristics independently predicted the outcome after re-do. CONCLUSIONS: In patients undergoing reablation, we could show that reconduction over previous substrate ablation as well as the development of new low voltage areas are frequent findings besides classical PV reconnection-without a clear leading cause for recurrences. These findings impact reablation strategies as well as the strategic focus during index procedures.

Left atrial fibrosis predicts left ventricular ejection fraction response after atrial fibrillation ablation in heart failure patients: the Fibrosis-HF Study.

AIMS: Atrial fibrillation (AF) and heart failure (HF) often coexist. Catheter ablation has been reported to restore left ventricular (LV) function but patients benefit differently. This study investigated the correlation between left atrial (LA) fibrosis extent and LV ejection fraction (LVEF) recovery after AF ablation. METHODS AND RESULTS: In this study, 103 patients [64 years, 69% men, 79% persistent AF, LVEF 33% interquartile range (IQR) (25-38)] undergoing first time AF ablation were investigated. Identification of LA fibrosis and selection of ablation strategy were based on sinus rhythm voltage mapping. Continuous rhythm monitoring was used to assess ablation success. Improvement in post-ablation LVEF was measured as primary study endpoint. An absolute increase in post-ablation LVEF ≥10% was defined as 'Super Response'. Left atrial fibrosis was present in 38% of patients. After ablation LVEF increased by absolute 15% (IQR 6-25) (P < 0.001). Left ventricular ejection fraction improvement was higher in patients without LA fibrosis [15% (IQR 10-25) vs. 10% (IQR 0-20), P < 0.001]. An inverse correlation between LVEF improvement and the extent of LA fibrosis was found (R2 = 0.931). In multivariate analysis, the presence of LA fibrosis was the only independent predictor for failing LVEF improvement [odds ratio 7.2 (95% confidence interval 2.2-23.4), P < 0.001]. Echocardiographic 'Super Response' was observed in 55/64 (86%) patients without and 21/39 (54%) patients with LA fibrosis, respectively (P < 0.001). CONCLUSION: Presence and extent of LA fibrosis predict LVEF response in HF patients undergoing AF ablation. The assessment of LA fibrosis may impact prognostic stratification and clinical management in HF patients with AF.

Prevalence and predictors of low voltage zones in the left atrium in patients with atrial fibrillation.

Aims: To describe the extent and distribution of low voltage zones (LVZ) in a large cohort of patients undergoing ablation for paroxysmal and persistent atrial fibrillation (AF), and to explore baseline predictors of LVZ in these patients. Methods and results: Consecutive patients who underwent a bipolar voltage map guided AF ablation, were enrolled. Voltage maps were conducted for each patient using 3-dimensional electroanatomical mapping system and LVZ were defined as areas of bipolar voltage < 0.5 mV. A total of 539 patients (309 male, age 65 ± 10 years) were included. Low voltage zones was present in 58 out of 292 patients with paroxysmal and 134 out of 247 persistent AF (P < 0.001). The area of LVZ was larger in patients with persistent as compare to paroxysmal AF, 5 cm2 (IQR 3-18.6) vs. 12.1 cm2 (IQR 3.6-28.5), P = 0.026, respectively. In the multivariate analysis age (OR 1.07, 95%CI 1.05-1.10, P < 0.001), female gender (OR 2.18, 95%CI 1.38-3.43, P = 0.001), sinoatrial node dysfunction (OR 3.90, 95%CI 1.24-12.21, P = 0.020), larger surface area of left atrium pr. cm2 (OR 1.01, 95%CI 1.00-1.02, P = 0.016), and persistent AF (OR 5.03, 95%CI 3.20-7.90, P<0.001) were associated with presence of LVZ. Conclusion: In a large cohort of patients undergoing ablation for AF, the prevalence of LVZ was higher and LVZ areas larger in patients with persistent as compared with paroxysmal AF. The most frequent localization of LVZ was anterior wall, septum and posterior wall. Presence of LVZ was associated with higher age, female gender, larger LA surface area, and sinoatrial node dysfunction.

Continuous monitoring after atrial fibrillation ablation: the LINQ AF study.

Aims: To study device performance, arrhythmia recurrence characteristics, and methods of outcome assessment using a novel implantable cardiac monitor (ICM) in patients undergoing ablation for atrial fibrillation (AF). Methods and results: In 419 consecutive patients undergoing first-time catheter ablation for symptomatic paroxysmal (n = 224) or persistent (n = 195) AF an ICM was injected at the end of the procedure. Telemedicine staff ensured full episode transmission coverage and manually evaluated all automatic arrhythmia episodes. Device detection metrics were calculated for ≥2, ≥6, and ≥10 min AF detection durations. Four methods of outcome assessment were studied: continuous recurrence analysis, discontinuous recurrence analysis, AF-burden analysis, and analysis of individual rhythm profiles. A total of 43 673 automatic AF episodes were transmitted over a follow-up of 15 ± 6 months. Episode-based positive predictive values changed significantly with longer AF detection durations (70.5% for ≥2 min, 81.8% for ≥6 min, and 85.9% for ≥10 min). Patients with exclusive short episode recurrences (≥2 to <6 min) were rare and their arrhythmia detection was clinically irrelevant. Different methods of outcome assessment showed a large variation (46-79%) in ablation success. Individual rhythm characteristics and subclinical AF added to this inconsistency. Analysis of AF-burden and individual rhythm profiles were least influenced and showed successful treatment in 60-70% of the patients. Conclusion: We suggest AF detection duration >6 min and AF burden >0.1% as a standardized outcome definition for AF studies to come in the future.

The Impact of Right Atrial Size to Predict Success of Direct Current Cardioversion in Patients With Persistent Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: The prognostic implication of right atrial (RA) and left atrial (LA) size for an immediate success of direct current cardioversion (DCCV) in atrial fibrillation (AF) remains unclear. This study aimed to compare RA and LA size for the prediction of DCCV success. METHODS: Between 2012 and 2018, 734 consecutive outpatients were screened for our prospective registry. Each eligible patient received a medical history, blood analysis, and transthoracic echocardiography with a focus on indexed RA (iRA) area and LA volume (iLAV) prior to DCCV with up to three biphasic shocks (200-300-360 J) or additional administration of amiodarone or flecainide to restore sinus rhythm. RESULTS: We enrolled 589 patients, and DCCV was in 89% (n=523) successful. Mean age was 68 ± 10 years, and 40% (n=234) had New York heart association class >II. A prevalence of the male sex (64%, n=376) and of persistent AF (86%, n=505) was observed. Although DCCV success was associated with female sex (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.06-3.65), with absence of coronary heart disease and normal left ventricular function (OR, 2.24; 95% CI, 1.26-4.25), with short AF duration (OR, 1.93; 95% CI, 1.05-4.04) in univariable regression, only iRA area remained a stable and independent predictor of DCCV success (OR, 0.27; 95% CI, 0.12-0.69; area under the curve 0.71), but not iLAV size (OR, 1.16; 95% CI, 1.05-1.56) in multivariable analysis. CONCLUSIONS: iRA area is superior to iLAV for the prediction of immediate DCCV success in AF.

Magnetic resonance imaging-guided conventional catheter ablation of isthmus-dependent atrial flutter using active catheter imaging.

Background: Interventional cardiac magnetic resonance (iCMR) has been established as a radiation-free alternative compared to standard fluoroscopy-guided catheter ablation for cavotricuspid isthmus (CTI)-dependent atrial flutter to image anatomy, structural alterations, and further catheter guidance. Objective: The purpose of this study was to explore the safety, feasibility, and efficacy of CTI ablations performed completely in the iCMR suite using active catheter imaging. Methods: Consecutive patients underwent iCMR-guided catheter ablation for CTI-dependent atrial flutter. Procedures were performed in a 1.5-T magnetic resonance (MR) imaging unit with MR-conditional ablation catheters. Catheter guidance was achieved using active catheter imaging via integrated MR receive tip coils. Acute success, periprocedural complications, and short-term follow-up were collected for further analysis. Results: All patients (N = 15; 73% male; median age 70 years; interquartile range [67-82]) achieved acute procedural success without any complication. Median procedural time was 43 minutes [33-58] with median radiofrequency delivery time of 18 minutes [12-26]. Postprocedural lesion visualization scanning was completed in a median of 32 minutes [10-42]. None of the patients with 6-month follow-up had atrial flutter recurrence. Conclusion: In the iCMR suite, CTI-dependent atrial flutter ablation could be achieved safely using active catheter imaging without any complication. It further allows detailed anatomic visualization of the CTI, intraprocedural lesion visualization, and exclusion of pericardial effusion.

Low-Voltage Myocardium-Guided Ablation Trial of Persistent Atrial Fibrillation.

BACKGROUND: Clinically effective ablation approaches for patients with persistent atrial fibrillation (AF) are still being debated. So far, ablation targets and strategies beyond pulmonary vein isolation (PVI) have failed to show systematic outcome improvement in randomized controlled clinical trials. METHODS: We conducted a multicenter, randomized trial to determine whether PVI plus individualized substrate ablation of atrial low-voltage myocardium improves outcome in patients with persistent AF. We randomly assigned 324 patients in a 1:1 ratio to receive PVI alone (163 patients; PVI only) or PVI plus substrate modification (161 patients; PVI+SM). The primary study end point was the first recurrence of an atrial arrhythmia longer than 30 seconds after single ablation, with 3 months blanking, using serial 7-day electrocardiogram recordings over 12 months of observation. Patients were also encouraged to receive implantable cardiac monitors. RESULTS: The primary study end point occurred in 75 PVI-only patients (50%) and in 54 PVI+SM patients (35%) (Kaplan­Meier event rate estimates: hazard ratio=0.62, 95% confidence interval [CI]=0.43 to 0.88, log rank P=0.006). Adverse events occurred in three PVI-only patients (1.8%) and in six PVI+SM patients (3.7%) (difference: −1.9 percentage points, 95% CI=−5.5 to 1.7 percentage points). Implant monitoring was used in 242 patients. Among them, 65 PVI-only patients (55%) versus 47 PVI+SM patients (39%) experienced recurrences (difference: 15 percentage points, 95% CI=3 to 28 percentage points). CONCLUSIONS: In this randomized trial, PVI plus individualized ablation of atrial low-voltage myocardium significantly improved outcomes in patients with persistent AF. (ClinicalTrials.gov number, NCT02732626.)

Left Atrial Isolation and Appendage Occlusion in Patients With Atrial Fibrillation at End-Stage Left Atrial Fibrotic Disease.

[Figure: see text].

Enhancement of the endothelial NO synthase attenuates experimental diastolic heart failure.

BACKGROUND: Diastolic heart failure is a rising problem with a high incidence and similar mortality and morbidity compared to patients with systolic heart failure. Nevertheless, the underlying pathophysiology is still debated. AIM: We investigated the effect of pharmacological enhancement of endothelial nitric oxide synthase (eNOS) on experimental diastolic heart failure (DHF). METHODS: DHF was induced in 60 DAHL salt-sensitive rats by salt diet in 8-week-old animals. 30 were treated with the eNOS enhancer AVE3085 (DHFeNOS) and 30 with placebo (DHF). Rats with normal salt intake served as controls. RESULTS AND CONCLUSION: Diastolic dysfunction with increased diastolic stiffness constant and increased left ventricular (LV) pressure was analyzed by invasive pressure-volume loop measurements in the DHF group compared to controls. Cardiac hypertrophy as indicated by LV mass measurements by echocardiography, and increased cardiac collagen content as measured by immunohistochemistry were associated with an increased activation state of calcineurin, AKT, ERK(1/2), but not JNK and p38 kinases. Titin isoforms were not altered in this model of DHF. Treatment with AVE3085 significantly increased eNOS mRNA and protein levels in the cardiac tissue and decreases NAD(P)H oxidase subunits p22phox and gp91phox. Diastolic dysfunction was attenuated and cardiac hypertrophy and fibrosis were improved in comparison with untreated DHF animals. This was associated with a normalized activation state of calcineurin, AKT and ERK(1/2). Therefore, we suggest that targeting the NO system might yield a future therapeutic aim for the treatment of DHF.

Endo-/Epicardial Catheter Ablation of Atrial Fibrillation: Feasibility, Outcome, and Insights Into Arrhythmia Mechanisms.

BACKGROUND: Until today, catheter interventional mapping and ablation of atrial fibrillation (AF) has been limited to the right and left atrial endocardium. We report feasibility, electrophysiological findings, and clinical outcome using a combined endo-/epicardial catheter approach for mapping and ablation of AF. METHODS AND RESULTS: Fifty-nine patients with permanence of pulmonary vein isolation and further symptomatic recurrences of paroxysmal AF, persistent AF, or atrial tachycardia underwent reablation using biatrial endo-/epicardial mapping and ablation. Identification of arrhythmia substrates and selection of ablation strategy were based on sinus rhythm voltage mapping. Using continuous monitoring and a 3-month blanking period, freedom from AF/atrial tachycardia ≥2 minutes was defined as primary end point. In all patients, endo-/epicardial mapping and ablation was feasible using standard technologies of catheter access, 3-dimensional mapping, and radiofrequency ablation. Epicardial mapping and ablation did not add procedural risks. Exclusively epicardial low voltage substrates were found in 14% of the patients. For the first time, novel epicardial conduction abnormalities located in the epicardial fiber network were described in human AF patients (19% of the cohort). Epicardial ablation was needed in 80% of the patients. Over 23±10 months of follow-up freedom from arrhythmia recurrences measured 73%. CONCLUSIONS: Catheter-based endo-/epicardial mapping and ablation of AF was feasible and safe. Epicardial mapping provided new insights into AF mechanisms. Epicardial ablation increased transmurality of ablation lesions. Clinical outcome in this cohort of complex AF patients was favorable, indicating potential further development of current AF treatment.

Heart-type fatty acid-binding protein and myocardial creatine kinase enable rapid risk stratification in normotensive patients with pulmonary embolism.

BACKGROUND: Risk assessments of hemodynamically stable patients with pulmonary embolisms (PE) remain challenging. In this context heart-type fatty acid-binding protein (H-FABP), creatine kinase isoenzyme MB (CK-MB), and troponin I (TnI) may hold prognostic utility for patients with pulmonary embolism. METHODS: We included 161 consecutive normotensive (systolic blood pressure above 90 mm Hg) patients with confirmed PE to study the combined utility of echocardiographic signs of right ventricular dysfunction and several biomarkers (TnI, CK-MB, H-FABP). The primary endpoint was defined as death within 30 days after admission to the hospital. RESULTS: Elevated biomarkers were measured in 26 patients (16.1%) for HFABP, in 66 (41%) for TnI and in 41 (25.5%) for CK-MB. Echocardiography revealed right ventricular dysfunction (RVD) in 99 (61.5%) patients. Overall, 16 patients (9.9%) died within the study period. In the H-FABP positive group 15 (57.7%) patients died compared to 13 (19.7%) patients in the TnI positive group and 15 (37.5%) patients in the CK-MB positive group (H-FABP positive vs TnI positive patients, P< .001; H-FABP positive vs CK-MB positive patients P= .13; CK-MB positive vs TnI positive patients P= .07). All elevated biomarkers correlated with the primary endpoint with H-FABP being strongly, CK-MB intermediately and TnI weakly associated with short term death (H-FABP r= 0.701, P< .001; CK-MB r= 0.486, P< .001; TnI r= 0.272, P= .001). In multivariate logistic regression analysis, a positive H-FABP test (OR 27.1, 95% CI 2.1-352.3, P= .001), elevated CK-MB levels (OR 5.3, 95% CI 1.3-23.3, P= .002) and a low systolic blood pressure on admission (OR 0.8, 95% CI 0.8-0.9, P< .001) emerged as independent predictors of 30-day mortality. CONCLUSIONS: Both H-FABP and CK-MB are associated with short term mortality in normotensive PE patients and could be advantageous for risk stratification in this intermediate risk group.

Determination of the acoustic output of a harmonic scalpel.

The acoustic output of a harmonic scalpel was experimentally determined, and both the airborne ultrasound and the ultrasound transmitted in water were taken into account. The sound pressure level of airborne ultrasound was measured with a microphone and an artificial head, so that the free-field value and the sound level at the entrance at the bottom of the cavum conchae of the ear could be determined. The derived output power in water was obtained from a hydrophone measurement. The results were strongly influenced by cavitation effects, and it is shown that the power values with and without cavitation differ by more than a factor of 5. The measurement of acoustic output parameters forms the basis for describing the performance of the devices and for an assessment of the risk of harmful bioeffects on both the operator and the patient.

Reduced MMP-2 activity contributes to cardiac fibrosis in experimental diabetic cardiomyopathy.

OBJECTIVE: To evaluate the regulation of matrix metalloproteinase (MMP)-2 in diabetic cardiomyopathy. METHODS: Left ventricle (LV) function was determined by a micro-tip catheter in streptozotocin (STZ)-induced diabetic rats, 2 or 6 weeks (w) after STZ-application. LV total collagen, collagen type I and III content were immunohistologically analyzed and quantified by digital image analysis. LV collagen type I, III and MMP-2 mRNA expression was quantified by real-time RT-PCR. LV pro- and active MMP-2 levels were analyzed by zymography; Smad 7, membrane type (MT)1-MMP and tissue inhibitor metalloproteinase (TIMP)-2 protein levels by Western Blot. RESULTS: STZ-induced diabetes was associated with a time-dependent impairment of LV diastolic and systolic function. This was paralleled by a time-dependent increase in LV total collagen content, despite reduced LV collagen type I and III mRNA levels, indicating a role of post-transcriptional/post-translational changes of extracellular matrix regulation. Six weeks (w) after STZ-injection, MMP-2 mRNA expression and pro-MMP-2 levels were 2.7-fold (P < 0.005) and 1.3-fold (P < 0.05) reduced versus controls, respectively, whereas active MMP-2 was decreased to undetectable levels 6 w post-STZ. Concomitantly, Smad 7 and TIMP-2 protein levels were 1.3-fold (P < 0.05) and 10-fold (P < 0.005) increased in diabetics versus controls, respectively, whereas the 45 kDa form of MT1-MMP was undetectable in diabetics. CONCLUSION: Under STZ-diabetic conditions, cardiac fibrosis is associated with a dysregulation in extracellular matrix degradation. This condition is featured by reduced MMP-2 activity, concomitant with increased Smad 7 and TIMP-2 and decreased MT1-MMP protein expression, which differs from mechanisms involved in dilated and ischemic heart disease.

Reference zero for the calibration of air-conduction audiometric equipment using 'tone bursts' as test signals.

The aim of this study was to determine reference peak-to-peak threshold sound pressure levels for air conduction sound transducers using groups of tone bursts as test signals. For this purpose, threshold measurements with five different earphones and a loudspeaker were carried out on groups of 25 young, otologically normal test subjects in the frequency range between 250 Hz and 8000 Hz, following as closely as possible the ISO Preferred Test Conditions. The dependence of the results on repetition rate, type of sound transducer, gender and age of the test subjects, and on reference pure tone thresholds was investigated. The results mainly depend on the reference equivalent sound pressure levels for pure tones of each sound transducer. Together with the results of another study carried out in Denmark, the data of the present study will form the basis for the International Standard ISO 389 Part 6 on reference hearing thresholds for acoustic test signals of short duration.

Reference zero for the calibration of audiometric equipment using 'clicks' as test signals.

Intended as an input to international standardisation, this study investigated reference hearing thresholds for the calibration of audiometric equipment, which have been determined using 'clicks' as test signals, several kinds of earphones, and two types of transducers (a loudspeaker and a bone vibrator). The threshold measurements were carried out with groups of 25 test persons with normal hearing capability following as far as possible the ISO-preferred test conditions. The influence of different parameters on the results, such as click duration, polarisation mode, repetition rate, gender and age of the test persons, or type of ear simulator, was studied. The results mainly depend on the type of ear simulator used to calibrate corresponding audiometers. Together with the results of another investigation carried out in Denmark, the data of the present study shall form the basis for the coming International Standard ISO 389-6 on reference hearing thresholds for acoustic test signals of short duration.

Recreational noise exposure and its effects on the hearing of adolescents. Part I: an interdisciplinary long-term study.

This interdisciplinary long-term study examined the effects of recreational noise exposure on the hearing of adolescents. Boys and girls (aged 14-17 years) were examined during a four-year period. Audiological, psychosocial, and sound measurements were performed yearly to determine the hearing threshold level (HTL) of participants in the 250-16000 Hz range, their participation in recreational activities, and the sound levels at discos and through personal music player use. A tendency of the mean HTL to increase in both genders during the study was observed, especially at 14000 Hz and 16000 Hz. Boys had a higher mean HTL than girls. The participation in musical activities increased yearly, 'attendance at discos' being the favourite musical activity for both groups. In general, boys were more exposed to high sound levels than girls. The equivalent sound levels in discos ranged between 104.3 and 112.4 dBA, and between 75 and 105 dBA from personal music players.