ABSTRACT
Dizziness is a common symptom with many potential causes. Medical and especially cardiac aetiologies are associated with a poor overall prognosis such that identification of the underlying cause is essential. This article gives an overview of possible causes of dizziness, how the differential diagnoses should be investigated, and describes potential therapeutic approaches to the treatment of the most important underlying conditions.
Subject(s)
Dizziness , Humans , Diagnosis, Differential , Dizziness/etiology , Dizziness/diagnosis , Dizziness/therapy , PrognosisABSTRACT
PURPOSE OF REVIEW: The distinction between 'acute' and 'chronic' heart failure persists. Our review aims to explore whether reclassifying heart failure decompensation more accurately as an event within the natural history of chronic heart failure has the potential to improve outcomes. RECENT FINDINGS: Although hospitalisation for worsening heart failure confers a poor prognosis, much of this reflects chronic disease severity. Most patients survive hospitalisation with most deaths occurring in the post-discharge 'vulnerable phase'. Current evidence supports four classes of medications proven to reduce cardiovascular mortality for those who have heart failure with a reduced ejection fraction, with recent trials suggesting worsening heart failure events are opportunities to optimise these therapies. Abandoning the term 'acute heart failure' has the potential to give greater priority to initiating proven pharmacological and device therapies during decompensation episodes, in order to improve outcomes for those who are at the greatest risk.
Subject(s)
Heart Failure , Humans , Heart Failure/drug therapy , Aftercare , Patient Discharge , Hospitalization , Chronic Disease , Stroke VolumeABSTRACT
BACKGROUND: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm. METHODS: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups. RESULTS: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group (P<0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups. CONCLUSIONS: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738.
Subject(s)
Arrhythmias, Cardiac/therapy , Atrial Fibrillation/therapy , Defibrillators, Implantable , Electric Countershock/methods , Aged , Aged, 80 and over , Equipment Failure , Female , Humans , Male , Middle Aged , RiskABSTRACT
The capacitive electrocardiograph (cECG) has been tested for several measurement scenarios, including hospital beds, car seats and chairs since it was first proposed. The inferior signal quality of the cECG compared to the gold standard ECG guides the ongoing research in the direction of out-of-hospital applications, where unobtrusiveness is sought and high-level diagnostic signal quality is not essential. This study aims to expand the application range of cECG not in terms of the measurement scenario but in the profile of the subjects by including subjects with implanted cardiac pacemakers. Within this study, 20 patients with cardiac pacemakers were recruited during their clinical device follow-up and cECG measurements were conducted using a seat equipped with integrated cECG electrodes. The multichannel cECG recordings of active unipolar and bipolar pacemaker stimulation were analyzed offline and evaluated in terms of Fß scores using a pacemaker spike detection algorithm. Fß scores from 3652 pacing events, varying from 0.62 to 0.78, are presented with influencing parameters in the algorithm and the comparison of cECG channels. By tuning the parameters of the algorithm, different ranges of Fß scores were found as 0.32 to 0.49 and 0.78 to 0.88 for bipolar and unipolar stimulations, respectively. For the first time, this study shows the feasibility of a cECG system allowing health monitoring in daily use on subjects wearing cardiac pacemakers.
Subject(s)
Automobiles , Electrocardiography , Electrodes , Monitoring, Physiologic/instrumentation , Pacemaker, Artificial , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedABSTRACT
Atrial fibrillation (AF) is the most common arrhythmia and has a major impact on morbidity and mortality; however, detection of asymptomatic AF is challenging. This study sims to evaluate the sensitivity and specificity of non-invasive AF detection by a medical wearable. In this observational trial, patients with AF admitted to a hospital carried the wearable and an ECG Holter (control) in parallel over a period of 24 h, while not in a physically restricted condition. The wearable with a tight-fit upper armband employs a photoplethysmography technology to determine pulse rates and inter-beat intervals. Different algorithms (including a deep neural network) were applied to five-minute periods photoplethysmography datasets for the detection of AF. A total of 2306 h of parallel recording time could be obtained in 102 patients; 1781 h (77.2%) were automatically interpretable by an algorithm. Sensitivity to detect AF was 95.2% and specificity 92.5% (area under the receiver operating characteristics curve (AUC) 0.97). Usage of deep neural network improved the sensitivity of AF detection by 0.8% (96.0%) and specificity by 6.5% (99.0%) (AUC 0.98). Detection of AF by means of a wearable is feasible in hospitalized but physically active patients. Employing a deep neural network enables reliable and continuous monitoring of AF.
Subject(s)
Atrial Fibrillation , Wearable Electronic Devices , Aged , Aged, 80 and over , Algorithms , Atrial Fibrillation/diagnosis , Electrocardiography , Female , Humans , Inpatients , Male , Middle Aged , Stroke Volume , Ventricular Function, LeftABSTRACT
Electromagnetic fields (EMF) in the intermediate frequency (IF) range are generated by many novel electrical appliances, including electric vehicles, radiofrequency identification systems, induction hobs, or energy supply systems, such as wireless charging systems. The aim of this systematic review is to evaluate whether cardiovascular implantable electronic devices (CIEDs) are susceptible to electromagnetic interference (EMI) in the IF range (1 kHz-1 MHz). Additionally, we discuss the advantages and disadvantages of the different types of studies used to investigate EMI. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, we collected and evaluated studies examining EMI in in vivo studies, in vitro studies (phantom studies, benchmark tests), and simulation studies. Our analysis revealed that cardiac implants are susceptible to malfunction induced by EMF in the IF range. Electromagnetic interference may in particular be provoked by security systems and induction hobs. The results of the studies evaluated in this systematic review further indicate that the likelihood for EMI is dependent on exposure-related parameters (field strength, frequency, and modulation) and on implant- as well as on lead-related parameters (model, type of implant, implant sensitivity setting, lead configuration, and implantation site). The review shows that the factors influencing EMI are not sufficiently characterized and EMF limit values for CIED patients cannot be derived yet. Future studies should therefore, consider exposure-related parameters as well as implant- and lead-related parameters systematically. Additionally, worst-case scenarios should be considered in all study types where possible.
Subject(s)
Defibrillators, Implantable , Electromagnetic Fields/adverse effects , Environmental Exposure/adverse effects , Pacemaker, Artificial , Prosthesis Failure , Animals , Cooking/instrumentation , Electric Power Supplies/adverse effects , Household Articles/instrumentation , Humans , Prosthesis Design , Risk Assessment , Risk FactorsABSTRACT
BACKGROUND: Pacemaker induced Cardiomyopathy (PICM) is an easily overlooked cause of heart failure with reduced ejection fraction. Data regarding this complication are sparse. Therefore, the aim of this study was to identify the incidence and predictors of PICM. METHODS: Between 2011 and 2017, 857 consecutive patients undergoing pacemaker (PM) implantation, were reviewed, and according to our inclusion criteria 173 individuals were enrolled in this retrospective single center study. All patients included had normal left ventricular ejection fraction (LVEF) before implantation, underwent single-chamber ventricular or dual-chamber PM implantation, had RV pacing burden ≥20%, and repeated echocardiogram was available ≥1â¯year after implantation. PICM was defined as deterioration LVEF ≥10%, resulting in LVEF <50%, which cannot be explained by other causes. RESULTS: During a mean follow-up of 39.9⯱â¯21.0â¯months, PICM occurred in 26 patients (16%). RV pacing percentage did not differ significantly between the both groups (76.5 vs 76.2%, pâ¯=â¯0.65). The PICM group patients were likely to be men (pâ¯=â¯0.002) and had a lower rate of arterial hypertension (pâ¯=â¯0.01). Multivariate analysis revealed male sex (HR 6.45, 0.95 CI 1.90-21.86, pâ¯=â¯0.003) and wider paced QRS complex (HR 1.04, 95% CI 1.02-1.07, pâ¯<â¯0.001) as predictors of PICM. CONCLUSIONS: In patients with frequent RV pacing, the prevalence of PICM is not uncommon. Male sex and wider paced QRS complex are independent predictors of PICM and these patients may require closer follow-up.
Subject(s)
Cardiomyopathies , Pacemaker, Artificial , Cardiac Pacing, Artificial , Cardiomyopathies/epidemiology , Electrocardiography , Humans , Incidence , Male , Pacemaker, Artificial/adverse effects , Retrospective Studies , Stroke Volume , Ventricular Function, LeftABSTRACT
Aims: Electromagnetic interferences (EMIs) with cardiovascular implantable electronic devices (CIEDs) are associated with potential risk for patients. Studies imply that CIED sensitivity setting and lead's tip-to-ring spacing determine the susceptibility of CIEDs with bipolar leads to electric and magnetic fields (EMFs); however, little is known about additional decisive parameters affecting EMI of CIEDs. We therefore investigated the influence of different patient-, device-, and lead-depending variables on EMIs in 160 patients. Methods and Results: We ran numerical simulations with human models to determine lead-depending variables on the risk of EMI by calculating the voltage induced in bipolar leads from 50/60 Hz EMF. We then used the simulation results and analysed 26 different patient-, device-, and lead-depending variables with respect to the EMI threshold of 160 CIED patients. Our analyses revealed that a horizontal orientation and a medial position of the bipolar lead's distal end (lead-tip) are most beneficial for CIED patients to reduce the risk of EMI. In addition, the effect of CIED sensitivity setting and lead's tip-to-ring spacing was confirmed. Conclusion: Our data suggest that in addition to the established influencing factors, a medial position of the lead-tip for the right ventricular lead as achievable at the interventricular septum and a horizontal orientation of the lead-tip can reduce the risk of EMI. In the right atrium, a horizontal orientation of the lead-tip should generally be striven independent of the chosen position. Still important to consider remains a good intrinsic sensing amplitude during implant procedure.
Subject(s)
Cardiac Resynchronization Therapy Devices , Defibrillators, Implantable , Electrodes, Implanted , Electromagnetic Fields , Adult , Aged , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Young AdultABSTRACT
Low adherence to cardiac rehabilitation (CR) might be improved by remote monitoring systems that can be used to motivate and supervise patients and tailor CR safely and effectively to their needs. The main objective of this study was to evaluate the feasibility of a smartphone-guided training system (GEX) and whether it could improve exercise capacity compared to CR delivered by conventional methods for patients with coronary artery disease (CAD). A prospective, randomized, international, multi-center study comparing CR delivered by conventional means (CG) or by remote monitoring (IG) using a new training steering/feedback tool (GEx System). This consisted of a sensor monitoring breathing rate and the electrocardiogram that transmitted information on training intensity, arrhythmias and adherence to training prescriptions, wirelessly via the internet, to a medical team that provided feedback and adjusted training prescriptions. Exercise capacity was evaluated prior to and 6 months after intervention. 118 patients (58 ± 10 years, 105 men) with CAD referred for CR were randomized (IG: n = 55, CG: n = 63). However, 15 patients (27 %) in the IG and 18 (29 %) in the CG withdrew participation and technical problems prevented a further 21 patients (38 %) in the IG from participating. No training-related complications occurred. For those who completed the study, peak VO2 improved more (p = 0.005) in the IG (1.76 ± 4.1 ml/min/kg) compared to CG (-0.4 ± 2.7 ml/min/kg). A newly designed system for home-based CR appears feasible, safe and improves exercise capacity compared to national CR. Technical problems reflected the complexity of applying remote monitoring solutions at an international level.
Subject(s)
Cardiac Rehabilitation/methods , Coronary Artery Disease/rehabilitation , Exercise Tolerance , Patient Compliance/statistics & numerical data , Patient Education as Topic/methods , Smartphone/statistics & numerical data , Aged , Electrocardiography, Ambulatory/methods , Exercise Test , Female , Germany , Heart Rate , Humans , Internet/statistics & numerical data , Linear Models , Male , Oxygen Consumption , Prospective Studies , Quality of Life , Spain , United KingdomABSTRACT
Utilization of cardiac implants such as pacemakers and implantable cardioverter defibrillators is now commonplace among heart disease patients. The ever-increasing technological complexity of these devices is matched by the near omnipresent exposure to electric, magnetic, and electromagnetic fields (EMFs), both in everyday life and the occupational environment. Given that electromagnetic interferences (EMIs) are associated with potential risk in device patients, physicians are increasingly confronted with managing device patients with intermittent EMI and chronic occupational exposure. The current review aims to provide a contemporary overview of cardiovascular implantable electronic devices, their function and susceptibility of non-medical EMFs and provide recommendations for physicians caring for cardiac device patients presenting with EMI.
Subject(s)
Defibrillators, Implantable , Electromagnetic Fields/adverse effects , Environmental Exposure/prevention & control , Pacemaker, Artificial , Activities of Daily Living , Algorithms , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/therapy , Equipment Design , Equipment Failure , Humans , Occupational Exposure/prevention & controlABSTRACT
BACKGROUND: The number of implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac death is continuing to increase. Given the technological complexity of ICDs, it is of critical importance to identify and control possible harmful electromagnetic interferences between various sources of electromagnetic fields and ICDs in daily life and occupational environments. METHODS AND RESULTS: Interference thresholds of 110 ICD patients (1-, 2-, and 3-chamber ICDs) were evaluated in a specifically developed test site. Patients were exposed to single and combined electric and magnetic 50-Hz fields with strengths of up to 30 kV·m⻹ and 2.55 mT. Tests were conducted considering worst-case conditions, including maximum sensitivity of the device or full inspiration. With devices being programmed to nominal sensitivity, ICDs remained unaffected in 91 patients (83%). Five of 110 devices (5%) showed transient loss of accurate right ventricular sensing, whereas 14 of 31 (45%) of the 2- and 3-chamber devices displayed impaired right atrial sensing. No interference was detected in 71 patients (65%) within the tested limits with programming to maximum sensitivity, whereas 20 of 110 subjects (18%) exhibited right ventricular disturbances and 19 of 31 (61%) subjects exhibited right atrial disturbances. CONCLUSIONS: Extremely low-frequency daily-life electromagnetic fields do not disturb sensing capabilities of ICDs. However, strong 50-Hz electromagnetic fields, present in certain occupational environments, may cause inappropriate sensing, potentially leading to false detection of atrial/ventricular arrhythmic events. When the right atrial/right ventricular interferences are compared, the atrial lead is more susceptible to electromagnetic fields. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/ct2/show/NCT01626261. Unique identifier: NCT01626261.
Subject(s)
Activities of Daily Living , Arrhythmias, Cardiac/therapy , Defibrillators, Implantable/adverse effects , Electromagnetic Fields/adverse effects , Occupational Exposure/adverse effects , Adult , Aged , Arrhythmias, Cardiac/physiopathology , Death, Sudden, Cardiac/prevention & control , Electrophysiologic Techniques, Cardiac , Female , Heart Atria/physiopathology , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Retrospective Studies , Risk AssessmentSubject(s)
Electricity , Electromagnetic Fields , Electromagnetic Phenomena , Magnetic Fields , Pacemaker, Artificial , HumansABSTRACT
Dizziness is a common symptom with many potential causes. Medical and especially cardiac aetiologies are associated with a poor overall prognosis such that identification of the underlying cause is essential. This article gives an overview of possible causes of dizziness, how the differential diagnoses should be investigated, and describes potential therapeutic approaches to the treatment of the most important underlying conditions.
Subject(s)
Dizziness , Physicians , Humans , Dizziness/etiology , Vertigo/etiology , Diagnosis, DifferentialABSTRACT
Background: Atrial fibrosis represents a major hallmark in disease progression of atrial fibrillation (AF). We have previously shown that circulating microRNA-21 (miR-21) correlates with the extent of left atrial fibrosis in patients undergoing catheter ablation for AF and can serve as a biomarker to predict ablation success. In this study, we aimed to validate the role of miR-21-5p as a biomarker in a large cohort of AF patients and to investigate its pathophysiological role in atrial remodeling. Methods: For the validation cohort, we included 175 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained, circulating miR-21-5p was measured, and patients were followed-up for 12 months including ECG holter monitoring. AF was simulated by tachyarrhythmic pacing of cultured cardiomyocytes, the culture medium was transferred to fibroblast, and fibrosis pathways were analysed. Results: 73.3% of patients with no/minor LVAs, 51.4% of patients with moderate LVAs and only 18.2% of patients with extensive LVAs were in stable sinus rhythm (SR) 12 months after ablation (p < 0.01). Circulating miR-21-5p levels significantly correlated with the extent of LVAs and event-free survival. In-vitro tachyarrhythmic pacing of HL-1 cardiomyocytes resulted in an increased miR-21-5p expression. Transfer of the culture medium to fibroblasts induced fibrosis pathways and collagen production. The HDAC1 inhibitor mocetinostat was found to inhibit atrial fibrosis development. Conclusion: We validated miR-21-5p as a biomarker that reflects the extent of left atrial fibrosis in AF patients. Furthermore, we found that miR-21-5p is released in-vitro from cardiomyocytes under tachyarrhythmic conditions and stimulates fibroblasts in a paracrine mode to induce collagen production.
ABSTRACT
Background: Cryoballoon ablation is a first-line therapy for atrial fibrillation. We compared the efficacy and safety of two ablation systems and addressed the influence of pulmonary vein (PV) anatomy on performance and outcome. Methods: We consecutively enrolled 122 patients who were planned for first-time cryoballoon ablation. Patients were assigned 1:1 for ablation with the POLARx or the Arctic Front Advance Pro (AFAP) system and followed-up for 12 months. Procedural parameters were recorded during the ablation. Before the procedure, a magnetic resonance angiography (MRA) of the PVs was generated and diameter, area, and shape of each PV ostium were assessed. We applied an evaluated PV anatomical scoring system on our MRA measurement data ranging from 0 (best anatomical combination) to 5. Results: Procedures performed with POLARx were associated with shorter time to balloon temperature -30°C (p < .001), lower balloon nadir temperature (p < .001), and longer thawing time till 0°C (p < .001) in all PVs, however, time to isolation was similar. We observed a decreasing performance with each increase in the score for the AFAP, whereas the POLARx performed constant regardless of the score. At 1 year, AF recurred in 14 of 44 patients treated with AFAP (31.8%) and in 10 of 45 patients treated with POLARx (22.2%) (hazard ratio, 0.61; 95% CI 0.28 to 1.37; p = .225). There was no significant correlation between PV anatomy and clinical outcome. Conclusion: We found significant differences in cooling kinetics, especially when anatomical conditions are difficult. However, both systems have a comparable outcome and safety profile.
ABSTRACT
Patients with cardiac pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy devices (CRT) are exposed to different types of electromagnetic interference (EMI) at home and at work. Due to the constantly increasing role of electrically active appliances in daily use and the introduction of new therapy concepts such as the leadless cardiac pacemaker and the subcutaneous defibrillator, this topic is of great relevance. The further development of the implanted devices and the almost complete use of bipolar leads has reduced the overall risk of EMI. This review article provides information about the current status of possible interference in the private environment and how to avoid it. In addition, information is provided on how to deal with occupational sources of interference.
Subject(s)
Cardiac Resynchronization Therapy , Defibrillators, Implantable , Pacemaker, Artificial , Cardiac Resynchronization Therapy Devices , Electricity , Electromagnetic Fields , HumansABSTRACT
Atrial fibrillation (AF) is the most common arrhythmia and is highly associated with increased morbidity and mortality. Since many AF episodes remain subclinical, screening for AF is considered a desirable approach for timely diagnosis, prevention of sequelae and effective treatment. Recently, devices for AF detection-stand-alone or integrated in mobile health technology-have become available and show promising preliminary results in the detection and monitoring of arrhythmia. This review describes the technical aspects of a single-lead ECG stick and summarizes the current literature, experience in large-scale screening for AF in pharmacies and potential fields of application.
Subject(s)
Atrial Fibrillation , Electrocardiography , Humans , Mass Screening , Treatment OutcomeABSTRACT
Bioelectrical impedance spectroscopy (BIS) measures body composition, including fluid status. Acute decompensated heart failure (ADHF) is associated with fluid overload in different body compartments. This investigation aimed to evaluate the feasibility of measuring and monitoring fluid accumulation in patients with ADHF using BIS. The extracellular impedance as a surrogate marker for fluid accumulation was measured in 67 participants (25 healthy reference volunteers and 42 patients admitted with ADHF) using BIS in the "transthoracic", "foot-to-foot", "whole-body" and "hand-to-hand" segments. At baseline, BIS showed significantly lower extracellular resistance values for the "whole-body" (P < 0.001), "foot-to-foot" (P = 0.03), "hand-to-hand" (P < 0.001) and "transthoracic" (P = 0.014) segments in patients with ADHF than the reference cohort, revealing a specific pattern for peripheral, central and general fluid accumulation. The "foot-to-foot" (AUC = 0.8, P < 0.001) and "hand-to-hand" (AUC = 0.74, P = 0.04) segments indicated compartments of fluid accumulation with good prediction. During cardiac recompensation, BIS values changed significantly and were in line with routine parameters for monitoring ADHF. Mean bodyweight change per day correlated moderately to good with BIS values in the "whole-body" (r = -0.4), "foot-to-foot" (r = -0.8) and "transthoracic" (r = -0.4) segments. Based on our analysis, we conclude that measuring and monitoring fluid accumulation in ADHF using segmental BIS is feasible and correlates with clinical parameters during recompensation.
Subject(s)
Body Fluids/chemistry , Heart Failure/metabolism , Spectrum Analysis/methods , Aged , Aged, 80 and over , Body Fluids/metabolism , Cohort Studies , Electric Impedance , Female , Hospitalization , Humans , Male , Middle AgedABSTRACT
BACKGROUND: In nonfailing myocardium, beta(3)-adrenergic signaling causes a decrease in contractility via endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) release. This study investigates the hypothesis that beta(3)-adrenergic signaling undergoes alterations in failing myocardium. METHODS: We compared eNOS- and beta(3)-adrenoceptor expression using Western blot analysis in human nonfailing myocardium versus failing myocardium. With the use of immunohistochemistry, we investigated the distribution of the beta(3)-adrenoceptor protein and eNOS translocation and phosphorylation under basal conditions. beta(3)-adrenergic, eNOS activation, and inotropy were measured in failing myocardium using BRL37344 (BRL, a beta(3)-adrenoceptor agonist). RESULTS: beta(3)-adrenoceptor expression was increased in failing myocardium. Under basal conditions, Akt- and eNOS(Ser1177) phosphorylation were reduced in failing myocardium. During stimulation with BRL in failing myocardium, a further dephosphorylation of eNOS(Ser1177) and Akt was observed, whereas eNOS(Ser114) phosphorylation was increased. These results suggest a deactivation of eNOS via beta(3)-adrenergic stimulation. Nevertheless, BRL decreased contractility in failing myocardium, but this effect was not observed in the presence of the NO blocker L-NMA. In failing myocardium, the beta(3)-adrenoceptor was predominantly expressed in endothelial cells. In the cardiomyocytes, the beta(3)-adrenoceptor was mainly located at the intercalated disks. CONCLUSION: In failing cardiomyocytes, beta(3)-adrenergic stimulation seems to deactivate rather than activate eNOS. At the same time, beta(3)-adrenergic stimulation induced a NO-dependent negative inotropic effect. Because beta(3)-adrenoceptors are expressed mainly in the endothelium in failing myocardium, our observations suggest a paracrine-negative inotropic effect via NO liberation from the cardiac endothelial cells.