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BACKGROUND: Paroxysmal atrial fibrillation (pAF) occurs sporadically and can impair athletic performance. Gold standard for diagnosis is surface electrocardiography (ECG), however, this requires AF to be sustained. Implantable loop recorders (ILRs) are routinely used for AF detection in human medicine. While ILR placement has been studied in horses, its AF detection performance is unknown. OBJECTIVES: (I) Validation of ILRs for AF detection in horses. (II) Determining pAF incidence using ILRs and estimate the positive predictive value (PPV). STUDY DESIGN: (I) Experimental study; (II) Longitudinal observational study. METHODS: (I) Implantation of ILRs in 15 horses with AF and 13 horses in sinus rhythm. Holter ECGs were recorded at: 1, 4, 8, 12 and 16 weeks of AF. The ILR ECGs were compared with surface ECGs to assess diagnostic sensitivity and specificity. (II) Eighty horses (43 Warmbloods, 37 Standardbreds) with ILRs were monitored for 367 days [IQR 208-621]. RESULTS: (I) ILRs detected AF on all recording days, in horses with AF, with a sensitivity of 66.1% (95% CI: 65.8-66.5) and a specificity of 99.99% (95% CI: 99.97-99.99). The sensitivity remained consistent across all time points. (II) The incidence of pAF was 6.3% (5/80). In horses with pAF, the PPV ranged from 8% to 87%. Increased body condition score (BCS > 6/9) was associated with an increased number of false positive episodes (p = 0.005). MAIN LIMITATIONS: (I) Horses were stabled during the ECG recordings, and AF was induced, rather than naturally occurring pAF. (II) Integrated algorithm in this ILR is optimised for AF detection in humans using remote monitors. Additionally, sensing is affected by motion artefacts. CONCLUSION: The ILR reliably detected AF in resting horses, particularly in horses with normal BCS (6/9). The ILR proved useful to detect pAF and is recommended alongside Holter monitoring for diagnostic workup of horses with suspected pAF.
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BACKGROUND: Obstructive sleep apnea (OSA) creates a complex substrate for atrial fibrillation (AF), which is refractory to many clinically available pharmacological interventions. We investigated atrial antiarrhythmogenic properties and ventricular electrophysiological safety of small-conductance Ca2+ -activated K+ (SK)-channel inhibition in a porcine model for obstructive respiratory events. METHODS: In spontaneously breathing pigs, obstructive respiratory events were simulated by intermittent negative upper airway pressure (INAP) applied via a pressure device connected to the intubation tube. INAP was applied for 75 s, every 10 min, three times before and three times during infusion of the SK-channel inhibitor AP14145. Atrial effective refractory periods (AERP) were acquired before (pre-INAP), during (INAP) and after (post-) INAP. AF-inducibility was determined by a S1S2 atrial pacing protocol. Ventricular arrhythmicity was evaluated by heart rate adjusted QT-interval duration (QT-paced) and electromechanical window (EMW) shortening. RESULTS: During vehicle infusion, INAP transiently shortened AERP (pre-INAP: 135 ± 10 ms vs. post-INAP 101 ± 11 ms; p = .008) and increased AF-inducibility. QT-paced prolonged during INAP (pre-INAP 270 ± 7 ms vs. INAP 275 ± 7 ms; p = .04) and EMW shortened progressively throughout INAP and post-INAP (pre-INAP 80 ± 4 ms; INAP 59 ± 6 ms, post-INAP 46 ± 10 ms). AP14145 prolonged baseline AERP, partially prevented INAP-induced AERP-shortening and reduced AF-susceptibility. AP14145 did not alter QT-paced at baseline (pre-AP14145 270 ± 7 ms vs. AP14145 268 ± 6 ms, p = .83) or QT-paced and EMW-shortening during INAP. CONCLUSION: In a pig model for obstructive respiratory events, the SK-channel-inhibitor AP14145 prevented INAP-associated AERP-shortening and AF-susceptibility without impairing ventricular electrophysiology. Whether SK-channels represent a target for OSA-related AF in humans warrants further study.
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Fibrilación Atrial , Apnea Obstructiva del Sueño , Humanos , Porcinos , Animales , Fibrilación Atrial/prevención & control , AcetamidasRESUMEN
During acute myocardial infarction (AMI), the ischemia and necrosis of the infarcted tissue result in local electrophysiological changes, which bring about deviations of the ST segment and T wave. In this case report, the aim was to investigate whether these changes could be detected with a 12-lead electrocardiogram (ECG) during acute occlusion of the coronary artery in a 15-year-old Standardbred mare (scheduled for euthanasia due to non-cardiac health problems). The left anterior descending (LAD) coronary artery was occluded using an angioplasty balloon catheter guided through the carotid artery. Two coronary occlusions of 30 min were induced, separated by a 10-min reperfusion phase. AMI led to ST deviations and T-wave amplitude changes (maximum ST deviation was 1.98 mV; T-wave amplitude increased from 6.58 to 9.25 mV). The ST segment almost returned to the baseline during the reperfusion phase. The ECG changes seen after the infarction were comparable to those reported in other species with AMI, suggesting that the 12-lead-ECG can potentially be used to detect signs of myocardial infarction in horses.
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BACKGROUND: There are emerging data of long-term effects of coronavirus disease 2019 (COVID-19) comprising a diversity of symptoms. The aim of this study was to systematically describe and measure pulmonary and extra-pulmonary post-COVID-19 complications in relation to acute COVID-19 severity. METHODS: Patients attending a standard of care 3â months post-hospitalisation follow-up visit and those referred by their general practitioner because of persistent post-COVID-19 symptoms were included. Patients underwent symptomatic, quality of life, pulmonary (lung function and high-resolution computed tomography (HRCT)), cardiac (high-resolution ECG), physical (1-min sit and stand test (1-MSTST), handgrip strength, cardiopulmonary exercise testing (CPET)) and cognitive evaluations. RESULTS: All 34 hospitalised and 22 out of 23 non-hospitalised patients had ≥1 complaint or abnormal finding at follow-up. Overall, 67% of patients were symptomatic (Medical Research Council (MRC) ≥2 or COPD assessment test (CAT) ≥10), with no difference between hospitalised versus non-hospitalised patients. Pulmonary function (forced expiratory volume in 1â s (FEV1) or diffusing capacity of the lung for carbon monoxide (D LCO)) <80% of predicted) was impaired in 68% of patients. D LCO was significantly lower in those hospitalised compared to non-hospitalised (70.1±18.0 versus 80.2±11.2% predicted, p=0.02). Overall, 53% had an abnormal HRCT (predominantly ground-glass opacities) with higher composite computed tomography (CT) scores in hospitalised versus non-hospitalised patients (2.3 (0.1-4.8) and 0.0 (0.0-0.3), p<0.001). 1-MSTST was below the 25th percentile in almost half of patients, but no signs of cardiac dysfunction were found. Cognitive impairments were present in 59-66% of hospitalised and 31-44% of non-hospitalised patients (p=0.08). CONCLUSION: Three months after COVID-19 infection, patients were still symptomatic and demonstrated objective respiratory, functional, radiological and cognitive abnormalities, which were more prominent in hospitalised patients. Our study underlines the importance of multidimensional management strategies in these patients.
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BACKGROUND: Impact of telemedicine with remote patient monitoring (RPM) in implantable cardioverter-defibrillator (ICD) patients on clinical outcomes has been investigated in various clinical settings with divergent results. However, role of RPM on patient-reported-outcomes (PRO) is unclear. The INFRARED-ICD trial aimed to investigate the effect of RPM in addition to standard-of-care on PRO in a mixed ICD patient cohort. METHODS AND RESULTS: Patients were randomized to RPM (n = 92) or standard in-office-FU (n = 88) serving as control group (CTL). At baseline and on a monthly basis over 1 year, study participants completed the EQ-5D questionnaire for the primary outcome Quality of Life (QoL), the Hospital Anxiety and Depression Scale, and the Florida Patient Acceptance Survey questionnaire for secondary outcomes. Demographic characteristics (82% men, mean age 62.3 years) and PRO at baseline were not different between RPM and CTL. Primary outcome analysis showed that additional RPM was not superior to CTL with respect to QoL over 12 months [+ 1.2 vs. + 3.9 points in CTL and RPM group, respectively (p = 0.24)]. Pre-specified analyses could not identify subgroups with improved QoL by the use of RPM. Neither levels of anxiety (- 0.4 vs. - 0.3, p = 0.88), depression (+ 0.3 vs. ± 0.0, p = 0.38), nor device acceptance (+ 1.1 vs. + 1.6, p = 0.20) were influenced by additional use of RPM. CONCLUSION: The results of the present study show that PRO were not improved by RPM in addition to standard-of-care FU. Careful evaluation and planning of future trials in selected ICD patients are warranted before implementing RPM in routine practice.
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Arritmias Cardíacas/terapia , Desfibriladores Implantables/psicología , Monitoreo Fisiológico/métodos , Calidad de Vida , Telemedicina/métodos , Ansiedad , Arritmias Cardíacas/psicología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Método Simple Ciego , Encuestas y CuestionariosRESUMEN
AIMS: Impaired myocardial sympathetic innervation assessed by 123Iodine-Metaiodobenzylguanidine (123I-MIBG) scintigraphy is associated with cardiac events. Since regional disparities of structural abnormalities are common in inherited arrhythmia syndromes (iAS), a chamber-specific innervation assessment of the right (RV) and left ventricle (LV) could provide important insights for a patient-individual therapy. Aim of this study was to evaluate chamber-specific patterns of autonomic innervation by Single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with iAS with respect to clinical outcome regarding cardiac events. METHODS AND RESULTS: We assessed ventricular sympathetic innervation (LV, RV and planar heart/mediastinum-ratios, and washout-rates) by 123I-MIBG-SPECT/CT in 48 patients (arrhythmogenic right ventricular cardiomyopathy [ARVC], n = 26; laminopathy, n = 8; idiopathic ventricular fibrillation [iVF], n = 14) in relation to a composite clinical endpoint (ventricular arrhythmia; cardiac death; cardiac hospitalization). RV tracer uptake was lower in patients with ARVC than in laminopathy and iVF patients (1.7 ± 0.4 vs. 2.1 ± 0.7 and 2.1 ± 0.5, respectively). Over a median follow-up of 2.2 years, the combined endpoint was met in 18 patients (n = 12 ventricular tachyarrhythmias, n = 5 hospitalizations, n = 1 death). LV, but not RV H/M ratio was associated with the combined endpoint (hazard-ratio 2.82 [1.30-6.10], p < 0.01). After adjustment for LV and RV function, LV H/M-ratio still remained a significant predictor for cardiac events (hazard-ratio 2.79 [1.06-7.35], p = 0.04). CONCLUSION: We demonstrated that chamber-specific 123MIBG-SPECT/CT imaging is feasible and that reduced LV sympathetic innervation was associated with worse outcome in iAS. These findings provide novel insights into the potential role of regional autonomic nervous system heterogeneity for the evolution of life-threatening cardiac events in iAS.
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Ventrículos Cardíacos , Sistema Nervioso Simpático , 3-Yodobencilguanidina , Arritmias Cardíacas/diagnóstico por imagen , Corazón , Humanos , Radioisótopos de Yodo , Radiofármacos , Síndrome , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Patients receiving psychiatric medication, like the antipsychotic drug haloperidol, are at an increased risk of sudden cardiac death (SCD). Haloperidol blocks the cardiac rapidly-activating delayed rectifier potassium current, thereby increasing electrical dispersion of repolarization which can potentially lead to arrhythmias. Whether these patients are also at a higher risk to develop SCD during an acute myocardial infarction (AMI) is unknown. AMI locally shortens action potential duration, which might further increase repolarization dispersion and increase the risk of arrhythmia in the presence of haloperidol compared to without. Our aim was to test whether treatment with haloperidol implies an increased risk of SCD when eventually experiencing AMI. Twenty-eight female Danish Landrace pigs were randomized into three groups: low dose haloperidol (0.1 mg/kg), high dose (1.0 mg/kg) or vehicle-control group. One hour after haloperidol/vehicle infusion, AMI was induced by balloon-occlusion of the mid-left anterior descending coronary artery and maintained for 120 min, followed by 60 min of reperfusion. VF occurred during occlusion in 7/11 pigs in the control group, 3/11 in the low dose (p = 0.198) and 2/6 in the high dose group (p = 0.335). High dose haloperidol significantly prolonged QT, and reduced heart rate, vascular resistance and blood pressure before and during AMI. Premature ventricular contractions in phase 1b during AMI were reduced with high dose haloperidol. AMI-induced arrhythmia was not aggravated in pigs with haloperidol treatment. Our results do not suggest that AMI is contributing to the excess mortality in patients treated with antipsychotic drugs seen in epidemiological studies.
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Ventricular fibrillation (VF) during acute myocardial infarction (AMI) is an important contributor to sudden cardiac death. Large animal models are widely used to study AMI-induced arrhythmia, but the mode of AMI induction ranges from thoracotomy and surgical ligation of a coronary vessel (open chest) to minimally invasive techniques, including balloon occlusion (closed chest). How the choice of induction affects arrhythmia development is unclear. The aim of this study was to compare an open-chest and a closed-chest model with regard to hemodynamics, electrophysiology, and arrhythmia development. Forty-two female Danish Landrace pigs (20 open chest, 22 closed chest) were anesthetized, and occlusion of the mid-left anterior descending coronary artery was performed for 60 min. Opening the chest reduced blood pressure and cardiac output (Δ -22 mmHg, Δ -1.5 L/min from baseline, both P < 0.001 intragroup). Heart rate decreased with opening of the chest but increased with balloon placement (P < 0.001). AMI-induced ST elevation was lower in the open-chest group (P < 0.001). Premature ventricular contractions occurred in two distinct phases (0-15 and 15-40 min), the latter of which was delayed in the open-chest group (P = 0.005). VF occurred in 7 out of 20 and 12 out of 22 pigs in the open-chest and closed-chest groups, respectively (P = 0.337), with longer time-to-VF in the open-chest group (23.4 ± 1.2 min in open chest and 17.8 ± 1.4 min in closed chest; P = 0.007). In summary, opening the chest altered hemodynamic parameters and delayed the onset of ventricular arrhythmias. Hence, in the search for mechanisms and novel treatments of AMI-induced arrhythmia, caution should be taken when choosing between or comparing the results from these two models.NEW & NOTEWORTHY We demonstrated pronounced differences in hemodynamic parameters and time course of ventricular arrhythmias in regard to mode of infarct induction. Inducing myocardial infarction by thoracotomy and subsequent ligation decreased blood pressure and cardiac output and delayed the onset of ventricular arrhythmia, whereas balloon occlusion resulted in higher heart rates during infarct.
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Arritmias Cardíacas/fisiopatología , Electrocardiografía , Corazón/fisiopatología , Hemodinámica , Infarto del Miocardio/fisiopatología , Potenciales de Acción/fisiología , Animales , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Técnicas Electrofisiológicas Cardíacas , Femenino , Contracción Miocárdica , Porcinos , Taquicardia Ventricular/fisiopatología , Complejos Prematuros Ventriculares/fisiopatologíaRESUMEN
BACKGROUND: Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model. METHOD: Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups. RESULTS: AFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed. CONCLUSION: Horses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.
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Potenciales de Acción , Fibrilación Atrial/fisiopatología , Función del Atrio Izquierdo , Remodelación Atrial , Atrios Cardíacos/fisiopatología , Frecuencia Cardíaca , Potenciales de Acción/efectos de los fármacos , Animales , Antiarrítmicos/farmacología , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/etiología , Fibrilación Atrial/metabolismo , Función del Atrio Izquierdo/efectos de los fármacos , Remodelación Atrial/efectos de los fármacos , Estimulación Cardíaca Artificial , Modelos Animales de Enfermedad , Femenino , Fibrosis , Flecainida/farmacología , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Caballos , Canales Iónicos/metabolismo , Factores de TiempoRESUMEN
AIMS: Acute myocardial infarction (AMI) is associated with intracellular Ca2+ build-up. In healthy ventricles, small conductance Ca2+-activated K+ (SK) channels are present but do not participate in repolarization. However, SK current is increased in chronic myocardial infarction and heart failure, and recently, SK channel inhibition was demonstrated to reduce arrhythmias in AMI rats. Hence, we hypothesized that SK channel inhibitors (NS8593 and AP14145) could reduce arrhythmia development during AMI in a porcine model. METHODS AND RESULTS: Twenty-seven pigs were randomized 1:1:1 to control, NS8593, or AP14145. Haemodynamic and electrophysiological parameters [electrocardiogram (ECG) and monophasic action potentials (MAP)] were continuously recorded. A balloon was placed in the mid-left anterior descending artery, blinded to treatment. Infusion lasted from 10 min before occlusion until 30 min after. Occlusion was maintained for 1 h, followed by 2 h of reperfusion. Upon occlusion, cardiac output dropped similarly in all groups, while blood pressure remained stable. Heart rate decreased in the NS8593 and AP14145 groups. QRS duration increased upon occlusion in all groups but more prominently in AP14145-treated pigs. Inhibition of SK channels did not affect QT interval. Infarct MAP duration shortened comparably in all groups. Ventricular fibrillation developed in 4/9 control-, 4/9 AP14145-, and 2/9 NS8593-treated pigs. Ventricular tachycardia was rarely observed in either group, whereas ventricular extrasystoles occurred comparably in all groups. CONCLUSION: Inhibition of SK channels was neither beneficial nor detrimental to ventricular arrhythmia development in the setting of AMI in this porcine model.
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1-Naftilamina/análogos & derivados , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Infarto del Miocardio/tratamiento farmacológico , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/antagonistas & inhibidores , Taquicardia Ventricular/etiología , 1-Naftilamina/farmacología , Animales , Modelos Animales de Enfermedad , Femenino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Porcinos , Taquicardia Ventricular/fisiopatologíaRESUMEN
Ventricular fibrillation (VF) occurring in the first minutes to hours of acute myocardial infarction (AMI) is a frequent cause of death and treatment options are limited. The aim was to test whether early infusion of amiodarone 10 min after onset of AMI reduced the incidence of VF in a porcine model. Eighteen female Danish landrace pigs were randomized to a control and an amiodarone group. AMI was induced by ligation of the mid-left anterior descending artery for 120 min followed by 60 min of reperfusion. VF occurred in 0/8 pigs treated with amiodarone compared to 7/10 controls (P < 0.01). Amiodarone treatment prolonged RR intervals, reduced dispersion of action potential duration in the infarcted area and mean number of ectopic beats. No negative effects on cardiac output and blood pressure were observed with amiodarone. Amiodarone qualifies as a potential drug candidate to prevent VF in the first minutes to hours of AMI.
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Amiodarona/farmacología , Antiarrítmicos/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Fibrilación Ventricular/prevención & control , Potenciales de Acción/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Factores de Tiempo , Fibrilación Ventricular/etiología , Fibrilación Ventricular/fisiopatologíaRESUMEN
BACKGROUND: Pharmacological treatment of atrial fibrillation (AF) in horses can be challenging because of low efficacy and adverse effects. Flecainide has been tested with variable efficacy. OBJECTIVE: To test whether the efficacy of flecainide is dependent on AF duration. ANIMALS: Nine Standardbred mares. METHODS: Factorial study design. All horses were instrumented with a pacemaker and assigned to a control or an AF group. On day 0, all horses were in sinus rhythm and received 2 mg/kg flecainide IV. Atrial fibrillation subsequently was induced in the AF group by pacemaker stimulation. On days 3, 9, 27, and 55, flecainide was administered to all horses, regardless of heart rhythm. RESULTS: All horses in AF cardioverted to sinus rhythm on days 3 and 9. On day 27, 5/6 horses cardioverted, whereas only 2/6 cardioverted on day 55. The time from the start of flecainide infusion to cardioversion (range, 3-185 min, log transformed) showed linear correlation with the cumulative duration of AF (r2 = .80, P < .0001). Flecainide induced abnormal QRS complexes in 4/6 AF horses and 1/3 controls. A positive correlation was found between heart rate before flecainide infusion and number of abnormal QRS complexes (0.14, P < .05). One horse suffered from cardiac arrest and died after flecainide infusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Flecainide is effective for cardioversion of short-term induced AF, but the effect decreases with AF duration. Controlling heart rate may minimize adverse effects caused by flecainide, but the drug should be used with great caution.
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Fibrilación Atrial/veterinaria , Flecainida/uso terapéutico , Enfermedades de los Caballos/tratamiento farmacológico , Animales , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Femenino , Caballos , Marcapaso Artificial , Factores de TiempoRESUMEN
Acute myocardial infarction (AMI) with development of ventricular fibrillation (VF) is a common cause of sudden cardiac death (SCD). At present, no pharmacological treatment has successfully been able to prevent VF in the acute stage of AMI. This study investigates the antiarrhythmic effect of inhibiting small conductance Ca2+-activated K+ (SK) channels using the pore blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) in AMI rats. Acute coronary ligation was performed in 26 anesthetized rats, and ECG, monophasic action potentials (MAPs), and ventricular effective refractory period (vERP) were recorded. Rats were randomized into four groups: (i) 3 mg/kg i.v. ICA with AMI (AMI-ICA-group, n = 9), (ii) vehicle with AMI (AMI-vehicle-group, n = 9), (iii) vehicle with sham operation (sham-vehicle-group, n = 8), and (iv) 3 mg/kg i.v. ICA with sham operation (sham-ICA-group, n = 6). At the end of experiments, hearts were stained for the non-perfused area at risk (AAR). AMI resulted in the development of ventricular tachycardia (VT) in all AMI-vehicle and AMI-ICA rats; however, ICA significantly decreased VT duration. VF occurred in 44% of AMI-vehicle rats but not in AMI-ICA rats. Monophasic action potential duration at 80% repolarization (MAPD80) in the ischemic area decreased rapidly in both AMI-vehicle and AMI-ICA rats. However, 5 min after occlusion, MAPD80 returned to baseline in AMI-ICA rats but not in AMI-vehicle rats. The vERP was prolonged in the AMI-ICA group compared to AMI-vehicle after ligation. AAR was similar between the AMI-vehicle group and the AMI-ICA group. In rats with AMI, ICA reduces the burden of arrhythmia.