RESUMO
Sodium glucose cotransporter 2 (SGLT2) have proven profound positive effects in heart failure with reduced ejection fraction (HFrEF). These effects are independent from the presence of diabetes. Metabolic effects, antiinflammatory, and antifibrotic properties are discussed as underlying mechanisms. Despite a strong correlation of ventricular arrhythmias with HFrEF, the impact of ertugliflozin on the ventricular arrhythmic burden has not been investigated, yet. Therefore, the Ertugliflozin to Reduce Arrhythmic burden in ICD ± CRT patientS (ERASe) trial was designed to investigate the efficacy and safety of ertugliflozin in patients with reduced and midrange ejection fraction (EF) with or without diabetes. METHODS: Within a multicentre, national, randomized, double-blind, placebo-controlled, phase 3b trial we aim to enrol a total of 402 patients across Austria. Patients with reduced or midrange EF and ICD ± CRT therapy >3 months and previous ventricular tachycardia (at least 10 documented VT episodes within the last 12 months) are randomized in a 1:1 ratio to ertugliflozin (5 mg once daily orally administered) or matching placebo. The primary endpoint of the ERASe trial is to investigate the impact of ertugliflozin on total burden of ventricular arrhythmias. Further objectives will include number of therapeutic interventions of implanted devices, atrial fibrillation and heart failure biomarkers. CONCLUSION: The ERASe trial will be the first trial to test ertugliflozin in heart failure patients with nonpreserved ejection fraction and ongoing ICD ± CRT therapy regardless of their diabetic status. The ERASe trial may therefore extend the concept of SGLT2 inhibition to improve cardiac remodelling, including reduced arrhythmic burden. Trial registration Identifier EudraCT Nr. 2020-002581-14 / ClinicalTrials.gov Identifier: NCT04600921.
Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Método Duplo-Cego , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/terapia , Humanos , Volume Sistólico/fisiologia , Resultado do Tratamento , Função Ventricular Esquerda/fisiologiaRESUMO
AIM: Cardiogenic shock (CS) is a hemodynamically complex multisystem syndrome associated with persistently high morbidity and mortality. As CS is characterized by progressive failure to provide adequate systemic perfusion, supporting end-organ perfusion using mechanical circulatory support (MCS) seems intriguing. Since most patients with CS present in the catheterization laboratory, percutaneously implantable systems have the widest adoption in the field. We evaluated feasibility, outcomes, and complications after the introduction of a full-percutaneous program for both the Impella CP device and venoarterial extracorporeal membrane oxygenator (VA-ECMO). METHODS: PREPARE CardShock (PRospective REgistry of PAtients in REfractory cardiogenic shock) is a prospective single-center registry, including 248 consecutive patients between May 2019 and April 2021, who underwent cardiac catheterization and displayed advanced cardiogenic shock. The median age was 70 (58-77) years and 28% were female. Sixty-five percent of the cases had cardiac arrest, of which 66% were out-of-hospital cardiac arrest. A local standard operating procedure (SOP) indicating indications as well as relative and absolute contraindications for different means of MCS (Impella CP or VA-ECMO) was used to guide MCS use. The primary endpoint was in-hospital death and secondary endpoints were spontaneous myocardial infarction and major bleedings during the hospital stay. RESULTS: Overall mortality was 50.4% with a median survival of 2 (0-6) days. Significant independent predictors of mortality were cardiac arrest during the index event (odds ratio [OR] with 95% confidence interval [CI]: 2.53 [1.43-4.51]; p = 0.001), age > 65 years (OR: 2.05 [1.03-4.09]; p = 0.036]), pH < 7.30 (OR: 2.69 [1.56-4.66]; p < 0.001), and lactate levels > 2 mmol/L (OR: 4.51 [2.37-8.65]; p < 0.001). CONCLUSIONS: Conclusive SOPs assist target-orientated MCS use in CS. This study provides guidance on the implementation, validation, and modification of newly established MCS programs to aid centers that are establishing such programs.
Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Coração Auxiliar , Idoso , Feminino , Coração Auxiliar/efeitos adversos , Mortalidade Hospitalar , Humanos , Masculino , Sistema de Registros , Estudos Retrospectivos , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Resultado do TratamentoRESUMO
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are gaining ground as standard therapy for heart failure with a class-I recommendation in the recently updated heart failure guidelines from the European Society of Cardiology. Different gliflozins have shown impressive beneficial effects in patients with and without diabetes mellitus type 2, especially in reducing the rates for hospitalization for heart failure, yet little is known on their antiarrhythmic properties. Atrial and ventricular arrhythmias were reported by clinical outcome trials with SGLT2 inhibitors as adverse events, and SGLT2 inhibitors seemed to reduce the rate of arrhythmias compared to placebo treatment in those trials. Mechanistical links are mainly unrevealed, since hardly any experiments investigated their impact on arrhythmias. Prospective trials are currently ongoing, but no results have been published so far. Arrhythmias are common in the heart failure population, therefore the understanding of possible interactions with SGLT2 inhibitors is crucial. This review summarizes evidence from clinical data as well as the sparse experimental data of SGLT2 inhibitors and their effects on arrhythmias.
Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Transportador 2 de Glucose-Sódio/metabolismo , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , HumanosRESUMO
A wearable cardioverter-defibrillator (WCD) is a temporary treatment option for patients at high risk for sudden cardiac death (SCD) and for patients who are temporarily not candidates for an implantable cardioverter defibrillator (ICD). In addition, the need for telemedical concepts in the detection and treatment of heart failure (HF) and its arrhythmias is growing. The WCD has evolved from a shock device detecting malignant ventricular arrhythmias (VA) and treating them with shocks to a heart-failure-monitoring device that captures physical activity and cardioacoustic biomarkers as surrogate parameters for HF to help the treating physician surveil and guide the HF therapy of each individual patient. In addition to its important role in preventing SCD, the WCD could become an important tool in heart failure treatment by helping prevent HF events by detecting imminent decompensation via remote monitoring and monitoring therapy success.
Assuntos
Desfibriladores Implantáveis , Dispositivos Eletrônicos Vestíveis , Arritmias Cardíacas , Morte Súbita Cardíaca , Cardioversão Elétrica , HumanosRESUMO
PURPOSE: Patients at risk for sudden cardiac death may temporarily need a wearable cardioverter-defibrillator (WCD). Exercise-based cardiac rehabilitation (CR) has a class I recommendation in patients with cardiac disease. The aim of this study was to evaluate the safety and feasibility of undergoing CR with a WCD. METHODS: We performed a retrospective analysis of all patients with a WCD who completed a CR in Austria (2010-2020). RESULTS: Patients (n = 55, 60 ± 11 yr, 16% female) with a median baseline left ventricular ejection fraction (LVEF) of 36 (30, 41)% at the start of CR showed a daily WCD wearing duration of 23.4 (22, 24) hr. There were 2848 (8 [1, 26]/patient) automatic alarms and 340 (3 [1, 7]/patient) manual alarms generated. No shocks were delivered by the WCD during the CR period. One patient had recurrent hemodynamically tolerated ventricular tachycardias that were controlled with antiarrhythmic drugs.No severe WCD-associated adverse events occurred during the CR stay of a median 28 (28, 28) d. The fabric garment and the device setting needed to be adjusted in two patients to diminish inappropriate automatic alarms. Left ventricular ejection fraction after CR increased significantly to 42 (30, 44)% ( P < .001). Wearable cardioverter-defibrillator therapy was stopped due to LVEF restitution in 53% of patients. In 36% of patients an implantable cardioverter-defibrillator was implanted, 6% had LVEF improvement after coronary revascularization, one patient received a heart transplantation (2%), two patients discontinued WCD treatment at their own request (4%). CONCLUSION: Completing CR is feasible and safe for WCD patients and may contribute positively to the restitution of cardiac function.
Assuntos
Reabilitação Cardíaca , Desfibriladores Implantáveis , Humanos , Feminino , Masculino , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Cardioversão ElétricaRESUMO
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial pleiotropic effects, contributing to improved cardiovascular and renal outcomes for patients with and without diabetes. The impact of SGLT2is on arrhythmic burden remains largely unexplored through randomized trials. METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial, we investigated the effects of ertugliflozin on arrhythmic burden among patients with heart failure with an ejection fraction less than 50%. All patients had an implantable cardioverter-defibrillator (ICD) with or without a cardiac resynchronization therapy device (CRT-D) and were randomized (1:1) to receive either ertugliflozin 5â mg once daily or placebo. The primary end point was the number of incident sustained (>30 seconds) ventricular tachycardia or ventricular fibrillation events from baseline to week 52. Secondary end points included the total number of non-sustained ventricular tachycardias, appropriate ICD therapies, changes in N-terminal pro-brain-type natriuretic peptide (NTproBNP) levels, and the number of heart failure hospitalizations. RESULTS: Randomization was prematurely terminated, after class IA guideline recommendations were published for SGLT2is in patients with heart failure regardless of the ejection fraction. The final analysis included 46 patients (11% of the originally planned sample size). The yearly rate of the primary end point was 3.5 (95% confidence interval [CI] 2.8 to 4.4) with ertugliflozin compared with 13.3 with placebo (95% CI 11.8 to 14.8; rate ratio 0.16, 95% CI 0.04 to 0.61; P<0.001). There were no apparent differences in appropriate ICD therapies, hospitalizations, NTproBNP levels, or predefined adverse and serious adverse events. CONCLUSIONS: Ertugliflozin reduced sustained ventricular tachycardia or ventricular fibrillation events in adults with heart failure and an ICD compared with placebo; however, our trial ended early and thus results should be interpreted with caution. (Funded by Investigator-initiated Studies Program of Merck Sharp & Dohme Corp and Pfizer; EudraCT number, 2020-002581-14; ClinicalTrials.gov number NCT04600921.).
RESUMO
BACKGROUND: After acute myocardial infarction (AMI), patients are at risk of sudden cardiac death. The VEST trial failed to show a reduction in arrhythmic mortality in AMI patients with an LVEF ≤ 35% prescribed with a WCD, having a lower-than-expected WCD wearing compliance. OBJECTIVES: The aim was to investigate on outcomes of patients in a real-world Austrian cohort with good compliance. METHODS: A retrospective analysis of all eligible Austrian WCD patients according to the VEST trial inclusion and exclusion criteria between 2010 and 2020 was performed. RESULTS: In total, 105 Austrian patients (64 ± 11 years, 12% female; LVEF 28 ± 6%) received a WCD for a median of 69 (1; 277) days after AMI (wearing duration 23.5 (0; 24) hours/day). Within the first 90 days, 4/105 (3.8%) patients received 9 appropriate shocks (2 (1; 5) shocks). No inappropriate shocks were delivered, and 3/105 (2.9%) patients died during follow-up. Arrhythmic mortality (1.9% Austria vs. 1.6% VEST, p = 0.52), as well as all-cause mortality (2.9% vs. 3.1%, p = 0.42) was comparable in both cohorts. CONCLUSIONS: The WCD is a safe treatment option in a highly selected cohort of patients with LVEF ≤ 35% after AMI. However, despite excellent WCD wearing duration in our cohort, the arrhythmic mortality rate was not significantly different.
RESUMO
Aims: To test the feasibility of postprocedural photoplethysmography (PPG) rhythm telemonitoring during the first week after atrial fibrillation (AF) ablation and its predictive value for later AF recurrence. Methods: PPG rhythm telemonitoring during the first week after the ablation procedure was offered to a total of 382 consecutive patients undergoing AF ablation. Patients were instructed to perform 1â min PPG recordings by a mobile health application 3 times per day and in case of symptoms. Clinicians assessed the PPG tracings via a secured cloud and the information was remotely integrated into the therapeutic pathway via teleconsultation (TeleCheck-AF approach). Results: 119 patients (31%) agreed to perform PPG rhythm telemonitoring after ablation. Patients included in the TeleCheck-AF approach were younger compared to those who declined participation (58 ± 10 vs. 62 ± 10 years, p < 0.001). Median follow up duration was 544 (53-883) days. 27% of patients had PPG tracings suggestive of AF in the week following the ablation. In 24% of patients, the integration of PPG rhythm telemonitoring resulted in a remote clinical intervention during teleconsultation. During follow-up of one year, 33% of patients had ECG-documented AF recurrences. PPG recordings suggestive of AF in the week after ablation were predictive of late recurrences (p < 0.001). Conclusion: PPG rhythm telemonitoring during the first week after AF ablation often triggered clinical interventions. Due to its high availability, PPG-based follow-up actively involving patients after AF ablation may close a diagnostic and prognostic gap in the blanking period and increase active patient-involvement.
RESUMO
Background: Out-of-hospital cardiac arrest (OHCA) is associated with poor survival rates. Factors that may enable survival include cardiopulmonary resuscitation (CPR) initiated by bystanders and early use of an automated external defibrillator (AED). This explorative simulation study was conceptualized to test the feasibility of a semi-autonomously operating drone that delivers an AED to a remote emergency location and its bystander-use. Methods: Ten paramedics and nineteen laypersons were confronted with a manikin simulating an OHCA as single bystanders within a field test located in a mountainous region between Austria and Slovenia. The scenario included a mock-call to the local emergency response center that dispatched a drone towards the caller's GPS coordinates and supported the ongoing CPR. The outcomes were the successful delivery of the AED, the time to the first shock, hands-off times, and the overall performance of the CPR. Results: The AED was delivered by drone and used in all 29 scenarios without serious adverse events. The flight time of the drone was in median 5:20 (range: 1:35-8:19) minutes. The paramedics delivered the first shock after a mean of 12:15 ± 2:03 min and hands-off times were 50 ± 22 s. The laypersons delivered the first shock after 14:04 ± 2:10 min and hands-off times were 2:11 ± 0:39 min. All participants felt confident in the handling of the delivered AED. Conclusion: The delivery and usage of an AED via a semi-autonomously flying drone in a remote region is feasible. This approach can lead to early administration of shocks.
RESUMO
Introduction: Public knowledge of out-of-hospital cardiac arrest (OHCA), and initiation of basic life support (BLS) is crucial to increase survival in OHCA. Methods: The study analysed the knowledge and willingness to perform BLS of laypersons passing an AED at a public train station. Interviewees were recruited at two time points before and after a four year-long structured regional awareness campaign, which focused on call, compress, shock in a mid-size European city (270,000 inhabitants). Complete BLS was defined as multiple responses for call for help; initiation of chest compressions; and usage of an AED, without mentioning recovery position. Minimal BLS was defined as call for help and initiation of chest compressions. Results: A total of 784 persons were interviewed, 257 at baseline and 527 post-campaign. Confronted with a fictional OHCA, at baseline 8.5% of the interviewees spontaneously mentioned actions for complete BLS and 17.9% post-campaign (p = 0.009). An even larger increase in knowledge was seen in minimal BLS (34.6% vs 60.6%, p < 0.001). Conclusion: After a regional cardiac arrest awareness campaign, we found an increase in knowledge of BLS actions in the lay public. However, our investigation revealed severe gaps in BLS knowledge, possibly resulting in weak first links of the chain of survival.
RESUMO
Atrial fibrillation is the most common sustained cardiac arrhythmia in adults. It is a complex arrhythmia leading to increased morbidity and mortality requiring thorough assessment and classification to guide therapy and to assess whether to pursue rate or rhythm control therapy. To obtain rhythm control, several strategies are available with different advantages and disadvantages concerning success rate and safety. Apart from antiarrhythmic drugs, catheter ablation is a well-established invasive therapy to treat atrial fibrillation. As quality of life is a very important factor to pursue rhythm control, several studies investigated on the specific impact of catheter ablation on quality of life. Catheter ablation shows a beneficial effect on quality of life in paroxysmal and persistent atrial fibrillation independent of the timepoint and strategy of catheter ablation.
RESUMO
INTRODUCTION: Direct oral anticoagulants (DOACs) are superior to vitamin K antagonists (VKAs) for the prevention of stroke in atrial fibrillation (AF) patients with elevated stroke risk. Possible antiarrhythmic effects of DOACs have been discussed. We analyzed impact of DOAC treatment on recurrence-free survival after AF catheter ablation. METHODS: Two-hundred and thirty-nine consecutive patients (median age 57 [IQR 48-64] years, 26.4% female) undergoing ablation for paroxysmal AF were included into this study. 68.6% of them received DOACs (DOAC group), 31.4% VKA (VKA group). The primary outcome was arrhythmia-free one-year survival. RESULTS: DOAC patients had lower BMI, shorter history of AF, less arterial hypertension, less vascular disease, less use of antiarrhythmics and consequently lower CHA2DS2-VASc and HAS-BLED Scores. There was no difference in arrhythmia-free survival between DOAC and VKA groups (DOAC: 86.6%, VKA: 76.7%, p = 0.286). CONCLUSIONS: Despite baseline characteristics favouring a better outcome of DOAC patients, arrhythmia-free survival was similar in both groups. Consequently, DOAC treatment did not have clinically relevant antiarrhythmic properties in these patients.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/uso terapêuticoRESUMO
AIMS: Preventing hospitalization by detecting early evidence of heart failure (HF) decompensation in an outpatient setting can improve patient's quality of life and reduce costs of care. The purpose of this study was to assess the value of cardiac acoustic biomarkers (CABs), a combination of cardiohaemic vibrations synchronized with ECG signals, and heart rate (HR) for detecting HF decompensation during first 3 months after hospital discharge for HF. METHODS AND RESULTS: Patients with an ejection fraction ≤35% (HFrEF) and hospitalized for decompensated HF were enrolled in a prospective observational study. All subjects wore a wearable cardioverter-defibrillator (ZOLL LifeVest® , Pittsburgh, PA, USA) that is capable of recording CABs and HR. The primary endpoint of the study was the first HF event, defined as HF readmission or HF emergency room visit. From June 2017 through August 2019, 671 patients with HFrEF were enrolled. Eighty-one patients (12.1%) had a total of 112 HF events. The algorithm detected HF events with a median of 32 days (interquartile range = 11-45) in advance of the first HF event. The algorithm had a sensitivity of 69%, specificity of 60%, positive predictive value of 19%, and a negative predictive value of 94%. Of note, the baseline (first 7 days post-enrolment) algorithm using CABs and HR was superior to New York Heart Association classification in detecting patients more likely to have HF decompensation (sensitivity and specificity of 61% and 68% vs. 46% and 55%, respectively). CONCLUSIONS: This prospective international registry showed that an algorithm incorporating CABs and HR data detected HF events 30 days in advance of the event in patients with HFrEF during first 3 months after hospital discharge. Therefore, integrating CAB technology into clinical practice may prevent HF rehospitalizations.
RESUMO
INTRODUCTION: The utility of accelerometer-based activity data to identify patients at risk of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) has not previously been investigated. The aim of the current study was to determine whether physical activity is associated with manifesting spontaneous sustained VT/VF requiring emergent defibrillation in patients with an ejection fraction of ≤35%. METHODS: Patients consecutively prescribed a wearable cardioverter defibrillator (WCD) from April 2015 to May 2018 were included. Shock data and 4 weeks of physical activity data, beginning with the first week of WCD wear, were analyzed. RESULTS: Based on the ROC curve outcome generated from 4057 patients, average daily step count during the first week accurately predicted those patients with sustained VT/VF compared to those without (shocked (n = 81) vs nonshocked (n = 3976) area under the curve, c-index = 0.71, 95% CI = 0.65-0.77, P < .001). An average cutoff of 3637 daily steps during week 1 separated the groups. Patients who averaged fewer than 3637 steps per day during the first week of WCD use were 4.3 times more likely to experience a shock than those who walked more than 3637 steps per day (OR = 4.29, 95% CI = 2.58-7.15, P < .001). DISCUSSION: Average daily step counts are lower in WCD patients who manifest spontaneous VT/VF. Whether these findings represent a causal or correlational relationship, future studies to encourage a minimum daily step count in high-risk patients may impact the incidence of sustained VT/VF.
Assuntos
Desfibriladores Implantáveis , Exercício Físico/fisiologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/terapia , Acelerometria , Idoso , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Retrospectivos , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/fisiopatologia , Dispositivos Eletrônicos VestíveisRESUMO
Development and progression of atrial fibrillation (AF) is driven by comorbidities such as arterial hypertension and diabetes mellitus. In animal models of chronic hyperglycaemia, progression of AF has been proposed to be triggered by oxidative stress, apoptosis and fibrosis. Acute glycosylation of CaMKII has been associated with increased susceptibility to arrhythmias in acute hyperglycaemia. However, the proarrhythmogenic effect of acute hyperglycaemia has not been investigated. Nine healthy, anesthetized pigs (54 ± 6 kg) were instrumented with electrophysiologic catheters and a multielectrode array on the epicardium of the left atrial anterior wall. Left and right atrial effective refractory periods (AERP), inducibility of AF and left atrial epicardial conduction velocities (CV) were measured at baseline (BL), increasing steps of blood glucose (200-500 mg/dL in steps of 100 mg/dL by glucose infusion) and repeated after normalisation of blood glucose levels (recovery). Serum electrolytes were kept constant during measurements by means of sodium and potassium infusion. There were no significant differences in AERP, CV or AF inducibility between BL and recovery. Heart rate remained constant regardless of blood glucose levels (BL: 103 ± 18 bpm, 500 mg/dL: 103 ± 18 bpm, r = 0.02, p = 0.346). Mean left as well as right AERP increased with higher glucose levels. CV increased with glucose levels (1.25 (1.04, 1.67) m/s at BL vs. 1.53 (1.22, 2.15) m/s at 500 mg/dL, r = 0.85, p = 0.034). Rate of AF inducibility in the left atrium remained constant throughout the whole protocol (AF episodes > 10 s: mean inducibility of 80% at BL vs. 69% at 500 mg/dL, p = 0.32, episodes > 30 s: 0% at BL vs. 0% at 500 mg/dL, p = 0.17). Our data imply that acute hyperglycaemia is associated with lower arrhythmogenic substrate and does not promote AF inducibility.
Assuntos
Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Hiperglicemia/complicações , Doença Aguda , Animais , Biomarcadores , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Hiperglicemia/sangue , Hiperglicemia/etiologia , Pericárdio/fisiopatologia , Período Refratário Eletrofisiológico , SuínosRESUMO
BACKGROUND: Arterial hypertension (HT) contributes to progression of atrial fibrillation (AF) via unknown mechanisms. OBJECTIVE: We aimed to characterize electrical and structural changes accounting for increased AF stability in a large animal model of rapid atrial pacing (RAP)-induced AF combined with desoxycorticosterone acetate (DOCA)-induced HT. METHODS: Eighteen pigs were instrumented with right atrial endocardial pacemaker leads and custom-made pacemakers to induce AF by continuous RAP (600 beats/min). DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (AF+HT group); the other 9 animals served as controls (AF group). Final experiments included electrophysiology studies, endocardial electroanatomic mapping, and high-density mapping with epicardial multielectrode arrays. In addition, 3-dimensional computational modeling was performed. RESULTS: DOCA implantation led to secondary HT (median [interquartile range] aortic pressure 109.9 [100-137] mm Hg in AF+HT vs 82.2 [79-96] mm Hg in AF; P < .05), increased AF stability (55.6% vs 12.5% of animals with AF episodes lasting >1 hour; P < .05), concentric left ventricular hypertrophy, atrial dilatation (119 ± 31 cm2 in AF+HT vs 78 ± 23 cm2 in AF; P < .05), and fibrosis. Collagen accumulation in the AF+HT group was mainly found in non-intermyocyte areas (1.62 ± 0.38 cm3 in AF+HT vs 0.96 ± 0.3 cm3 in AF; P < .05). Left and right atrial effective refractory periods, action potential durations, endo- and epicardial conduction velocities, and measures of AF complexity were comparable between the 2 groups. A 3-dimensional computational model confirmed an increase in AF stability observed in the in vivo experiments associated with increased atrial size. CONCLUSION: In this model of secondary HT, higher AF stability after 2 weeks of RAP is mainly driven by atrial dilatation.
Assuntos
Fibrilação Atrial/fisiopatologia , Remodelamento Atrial , Pressão Sanguínea/fisiologia , Simulação por Computador , Átrios do Coração/fisiopatologia , Frequência Cardíaca/fisiologia , Hipertensão/complicações , Animais , Fibrilação Atrial/etiologia , Fibrilação Atrial/terapia , Modelos Animais de Doenças , Eletrocardiografia , Átrios do Coração/diagnóstico por imagem , Hipertensão/fisiopatologia , Marca-Passo Artificial , SuínosRESUMO
Extracts or alkaloids isolated from Mahonia aquifolium exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi, and protozoa. In this study the bacteriostatic and bacteriocidal activities of a M. aquifolium extract and two of its major alkaloids, berberine chloride and oxyacanthine sulphate, were tested in vitro against nine different oral bacteria. Minimum inhibitory concentrations were in the range from < or = 0.0031% to 0.1993% for the M. aquifolium extract, from 0.002% to > 0.125% for berberine chloride, and from 0.0156% to > 0.0625% for oxyacanthine sulphate. The values for the minimum bactericidal concentrations were in the same range, indicating that the test substances most probably acted in a bactericidal manner. The most susceptible bacterium against all three test substances was Porphyromonas gingivalis.