RESUMO
The clinical use of irreversible electroporation in invasive cardiac laboratories, termed pulsed field ablation (PFA), is gaining early enthusiasm among electrophysiologists for the management of both atrial and ventricular arrhythmogenic substrates. Though electroporation is regularly employed in other branches of science and medicine, concerns regarding the acute and permanent vascular effects of PFA remain. This comprehensive review aims to summarize the preclinical and adult clinical data published to date on PFA's effects on pulmonary veins and coronary arteries. These data will be contrasted with the incidences of iatrogenic pulmonary vein stenosis and coronary artery injury secondary to thermal cardiac ablation modalities, namely radiofrequency energy, laser energy, and liquid nitrogen-based cryoablation.
Assuntos
Mapeamento Potencial de Superfície Corporal , Átrios do Coração , Humanos , Átrios do Coração/fisiopatologia , Átrios do Coração/diagnóstico por imagem , Mapeamento Potencial de Superfície Corporal/métodos , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Sistema de Condução Cardíaco/fisiopatologiaAssuntos
Ablação por Cateter , Taquicardia Ventricular , Humanos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Coração , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Ablação por Cateter/efeitos adversos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/cirurgia , EletrocardiografiaRESUMO
PURPOSE OF REVIEW: Heart failure often progresses despite optimal medical and device therapies, and advanced mechanical circulatory support has limited availability and substantial associated morbidity. Cardiac contractility modulation (CCM) provides nonexcitatory stimulation to ventricular myocardium which increases cardiac contractility without increasing oxygen demand. This review describes the emerging role of CCM in heart failure treatment. RECENT FINDINGS: The FIX-HF-5C2 study demonstrated similar safety and efficacy profile of the two-lead Optimizer device in comparison with the prior three-lead system, thereby decreasing procedural complexity and minimizing endocardial hardware. The FIX-HF-5C trial underscored the benefit of CCM in patients with mild-moderate left ventricular dysfunction (ejection fraction, 25-45%) with New York Heart Association (NYHA) Class III symptoms. The summarized randomized trial data show consistent improvements in peak VO2, 6-min walk distance, and NYHA functional class with CCM. Future trials are planned to determine the role of CCM in heart failure patients with preserved ejection fraction, obligate ventricular pacing, and atrial arrhythmias. SUMMARY: Nonexcitatory extracellular electric potentials can facilitate inotropic improvements in the failing heart. The mechanism of CCM does not increase myocardial oxygen consumption and has been shown to mitigate heart failure symptoms, decrease hospitalizations, and work in synergy with guideline-directed therapy for heart failure.
Assuntos
Insuficiência Cardíaca , Contração Miocárdica , Humanos , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologia , Resultado do Tratamento , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Patients with atrial fibrillation are increasingly prescribed a direct oral anticoagulant (DOAC) over warfarin and seek to avoid anticoagulation even without a history of major bleeding. This study explores the outcomes of patients implanted with a Watchman device in relation to anticoagulation choice (warfarin versus DOAC) in the post-procedure period and a history of bleeding. METHODS: Patients implanted with a Watchman device at a single center were retrospectively analyzed. Characteristics including anticoagulation in the first 45 days and history of major bleed were assessed and efficacy (thromboembolism) and safety (bleeding) outcomes compared by Kaplan-Meier analysis. RESULTS: Two hundred nine patients were implanted (57% male, age 74.6 ± 7.8 years) and followed for 23.5 ± 7.1 months. In the first half of patients, 98% were prescribed warfarin, which dropped to 51% in the second half (p < 0.0001). A history of major bleed was present in 80.8% of the first half of patients and decreased to 60% in the second half (p = 0.001). There were 16 safety and 4 efficacy events. There was no difference in safety outcomes according to history of major bleeding or anticoagulant choice in the first 45 days. There was no difference in efficacy outcomes over the duration of follow-up according to anticoagulation choice in the first 45 days. CONCLUSIONS: Patients implanted with a Watchman device were increasingly over time prescribed a DOAC and implanted without a history of major bleeding. Bleeding and thromboembolic events were infrequent and related neither to choice of anticoagulant nor to prior major bleeding.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/cirurgia , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Estudos Retrospectivos , Tromboembolia/prevenção & controle , Resultado do Tratamento , Varfarina/efeitos adversosRESUMO
IMPORTANCE: Despite efforts to enhance serious illness communication, patients with advanced heart failure (HF) lack prognostic understanding. OBJECTIVES: To determine rate of concordance between HF patients' estimation of their prognosis and their physician's estimate of the patient's prognosis, and to compare patient characteristics associated with concordance. DESIGN: Cross-sectional analysis of a cluster randomized controlled trial with 24-month follow-up and analysis completed on 09/01/2020. Patients were enrolled in inpatient and outpatient settings between September 2011 to February 2016 and data collection continued until the last quarter of 2017. SETTING: Six teaching hospitals in the U.S. PARTICIPANTS: Patients with advanced HF and implantable cardioverter defibrillators (ICDs) at high risk of death. Of 537 patients in the parent study, 407 had complete data for this analysis. INTERVENTION: A multi-component communication intervention on conversations between HF clinicians and their patients regarding ICD deactivation and advance care planning. MAIN OUTCOME(S) AND MEASURE(S): Patient self-report of prognosis and physician response to the "surprise question" of 12-month prognosis. Patient-physician prognostic concordance (PPPC) measured in percentage agreement and kappa. Bivariate analyses of characteristics of patients with and without PPPC. RESULTS: Among 407 patients (mean age 62.1 years, 29.5% female, 42.4% non-white), 300 (73.7%) dyads had non-PPPC; of which 252 (84.0%) reported a prognosis >1 year when their physician estimated <1 year. Only 107 (26.3%) had PPPC with prognosis of ≤ 1 year (n=20 patients) or > 1 year (n=87 patients); (Κâ¯=â¯-0.20, pâ¯=â¯1.0). Of those with physician estimated prognosis of < 1 year, non-PPPC was more likely among patients with lower symptom burden- number and severity (both p ≤.001), without completed advance directive (p=.001). Among those with physician prognosis estimate > 1 year, no patient characteristic was associated with PPPC or non-PPPC. CONCLUSIONS AND RELEVANCE: Non-PPPC between HF patients and their physicians is high. HF patients are more optimistic than clinicians in estimating life expectancy. These data demonstrate there are opportunities to improve the quality of prognosis disclosure between patients with advanced HF and their physicians. Interventions to improve PPPC might include serious illness communication training.
Assuntos
Planejamento Antecipado de Cuidados , Desfibriladores Implantáveis , Insuficiência Cardíaca , Estudos Transversais , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
The effective diagnosis and management of procedural complications remains an important challenge for electrophysiology operators. Intracardiac echocardiography provides a real-time imaging modality with spectral and color Doppler capabilities that integrates directly with electroanatomic mapping systems. It provides detailed characterization of anatomic variants, which allows the operator to optimize the ablation strategy to the individual thereby avoiding the inherent risk of excessive or ineffective lesions. Complications, such as intracardiac thrombus or pericardial effusion, can be detected and managed before the onset of clinical symptoms. Intracardiac echocardiography facilitates the diagnosis and management of intraoperative hypotension.
Assuntos
Ablação por Cateter/efeitos adversos , Ecocardiografia/métodos , Complicações Intraoperatórias , Cardiopatias/diagnóstico por imagem , Cardiopatias/prevenção & controle , Cardiopatias/cirurgia , Humanos , Complicações Intraoperatórias/diagnóstico por imagem , Complicações Intraoperatórias/prevenção & controle , Trombose/diagnóstico por imagem , Trombose/prevenção & controleRESUMO
Heart failure (HF) post-myocardial infarction (MI) presents with increased vulnerability to monomorphic ventricular tachycardia (mmVT). To appropriately evaluate new therapies for infarct-mediated reentrant arrhythmia in the preclinical setting, chronologic characterization of the preclinical animal model pathophysiology is critical. This study aimed to evaluate the rigor and reproducibility of mmVT incidence in a rodent model of HF. We hypothesize a progressive increase in the incidence of mmVT as the duration of HF increases. Adult male Sprague-Dawley rats underwent permanent left coronary artery ligation or SHAM surgery and were maintained for either 6 or 10 wk. At end point, SHAM and HF rats underwent echocardiographic and invasive hemodynamic evaluation. Finally, rats underwent electrophysiologic (EP) assessment to assess susceptibility to mmVT and define ventricular effective refractory period (ERP). In 6-wk HF rats (n = 20), left ventricular (LV) ejection fraction (EF) decreased (P < 0.05) and LV end-diastolic pressure (EDP) increased (P < 0.05) compared with SHAM (n = 10). Ten-week HF (n = 12) revealed maintenance of LVEF and LVEDP (P > 0.05), (P > 0.05). Electrophysiology studies revealed an increase in incidence of mmVT between SHAM and 6-wk HF (P = 0.0016) and ERP prolongation (P = 0.0186). The incidence of mmVT and ventricular ERP did not differ between 6- and 10-wk HF (P = 1.0000), (P = 0.9831). Findings from this rodent model of HF suggest that once the ischemia-mediated infarct stabilizes, proarrhythmic deterioration ceases. Within the 6- and 10-wk period post-MI, no echocardiographic, invasive hemodynamic, or electrophysiologic changes were observed, suggesting stable HF. This is the necessary context for the evaluation of experimental therapies in rodent HF.NEW & NOTEWORTHY Rodent model of ischemic cardiomyopathy exhibits a plateau of inducible monomorphic ventricular tachycardia incidence between 6 and 10 wk postinfarction.
Assuntos
Potenciais de Ação , Insuficiência Cardíaca/etiologia , Frequência Cardíaca , Infarto do Miocárdio/complicações , Taquicardia Ventricular/etiologia , Função Ventricular Esquerda , Animais , Modelos Animais de Doenças , Progressão da Doença , Insuficiência Cardíaca/fisiopatologia , Masculino , Infarto do Miocárdio/fisiopatologia , Ratos Sprague-Dawley , Período Refratário Eletrofisiológico , Volume Sistólico , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Pressão VentricularRESUMO
BACKGROUND: Prognostic awareness (PA)-the understanding of limited life expectancy-is critical for effective goals of care discussions (GOCD) in which patients discuss their goals and values in the context of their illness. Yet little is known about PA and GOCD in patients with advanced heart failure (HF). This study aims to determine the prevalence of PA among patients with advanced HF and patient characteristics associated with PA and GOCD. METHODS: We assessed the prevalence of self-reported PA and GOCD using data from a multisite communication intervention trial among patients with advanced HF with an implantable cardiac defibrillator at high risk of death. RESULTS: Of 377 patients (mean age 62 years, 30% female, 42% nonwhite), 78% had PA. Increasing age was a negative predictor of PA (odds ratio, 0.95 [95% CI, 0.92-0.97]; P<0.01). No other patient characteristics were associated with PA. Of those with PA, 26% had a GOCD. Higher comorbidities and prior advance directives were associated with GOCD but were of only borderline statistical significance in a fully adjusted model. Symptom severity (odds ratio, 1.77 [95% CI, 1.19-2.64]; P=0.005) remained a robust and statistically significant positive predictor of having a GOCD in the fully adjusted model. CONCLUSIONS: In a sample of patients with advanced HF, the frequency of PA was high, but fewer patients with PA discussed their end-of-life care preferences with their physician. Improved efforts are needed to ensure all patients with advanced HF have an opportunity to have GOCD with their doctors. Clinicians may need to target older patients with HF and continue to focus on those with signs of worsening illness (higher symptoms). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01459744.
Assuntos
Insuficiência Cardíaca/psicologia , Diretivas Antecipadas , Fatores Etários , Comorbidade , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de DoençaRESUMO
Background: Implantable cardioverter-defibrillators (ICDs) reduce the incidence of sudden cardiac death for high-risk patients with heart failure (HF), but shocks from these devices can also cause pain and anxiety at the end of life. Although professional society recommendations encourage proactive discussions about ICD deactivation, clinicians lack training in conducting these conversations, and they occur infrequently. Methods: As part of a six-center randomized controlled trial, we evaluated the educational component of a multicomponent intervention shown to increase conversations about ICD deactivation by clinicians who care for a subset of patients with advanced HF. This consisted of a 90-minute training workshop designed to improve the quality and frequency of conversations about ICD management. To characterize its utility as an isolated intervention, we compared HF clinicians' pre- and postworkshop scores (on a 5-point Likert scale) assessing self-reported confidence and skills in specific practices of advance care planning, ICD deactivation discussions, and empathic communication. Results: Forty intervention-group HF clinicians completed both pre- and postworkshop surveys. Preworkshop scores showed high baseline levels of confidence (4.36, standard deviation [SD] = 0.70) and skill (4.08, SD = 0.72), whereas comparisons of pre- and postworkshop scores showed nonsignificant decreases in confidence (-1.16, p = 0.252) and skill (-0.20, p = 0.843) after the training session. Conclusions: Our findings showed no significant changes in self-assessment ratings immediately after the educational intervention. However, our data did demonstrate that HF clinicians had high baseline self-perceptions of their skills in advance care planning conversations and appear to be well-primed for further professional development to improve communication in the setting of advanced HF.
Assuntos
Planejamento Antecipado de Cuidados , Desfibriladores Implantáveis , Insuficiência Cardíaca , Comunicação , Insuficiência Cardíaca/terapia , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Although implantable cardioverter-defibrillators (ICDs) reduce sudden death, these patients die of heart failure (HF) or other diseases. To prevent shocks at the end of life, clinicians should discuss deactivating the defibrillation function. OBJECTIVES: The purpose of this study was to determine if a clinician-centered teaching intervention and automatic reminders increased ICD deactivation discussions and increased device deactivation. METHODS: In this 6-center, single-blinded, cluster-randomized, controlled trial, primary outcomes were proportion of patients: 1) having ICD deactivation discussions; and 2) having the shocking function deactivated. Secondary outcomes included goals of care conversations and advance directive completion. RESULTS: A total of 525 subjects were included with advanced HF who had an ICD: 301 intervention and 224 control. At baseline, 52% (n = 272) were not candidates for advanced therapies (i.e., cardiac transplant or mechanical circulatory support). There were no differences in discussions (41 [14%] vs. 26 [12%]) or deactivation (33 [11%] vs. 26 [12%]). In pre-specified subgroup analyses of patients who were not candidates for advanced therapies, the intervention increased deactivation discussions (32 [25%] vs. 16 [11%]; odds ratio: 2.90; p = 0.003). Overall, 99 patients died; there were no differences in conversations or deactivations among decedents. SECONDARY OUTCOMES: Among all participants, there was an increase in goals of care conversations (47% intervention vs. 38% control; odds ratio: 1.53; p = 0.04). There were no differences in completion of advance directives. CONCLUSIONS: The intervention increased conversations about ICD deactivation and goals of care. HF clinicians were able to apply new communication techniques based on patients' severity of illness. (An Intervention to Improve Implantable Cardioverter-Defibrillator Deactivation Conversations [WISDOM]; NCT01459744).
Assuntos
Desfibriladores Implantáveis/psicologia , Cardioversão Elétrica/psicologia , Insuficiência Cardíaca/psicologia , Assistência ao Paciente/psicologia , Papel do Médico/psicologia , Relações Médico-Paciente , Planejamento Antecipado de Cuidados/normas , Idoso , Comunicação , Desfibriladores Implantáveis/efeitos adversos , Desfibriladores Implantáveis/normas , Cardioversão Elétrica/normas , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Assistência ao Paciente/normas , Método Simples-CegoRESUMO
BACKGROUND: Identification of ST elevation myocardial infarction (STEMI) is critical because early reperfusion can save myocardium and increase survival. ST elevation (STE) in lead augmented vector right (aVR), coexistent with multilead ST depression, was endorsed as a sign of acute occlusion of the left main or proximal left anterior descending coronary artery in the 2013 STEMI guidelines. We investigated the incidence of an acutely occluded coronary in patients presenting with STE-aVR with multilead ST depression. METHODS: STEMI activations between January 2014 and April 2018 at the University of Arizona Medical Center were identified. All electrocardiograms (ECGs) and coronary angiograms were blindly analyzed by experienced cardiologists. Among 847 STEMI activations, 99 patients (12%) were identified with STE-aVR with multilead ST depression. RESULTS: Emergent angiography was performed in 80% (79/99) of patients. Thirty-six patients (36%) presented with cardiac arrest, and 78% (28/36) underwent emergent angiography. Coronary occlusion, thought to be culprit, was identified in only 8 patients (10%), and none of those lesions were left main or left anterior descending occlusions. A total of 47 patients (59%) were found to have severe coronary disease, but most had intact distal flow. Thirty-two patients (40%) had mild to moderate or no significant disease. However, STE-aVR with multilead ST depression was associated with 31% in-hospital mortality compared with only 6.2% in a subgroup of 190 patients with STEMI without STE-aVR (p<0.00001). CONCLUSIONS: STE-aVR with multilead ST depression was associated with acutely thrombotic coronary occlusion in only 10% of patients. Routine STEMI activation in STE-aVR for emergent revascularization is not warranted, although urgent, rather than emergent, catheterization appears to be important.
Assuntos
Angiografia Coronária , Doença das Coronárias , Oclusão Coronária , Eletrocardiografia , Revascularização Miocárdica , Infarto do Miocárdio com Supradesnível do Segmento ST , Idoso , Arizona/epidemiologia , Angiografia Coronária/métodos , Angiografia Coronária/estatística & dados numéricos , Doença das Coronárias/complicações , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/terapia , Oclusão Coronária/diagnóstico , Oclusão Coronária/epidemiologia , Oclusão Coronária/etiologia , Oclusão Coronária/terapia , Vasos Coronários/diagnóstico por imagem , Eletrocardiografia/métodos , Eletrocardiografia/estatística & dados numéricos , Serviços Médicos de Emergência/métodos , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/métodos , Revascularização Miocárdica/estatística & dados numéricos , Avaliação de Processos e Resultados em Cuidados de Saúde , Seleção de Pacientes , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The presence of inferior vena cava filters (IVCFs) has been considered a relative contraindication to electrophysiology (EP) procedures that require transfemoral venous placement of multiple catheters and/or long sheaths. There are inadequate data related to complex EP procedures in this population. OBJECTIVE: The purpose of this study was to describe the experience of a single high-volume center with respect to complex EP procedures in patients with IVCFs. METHODS: Patients with IVCFs undergoing complex EP procedures between 2004 and 2018 were identified. Clinical characteristics, IVCF type, procedural findings, and complications were analyzed. RESULTS: Fifty complex ablation procedures were performed in 40 patients (mean age 63.8 ± 10.9 years; 68% men). The mean IVCF dwell time was 69.1 ± 19.1 months, and 48 patients (96%) were on chronic oral anticoagulation. Procedures included ablation of atrial fibrillation (n = 21), ventricular tachycardia (n = 20), supraventricular tachycardia (n = 3), cavotricuspid isthmus flutter (n = 3), supraventricular tachycardia and cavotricuspid isthmus flutter (n = 1), and transvenous lead extraction (n = 3). Twenty procedures included quadripolar catheters (mean 1.4 ± 0.75), and 33 procedures involved deflectable decapolar catheters (mean 1.7 ± 0.47). Long sheaths were used in 35 cases (mean 1.63 ± 0.49) and intracardiac echocardiography in 38. In 4 cases (involving 3 patients), the IVCF was occluded and could not be crossed. There were no procedural complications related to the IVCF. CONCLUSION: The substantial majority of IVCFs in patients presenting for complex EP procedures were patent and easily crossed under fluoroscopic guidance. The presence of an IVCF should not discourage operators from performing procedures that require transfemoral deployment of multiple catheters and/or sheaths.
Assuntos
Arritmias Cardíacas/cirurgia , Cateterismo Cardíaco , Cateterismo Periférico , Veia Femoral , Filtros de Veia Cava , Trombose Venosa , Anticoagulantes/uso terapêutico , Arritmias Cardíacas/classificação , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/métodos , Ablação por Cateter/métodos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Cateterismo Periférico/métodos , Catéteres , Remoção de Dispositivo/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Estudos de Viabilidade , Feminino , Veia Femoral/diagnóstico por imagem , Veia Femoral/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Cirurgia Assistida por Computador/métodos , Trombose Venosa/tratamento farmacológico , Trombose Venosa/cirurgiaRESUMO
OBJECTIVES: This study sought to characterize septal substrate in patients with nonischemic left ventricular cardiomyopathy (NILVCM) undergoing ventricular tachycardia (VT) ablation. BACKGROUND: The interventricular septum is an important site of VT substrate in NILVCM. METHODS: The authors studied 95 patients with NILVCM and VT. Electroanatomic mapping using standard bipolar (<1.5 mV) and unipolar (<8.3 mV) low-voltage criteria identified septal scar location and size. Analysis of unipolar voltage was performed and scars quantified using graded unipolar cutoffs from 4 to 8.3 mV were correlated with delayed gadolinium-enhanced cardiac magnetic resonance (DE-CMR), performed in 57 patients. RESULTS: Detailed LV endocardial mapping (mean 262 ± 138 points) showed septal bipolar and unipolar voltage abnormalities (VAs) in 44 (46%) and 79 (83%) patients, most commonly with basal anteroseptal involvement. Of the 59 patients in whom the septum was targeted, bipolar and unipolar septal VAs were seen in 36 (61%) and 54 (92%). Of the 35 with CMR-defined septal scar, bipolar and unipolar septal VAs were seen in 18 (51%) and 31 (89%). In 12 patients without CMR septal scar, 6 (50%) had isolated unipolar septal VAs on electroanatomic mapping, a subset of whom the septum was targeted for ablation (44%). In the graded unipolar analysis, the optimal cutoff associated with magnetic resonance imaging septal scar was 4.8 mV (sensitivity 75%, specificity 70%; area under the curve: 0.75; 95% confidence interval: 0.60 to 0.90). CONCLUSIONS: Septal substrate by unipolar or bipolar voltage mapping in patients with NILVCM and VT is common. A unipolar voltage cutoff of 4.8 mV provides the best correlation with DE-CMR. A subset of patients with septal VT had normal DE-CMR or endocardial bipolar voltage with abnormal unipolar voltage.