RESUMEN
PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT), the predictive value of PSMA PET/CT-derived response is still under investigation. Early molecular imaging response based on total viable tumor burden and its association with overall survival (OS) was explored in this study. METHODS: Sixty-six mCRPC patients who received [177Lu]Lu-PSMA-617 RLT within a prospective patient registry (REALITY Study, NCT04833517) were analyzed. Patients received a [68Ga]Ga-PSMA-11 PET/CT scan before the first and after the second cycle of PSMA-RLT. Total lesion PSMA (TLP) was determined by semiautomatic whole-body tumor segmentation. Molecular imaging response was assessed by change in TLP and modified PERCIST criteria. Biochemical response was assessed using standard serum PSA and PCWG3 criteria. Both response assessment methods and additional baseline parameters were analyzed regarding their association with OS by univariate and multivariable analysis. RESULTS: By molecular imaging, 40/66 (60.6%) patients showed partial remission (PR), 19/66 (28.7%) stable disease (SD), and 7/66 (10.6%) progressive disease (PD). Biochemical response assessment revealed PR in 34/66 (51.5%) patients, SD in 20/66 (30.3%), and PD in 12/66 (18.2%). Response assessments were concordant in 49/66 (74.3%) cases. On univariate analysis, both molecular and biochemical response (p = 0.001 and 0.008, respectively) as well as two baseline characteristics (ALP and ECOG) were each significantly associated with OS. The median OS of patients showing molecular PR was 24.6 versus 10.7 months in the remaining patients (with SD or PD). On multivariable analysis molecular imaging response remained an independent predictor of OS (p = 0.002), eliminating biochemical response as insignificant (p = 0.515). CONCLUSION: The new whole-body molecular imaging-derived biomarker, early change of total lesion PSMA (TLP), independently predicts overall survival in [177Lu]Lu-PSMA-617 RLT in mCRPC, outperforming conventional PSA-based response assessment. TLP might be considered a more distinguished and advanced biomarker for monitoring PSMA-RLT over commonly used serum PSA.
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Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Dipéptidos/uso terapéutico , Radioisótopos de Galio , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Humanos , Lutecio , Masculino , Imagen Molecular , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Estudios Retrospectivos , Resultado del Tratamiento , Carga TumoralRESUMEN
Current guidelines recommend opportunistic screening for subclinical atrial fibrillation (AF) taking advantage of e-health-based technologies. However, the efficacy of a fully scalable e-health-based strategy for AF detection in a head-to-head comparison with routine symptom-based screening is unknown. eBRAVE-AF is an investigator-initiated, digital, prospective, randomized, siteless, open-label, cross-over study to evaluate an e-health-based strategy for detection of AF in a real-world setting. 67,488 policyholders of a large German health insurance company (Versicherungskammer Bayern, Germany) selected by age ≥ 50 years and a CHA2DS2-VASc score ≥ 1 (females ≥2) are invited to participate. Subjects with known AF or on treatment with oral anticoagulation are excluded. After obtaining electronic informed consent, at least 4,400 participants will be randomly assigned to an e-health-based screening strategy or routine symptom-based screening. The e-health-based strategy consists of repetitive one-minute photoplethysmographic (PPG) pulse wave assessments using a certified smartphone app (Preventicus Heartbeats, Preventicus, Jena, Germany), followed by a confirmatory 14-day ECG patch (CardioMem CM 100 XT, Getemed, Teltow, Germany) in case of abnormal findings. After 6 months, participants are crossed over to the other study arm. Primary endpoint is the incidence of newly diagnosed AF leading to oral anticoagulation indicated by an independent physician. Clinical follow-up will be at least 12 months. In both groups, follow-up is performed by 4-week app-based questionnaires, personal contact in case of abnormal findings, and matching with claim-based insurance data and medical reports. At time of writing enrollment is completed. First results are expected to be available in mid-2021.
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Enfermedades Asintomáticas/epidemiología , Fibrilación Atrial , Aplicaciones Móviles , Monitoreo Ambulatorio , Telemedicina , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Estudios Cruzados , Femenino , Alemania/epidemiología , Humanos , Seguro de Salud/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio/instrumentación , Monitoreo Ambulatorio/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Teléfono Inteligente , Telemedicina/instrumentación , Telemedicina/métodosRESUMEN
Digital smart devices have the capability of detecting atrial fibrillation (AF), but the efficacy of this type of digital screening has not been directly compared to usual care for detection of treatment-relevant AF. In the eBRAVE-AF trial ( NCT04250220 ), we randomly assigned 5,551 policyholders of a German health insurance company who were free of AF at baseline (age 65 years (median; interquartile range (11) years, 31% females)) to digital screening (n = 2,860) or usual care (n = 2,691). In this siteless trial, for digital screening, participants used a certified app on their own smartphones to screen for irregularities in their pulse waves. Abnormal findings were evaluated by 14-day external electrocardiogram (ECG) loop recorders. The primary endpoint was newly diagnosed AF within 6 months treated with oral anti-coagulation by an independent physician not involved in the study. After 6 months, participants were invited to cross-over for a second study phase with reverse assignment for secondary analyses. The primary endpoint of the trial was met, as digital screening more than doubled the detection rate of treatment-relevant AF in both phases of the trial, with odds ratios of 2.12 (95% confidence interval (CI), 1.19-3.76; P = 0.010) and 2.75 (95% CI, 1.42-5.34; P = 0.003) in the first and second phases, respectively. This digital screening technology provides substantial benefits in detecting AF compared to usual care and has the potential for broad applicability due to its wide availability on ordinary smartphones. Future studies are needed to test whether digital screening for AF leads to better treatment outcomes.
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Fibrilación Atrial , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Niño , Atención a la Salud , Electrocardiografía , Femenino , Humanos , Masculino , Tamizaje Masivo , Teléfono InteligenteRESUMEN
BACKGROUND: Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events. METHODS: We did a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial at 33 centres in Germany and Austria. Survivors of acute myocardial infarction with left ventricular ejection fraction of 36-50% had biosignal analysis for assessment of cardiac autonomic function. Patients with abnormal periodic repolarisation dynamics (≥5·75 deg2) or abnormal deceleration capacity (≤2·5 ms) were randomly assigned (1:1) to telemedical monitoring with implantable cardiac monitors or conventional follow-up. Primary endpoint was time to detection of serious arrhythmic events defined by atrial fibrillation 6 min or longer, atrioventricular block class IIb or higher and fast non-sustained (>187 beats per min; ≥40 beats) or sustained ventricular tachycardia or fibrillation. This study is registered with ClinicalTrials.gov, NCT02594488. FINDINGS: Between May 12, 2016, and July 20, 2020, 1305 individuals were screened and 400 patients at high risk were randomly assigned (median age 64 years [IQR 57-73]); left ventricular ejection fraction 45% [40-48]) to telemedical monitoring with implantable cardiac monitors (implantable cardiac monitor group; n=201) or conventional follow-up (control group; n=199). During median follow-up of 21 months, serious arrhythmic events were detected in 60 (30%) patients of the implantable cardiac monitor group and 12 (6%) patients of the control group (hazard ratio 6·33 [IQR 3·40-11·78]; p<0·001). An improved detection rate by implantable cardiac monitors was observed for all types of serious arrhythmic events: atrial fibrillation 6 min or longer (47 [23%] patients vs 11 [6%] patients; p<0·001), atrioventricular block class IIb or higher (14 [7%] vs 0; p<0·001) and ventricular tachycardia or ventricular fibrillation (nine [4%] patients vs two [1%] patients; p=0·054). INTERPRETATION: In patients at high risk after myocardial infarction and cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction, telemedical monitoring with implantable cardiac monitors was highly effective in early detection of subclinical, prognostically relevant serious arrhythmic events. FUNDING: German Centre for Cardiovascular Research (DZHK) and Medtronic Bakken Research Center.
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Arritmias Cardíacas/diagnóstico , Monitoreo Fisiológico/métodos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Medición de Riesgo/métodos , Telemedicina/métodos , Anciano , Austria , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Patients with end-stage kidney disease are at high risk for the development of arrhythmias and sudden cardiac death (SCD). This has been especially attributed to large potassium shifts during hemodialysis (HD), and malignant arrhythmias are closely linked to dysfunction of the autonomic nervous system. Nevertheless, there is still a lack of methods for risk stratification in these patients. METHODS: In the present pilot study we investigated changes of the novel ECG-based biomarker periodic repolarization dynamics (PRD) mirroring the effect of efferent sympathetic nervous activity on the ventricular myocardium in 18 patients undergoing routine hemodialysis. High-resolution ECGs were recorded throughout the dialysis and PRD values were calculated out of 30 min intervals at the start and the end of dialysis. RESULTS: We detected a clear correlation between the intradialytic potassium shift and the increase in PRD levels (Spearman correlation coefficient R = 0.62, p = 0.006). Patients with a potassium shift > 1 mmol/l showed significantly increased levels of PRD at the end of dialysis when compared to patients with potassium shifts ≤ 1.0 mmol/l [delta PRD 2.82 (IQR 2.13) vs. - 2.08 (IQR 3.60), p = 0.006]. Spearman analysis showed no significant correlation between PRD changes and fluid removal (R = - 0.23, p = 0.36). CONCLUSIONS: We provide evidence that large potassium shifts during HD enhance sympathetic activity-associated repolarization instability. This could facilitate the occurrence of malignant arrhythmias, and PRD measurements might serve as a non-invasive monitoring tool in HD patients in future.