Prediction of imminent sudden cardiac death based on warning signs

心脏骤停（SCA）是一种突然的灾难性脉搏丧失，影响了超过350，000人， 美国每年大多数人会在发病后10分钟内发生心源性猝死（SCD）， 死亡率> 90%。基于我们最近的工作，我们提出了一个新的范式， 称为“近期预防”。SCA通常不像人们想象的那么突然。至少 50%的人会在SCD前4周的某个时候出现警告症状， 这些可能是非特异性的，因此通常不采取行动。本提案的总体目标是 在这4周内，完善SCD高风险症状个体的识别 机会之窗我们建议，同时检查症状，临床 因子和生物标志物可以识别出即将发生SCD的最高风险个体， 实现预测和抢先管理，从而防止SCD。我们建议 根据PI建立的两项基于人群的研究制定综合风险评分。的 波特兰，俄勒冈州突发意外死亡研究（俄勒冈州-SUDS，集水区100万） 现在是在其第17个年头，文图拉，加州PRESTO研究（预测猝死， 多民族社区，集水区850 000）是在其第五年。所得到的组合 数据库包含超过7500例SCD病例和对照的信息， 表型分析和血浆样本生物库。从俄勒冈州南部，我们最近报道说， 在839名患有SCD的患者中，51%（n=430）的患者在 在致命事件发生前的4周主要症状是胸痛，但呼吸困难、疲劳， 还记录了晕厥和心悸。警告信号可能是一个机会， SCD的近期预测。虽然这些症状是常见的，可能是非特异性的， SCD，我们假设特定症状和临床特征的组合可能有助于 识别即将发生SCA的高风险患者。此外，小说的发现 SCD的血浆生物标志物对于危险分层可能具有额外的效用。因此我们 假设生物标志物，当与特定症状和临床特征结合时， 最大限度地提高识别SCD风险最高的有症状受试者的可能性， 早期干预。SCD仍然是一个主要的公共卫生问题，迫切需要新的治疗方法。 预测和预防。开发这种用户友好的即将发生SCD的风险评分， 那些有警告症状的人将代表一个实际的和临床上有意义的进步， 对病人进行分类以获得最佳护理。

Sudden cardiac arrest (SCA), a sudden catastrophic loss of the pulse, affects >350,000 in the US annually. Most will suffer sudden cardiac death (SCD) within 10 minutes of presentation, yielding a mortality rate >90%. Based on our recent work, we have proposed a novel paradigm for SCD called “near-term prevention”. SCA is often not as sudden as one might expect. At least 50% of individuals will have warning symptoms at some time in the 4 weeks prior to SCD, but these can be non-specific, so are often not acted upon. The overall goal of this proposal is to refine the identification of the symptomatic individual at high-risk of SCD, during this 4-week window of opportunity. We propose that a simultaneous examination of symptoms, clinical factors and biomarkers may identify individuals at highest risk of imminent SCD, which could enable prediction and pre-emptive management, thereby preventing SCD. We are proposing to develop a comprehensive risk score from two population-based studies founded by the PI. The Portland, Oregon Sudden Unexpected Death Study (Oregon-SUDS, catchment area ≈ 1 million) is now in its 17th year and the Ventura, California PRESTO study (Prediction of Sudden Death in Multi-Ethnic Communities, catchment area ≈ 850,000) is in its 5th year. The resulting combined databank contains information on >7500 SCD cases and controls, with detailed clinical phenotyping and a biobank of plasma samples. From Oregon-SUDS, we recently reported that 51% (n=430) of 839 individuals who suffered SCD presented with at least one symptom within the 4 weeks prior to their lethal event. The main symptom was chest pain, but dyspnea, fatigue, syncope and palpitations were also recorded. Warning signs could represent an opportunity for near-term prediction of SCD. While these symptoms are common and may be non-specific for SCD, we hypothesize that a combination of specific symptoms and clinical profile could facilitate the identification of patients at high risk of impending SCA. In addition, the discovery of novel plasma biomarkers for SCD could have additional utility for risk stratification. We therefore hypothesize that biomarkers, when combined with specific symptoms and clinical profile, will maximize the likelihood of identifying symptomatic subjects at highest risk of SCD, allowing for early intervention. SCD remains a major public health problem with a critical need for novel prediction and prevention. Development of this user-friendly risk score for imminent SCD in those with warning symptoms would represent a practical and clinically meaningful advance for triage of patients for optimal care.