Prediction of imminent sudden cardiac death based on warning signs

心脏骤停(SCA)，一种突然的灾难性脉搏丧失，影响&gt；350,000人 我们每年一次。大多数人会在出现后10分钟内发生心脏性猝死(SCD)， 死亡率高达90%。基于我们最近的工作，我们提出了一种新的范式 被称为“近期预防”的SCD。SCA通常不像人们预期的那样突然。至少 50%的人会在SCD前4周的某个时间出现警示症状，但 这些可以是非特定的，因此通常不会采取行动。这项提案的总体目标是 在这4周内，完善对SCD高危症状个体的识别 机会之窗。我们建议同时检查症状，临床上 因子和生物标记物可以确定即将发生SCD的风险最高的个人，这可能 启用预测和先发制人的管理，从而防止SCD。我们正在提议 从PI创建的两项基于人群的研究中得出综合风险评分。这个 俄勒冈州波特兰意外死亡研究(俄勒冈州-苏伊士，集水区≈100万) 现已进入第17个年头，加利福尼亚州文图拉的Presto研究(预测猝死 多民族社区，集水区(≈850,000)已进入第5个年头。由此产生的组合 数据库包含&gt；7500个SCD病例和对照的信息，以及详细的临床 表型鉴定和血浆样本的生物库。来自俄勒冈州的苏德，我们最近报道了 在839名患有SCD的人中，51%(n=430)出现至少一种症状 在他们致命事件的前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。警告信号可能代表着 SCD的近期预测。虽然这些症状是常见的，并且可能不是 SCD，我们假设结合特定的症状和临床特征可以促进 识别即将发生SCA的高危患者。此外，小说的发现 SCD的血浆生物标记物可能对风险分层有额外的作用。因此，我们 假设生物标志物，当结合特定的症状和临床特征时，将 最大限度地确定SCD风险最高的有症状的受试者，允许 早期干预。SCD仍然是一个主要的公共卫生问题，迫切需要有新的 预测和预防。为即将到来的SCD开发这一用户友好的风险评分 那些有警告性症状的人将代表着一项具有实际和临床意义的进步 对病人进行分诊，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.