Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Early Cardiac Catheterization is Associated with Improved Survival in Comatose Survivors of Cardiac Arrest Without STEMI

AIM: To determine if early cardiac catheterization (CC) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infarction (STEMI) is absent. METHODS: We conducted a retrospective observational study of a prospective cohort of 754 consecutive comatose patients treated with therapeutic hypothermia (TH) following cardiac arrest. RESULTS: A total of 269 (35.7%) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH. Of these, 122 (45.4%) received CC while comatose (early CC). Acute coronary occlusion was discovered in 26.6% of patients treated with early CC compared to 29.3% of patients treated with late CC (p=0.381). Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC (65.6% vs. 48.6%; p=0.017). In a multivariate regression model that included study site, age, bystander CPR, shock on admission, comorbid medical conditions, witnessed arrest, and time to return of spontaneous circulation, early CC was independently associated with a significant reduction in the risk of death (OR 0.35, 95% CI 0.18-0.70, p=0.003). CONCLUSIONS: In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality. The incidence of acute coronary occlusion is high, even when STEMI is not present on the postresuscitation electrocardiogram

Outcomes of Comatose Cardiac Arrest Survivors With and Without ST-Segment Elevation Myocardial Infarction: Importance of Coronary Angiography.

OBJECTIVES: The aim of this study was to compare outcomes and coronary angiographic findings in post-cardiac arrest patients with and without ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The 2013 STEMI guidelines recommend performing immediate angiography in resuscitated patients whose initial electrocardiogram shows STEMI. The optimal approach for those without STEMI post-cardiac arrest is less clear. METHODS: A retrospective evaluation of a post-cardiac arrest registry was performed. RESULTS: The database consisted of 746 comatose post-cardiac arrest patients including 198 with STEMI (26.5%) and 548 without STEMI (73.5%). Overall survival was greater in those with STEMI compared with those without (55.1% vs. 41.3%; p = 0.001), whereas in all patients who underwent immediate coronary angiography, survival was similar between those with and without STEMI (54.7% vs. 57.9%; p = 0.60). A culprit vessel was more frequently identified in those with STEMI, but also in one-third of patients without STEMI (80.2% vs. 33.2%; p = 0.001). The majority of culprit vessels were occluded (STEMI, 92.7%; no STEMI, 69.2%; p \u3c 0.0001). An occluded culprit vessel was found in 74.3% of STEMI patients and in 22.9% of no STEMI patients. Among cardiac arrest survivors discharged from the hospital who had presented without STEMI, coronary angiography was associated with better functional outcome (93.3% vs. 78.7%; p \u3c 0.003). CONCLUSIONS: Early coronary angiography is associated with improved functional outcome among resuscitated patients with and without STEMI. Resuscitated patients with a presumed cardiac etiology appear to benefit from immediate coronary angiography

Geriatric Experience Following Cardiac Arrest at Six Interventional Cardiology Centers in the United States 2006-2011: Interplay of Age, Do-Not-Resuscitate Order, and Outcomes

OBJECTIVES:: It is not known if aggressive postresuscitation care, including therapeutic hypothermia and percutaneous coronary intervention, benefits cardiac arrest survivors more than 75 years old. We compared treatments and outcomes of patients at six regional percutaneous coronary intervention centers in the United States to determine if aggressive care of elderly patients was warranted. DESIGN:: Retrospective evaluation of registry data. SETTING:: Six interventional cardiology centers in the United States. PATIENTS:: Six hundred and twenty-five unresponsive cardiac arrest survivors aged 18-75 were compared with 129 similar patients aged more than 75. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Cardiac arrest survivors aged more than 75 had more comorbidities (3.0 ± 1.6 vs 2.0 ± 1.6, p \u3c 0.001), but were matched to younger patients in initial heart rhythm, witnessed arrests, bystander cardiopulmonary resuscitation, and total ischemic time. Patients aged more than 75 frequently underwent therapeutic hypothermia (97.7%), urgent coronary angiography (44.2%), and urgent percutaneous coronary intervention (24%). They had more sustained hyperglycemia (70.5% vs 59%, p = 0.015), less postcooling fever (25.2% vs 35.2%, p = 0.03), were more likely to have do-not-resuscitate orders (65.9% vs 48.2%, p \u3c 0.001), and undergo withdrawal of life support (61.2% vs 47.5%, p = 0.005). Good functional outcome at 6 months (Cerebral Performance Category 1-2) was seen in 27.9% elderly versus 40.4% younger patients overall (p = 0.01) and in 44% versus 55% (p = 0.13) of patients with an initial shockable rhythm. Of 35 survivors more than 75 years old, 33 (94.8%) were classified as Cerebral Performance Category 1 or 2 at (mean) 6.5-month follow-up. In multivariable logistic regression modeling, age more than 75 was significantly associated with outcome only when the presence of a do-not-resuscitate order was excluded from the model. CONCLUSIONS:: Elderly patients were more likely to have do-not-resuscitate orders and to undergo withdrawal of life support. Age was independently associated with outcome only when correction for do-not-resuscitate status was excluded, and functional outcomes of elderly survivors were similar to younger patients. Exclusion of patients more than 75 years old from aggressive care is not warranted on the basis of age alone

Derivation and Validation of the CREST Model for Very Early Prediction of Circulatory Etiology Death in Patients Without ST-Segment-Elevation Myocardial Infarction After Cardiac Arrest.

BACKGROUND: No practical tool quantitates the risk of circulatory-etiology death (CED) immediately after successful cardiopulmonary resuscitation in patients without ST-segment-elevation myocardial infarction. We developed and validated a prediction model to rapidly determine that risk and facilitate triage to individualized treatment pathways. METHODS: With the use of INTCAR (International Cardiac Arrest Registry), an 87-question data set representing 44 centers in the United States and Europe, patients were classified as having had CED or a combined end point of neurological-etiology death or survival. Demographics and clinical factors were modeled in a derivation cohort, and backward stepwise logistic regression was used to identify factors independently associated with CED. We demonstrated model performance using area under the curve and the Hosmer-Lemeshow test in the derivation and validation cohorts, and assigned a simplified point-scoring system. RESULTS: Among 638 patients in the derivation cohort, 121 (18.9%) had CED. The final model included preexisting coronary artery disease (odds ratio [OR], 2.86; confidence interval [CI], 1.83-4.49; P≤0.001), nonshockable rhythm (OR, 1.75; CI, 1.10-2.77; P=0.017), initial ejection fraction25 minutes (OR, 1.42; CI, 0.90-2.23; P=0.13). The derivation model area under the curve was 0.73, and Hosmer-Lemeshow test P=0.47. Outcomes were similar in the 318-patient validation cohort (area under the curve 0.68, Hosmer-Lemeshow test P=0.41). When assigned a point for each associated factor in the derivation model, the average predicted versus observed probability of CED with a CREST score (coronary artery disease, initial heart rhythm, low ejection fraction, shock at the time of admission, and ischemic time \u3e25 minutes) of 0 to 5 was: 7.1% versus 10.2%, 9.5% versus 11%, 22.5% versus 19.6%, 32.4% versus 29.6%, 38.5% versus 30%, and 55.7% versus 50%. CONCLUSIONS: The CREST model stratified patients immediately after resuscitation according to risk of a circulatory-etiology death. The tool may allow for estimation of circulatory risk and improve the triage of survivors of cardiac arrest without ST-segment-elevation myocardial infarction at the point of care