The Fast and the Furious: Low-Risk Chest Pain and the Rapid Rule-Out Protocol

Accelerated diagnostic pathways (ADP) have been designed to identify low-risk chest pain patients in the emergency department. This review article discusses the Asia-Pacific Evaluation of Chest Pain Trial (ASPECT) score, the Accelerated Diagnostic Protocol for Chest Pain Trial (ADAPT) score, the Emergency Department Assessment of Chest Pain Score (EDACS), the HEARTScore and the HEART pathway. These ADPs have been validated in various studies and aid the emergency provider with identifying the low-risk chest pain patient who is appropriate for discharge home, while at the same time highlighting those patients who would benefit from further in-patient work up. These approaches should be paired with patient input and shared decision-making strategies. [West J Emerg Med. 2017;18(3)474-478.

Hemodynamic Effects of Pulmonary Arterial Hypertension-Specific Therapy in Patients With Heart Failure With Preserved Ejection Fraction and With Combined Post- and Precapillay Pulmonary Hypertension

Background: Drugs approved for pulmonary arterial hypertension have been considered for patients with heart failure with preserved ejection fraction and combined post- and precapillary pulmonary hypertension (Cpc-PH). We aimed to study changes in cardiac volumes, cardiac load and left ventricular (LV) filling pressures in patients with heart failure with preserved ejection fraction and Cpc-PH in response to pulmonary arterial hypertension-specific treatment. Methods and Results: In this prospective study, 23 patients with heart failure with preserved ejection fraction and Cpc-PH underwent right-heart catheterization, including acute provocation testing (fluid loading and inhaled nitric oxide) and cardiac MRI at baseline. Right-heart catheterization and cardiac MRI were repeated after 4 months of treatment. At baseline, acutely increasing preload by fluid loading resulted in a significant increase in pulmonary arterial wedge pressure (PAWP), whereas reducing right ventricular (RV) afterload and increasing LV distensability by acute administration of inhaled nitric oxide had no effect on PAWP. After 4 months of treatment, we observed a significant reduction in RV and LV afterload and increased RV and LV stroke volume, but PAWP significantly increased. Conclusions: In patients with heart failure with preserved ejection fraction and Cpc-PH, 4 months of pulmonary arterial hypertension-specific treatment increased RV and LV stroke volume at the expense of increased PAWP. This increase in PAWP was similarly observed acutely after fluid loading

Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension

Rationale: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking. Objectives: In this study, we provide evidence that blood platelets contain a distinctive ribonucleic acid (RNA) profile that may be exploited for the detection of pulmonary hypertension. Methods: Blood platelet RNA was isolated prospectively from 177 prevalent patients with different subtypes of pulmonary hypertension as well as 195 control subjects clinically not suspected of pulmonary hypertension. Sequencing libraries were created using SMARTer (Switching Mechanism at 5' end of RNA Template) copy desoxyribonucleic acid amplification and sequenced on the Illumina High Throughput Sequencing platform. RNA-sequencing reads were mapped to the human reference genome, and intron-spanning spliced RNA reads were selected. Differential spliced RNA panels were calculated by analysis of variance statistics. A particle swarm optimization-enhanced classification algorithm was built employing a development (n = 213 samples) and independent validation series (n = 159 samples). Results: We detected a total of 4,014 different RNAs in blood platelets from patients with pulmonary hypertension (n = 177) and asymptomatic control subjects (n = 195). Gene ontology analysis revealed enhanced RNA concentrations for genes related to RNA processing, translation, and mitochondrial function. A particle swarm optimization-selected RNA panel of 408 distinctive differentially spliced RNAs mediated detection of pulmonary hypertension with 93% sensitivity, 62% specificity, 77% accuracy, 0.89 (95% confidence interval, 0.83-0.93) area under the curve, and a negative predictive value of 91% in the independent validation series. The prediction score was independent of age, sex, smoking, pulmonary hypertension subtype, and the use of pulmonary hypertension-specific medication or anticoagulants. Conclusions: A platelet RNA panel may accurately discriminate patients with pulmonary hypertension from asymptomatic control subjects. In the light of current diagnostic delays, this study is the starting point for further development and evaluation of a platelet RNA-based blood test to ultimately improve early diagnosis and clinical outcomes in patients with pulmonary hypertension

Functional outcome of very preterm-born and small-for-gestational-age children at school age

BACKGROUND: Our aim was to determine functional outcome of very preterm-born and small-for-gestational-age (SGA) children as compared with matched controls at school age. METHODS: We included 28 very preterm SGA children (GA <32 wk, birth weight (BW) <10th percentile), born in 2000-2001. We also included 28 very preterm but appropriate-for-gestational-age (AGA) children, matched for GA, gender, and birth year, as controls. We assessed motor skills, intelligence quotient (IQ), attention, verbal memory, visual perception, visuomotor integration, executive functioning, and behavior of both sets of children at school age. RESULTS: The SGA children had a median GA of 29.7 wk and BW of 888 g, whereas the controls had a median GA of 29.4 wk and BW of 1,163 g. At 8.6 y, the median total IQ of the SGA children was 94 as compared with 95 in the controls (not significant). Performance IQ was significantly lower in SGA children (89 vs. 95, P = 0.043), whereas verbal IQ was not (95 vs. 95). Total motor skills (P = 0.048) and fine motor skills (P = 0.021) were worse in SGA children. Furthermore, SGA children scored lower on selective attention (P = 0.026) and visual perception (P = 0.025). Other scores did not differ significantly between groups. CONCLUSION: The differences we found between the groups were small. This suggests that the impaired functioning of very preterm-born SGA children is attributable to their having been born very preterm rather than to being SGA

Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p &lt; 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p &lt; 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources

Noninvasive Prediction of Elevated Wedge Pressure in Pulmonary Hypertension Patients Without Clear Signs of Left-Sided Heart Disease: External Validation of the OPTICS Risk Score

Background Although most newly presenting patients with pulmonary hypertension (PH) have elevated pulmonary artery wedge pressure, identification of so-called postcapillary PH can be challenging. A noninvasive tool predicting elevated pulmonary artery wedge pressure in patients with incident PH may help avoid unnecessary invasive diagnostic procedures. Methods and Results A combination of clinical data, ECG, and echocardiographic parameters was used to refine a previously developed left heart failure risk score in a retrospective cohort of pre- and postcapillary PH patients. This updated score (renamed the OPTICS risk score) was externally validated in a prospective cohort of patients from 12 Dutch nonreferral centers the OPTICS network. Using the updated OPTICS risk score, the presence of postcapillary PH could be predicted on the basis of body mass index ≥30, diabetes mellitus, atrial fibrillation, dyslipidemia, history of valvular surgery, sum of SV1 (deflection in V1 in millimeters) and RV6 (deflection in V6 in millimeters) on ECG, and left atrial dilation. The external validation cohort included 81 postcapillary PH patients and 66 precapillary PH patients. Using a predefined cutoff of >104, the OPTICS score had 100% specificity for postcapillary PH (sensitivity, 22%). In addition, we investigated whether a high probability of heart failure with preserved ejection fraction, assessed by the H2FPEF score (obesity, atrial fibrillation, age >60 yrs, ≥2 antihypertensives, E/e' >9, and pulmonary artery systolic pressure by echo >35 mmHg), similarly predicted the presence of elevated pulmonary artery wedge pressure. High probability of heart failure with preserved ejection fraction (H2FPEF score ≥6) was less specific for postcapillary PH. Conclusions In a community setting, the OPTICS risk score can predict elevated pulmonary artery wedge pressure in PH patients without clear signs of left-sided heart disease. The OPTICS risk score may be used to tailor the decision to perform invasive diagnostic testing

Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)

An amendment to this paper has been published and can be accessed via a link at the top of the paper