Novel multi-marker proteomics in phenotypically matched patients with ST-segment myocardial infarction:association with clinical outcomes

Early prediction of significant morbidity or mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) represents an unmet clinical need. In phenotypically matched population of 139 STEMI patients (72 cases, 67 controls) treated with primary percutaneous coronary intervention, we explored associations between a 24-h relative change from baseline in the concentration of 91 novel biomarkers and the composite outcome of death, heart failure, or shock within 90 days. Additionally, we used random forest models to predict the 90-day outcomes. After adjustment for false discovery rate, the 90-day composite was significantly associated with concentration changes in 14 biomarkers involved in various pathophysiologic processes including: myocardial fibrosis/remodeling (collagen alpha-1, cathepsin Z, metalloproteinase inhibitor 4, protein tyrosine phosphatase subunits), inflammation, angiogenesis and signaling (interleukin 1 and 2 subunits, growth differentiation factor 15, galectin 4, trefoil factor 3), bone/mineral metabolism (osteoprotegerin, matrix extracellular phosphoglycoprotein and tartrate-resistant acid phosphatase), thrombosis (tissue factor pathway inhibitor) and cholesterol metabolism (LDL-receptor). Random forest models suggested an independent association when inflammatory markers are included in models predicting the outcomes within 90 days. Substantial heterogeneity is apparent in the early proteomic responses among patients with acutely reperfused STEMI patients who develop death, heart failure or shock within 90 days. These findings suggest the need to consider synergistic multi-biomarker strategies for risk stratification and to inform future development of novel post-myocardial infarction therapies

Chemoreflex Mediated Arrhythmia during Apnea at 5050m in Low but not High Altitude Natives

Peripheral chemoreflex mediated increases in both parasympathetic and sympathetic drive under chronic hypoxia may evoke bradyarrhythmias during apneic periods. We determined whether 1) voluntary apnea unmasks arrhythmia at low (344 m) and high (5,050 m) altitude, 2) high-altitude natives (Nepalese Sherpa) exhibit similar cardiovagal responses at altitude, and 3) bradyarrhythmias at altitude are partially chemoreflex mediated. Participants were grouped as Lowlanders ( n = 14; age = 27 ± 6 yr) and Nepalese Sherpa ( n = 8; age = 32 ± 11 yr). Lowlanders were assessed at 344 and 5,050 m, whereas Sherpa were assessed at 5,050 m. Heart rate (HR) and rhythm (lead II ECG) were recorded during rest and voluntary end-expiratory apnea. Peripheral chemoreflex contributions were assessed in Lowlanders ( n = 7) at altitude after 100% oxygen. Lowlanders had higher resting HR at altitude (70 ± 15 vs. 61 ± 15 beats/min; P &lt; 0.01) that was similar to Sherpa (71 ± 5 beats/min; P = 0.94). High-altitude apnea caused arrhythmias in 11 of 14 Lowlanders [junctional rhythm ( n = 4), 3° atrioventricular block ( n = 3), sinus pause ( n = 4)] not present at low altitude and larger marked bradycardia (nadir −39 ± 18 beats/min; P &lt; 0.001). Sherpa exhibited a reduced bradycardia response during apnea compared with Lowlanders ( P &lt; 0.001) and did not develop arrhythmias. Hyperoxia blunted bradycardia (nadir −10 ± 14 beats/min; P &lt; 0.001 compared with hypoxic state) and reduced arrhythmia incidence (3 of 7 Lowlanders). Degree of bradycardia was significantly related to hypoxic ventilatory response (HVR) at altitude and predictive of arrhythmias ( P &lt; 0.05). Our data demonstrate apnea-induced bradyarrhythmias in Lowlanders at altitude but not in Sherpa (potentially through cardioprotective phenotypes). The chemoreflex is an important mechanism in genesis of bradyarrhythmias, and the HVR may be predictive for identifying individual susceptibility to events at altitude. NEW &amp; NOTEWORTHY The peripheral chemoreflex increases both parasympathetic and sympathetic drive under chronic hypoxia. We found that this evoked bradyarrhythmias when combined with apneic periods in Lowlanders at altitude, which become relieved through supplemental oxygen. In contrast, high-altitude residents (Nepalese Sherpa) do not exhibit bradyarrhythmias during apnea at altitude through potential cardioprotective adaptations. The degree of bradycardia and bradyarrhythmias was related to the hypoxic ventilatory response, demonstrating that the chemoreflex plays an important role in these findings. </jats:p

Global REACH: Assessment of brady-arrhythmias in Andeans and Lowlanders during apnea at 4330m

BACKGROUND: Ascent to altitude increases the prevalence of arrhythmogenesis in low-altitude dwelling populations (Lowlanders). High altitude populations (ie. Nepalese Sherpa) may have arrhythmias resistant adaptations that prevent arrhythmogenesis at altitude, though this has not been documented in other High altitude groups, including those diagnosed with chronic mountain sickness (CMS). We investigated whether healthy (CMS-) and CMS afflicted (CMS+) Andeans exhibit cardiac arrhythmias under acute apneic stress at altitude. METHODS AND RESULTS: Electrocardiograms (lead II) were collected in CMS- (N=9), CMS+ (N=8), and Lowlanders (N= 13) following several days at 4330m (Cerro de Pasco, Peru). ECG rhythm and HR were assessed at both rest and during maximal volitional apnea (End-Expiratory [EXP]). Both CMS- and CMS+ had similar basal HR (69 ± 8 beats/min vs. 62 ± 11 beats/min), while basal HR was higher in Lowlanders (77 ± 18 beats/min; P<0.05 versus CMS+). Apnea elicited significant bradycardia (nadir -32 ± 15 beats/min; P<0.01) and the development of arrhythmias in 8/13 Lowlanders (junctional rhythm, 3° atrio-venticular block, sinus pause). HR was preserved was prior to volitional breakpoint in both CMS- (nadir -6 ± 1 beat/min) and CMS+ (1 ±12 beats/min), with 2/17 Andeans developing arrhythmias ( 1 CMS+ and 1 CMS-; both Premature Atrial Contraction) prior to breakpoint. CONCLUSIONS: Andeans showed an absence of arrhythmias and preserved HR response to volitional apnea at altitude, demonstrating that potential cardio-resistant adaptations to arrhythmogenesis exist across permanent HA populations. Acclimatized Lowlanders have further demonstrated an increased prevalence of arrhythmias at altitude

Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation : insights from the ARISTOTLE trial

We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin

How Evidence-Based Are the Recommendations in Evidence-Based Guidelines?

From an analysis of cardiovascular risk-management recommendations in guidelines produced by pan-national panels, McAlister and colleagues concluded that fewer than half were based on high-quality evidence

Cardiovascular Critical Care: A Perceived Deficiency Among U.S. Trainees

Acute and chronic cardiovascular comorbidities are common among critically ill individuals. It is unclear if current critical care fellowship trainees feel adequately prepared to manage these conditions. Design: Prospective, cross-sectional survey. Patients or Subjects: Trainees enrolled in U.S. critical care training programs. Setting: Accredited pulmonary/critical care, surgery/critical care, anesthesiology/critical care, and stand-alone critical care training programs. Interventions: None. Measurements and Main Results: A 19-item survey assessing trainee confidence in the management of cardiac critical illness and the performance of cardiac-specific critical care interventions was constructed using Accreditation Council for Graduate Medical Education recommendations as a reference. After validation, the survey was electronically sent to all training programs for dissemination to their trainees. Confidence scores were measured on a Likert scale from 1 to 5. A total of 134 completed surveys were analyzed. Overall, respondents reported lower confidence in managing cardiovascular compared with noncardiovascular diseases in the ICU (4.0 vs 4.6 out of 5). Likewise, they reported lower perceived competence in performing cardiovascular procedures specific to the ICU (2.9 vs 4.5 out of 5). The majority (88%) of those surveyed felt that they would benefit from increased didactic and clinical experience in the management of cardiovascular critical illness. Conclusions: Current critical care fellows may be unprepared to deal with the increasing prevalence of cardiovascular illness in the ICU. This potential educational gap warrants timely attention to ensure that future graduates have the requisite skills necessary to manage these critically ill patients and presents a unique opportunity to develop multidisciplinary partnerships for enhancing training