Prognostic echocardiographic findings in patients supported with venoarterial extracorporeal membrane oxygenation for cardiogenic shock.

AIMS: Echocardiography is critical in the management of patients supported with veno-arterial extracorporeal membrane oxygenation (V-A ECMO). This study aimed to identify the incidence of critical echocardiographic findings and determine their prognostic significance. METHODS AND RESULTS: All available echocardiograms, hemodynamic variables and outcomes of patients with CS supported with V-A in the period of 2011-2018 at the Toronto General Hospital were retrospectively reviewed. Critical echocardiographic findings were defined as minimal to no left ventricular (LV) ejection, the presence of intra-cardiac clot, significant pericardial effusion and malpositioning of ECMO cannulae. 130 patients were included in this study with in-hospital mortality of 58.5%. Critical findings were most often seen in the first echocardiogram (42/121; 35%). The incidence of critical findings in the first echocardiogram was minimal to no LV ejection in 28 patients (23%), intracardiac thromboses in 8 patients (6.6%), tamponade in 5 patients (4%) and malpositioned cannulae in 1 patient (0.8%). Presence of a critical finding in the first study was associated with an odds ratio for in-hospital mortality of 2.32 (95% CI 1.01-5.06, P = 0.011). CONCLUSION: The initial echocardiogram was most likely to demonstrate a critical finding of which the most common was minimal to no LV ejection. Critical echocardiographic findings carried prognostic significance for in-hospital mortality.

Pulse pressure within the first 2 days of veno-arterial extracorporeal membrane oxygenation is predictive of death prior to hospital discharge, renal dysfunction requiring dialysis and pulmonary oedema.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) flows are titrated to achieve adequate perfusion while attempting to ideally maintain arterial pulse pressure (PP). We assessed risk in patients with low PP defined as <10 mmHg within the first 2 days of support. METHODS: Demographics, haemodynamics, echocardiographic and radiological findings were recorded retrospectively in cases conducted between 2014 and 2016. Outcomes were hospital mortality, requirement for renal replacement therapy (RRT) and severe pulmonary oedema (PO). RESULTS: Of 101 patients, 66.3% were male, mean age was 56 (range 18-71 years), mean duration of support was 6.3 days ± 4.1 days, 37.6% died prior to hospital discharge, 39.6% needed RRT and 11.9% had severe PO. Areas under the receiver operating curves of PP at 48 h for hospital mortality, RRT and severe PO were (respectively): 0.69 (95% CI 0.58-0.80, p = .001), 0.64 (95% CI 0.50-0.77, p = .044), 0.69 (95% CI 0.55-0.82, p = .009). The odds ratio for mortality, RRT, severe PO for those with low PP were (respectively) 2.8 (95% CI 1.01-7.5, p = .04), 3.1 (95% CI 1.11-8.40, p = .026), 7.6 (95% CI 2.06-27.89, p = .001). Central venous pressure, mean arterial pressure were not predictive. CONCLUSION: PP during the first 2 days of support is predictive of clinically important outcomes in patients supported with VA-ECMO.

Assessment of the Clinical Pulmonary Infection Scores for prediction of ventilator associated pneumonia in patients with out of hospital cardiac arrest.

BACKGROUND: Patients suffering out-of-hospital cardiac arrest (OHCA) are at an increased risk of aspiration pneumonitis and development of subsequent aspiration pneumonia. The diagnostic uncertainty in this context can lead to a large proportion receiving broad spectrum antibiotics. METHODS: This was a three-year, retrospective cohort study of consecutive patients admitted with OHCA. Data were collected in an Australian tertiary centre intensive care unit (ICU) between December 2016-December 2019. We assessed the incidence of Ventilator associated pneumonia (VAP), admission Clinical Pulmonary Infection Scores (CPIS) in patients with OHCA and its' association with VAP at day 3 [1]. We also assessed antibiotics prescribing (timing of initiation and drug choice) and intensive care mortality relative to the day 1 CPIS. RESULTS: Over the three years, 100 patients were admitted with OHCA. The incidence of VAP was 6%. The CPIS on admission was not associated with development of VAP at day 3 (p = 0.75) and no significant association was found between choice of antibiotic regimens and VAP incidence. Timing of initiation of antibiotics was associated with VAP (12hrs vs 48hrs, p = 0.035) but not the choice of antibiotic (penicillin and cephalosporins vs antipseudomonal antibiotics). CPIS score at day 1 was not associated with ICU mortality in a multivariate analysis. CONCLUSION: We demonstrated a very low incidence of VAP in OHCA patients in comparison to published studies. In this context, there was no evidence for an association between CPIS score and VAP at day 3. The CPIS may have utility as a decision support tool for targeted antibiotic prescribing in this cohort.

Hemodynamic Aspects of Veno-Arterial Extracorporeal Membrane Oxygenation for Cardiac Support: A Worldwide Survey.

There is limited data available to guide management of patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). An international cross-sectional survey of medical directors/program coordinators from Extracorporeal Life Support Organization centers was conducted. A hierarchical clustering on principle components was used. A total of 243 (55%) centers responded and were divided into three clusters: Cluster 1 (n = 102) had few high volumes and low specialized heart failure (HF) involvement; Cluster 2 (n = 75) had few high volumes and moderate HF involvement; Cluster 3 (n = 66) contained the majority of centers with >50 annual cases and high HF involvement. The most divergent responses were observed between Clusters 1 and 3 wherein Cluster 1 centers were less likely to change management based on pulse pressure (77% vs. 100%; p < 0.001) and would rather avoid inotropes to "rest the heart" (28%). Cluster 3 centers were more likely to perform daily echocardiograms (50% vs. 24%, p < 0.001), which were less likely to be exclusively performed by cardiologist (36% vs. 58%, p < 0.046) and base weaning on echocardiographic findings, when compared to Cluster 1 (3.97/5 vs. 3.56, p < 0.001). Responses were variable in management reflecting the lack of evidence for hemodynamic care for those supported with VA-ECMO.

Prognostic Implications of Point-of-Care and Serial B-type Natriuretic Peptide Levels in Patients With Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HC) is a heterogenous disease with a variable clinical course. Predictors of long-term adverse cardiovascular events are needed. Our objectives were to determine the long-term prognostic value of a single and serial point of care (POC) B-type natriuretic-peptide (BNP) measurements in HC. One hundred and eleven ambulatory patients with HC (mean age 53 ± 16 years) were prospectively recruited over a 2-year period (2004 to 2006). A clinical assessment, comprehensive echocardiogram, and a POC BNP level was obtained at baseline and at a 1- to 2-year follow-up. They were subsequently followed for the occurrence of major adverse cardiac events (MACE). The median baseline BNP concentration was 114 pg/ml (range 5.3 to 1550 pg/ml). During a mean follow-up of 6.2 ± 3.4 years, 42 patients (38%) had a MACE. In a multivariable Cox model including clinical and echocardiographic predictors, logBNP (HR 4.30; 95% confidence interval 1.97 to 9.37, p <0.001) and left ventricualr ejection fraction (LVEF) (HR 0.96; 95% confidence interval 0.94 to 0.99, p = 0.011) remained significant predictors of MACE. Nested models demonstrated incremental prognostic value of logBNP for MACE (chi-square increased from 4.3 to 22.8, p <0.01) over clinical and echocardiographic factors. Patients with persistently elevated BNP (>100 pg/ml) at baseline and at the second visit were at a higher risk of developing MACE during follow-up (5-year MACE-free survival of 0.91 (SE 0.06) vs 0.45 (SE 0.09), p <0.001). In conclusion, POC BNP levels in patients with HC were predictive of long-term MACE and had independent and incremental value. Patients with persistently elevated BNP levels were at a higher risk of MACE.

Primary percutaneous coronary intervention for inferior ST-segment elevation myocardial infarction in a patient supported by the HeartWare left ventricular assist device.

A 63-year-old man with an ischaemic cardiomyopathy, supported by the HeartWare left ventricular assist device (LVAD), presented with ventricular tachycardia and inferior ST-elevation myocardial infarction (STEMI) with associated acute right ventricular (RV) dysfunction. He underwent primary percutaneous coronary intervention with balloon angioplasty and placement of three drug-eluting stents in the proximal-to-mid right coronary artery. Post-procedure, ventricular arrhythmias abated, RV systolic dysfunction resolved and RV size normalised. Percutaneous coronary intervention (PCI) facilitated by the use of miniaturised percutaneous LVAD has become an increasingly available treatment option for high-risk patients. PCI in patients on established full mechanical circulatory support is not a common occurrence. Indeed, to our knowledge, this is the first case of primary percutaneous coronary intervention on an LVAD-supported heart reported in the medical literature. The case raises several specific issues that are of peculiar interest to clinicians involved in the care of patients supported by mechanical assist devices who experience an acute coronary syndrome requiring emergent revascularisation.

C-type natriuretic peptide (CNP) signal peptide fragments are present in the human circulation.

BACKGROUND: Signal peptides may be novel biomarkers in cardiovascular diseases. METHODS: We developed a novel immunoassay to the signal peptide of preproCNP (CNPsp) and used this to document circulating venous concentrations of CNPsp in normal healthy volunteers (n=109), regional plasma CNPsp concentrations in patients undergoing clinically indicated catheterisation (n=24) and temporal CNPsp concentrations in patients with ST-elevation myocardial infarction (STEMI) <4h after symptom onset (n=8). The structure/sequence of circulating CNPsp was confirmed by tandem mass spectrometry (MS/MS). RESULTS: In normal human plasma, CNPsp was detectable at levels higher than NT-proCNP (74±17 vs. 20 ± 5.5 pmol/L). There was no correlation between NTproCNP and CNPsp, but plasma concentrations of sibling signal peptides - CNPsp and BNPsp - were strongly correlated (r=0.532, P<0.001). In patients undergoing catheterisation, there were significant arterio-venous step-ups in CNPsp concentrations across the heart (P<0.01) and kidney (P<0.01). Arterial concentrations of CNPsp significantly correlated with heart rate (r=0.446, P<0.05). In STEMI patients, plasma concentrations of CNPsp showed a biphasic elevation pattern between 6 and 12h after symptom onset, with 12h values significantly elevated (∼ 3-fold) compared with levels at presentation (P<0.05). MS/MS verified circulating CNPsp to be preproCNP(14-23) and preproCNP(16-23) peptides. CONCLUSIONS: This is the first report of a circulating preproCNP derived signal peptide. Given the clear cardiac and renal secretion profiles of CNPsp and its response in STEMI patients, further studies on potential biological functions and biomarker applications of CNPsp in cardiovascular disease are warranted.

First identification of circulating prepro-A-type natriuretic peptide (preproANP) signal peptide fragments in humans: initial assessment as cardiovascular biomarkers.

BACKGROUND: New biomarkers are needed to assist clinical decision making in cardiovascular disease. We have recently shown that signal peptides may represent a novel biomarker target in cardiovascular diseases. METHODS: We developed a novel immunoassay for the signal peptide of preproANP (ANPsp) and used it to document cardiac tissue levels of ANPsp in explant human hearts (n = 9), circulating venous concentrations of ANPsp in healthy volunteers (n = 65), temporal ANPsp concentrations in patients with ST-elevation myocardial infarction (STEMI) <4 h after chest pain onset (n = 23), and regional plasma ANPsp concentrations in patients undergoing clinically indicated catheterization (n = 10). We analyzed the structure and sequence of circulating ANPsp by tandem mass spectrometry (MS/MS). RESULTS: ANPsp levels in human heart tissue were 50-1000 times lower than those of ANP/NT-proANP. ANPsp was detectable in control human plasma at concentrations comparable with ANP itself (approximately 20 ng/L). In STEMI patients, plasma concentrations of ANPsp rose to peak values at 5 h after symptom onset, significantly earlier than myoglobin, creatine kinase-MB, and troponin (P < 0.001). There were significant arteriovenous increases in ANPsp concentrations (P < 0.05) across the heart and kidney; arterial and coronary sinus concentrations of ANPsp both negatively correlated with systolic and mean arterial blood pressures (both P < 0.01). MS/MS verified circulating ANPsp to be preproANP(16-25) and preproANP(18-25). CONCLUSIONS: ANPsp is a novel circulating natriuretic peptide with potential to act as a cardiovascular biomarker. The rapid increase of plasma ANPsp in STEMI and its significant relationship with blood pressure encourage further study of its potential clinical utility.

B-type natriuretic peptide signal peptide circulates in human blood: evaluation as a potential biomarker of cardiac ischemia.

BACKGROUND: The diagnosis of cardiac necrosis such as myocardial infarction can be difficult and relies on the use of circulating protein markers like troponin. However, there is a clear need to identify circulating, specific biomarkers that can detect cardiac ischemia without necrosis. METHODS AND RESULTS: Using specific immunoassay and tandem mass spectrometry, we show that a fragment derived from the signal peptide of B-type natriuretic peptide (BNPsp) not only is detectable in cytosolic extracts of explant human heart tissue but also is secreted from the heart into the circulation of healthy individuals. Furthermore, plasma levels of BNPsp in patients with documented acute ST-elevation myocardial infarction (n=25) rise to peak values ( approximately 3 times higher than the 99th percentile of the normal range) significantly earlier than the currently used biomarkers myoglobin, creatine kinase-MB, and troponin. Preliminary receiver-operating characteristic curve analysis comparing BNPsp concentrations in ST-elevation myocardial infarction patients and other patient groups was positive (area under the curve=0.97; P<0.001), suggesting that further, more rigorous studies in heterogeneous chest pain patient cohorts are warranted. CONCLUSIONS: Our results demonstrate for the first time that BNPsp exists as a distinct entity in the human circulation and could serve as a new class of circulating biomarker with the potential to accelerate the clinical diagnosis of cardiac ischemia and myocardial infarction. Clinical Trial Registration- URL: http://www.anzctr.org.au. Unique identifier: ACTRN12609000040268.