Bert Ferdinande

An observational near-infrared spectroscopy study on cerebral autoregulation in post-cardiac arrest patients: Time to drop ‘one-size-fits-all’ hemodynamic targets?

AIMS A subgroup of patients with ROSC after cardiac arrest (CA) with disturbed cerebral autoregulation might benefit from higher mean arterial pressures (MAP). We aimed to (1) phenotype patients with disturbed autoregulation, (2) investigate whether these patients have a worse prognosis, (3) define an individual optimal MAP per patient and (4) investigate whether time under this individual optimal MAP is associated with outcome. METHODS Prospective observational study in 51 post-CA patients monitored with near infrared spectroscopy. RESULTS (1) 18/51 patients (35%) had disturbed autoregulation. Phenotypically, a higher proportion of patients with disturbed autoregulation had pre-CA hypertension (31±47 vs. 65±49%, p=0.02) suggesting that right shifting of autoregulation is caused by chronic adaptation of cerebral blood flow to higher blood pressures. (2) In multivariate analysis, patients with preserved autoregulation (n=33, 65%) had a significant higher 180-days survival rate (OR 4.62, 95% CI [1.06:20.06], p=0.04]. Based on an index of autoregulation (COX), the average COX-predicted optimal MAP was 85 mmHg in patients with preserved and 100 mmHg in patients with disturbed autoregulation. (3) An individual optimal MAP could be determined in 33/51 patients. (4) The time under the individual optimal MAP was negatively associated with survival (OR 0.97, 95% CI [0.96:0.99], p=0.02). The time under previously proposed fixed targets (65, 70, 75, 80 mmHg) was not associated with a differential survival rate. CONCLUSION Cerebral autoregulation showed to be disturbed in 35% of post-CA patients of which a majority had pre-CA hypertension. Disturbed cerebral autoregulation within the first 24h after CA is associated with a worse outcome. In contrast to uniform MAP goals, the time spent under a patient tailored optimal MAP, based on an index of autoregulation, was negatively associated with survival.

Hemodynamic targets during therapeutic hypothermia after cardiac arrest: A prospective observational study ☆

AIM In analogy with sepsis, current post-cardiac arrest (CA) guidelines recommend to target mean arterial pressure (MAP) above 65 mmHg and SVO2 above 70%. This is unsupported by mortality or cerebral perfusion data. The aim of this study was to explore the associations between MAP, SVO2, cerebral oxygenation and survival. METHODS Prospective, observational study during therapeutic hypothermia (24h - 33 °C) in 82 post-CA patients monitored with near-infrared spectroscopy. RESULTS Forty-three patients (52%) survived in CPC 1-2 until 180 days post-CA. The mean MAP range associated with maximal survival was 76-86 mmHg (OR 2.63, 95%CI [1.01; 6.88], p = 0.04). The mean SVO2 range associated with maximal survival was 67-72% (OR 8.23, 95%CI [2.07; 32.68], p = 0.001). In two separate multivariate models, a mean MAP (OR 3.72, 95% CI [1.11; 12.50], p=0.03) and a mean SVO2 (OR 10.32, 95% CI [2.03; 52.60], p = 0.001) in the optimal range persisted as independently associated with increased survival. Based on more than 1625000 data points, we found a strong linear relation between SVO2 (range 40-90%) and average cerebral saturation (R(2) 0.86) and between MAP and average cerebral saturation for MAPs between 45 and 101 mmHg (R(2) 0.83). Based on our hemodynamic model, the MAP and SVO2 ranges associated with optimal cerebral oxygenation were determined to be 87-101 mmHg and 70-75%. CONCLUSION we showed that a MAP range between 76-86 mmHg and SVO2 range between 67% and 72% were associated with maximal survival. Optimal cerebral saturation was achieved with a MAP between 87-101 mmHg and a SVO2 between 70% and 75%. Prospective interventional studies are needed to investigate whether forcing MAP and SVO2 in the suggested range with additional pharmacological support would improve outcome.

Time course of electrocardiographic changes in transient left ventricular ballooning syndrome.

BACKGROUND We sought to describe, for the first time, in detail the time course of electrocardiographic (ECG) changes in transient left ventricular ballooning syndrome (TLVBS) from acute onset until 1 year after presentation. METHODS The serial ECGs of all patients identified with TLVBS who presented to our cardiology department from August 1998 to August 2012 were analyzed, from admission to 1-year follow-up, with respect to time from onset of symptoms. RESULTS In total, 145 TLVBS episodes were identified in 139 patients. In 53% of patients, ST segment elevation was present in the first 3h after symptom onset, after which there was a steady decline with complete resolution in all patients by 1 month. The presence of T wave inversion (TWI), with or without ST segment depression, was most prevalent between day 1 (60%) and day 30 (71%) from symptom onset, with 17% of patients still exhibiting TWI after 6 to 12 months. At 1 year, approximately 80% of patients had no significant residual ST-T wave changes. In 86% of patients, there was prolongation of the corrected QT (QTc) interval in the acute phase, with normalization of all QTc intervals by day 14. CONCLUSIONS During the early phase, ECG mimics acute ST elevation myocardial infarction with initial regional ST segment elevation progressing to T wave inversion with or without ST depression. In the majority of patients, significant QTc interval prolongation occurs in the early phase, normalizing by day 14.

Low hemoglobin levels are associated with lower cerebral saturations and poor outcome after cardiac arrest

PURPOSE Post-cardiac arrest (CA) patients have a large cerebral penumbra at risk for secondary ischemic damage in case of suboptimal brain oxygenation during ICU stay. The aims of this study were to investigate the association between hemoglobin, cerebral oxygenation (SctO2) and outcome in post-CA patients. METHODS Prospective observational study in 82 post-CA patients. Hemoglobin, a corresponding SctO2 measured by NIRS and SVO2 in patients with a pulmonary artery catheter (n=62) were determined hourly during hypothermia in the first 24h of ICU stay. RESULTS We found a strong linear relationship between hemoglobin and mean SctO2 (SctO2=0.70×hemoglobin+56 (R(2) 0.84, p=10(-6))). Hemoglobin levels below 10g/dl generally resulted in lower brain oxygenation. There was a significant association between good neurological outcome (43/82 patients in CPC 1-2 at 180 days post-CA) and admission hemoglobin above 13g/dl (OR 2.76, 95% CI 1.09:7.00, p=0.03) or mean hemoglobin above 12.3g/dl (OR 2.88, 95%CI 1.02:8.16, p=0.04). This association was entirely driven by results obtained in patients with a mean SVO2 below 70% (OR 6.25, 95%CI 1.33:29.43, p=0.01) and a mean SctO2 below 62.5% (OR 5.87, 95%CI 1.08:32.00, p=0.03). CONCLUSION Hemoglobin levels below 10g/dl generally resulted in lower cerebral oxygenation. Average hemoglobin levels below 12.3g/dl were associated with worse outcome in patients with suboptimal SVO2 or SctO2. The safety of a universal restrictive transfusion threshold of 7g/dl can be questioned in post-CA patients.

The apical nipple sign: a useful tool for discriminating between anterior infarction and transient left ventricular ballooning syndrome.

Aims: Even after coronary angiography, transient left ventricular ballooning syndrome (TLVBS) can be misdiagnosed as ST-elevation myocardial infarction (STEMI) caused by transient thrombotic occlusion of the left anterior descending artery, as the appearance of the left ventricular angiograms is often very similar. As prognosis and antithrombotic treatment of these two conditions differ widely, it is desirable to make a correct diagnosis as early as possible. Methods: Between January 1998 and August 2012, we identified 145 patients diagnosed with TLVBS in a single tertiary hospital, based on the Mayo criteria and (near) normalization of left ventricular function over weeks. For 119 of these patients, coronary and left ventricular angiograms were available for detailed study. Results: In 27 (22.7%) patients, mid-ventricular ballooning was observed, with preserved contractility of the apex, while in 92 (77.3%) typical apical ballooning was seen, with extensive akinesis of the apex. In 28 of the patients with typical apical ballooning (30.4%), we observed the presence of a very small zone with preserved contractility in the most apical portion of the left ventricle. We coined this phenomenon ‘apical nipple sign’. For comparison, we reviewed the left ventricular angiograms of 405 patients who had been treated for anterior STEMI by emergency percutaneous intervention on the left anterior descending artery in our hospital between February 2007 and October 2012. On careful review, the apical nipple sign was not seen in any of these. Conclusion: While discrimination between TLVBS and anterior STEMI is warranted as early as possible after admission, this is very difficult, especially in the majority of cases presenting with the classical apical ballooning phenotype. By observing the herein-described apical nipple sign, the attending physician can make the diagnosis of TLVBS with virtual certainty in almost one-third of cases.

Detailed in vivo visualization of stent fracture causing focal restenosis using 3D reconstruction software for high-resolution optical coherence tomography images

A 55-year-old female underwent repeat coronary angiography for recurrent angina, 9 months after percutaneous coronary intervention (PCI) of a mid-right coronary artery (RCA) chronic total occlusion with implantation of two overlapping Orsiro™ sirolimus-eluting stents (3.0 × 30 mm at 20 atm; 2.5 × 30 mm at 16 atm) (see Supplementary data online, Video S1 ). The distal part of the stented segment showed a focal in-stent restenosis (ISR) with the abnormal motion pattern (see Supplementary data online, Video S2 ). Optical coherence tomography (OCT) with 3D reconstruction confirmed suspected stent …

From therapeutic hypothermia towards targeted temperature management: a decade of evolution

More than a decade after the first randomised controlled trials with targeted temperature management (TTM), it remains the only treatment with proven favourable effect on postanoxemic brain damage after out-of-hospital cardiac arrest. Other well-known indications include neurotrauma, subarachnoidal haemorrhage, and intracranial hypertension. When possible pitfalls are taken into consideration when implementing TTM, the side effects are manageable. After the recent TTM trials, it seems that classic TTM (32-34°C) is as effective and safe as TTM at 36°C. This supports the belief that fever prevention is one of the pivotal mechanisms that account for the success of TTM. Uncertainty remains concerning cooling method, timing, speed of cooling and rewarming. New data indicates that TTM is safe and feasible in cardiogenic shock, one of its classic contra-indications. Moreover, there are limited indications that TTM might be considered as a therapy for cardiogenic shock per se.

Mean arterial pressure of 65 mm Hg versus 85-100 mm Hg in comatose survivors after cardiac arrest: Rationale and study design of the Neuroprotect post–cardiac arrest trial

Background Post–cardiac arrest (CA) patients admitted to the intensive care unit (ICU) have a poor prognosis, with estimated survival rates of around 30%‐50%. On admission, these patients have a large cerebral penumbra at risk for additional damage in case of suboptimal brain oxygenation during their stay in the ICU. The aim of the Neuroprotect post‐CA trial is to investigate whether forcing mean arterial blood pressure (MAP) and mixed venous oxygen saturation (SVO2) in a specific range (MAP 85–100 mm Hg, SVO2 65%‐75%) with additional pharmacological support (goal‐directed hemodynamic optimization) may better salvage the penumbra, reduce cerebral ischemia, and improve functional outcome when compared with current standard of care (MAP 65 mm Hg). Design The Neuroprotect post‐CA trial (NCT02541591) is a multicenter, randomized, parallel‐group, open‐label, assessor‐blinded, monitored, and investigator‐driven clinical trial. The trial will be conducted in 2 tertiary care hospitals in Belgium (UZ Leuven and ZOL‐Genk). A total of 112 eligible patients will be randomly assigned in a 1:1 ratio to goal‐directed hemodynamic optimization or standard care strategy by an interactive voice response system. Patients will be stratified according to the presence of an initial shockable rhythm. Adult patients (≥18 years) resuscitated from out‐of‐hospital CA of a presumed cardiac cause who are unconscious upon hospital admission are eligible for inclusion. Patients can be included irrespective of their presenting heart rhythm but need to have a sustained return of spontaneous circulation. Trial interventions will take 36 hours starting from ICU admission. The primary outcome is the extent of cerebral ischemia as quantified by the apparent diffusion coefficient on diffusion‐weighted magnetic resonance imaging to be performed at day 4–5 post‐CA. Secondary outcomes include surrogate biomarkers of brain injury (neuron specific enolase) at day 1–5, neuropsychological and functional testing at hospital discharge, a Short Form–36 health questionnaire at 180 days, and outcome as assessed with cerebral performance category scores at ICU discharge and at 180 days. Conclusions The Neuroprotect post‐CA trial will investigate whether a more aggressive hemodynamic strategy to obtain a MAP 85–100 mm Hg and SVO2 65%‐75% reduces brain ischemia and improves outcome when compared with standard treatment (MAP 65 mm Hg) in comatose post‐CA survivors.

Drug-eluting versus bare metal stents after rotational atherectomy: clinical outcome in a single centre.

Purpose Heavily calcified atherosclerotic plaques can be prepared for stenting by rotational atherectomy (RA). Clinical outcomes with drug-eluting stents (DES) versus bare-metal stents (BMS) after RA have not been investigated sufficiently. We present a single-centre study comparing the efficacy and long-term outcome of DES versus BMS after RA. Methods and results We performed a retrospective cohort study of all patients who were treated with RA at our institution between January 2004 and March 2012. Clinical follow-up was obtained at 1 year. Procedural success (defined as a residual stenosis < 30%) was recorded, as was the 1-year incidence of myocardial infarction (MI), stent thrombosis (ST) and major adverse cardiac events (MACE), a composite end point of cardiac death, MI or target lesion revascularization (TLR). Eighty-five patients underwent RA followed by stenting, 30 receiving a BMS and 55 a DES, and completed 1-year clinical follow-up. Baseline clinical and angiographic characteristics were similar, and procedural success was achieved in 99% of the patients. At 1 year the overall incidence of MACE was 19%, and no significant differences in clinical outcome between DES and BMS were seen (MACE: 9 (16%) vs 7 (23%), P= 0.44; cardiac death: 3 (5%) vs 0 (0%); MI: 4 (7%) vs 5 (17%), P= 0.2; TLR: 2 (4%) vs 3 (10%), P= 0.25; ST: 2 (4%) vs 2 (7%), P= 0.52, respectively). Conclusions In this study, no significant differences in medium-term clinical outcomes between DES and BMS after RA were observed, although there was a definite trend to improved outcomes with DES.

The impact of global hemodynamics, oxygen and carbon dioxide on epileptiform EEG activity in comatose survivors of out-of-hospital cardiac arrest

AIM To study the association between global hemodynamics, blood gases, epileptiform EEG activity and survival after out-of-hospital CA (0HCA). METHODS We retrospectively analyzed 195 comatose post-CA patients. At least one EEG recording per patient was evaluated to diagnose epileptiform EEG activity. Refractory epileptiform EEG activity was defined as persisting epileptic activity on EEG despite the use of 2 or more anti-epileptics. The time weighted average mean arterial pressure 48h (TWA-MAP48), the percentage of time with a MAP below 65 and above 85mmHg and the percentage of time with normoxia, hypoxia (<70mmHg), hyperoxia (>150mmHg), normocapnia, hypocapnia (<35mmHg) and hypercapnia (>45mmHg) were calculated. RESULTS We observed epileptiform EEG activity in 57 patients (29%). A shockable rhythm was associated with a decreased likelihood of epileptic activity on the EEG (OR: 0.41, 95%CI 0.22-0.79). We did not identify an association between the TWA-MAP48, the percentage of time with MAP below 65mmHg or above 85mmHg, blood gas variables and the risk of post-CA epileptiform EEG activity. The presence of epileptiform activity decreased the likelihood of survival independently (OR: 0.10, 95% CI: 0.04-0.24). Interestingly, survival rates of patients in whom the epileptiform EEG resolved (n=20), were similar compared to patients without epileptiform activity on EEG (60% vs 67%,p=0.617). Other independent predictors of survival were presence of basic life support (BLS) (OR:5.08, 95% CI 1.98-13.98), presence of a shockable rhythm (OR: 7.03, 95% CI: 3.18-16.55), average PaO2 (OR=0.93, CI 95% 0.90-0.96) and% time MAP<65mmHg (OR: 0.96, CI 95% 0.94-0.98). CONCLUSION Epileptiform EEG activity in post-CA patients is independently and inversely associated with survival and this effect is mainly driven by patients in whom this pattern is refractory over time despite treatment with anti-epileptic drugs. We did not identify an association between hemodynamic factors, blood gas variables and epileptiform EEG activity after CA, although both hypotension, hypoxia and epileptic EEG activity were predictors of survival.