Effect of Alcohol-Mediated Renal Denervation on Blood Pressure in the Presence of Antihypertensive Medications: Primary Results from the TARGET BP I Randomized Clinical Trial.

BACKGROUND: Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN has not been formally studied in this indication. METHODS: TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic blood pressure (SBP) ≥150 and ≤180 mmHg, office diastolic BP ≥90 mmHg and mean 24-hour ambulatory SBP ≥135 and ≤170 mmHg, despite prescription of 2-5 antihypertensive medications were enrolled. The primary endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 3 months post procedure. Secondary endpoints include mean between-group differences in office and ambulatory BP at additional time points. RESULTS: Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean ± standard deviation -10.0 ± 14.2 mmHg versus -6.8 ± 12.1 mmHg, treatment difference -3.2 mmHg, 95% confidence interval [CI] -6.3, 0.0 mmHg; P=0.0487). Subgroup analysis of the primary endpoint revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7 ± 18.3 mmHg and -9.7 ± 17.3 mmHg (difference, -3.0, 95% CI -7.0, 1.0; P=0.173), for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon with 1 instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified. CONCLUSIONS: Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory systolic BP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed.

Timing of Complete Multivessel Revascularization in Patients Presenting With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Complete revascularization of the culprit and all significant nonculprit lesions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD) reduces major adverse cardiac events, but optimal timing of revascularization remains unclear. OBJECTIVES: This study aims to compare immediate complete revascularization (ICR) and staged complete revascularization (SCR) in patients presenting with NSTE-ACS and MVD. METHODS: This prespecified substudy of the BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease) trial included patients with NSTE-ACS and MVD. Risk differences of the primary composite outcome of all-cause mortality, myocardial infarction (MI), unplanned ischemia-driven revascularization (UIDR), or cerebrovascular events and its individual components were compared between ICR and SCR at 1 year. RESULTS: The BIOVASC trial enrolled 1,525 patients; 917 patients presented with NSTE-ACS, of whom 459 were allocated to ICR and 458 to SCR. Incidences of the primary composite outcome were similar in the 2 groups (7.9% vs 10.1%; risk difference 2.2%; 95% CI: -1.5 to 6.0; P = 0.15). ICR was associated with a significant reduction of MIs (2.0% vs 5.3%; risk difference 3.3%; 95% CI: 0.9 to 5.7; P = 0.006), which was maintained after exclusion of procedure-related MIs occurring during the index or staged procedure (2.0% vs 4.4%; risk difference 2.4%; 95% CI: 0.1 to 4.7; P = 0.032). UIDRs were also reduced in the ICR group (4.2% vs 7.8%; risk difference 3.5%; 95% CI: 0.4 to 6.6; P = 0.018). CONCLUSIONS: ICR is safe in patients with NSTE-ACS and MVD and was associated with a reduction in MIs and UIDRs at 1 year.

ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions: Design and rationale of the SONAR trial.

BACKGROUND: The percutaneous treatment of calcified coronary lesions remains challenging and is associated with worse clinical outcomes. In addition, coronary artery calcification is associated with more frequent peri-procedural myocardial infarction. STUDY DESIGN AND OBJECTIVES: The ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions (SONAR) study is an investigator-initiated, prospective, randomized, international, multicenter, open label trial (NCT05208749) comparing a lesion preparation strategy with either shockwave intravascular lithotripsy (IVL) or rotational atherectomy (RA) before drug-eluting stent implantation in 170 patients with moderate to severe calcified coronary lesions. The primary endpoint is difference in the rate of peri-procedural myocardial infarction. Key secondary endpoints include rate of peri-procedural microvascular dysfunction, peri-procedural myocardial injury, descriptive study of IMR measurements in calcified lesions, technical and procedural success, interaction between OCT calcium score and primary endpoint, 30-day and 1-year major adverse clinical events. CONCLUSIONS: The SONAR trial is the first randomized controlled trial comparing the incidence of peri-procedural myocardial infarction between 2 contemporary calcium modification strategies (Shockwave IVL and RA) in patients with calcified coronary artery lesions. Furthermore, for the first time, the incidence of peri-procedural microvascular dysfunction after Shockwave IVL and RA will be evaluated and compared.

The effect of higher or lower mean arterial pressure on kidney function after cardiac arrest: a post hoc analysis of the COMACARE and NEUROPROTECT trials.

BACKGROUND: We aimed to study the incidence of acute kidney injury (AKI) in out-of-hospital cardiac arrest (OHCA) patients treated according to low-normal or high-normal mean arterial pressure (MAP) targets. METHODS: A post hoc analysis of the COMACARE (NCT02698917) and Neuroprotect (NCT02541591) trials that randomized patients to lower or higher targets for the first 36 h of intensive care. Kidney function was defined using the Kidney Disease Improving Global Outcome (KDIGO) classification. We used Cox regression analysis to identify factors associated with AKI after OHCA. RESULTS: A total of 227 patients were included: 115 in the high-normal MAP group and 112 in the low-normal MAP group. Eighty-six (38%) patients developed AKI during the first five days; 40 in the high-normal MAP group and 46 in the low-normal MAP group (p = 0.51). The median creatinine and daily urine output were 85 µmol/l and 1730 mL/day in the high-normal MAP group and 87 µmol/l and 1560 mL/day in the low-normal MAP group. In a Cox regression model, independent AKI predictors were no bystander cardiopulmonary resuscitation (p < 0.01), non-shockable rhythm (p < 0.01), chronic hypertension (p = 0.03), and time to the return of spontaneous circulation (p < 0.01), whereas MAP target was not an independent predictor (p = 0.29). CONCLUSION: Any AKI occurred in four out of ten OHCA patients. We found no difference in the incidence of AKI between the patients treated with lower and those treated with higher MAP after CA. Higher age, non-shockable initial rhythm, and longer time to ROSC were associated with shorter time to AKI. CLINICAL TRIAL REGISTRATION: COMACARE (NCT02698917), NEUROPROTECT (NCT02541591).

Long-term clinical outcomes of excimer laser coronary atherectomy for the management of recurrent in-stent restenosis.

BACKGROUND: Recurrent in-stent restenosis (ISR) remains a serious problem. Optimal modification of the underlying mechanism during index percutaneous coronary intervention (PCI) is key to prevent ISR. Excimer laser coronary atherectomy (ELCA) has its own indications and is among others used in recurrent ISR in case of stent underexpansion and/or diffuse neointimal hyperplasia. We aimed to assess the long-term clinical outcomes of ELCA for the management of recurrent ISR. METHODS: A multicenter, retrospective observational study was conducted. Patients with recurrent ISR who were additionally treated with ELCA were included. The primary outcome was major adverse cardiac events (MACE) defined as a composite of cardiovascular death, myocardial infarction, stroke, target lesion revascularization at 12 months, and longer term. RESULTS: Between 2014 and 2022, 51 patients underwent PCI with the additional use ELCA for recurrent ISR. Primary outcome occurred in 6 patients (11.8%) at 12 months and in 12 patients (23.5%) at a median follow-up of 4 (1-6) years. Technical and procedural success were achieved in 92% and 90% of cases, respectively. Coronary perforation occurred in 2 patients as a result of distal wire perforation, but was not ELCA-related. There were no in-hospital MACE. CONCLUSIONS: ELCA appears to be a safe method with acceptable long-term results for the management of recurrent ISR.

Higher versus lower blood pressure targets after cardiac arrest: Systematic review with individual patient data meta-analysis.

PURPOSE: Guidelines recommend targeting mean arterial pressure (MAP) > 65 mmHg in patients after cardiac arrest (CA). Recent trials have studied the effects of targeting a higher MAP as compared to a lower MAP after CA. We performed a systematic review and individual patient data meta-analysis to investigate the effects of higher versus lower MAP targets on patient outcome. METHOD: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS, BIOSIS, CINAHL, Scopus, the Web of Science Core Collection, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, Google Scholar and the Turning Research into Practice database to identify trials randomizing patients to higher (≥71 mmHg) or lower (≤70 mmHg) MAP targets after CA and resuscitation. We used the Cochrane Risk of Bias tool, version 2 (RoB 2) to assess for risk of bias. The primary outcomes were 180-day all-cause mortality and poor neurologic recovery defined by a modified Rankin score of 4-6 or a cerebral performance category score of 3-5. RESULTS: Four eligible clinical trials were identified, randomizing a total of 1,087 patients. All the included trials were assessed as having a low risk for bias. The risk ratio (RR) with 95% confidence interval for 180-day all-cause mortality for a higher versus a lower MAP target was 1.08 (0.92-1.26) and for poor neurologic recovery 1.01 (0.86-1.19). Trial sequential analysis showed that a 25% or higher treatment effect, i.e., RR < 0.75, can be excluded. No difference in serious adverse events was found between the higher and lower MAP groups. CONCLUSIONS: Targeting a higher MAP compared to a lower MAP is unlikely to reduce mortality or improve neurologic recovery after CA. Only a large treatment effect above 25% (RR < 0.75) could be excluded, and future studies are needed to investigate if relevant but lower treatment effect exists. Targeting a higher MAP was not associated with any increase in adverse effects.

Blood pressure targets and management during post-cardiac arrest care.

Blood pressure is one modifiable physiological target in patients treated in the intensive care unit after cardiac arrest. Current Guidelines recommend targeting a mean arterial pressure (MAP) of higher than 65-70 mmHg using fluid resuscitation and the use of vasopressors. Management strategies will vary based in the setting, i.e. the pre-hospital compared to the in-hospital phase. Epidemiological data suggest that some degree of hypotension requiring vasopressors occur in almost 50% of patients. A higher MAP could theoretically increase coronary blood flow but on the other hand the use of vasopressor may result in an increase in cardiac oxygen demand and arrhythmia. An adequate MAP is paramount for maintaining cerebral blood flow. In some cardiac arrest patients the cerebral autoregulation may be disturbed resulting in the need for higher MAP in order to avoid decreasing cerebral blood flow. Thus far, four studies including little more than 1000 patients have compared a lower and higher MAP target in cardiac arrest patients. The achieved mean difference of MAP between groups has varied from 10-15 mmHg. Based on these studies a Bayesian meta-analysis suggests that the posterior probability that a future study would find treatment effects higher than a 5% difference between groups to be less than 50%. On the other hand, this analysis also suggests, that the likelihood of harm with a higher MAP target is also low. Noteworthy is that all studies to date have focused mainly on patients with a cardiac cause of the arrest with the majority of patients being resuscitated from a shockable initial rhythm. Future studies should aim to include also non-cardiac causes and aim to target a wider separation in MAP between groups.

Comparison of Radifocus versus Silverway Guidewires for Percutaneous Radial Angiography Following Failed Use of a J-Tip Guidewire.

BACKGROUND During transradial coronary angiography, when conventional J-tip wires fail to deliver catheters to the aortic root due to anatomical obstacles, additional hydrophilic wires, such as Radifocus (Terumo) or Silverway (Asahi), are used. We recently showed that the Silverway guidewire was effective at delivering the catheter to the aortic root. In this study, we aimed to compare the efficacy and safety of Radifocus and Silverway guidewires in 100 patients after failed use of the J-tip guidewire. MATERIAL AND METHODS After patients had a failure of a conventional J-tip wire to reach the aortic root, 100 patients were 1:1 randomized to either the Silverway or Radifocus wire. All patients with failure of the J-tip wire were eligible. The primary endpoint was the time between wire entry in the catheter and successful delivery of the catheter to the aortic root. Secondary endpoints included change of access site, number of complications, and questionnaires on subjective wire assessments by the performing interventional cardiologist. RESULTS The primary endpoint was significantly shorter in patients randomized to the Silverway arm (median 30 s [21-39] vs 48 s [36-66]; P<0.001)). The percentage of patients with change of access site was not different between the groups (2 vs 2, not significant). Only 1 minor complication (2%) occurred, in the Radifocus group. Questionnaires revealed that torque control, crossing, and support were all significantly better with the Silverway wire (P<0.001). CONCLUSIONS Silverway showed superior torque control, resulting in faster catheter delivery to the aortic root when compared with the Radifocus guidewire.

Giant coronary artery aneurysm of the left main treated with a covered stent: a case report.

Background: Coronary artery aneurysms (CAAs) of the left main represent a small subset of coronary artery disease and are associated with cardiovascular death. Because of its rare entity, large data are lacking and therefore treatment guidelines are missing. Case summary: We describe a case of a 56-year-old female with a past medical history of spontaneous dissection of the distal descending left artery (LAD) 6 years before. She presented to our hospital with a non-ST elevation myocardial infarction and a coronary angiogram showed a giant saccular aneurysm of the shaft of the left main coronary artery (LMCA). Given the risk of rupture and distal embolization, the heart team decided to go for a percutaneous approach. Based on a pre-interventional 3D reconstructed CT scan and guided by intravascular ultrasound, the aneurysm was successfully excluded with a 5 mm papyrus-covered stent. At 3-month and 1-year follow-up, the patient is still asymptomatic and repeat angiographies showed full exclusion of the aneurysm and the absence of restenosis in the covered stent. Discussion: We describe the successful percutaneous IVUS-guided treatment of a giant LMCA shaft coronary aneurysm with a papyrus-covered stent with an excellent 1-year angiographic follow-up showing no residual filling of the aneurysm and no stent restenosis.

Immediate versus staged complete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial.

BACKGROUND: In patients with acute coronary syndrome and multivessel coronary disease, complete revascularisation by percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. We aimed to investigate whether PCI for non-culprit lesions should be attempted during the index procedure or staged. METHODS: This prospective, open-label, non-inferiority, randomised trial was done at 29 hospitals across Belgium, Italy, the Netherlands, and Spain. We included patients aged 18-85 years presenting with ST-segment elevation myocardial infarction or non-ST-segment elevation acute coronary syndrome and multivessel (ie, two or more coronary arteries with a diameter of 2·5 mm or more and ≥70% stenosis based on visual estimation or positive coronary physiology testing) coronary artery disease with a clearly identifiable culprit lesion. A web-based randomisation module was used to randomly assign patients (1:1), with a random block size of four to eight, stratified by study centre, to undergo immediate complete revascularisation (PCI of the culprit lesion first, followed by other non-culprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularisation (PCI of only the culprit lesion during the index procedure and PCI of all non-culprit lesions deemed to be clinically significant by the operator within 6 weeks after the index procedure). The primary outcome was the composite of all-cause mortality, myocardial infarction, any unplanned ischaemia-driven revascularisation, or cerebrovascular events at 1 year after the index procedure. Secondary outcomes included all-cause mortality, myocardial infarction, and unplanned ischaemia-driven revascularisation at 1 year after the index procedure. Primary and secondary outcomes were assessed in all randomly assigned patients by intention to treat. Non-inferiority of immediate to staged complete revascularisation was considered to be met if the upper boundary of the 95% CI of the hazard ratio (HR) for the primary outcome did not exceed 1·39. This trial is registered with ClinicalTrials.gov, NCT03621501. FINDINGS: Between June 26, 2018, and Oct 21, 2021, 764 patients (median age 65·7 years [IQR 57·2-72·9] and 598 [78·3%] males) were randomly assigned to the immediate complete revascularisation group and 761 patients (median age 65·3 years [58·6-72·9] and 589 [77·4%] males) were randomly assigned to the staged complete revascularisation group, and were included in the intention-to-treat population. The primary outcome at 1 year occurred in 57 (7·6%) of 764 patients in the immediate complete revascularisation group and in 71 (9·4%) of 761 patients in the staged complete revascularisation group (HR 0·78, 95% CI 0·55-1·11, pnon-inferiority=0·0011). There was no difference in all-cause death between the immediate and staged complete revascularisation groups (14 [1·9%] vs nine [1·2%]; HR 1·56, 95% CI 0·68-3·61, p=0·30). Myocardial infarction occurred in 14 (1·9%) patients in the immediate complete revascularisation group and in 34 (4·5%) patients in the staged complete revascularisation group (HR 0·41, 95% CI 0·22-0·76, p=0·0045). More unplanned ischaemia-driven revascularisations were performed in the staged complete revascularisation group than in the immediate complete revascularisation group (50 [6·7%] patients vs 31 [4·2%] patients; HR 0·61, 95% CI 0·39-0·95, p=0·030). INTERPRETATION: In patients presenting with acute coronary syndrome and multivessel disease, immediate complete revascularisation was non-inferior to staged complete revascularisation for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischaemia-driven revascularisation. FUNDING: Erasmus University Medical Center and Biotronik.

Protocol for an individual patient data meta-analysis on blood pressure targets after cardiac arrest.

BACKGROUND: Hypotension is common after cardiac arrest (CA), and current guidelines recommend using vasopressors to target mean arterial blood pressure (MAP) higher than 65 mmHg. Pilot trials have compared higher and lower MAP targets. We will review the evidence on whether higher MAP improves outcome after cardiac arrest. METHODS: This systematic review and meta-analysis will be conducted based on a systematic search of relevant major medical databases from their inception onwards, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as clinical trial registries. We will identify randomised controlled trials published in the English language that compare targeting a MAP higher than 65-70 mmHg in CA patients using vasopressors, inotropes and intravenous fluids. The data extraction will be performed separately by two authors (a third author will be involved in case of disagreement), followed by a bias assessment with the Cochrane Risk of Bias tool using an eight-step procedure for assessing if thresholds for clinical significance are crossed. The outcomes will be all-cause mortality, functional long-term outcomes and serious adverse events. We will contact the authors of the identified trials to request individual anonymised patient data to enable individual patient data meta-analysis, aggregate data meta-analyses, trial sequential analyses and multivariable regression, controlling for baseline characteristics. The certainty of the evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. We will register this systematic review with Prospero and aim to redo it when larger trials are published in the near future. CONCLUSIONS: This protocol defines the performance of a systematic review on whether a higher MAP after cardiac arrest improves patient outcome. Repeating this systematic review including more data likely will allow for more certainty regarding the effect of the intervention and possible sub-groups differences.

FFR pressure wire comparative study for drift: piezo resistive versus optical sensor.

BACKGROUND: This study aimed to assess the stability of pressure derived fractional flow reserve (FFR) measurement and the handling performance of the OptoWire Deux with an optical pressure sensor relative to the PressureWire X with piezo resistive pressure sensors. METHODS: This multicenter centre observational study included 50 patients between June 2017 and November 2018 undergoing a diagnostic coronary angiography with FFR measurement of moderate to severe lesions. The reliability of FFR measurement measured with the OptoWire Deux relative to the PressureWire X in each lesion was assessed by the presence of drift. Handling characteristics for both pressure wires were assessed by a 5-point scale and by comparing the time between equalization and crossing the distal target lesion. RESULTS: Hundred and sixteen measurements in 50 patients were performed. Very stable and reliable FFR measurements with the optical sensors were registered, relative to the piezo resistive pressure sensors. There is statistically significant difference in favor of the OptoWire Deux over the PressureWire X (P=0.001). However, the differences are small, when drift values were compared as continuous variables, no statistically significant difference was found for both directional (P=0.435) as for absolute drift (P=0.058). CONCLUSIONS: In patients undergoing FFR measurement, both optical sensor pressure wires (Optowire Deux) as piezo resistive sensor pressure wires (PressureWire X) generate stable and reliable pressure and thus FFR measurement. The optical pressure sensor is less susceptible for drift relative to the piezo resistive pressure sensor, but the difference is within an acceptable range.

Postdischarge prognostic significance of periprocedural myocardial injury after percutaneous intervention of chronic total occlusion.

BACKGROUND: The postdischarge prognostic implication of periprocedural myocardial injury in patients undergoing percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) remains scarcely studied. AIMS: The aim of this study is to assess the prognostic value of periprocedural myocardial injury, defined by increased high-sensitive troponin T (hs-TnT) levels according to updated guidelines, after CTO PCI. METHODS: Between September 2011 and April 2020, 726 patients undergoing CTO PCI at 2 Belgian referral centres were prospectively included and divided into 4 groups based on postprocedural hs-TnT levels (unelevated; ≥5 times the upper limit of normal (ULN); ≥35 times the ULN; ≥70 times the ULN). Postprocedural hs-TnT levels were subsequently related to patient and procedural characteristics, 1-year major adverse cardiac and cerebrovascular events (MACCE; excluding in-hospital MACCE) as well as 1-year mortality. RESULTS: At 1 year follow-up (FU), elevated hs-TnT≥5 times and ≥35 times the ULN were associated with higher MACCE rates (p=0.001; p=0.007, respectively). In addition, they also resulted in a higher 1-year mortality rate (p=0.009;p=0.021, respectively). Patients with increased hs-TnT≥5 times the ULN (35% of patients) more frequently had signs of more advanced atherosclerotic disease (previous CABG p<0.001; stroke p≤0.001 and peripheral vascular disease p<0.001) and had higher procedural complexity (Japanese CTO Score p=<0.001, stent length>48 mm p<0.001, procedure time p<0.001). Antegrade wire escalation did not result in lower event rate of postdischarge MACCE compared with the other CTO crossing techniques combined (p=0.158). CONCLUSION: Periprocedural myocardial injury was associated with a significantly higher rate of MACCE and all-cause mortality after 12 months of FU.

Left ventricular function recovery after ST-elevation myocardial infarction: correlates and outcomes.

BACKGROUND: Contemporary data on left ventricular function (LVF) recovery in patients with left ventricular dysfunction after ST-elevation myocardial infarction (STEMI) are scarce and to date, no comparison has been made with patients with a baseline normal LVF. This study examined predictors of LVF recovery and its relation to outcomes in STEMI. METHODS: Patients presenting with STEMI between January 2010 and December 2016 were categorized in three groups after 3 months according to left ventricular ejection fraction (EF): (i) baseline normal LVF (EF ≥ 50% at baseline); (ii) recovered LVF (EF < 50% at baseline and ≥ 50% after 3 months); and (iii) reduced LVF (EF < 50% at baseline and after 3 months). Heart failure hospitalization, all-cause mortality and cardiovascular mortality were compared between the three groups. RESULTS: Of 577 patients, 341 (59%) patients had a baseline normal LVF, 112 (19%) had a recovered LVF and 124 (22%) had a reduced LVF. Independent correlates of LVF recovery were higher baseline EF, lower peak troponin and cardiac arrest. After median 5.8 years, there was no difference in outcomes between patients with LVF recovery and baseline normal LVF. In contrast, even after multivariate adjustment, patients with persistently reduced LVF had a higher risk for heart failure hospitalization (HR 5.00; 95% CI 2.17-11.46) and all-cause mortality (HR 1.87; 95% CI 1.11-3.16). CONCLUSION: In contemporary treated STEMI patients, prognosis is significantly worse in those with a persistently reduced LVF after 3 months, compared with patients with a baseline normal LVF and those with LVF recovery.

Added Value of Quantitative Apparent Diffusion Coefficient Values for Neuroprognostication After Cardiac Arrest.

OBJECTIVE: To test the prognostic value of brain MRI in addition to clinical and electrophysiologic variables in patients post-cardiac arrest (CA), we explored data from the randomized Neuroprotect Post-CA trial (NCT02541591). METHODS: In this trial, brain MRIs were prospectively obtained. We calculated receiver operating characteristic (ROC) curves for the average apparent diffusion coefficient (ADC) value and percentage of brain voxels with an ADC value <650 × 10-6 mm2/s and <450 × 10-6 mm2/s. We constructed multivariable logistic regression models with clinical characteristics, EEG, somatosensory evoked potentials (SSEP), and ADC value as independent variables to predict good neurologic recovery. RESULTS: In 79/102 patients, MRI data were available and in 58/79 patients all other data were available. At 180 days post-CA, 25/58 (43%) patients had good neurologic recovery. In univariable analysis of all tested MRI measures, average ADC value in the postcentral cortex had the highest accuracy to predict good neurologic recovery, with an area under the ROC curve (AUC) of 0.78. In the most optimal multivariable model, which also included corneal reflexes and EEG, this measure remained an independent predictor of good neurologic recovery (AUC 0.96, false-positive 27%). This model provided a more accurate prediction compared to the most optimal combination of EEG, corneal reflexes, and SSEP (p = 0.03). CONCLUSIONS: Adding information on brain MRI in a multivariable model may improve the prediction of good neurologic recovery in patients post-CA. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that MRI ADC features predict neurologic recovery in patients post-CA.

Cardiac function after cardiac arrest: what do we know?

Postcardiac arrest myocardial dysfunction (PCAMD) is a frequent complication faced during post-resuscitation care that adversely impacts survival and neurological outcome. Both mechanical and electrical factors contribute to the occurrence of PCAMD. Prearrest ventricular function, the cause of cardiac arrest, global ischemia, resuscitation factors, ischemia/reperfusion injury and post-resuscitation treatments contribute to the severity of PCMAD. The pathophysiology of PCAMD is complex and include myocytes energy failure, impaired contractility, cardiac edema, mitochondrial damage, activation of inflammatory pathways and the coagulation cascade, persistent ischemic injury and myocardial stiffness. Hypotension and low cardiac output with vasopressor/inotropes need are frequent after resuscitation. However, clinical, hemodynamic and laboratory signs of shock are frequently altered by cardiac arrest pathophysiology and post-resuscitation treatment, potentially being misleading and not fully reflecting the severity of postcardiac arrest syndrome. Even if validated criteria are lacking, an extensive hemodynamic evaluation is useful to define a "benign" and a "malign" form of myocardial dysfunction and circulatory shock, potentially having treatment and prognostic implications. Cardiac output is frequently decreased after cardiac arrest, particularly in patients treated with target temperature management (TTM); however, it is not independently associated with outcome. Sinus bradycardia during TTM seems independently associated with survival and good neurological outcome, representing a promising prognostic indicator. Higher mean arterial pressure (MAP) seems to be associated with improved survival and cerebral function after cardiac arrest; however, two recent randomized clinical trials failed to replicate these results. Recommendations on hemodynamic optimization are relatively poor and are largely based on general principle of intensive care medicine.

Optimum Blood Pressure in Patients With Shock After Acute Myocardial Infarction and Cardiac Arrest.

BACKGROUND: In patients with shock after acute myocardial infarction (AMI), the optimal level of pharmacologic support is unknown. Whereas higher doses may increase myocardial oxygen consumption and induce arrhythmias, diastolic hypotension may reduce coronary perfusion and increase infarct size. OBJECTIVES: This study aimed to determine the optimal mean arterial pressure (MAP) in patients with AMI and shock after cardiac arrest. METHODS: This study used patient-level pooled analysis of post-cardiac arrest patients with shock after AMI randomized in the Neuroprotect (Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients; NCT02541591) and COMACARE (Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation; NCT02698917) trials who were randomized to MAP 65 mm Hg or MAP 80/85 to 100 mm Hg targets during the first 36 h after admission. The primary endpoint was the area under the 72-h high-sensitivity troponin-T curve. RESULTS: Of 235 patients originally randomized, 120 patients had AMI with shock. Patients assigned to the higher MAP target (n = 58) received higher doses of norepinephrine (p = 0.004) and dobutamine (p = 0.01) and reached higher MAPs (86 ± 9 mm Hg vs. 72 ± 10 mm Hg, p < 0.001). Whereas admission hemodynamics and angiographic findings were all well-balanced and revascularization was performed equally effective, the area under the 72-h high-sensitivity troponin-T curve was lower in patients assigned to the higher MAP target (median: 1.14 µg.72 h/l [interquartile range: 0.35 to 2.31 µg.72 h/l] vs. median: 1.56 µg.72 h/l [interquartile range: 0.61 to 4.72 µg. 72 h/l]; p = 0.04). Additional pharmacologic support did not increase the risk of a new cardiac arrest (p = 0.88) or atrial fibrillation (p = 0.94). Survival with good neurologic outcome at 180 days was not different between both groups (64% vs. 53%, odds ratio: 1.55; 95% confidence interval: 0.74 to 3.22). CONCLUSIONS: In post-cardiac arrest patients with shock after AMI, targeting MAP between 80/85 and 100 mm Hg with additional use of inotropes and vasopressors was associated with smaller myocardial injury.

Effects of dapagliflozin on congestion assessed by remote pulmonary artery pressure monitoring.

AIMS: To explore the effects of dapagliflozin on congestion through CardioMEMS (Abbott Inc., Atlanta, USA) and Cordella™ pulmonary artery Sensor (Endotronix Inc., Lisle, Il, USA) devices, which are implantable systems that provide real-time remote monitoring of pulmonary artery pressure (PAP). METHODS AND RESULTS: Single-centre open label observational pilot trial, to investigate the short-term effects of dapagliflozin in consecutive heart failure and reduced ejection fraction patients with elevated PAP between October and December 2019, previously implanted with CardioMEMS or Cordella™ Sensor. Changes in PAP were evaluated with an area under the curve methodology to estimate the total sum increase or decrease in pressures (mmHg/day) for 7 days before and after starting dapagliflozin relative to the first day of each period. Nine patients (72 ± 10 years, N-terminal pro b-type natriuretic peptide 1027 ± 510 pg/mL, estimated glomerular filtration rate 45 ± 15 mL/kg/m2, left ventricular ejection fraction 35 ± 10%), all on optimal guideline-directed therapy was included. The mean PAP was reduced from 42 ± 9.16 to 38 ± 9.95 mmHg with dapagliflozin therapy (P < 0.05). The average area under the curve for the week leading to dapagliflozin therapy remained unchanged compared to the drop observed for the week after therapy (P < 0.05). Interestingly, the drop in PAP occurred within the first 2 days of dapagliflozin and remained stable for the week following the start of the therapy. CONCLUSIONS: This is the first study to demonstrate a direct effect of dapagliflozin on achieving effective hemodynamic decongestion, providing further mechanistic data regarding the potential mechanisms of sodium-glucose co-transporter-2 inhibitor benefits on heart failure.

Qualitative and quantitative analysis of diffusion-weighted brain MR imaging in comatose survivors after cardiac arrest.

PURPOSE: The aim of this study is to compare a qualitative and a quantitative assessment of brain diffusion-weighted imaging (DWI) in predicting outcome of comatose patients after cardiac arrest (CA). METHODS: Two observers used a scoring template to analyze the DWI of 75 patients. A total of 13 regions were scored from 0 to 3 (0 = normal, 1 = probably normal, 2 = probably abnormal, 3 = definitely abnormal). The total cerebral cortex (TCC), the total deep grey nuclei (TDGN), the total brain stem, the total cerebellum, and the total brain score were calculated. Intra- and inter-observer variability were tested. The mean whole brain apparent diffusion coefficient (ADC) values and percentage of voxels below a specific ADC value cut-off were calculated. The data were correlated with clinical outcome (cerebral performance category score after 180 days, dichotomized in a score 1-2 with favorable outcome and score 3-5 with unfavorable outcome) using ROC analysis. RESULTS: Intra-observer variability was excellent for the TCC score (ICC 0.95 and 0.86) and the TDGN score (ICC 0.89 and 0.75). Inter-observer variability was good to excellent for total cerebral cortex score and total deep grey nuclei score in both the first (ICC 0.78 and 0.69) and third (ICC 0.86 and 0.83) image assessment. TCC and TDGN score show the best correlation with clinical outcome (highest AUC values 0.87 and 0.87). Quantitative parameters did not show good correlation with clinical outcome (AUC values 0.57 and 0.60). CONCLUSION: A qualitative assessment of brain DWI using a scoring template provides useful data regarding patient outcome while quantitative data appeared less reliable.