Duration of Device-Based Fever Prevention after Cardiac Arrest.

BACKGROUND: Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking. METHODS: We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months. RESULTS: A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events. CONCLUSIONS: Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

BACKGROUND: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. METHODS: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. RESULTS: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, -0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P<0.001). CONCLUSIONS: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03243890.

Serial assessments of cardiac output and mixed venous oxygen saturation in comatose patients after out-of-hospital cardiac arrest.

AIM: To assess the association with outcomes of cardiac index (CI) and mixed venous oxygen saturation (SvO2) in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). METHODS: In the cohort study of 789 patients included in the "BOX"-trial, 565 (77%) patients were included in this hemodynamic substudy (age 62 ± 13 years, male sex 81%). Pulmonary artery catheters were inserted shortly after ICU admission. CI and SvO2 were measured as soon as possible in the ICU and until awakening or death. The endpoints were all-cause mortality at 1 year and renal failure defined as need for renal replacement therapy. RESULTS: First measured CI was median 1.7 (1.4-2.1) l/min/m2, and first measured SvO2 was median 67 (61-73) %. CI < median with SvO2 > median was present in 222 (39%), and low SvO2 with CI < median was present in 59 (11%). Spline analysis indicated that SvO2 value < 55% was associated with poor outcome. Low CI at admission was not significantly associated with mortality in multivariable analysis (p = 0.14). SvO2 was significantly inversely associated with mortality (hazard ratioadjusted: 0.91 (0.84-0.98) per 5% increase in SvO2, p = 0.01). SvO2 was significantly inversely associated with renal failure after adjusting for confounders (ORadjusted: 0.73 [0.62-0.86] per 5% increase in SvO2, p = 0.001). The combination of lower CI and lower SvO2 was associated with higher risk of mortality (hazard ratioadjusted: 1.54 (1.06-2.23) and renal failure (ORadjusted: 5.87 [2.34-14.73]. CONCLUSION: First measured SvO2 after resuscitation from OHCA was inversely associated with mortality and renal failure. If SvO2 and CI were below median, the risk of poor outcomes increased significantly. REGISTRATION: The BOX-trial is registered at clinicaltrials.gov (NCT03141099, date 2017-30-04, retrospectively registered).

Circulating biomarkers, echocardiographic parameters, and incident subclinical atrial fibrillation in patients with diabetes and hypertension.

BACKGROUND: Long-term rhythm monitoring (LTRM) can detect undiagnosed atrial fibrillation (AF) in patients at high risk of AF and stroke. Biomarkers and echocardiographic parameters could, however, help identify patients benefitting most from LTRM. The aim of this study was to investigate, whether circulating biomarkers of cardiac and vascular function (brain natriuretic peptide (BNP), cardiac troponin I (cTnI), copeptin, and mid-regional proadrenomedullin (MR-proADM)) and echocardiographic parameters were associated with incident subclinical AF (SCAF) in a population at high risk of stroke in the presence of AF. For this purpose, we investigated individuals ≥65 years of age with hypertension and diabetes mellitus, but no history or symptoms of AF or other cardiovascular disease (CVD). METHODS: We included 82 consecutive patients (median age 71.3 years (IQR 67.4-75.1)). All patients received an insertable cardiac monitor (ICM) and were followed for a median of 588 days (IQR 453-712). On the day of ICM implantation, a comprehensive echocardiogram and blood samples were obtained. RESULTS: During a median follow-up of 588 days (IQR: 453-712 days), incident SCAF occurred in 17 patients (20.7%) with a median time to first-detected episode of 91 days (IQR 41-251 days). MR-proADM (median 0.87 nmol/L (IQR 0.76-1.02) vs 0.78 nmol/L (IQR 0.68-0.98)) and copeptin (median 13 pmol/L (IQR 9-17) vs 8 pmol/L (IQR 4-18)) levels were insignificantly higher in patients with incident SCAF. BNP and cTnI concentrations and echocardiographic parameters were similar in the two groups. CONCLUSIONS: MR-proADM, BNP, cTnI, copeptin, and several echocardiographic parameters were not associated with incident SCAF in this cohort of patients with hypertension and diabetes, but without any underlying CVD.

Hemodynamic changes during aortic valve surgery among patients with aortic stenosis.

Introduction. Patients with severe aortic stenosis (AS) undergoing surgery are at increased risk of hypotension and hypoperfusion. Although treatable with inotropic agents or fluid, little is known about how these therapies affect central hemodynamics in AS patients under general anesthesia. We measured changes in central hemodynamics after dobutamine infusion and fluid bolus among patients with severe AS and associated these changes with preoperative echocardiography. Methods. We included 33 patients with severe AS undergoing surgical AVR. After induction of general anesthesia, hemodynamic measurements were obtained with a pulmonary artery catheter, including Cardiac index (CI), stroke volume index (SVi) and pulmonary capillary wedge pressure (PCWP). Measurements were repeated during dobutamine infusion, after fluid bolus and lastly after sternotomy. Results. General anesthesia resulted in a decrease in CI and SVi compared to preoperative values. During dobutamine infusion CI increased but mean SVi did not (38 ± 12 vs 37 ± 13 ml/m2, p = .90). Higher EF and SVi before surgery and a larger decrease in SVi after induction of general anesthesia were associated with an increase in SVi during dobutamine infusion. After fluid bolus both CI, SVi (48 ± 12 vs 37 ± 13 ml/min/m2, p < .0001) and PCWP increased. PCWP increased mostly among patients with a larger LA volume index. Conclusion. In patients with AS, CI can be increased with both dobutamine and fluid during surgery. Dobutamine's effect on SVI was highly variable and associated with baseline LVEF, and an increase in CI was mostly driven by an increase in heart rate. Fluid increased SVi at the cost of an increase in PCWP.

Assessment of patients with a suspected cardioembolic ischemic stroke. A national consensus statement.

OBJECTIVES: Several cardiovascular, structural, and functional abnormalities have been considered as potential causes of cardioembolic ischemic strokes. Beyond atrial fibrillation, other sources of embolism clearly exist and may warrant urgent action, but they are only a minor part of the many stroke mechanisms and strokes that seem to be of embolic origin remain without a determined source. The associations between stroke and findings like atrial fibrillation, valve calcification, or heart failure are confounded by co-existing risk factors for atherosclerosis and vascular disease. In addition, a patent foramen ovale which is a common abnormality in the general population is mostly an innocent bystander in patients with ischemic stroke. For these reasons, experts from the national Danish societies of cardiology, neurology, stroke, and neuroradiology sought to develop a consensus document to provide national recommendations on how to manage patients with a suspected cardioembolic stroke. Design: Comprehensive literature search and analyses were done by a panel of experts and presented at a consensus meeting. Evidence supporting each subject was vetted by open discussion and statements were adjusted thereafter. Results: The most common sources of embolic stroke were identified, and the statement provides advise on how neurologist can identify cases that need referral, and what is expected by the cardiologist. Conclusions: A primary neurological and neuroradiological assessment is mandatory and neurovascular specialists should manage the initiation of secondary prophylactic treatment. If a cardioembolic stroke is suspected, a dedicated cardiologist experienced in the management of cardioembolism should provide a tailored clinical and echocardiographic assessment.

Assessment of diastolic function in aortic stenosis: A comparison between 2009 and 2016 guidelines.

AIMS: New diastolic dysfunction (DD) guidelines were introduced in 2016 to replace the 2009 guidelines, but have not yet been evaluated in aortic stenosis (AS). We aimed to compare the 2009 and 2016 DD guidelines in severe AS patients in terms of association with left ventricular (LV) and left atrial (LA) remodeling, with pulmonary capillary wedge pressure (PCWP) at rest and exercise, and with prognosis. METHODS AND RESULTS: We included 212 patients with severe AS (112 undergoing AVR, 100 asymptomatic). Echocardiography, magnetic resonance imaging, and brain natriuretic peptides (BNP) were performed/measured. Thirty-nine asymptomatic patients had PCWP measured during rest and maximal exertion. Asymptomatic patients were followed for 3.1 years for the combined endpoint of death, AVR or admission with heart failure. The 2009 and 2016 DD guidelines agreed poorly with each other (Cohens' κ = .15). 2009 guidelines showed many ambiguous DD findings. With the 2016 guidelines, 20% of patients had indeterminate DD. DD grade 2 according to 2016 guidelines showed stronger association with symptom status, BNP, global longitudinal strain (GLS) and peak exercise PCWP than 2009 guidelines. For indeterminate DD patients according to 2009 guidelines, GLS above the median was associated with event-free survival (HR .11 (95% CI .02-.53)). For neither guideline was DD associated with the combined endpoint in asymptomatic patients. CONCLUSION: The 2016 guidelines show a stronger association with BNP, GLS, and exercise PCWP than the 2009 guidelines. The 2016 guidelines result in 20% of patients with indeterminate DD; however, these patients may possibly be stratified according to GLS.

Causes and characteristics associated with early and late readmission after open-heart valve surgery.

OBJECTIVES: The objectives of the study were to describe the causes of readmission from discharge to 30 days and from day 31 to 180 after discharge and to investigate the characteristics associated with overall and cause-specific readmissions after open-heart valve surgery. METHODS: A single-center, retrospective cohort of 980 patients undergoing open-heart valve surgery from 2013 to 2016. Time to the first readmission was analyzed using univariable and multivariable Cox proportional hazard models. Results are reported as hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: In total, 366 patients (37%) experienced unplanned cardiac readmission within 180 days after discharge. Within 30 days after discharge, the most frequent causes of readmission were pericardial/pleural effusions (n = 87), infections (n = 50), and atrial fibrillation/flutter (n = 45). Accordingly, infections (n = 32) were the most common cause from day 31 to 180. No powerful predictors of overall cardiac readmission were identified, but several characteristics were associated with cause-specific readmissions: age ≤65 years (HR: 1.85; CI: 1.18-2.88), male gender (HR: 1.85; CI: 1.11-3.09), high alcohol intake (HR: 1.99; CI: 1.22-3.24) and mitral valve procedures (HR: 1.86; CI: 1.11-3.10) were associated with readmissions due to effusions. Ischemic heart disease with a prior percutaneous coronary intervention (HR: 2.94; CI: 1.53-5.63), mitral valve procedures (HR: 2.10; CI: 1.23-3.59), and postoperative atrial fibrillation/flutter (HR: 1.71; CI: 1.03-2.85) were associated with atrial fibrillation/flutter readmissions. CONCLUSION: Predicting overall readmissions after open-heart valve surgery is difficult as causes of readmissions vary and different causes are associated with different characteristics. Future studies should target reducing cause-specific readmissions.

Right Ventricular and Pulmonary Vascular Function are Influenced by Age and Volume Expansion in Healthy Humans.

BACKGROUND: Patients with heart failure (HF) often show signs of right ventricular (RV) dysfunction. The RV function of coupled with the pulmonary circulation (tricuspid annular plane systolic excursion [TAPSE]/pulmonary arterial systolic pressure [PASP]) has been shown to divide HF patients into distinct prognostic strata, but less is known about which factors influence this prognostic marker, and whether those factors can be modified. We sought to obtain normative values and discern the individual effects of age, sex, and fluid overload on RV function. METHODS AND RESULTS: Sixty healthy subjects aged 20-80 years were enrolled in this prospective study. Right heart catheterization with hemodynamic measurements were performed at rest after a rapid saline solution infusion (10 mL/kg, 150 mL/min). Linear regression and Spearman correlation models were used to estimate associations between TAPSE/PASP and relevant variables. In healthy persons of all ages, the median (5th-95th percentiles) normative TASPE-PASP ratio was 1.25 (0.81-1.78) mm/mm Hg. The correlation between progressive age and declining TAPSE/PASP was significant (r = -0.35; P = .006). Sex did not influence TAPSE/PASP (P = .30). Rapid fluid expansion increased central venous pressure from 5 ± 2 mm Hg to 11 ± 4 mm Hg after fluid infusion (P < .0001). This resulted in a 32% decrease in the TAPSE-PASP ratio after fluid infusion, compared to baseline (P < .0001). CONCLUSIONS: The TAPSE-PASP ratio was affected by age, but not sex. TAPSE/PASP is not only a reflection of intrinsic RV function and pulmonary vascular coupling, but fluid status also dynamically affects this index of RV function. Normative values with invasive measurements were obtained for future assessment of HF patients.

Layer-specific deformation analysis in severe aortic valve stenosis, primary mitral valve regurgitation, and healthy individuals validated against invasive hemodynamic measurements of heart function.

AIM: Speckle tracking echocardiography is considered valuable in assessing left ventricular (LV) function. The method has been refined to assess deformation in different myocardial layers, but the effect of volume vs pressure overload on this pattern is unknown. The aim was to test whether layer-specific myocardial strain (LSS) obtained by speckle tracking echocardiography exhibits different patterns in conditions with different loading conditions. METHODS AND RESULTS: Forty patients with asymptomatic severe aortic stenosis (AS) (AVA 0.81 ± 0.15 cm2 , LV ejection fraction [LVEF] 66% ± 7%), 43 patients with asymptomatic or mildly symptomatic significant primary mitral regurgitation (MR) (effective regurgitant orifice (ERO) 0.51 (IQR 0.37-0.67) cm2 , LVEF 70% ± 7%), and 23 healthy individuals (LVEF 65% ± 6%) were enrolled. Echocardiography and right heart catheterization were performed in all patients. In MR, strain values in each myocardial layer (endocardial/global longitudinal strain (GLS)/epicardial) were higher (25.0% ± 3.4%/21.6% ± 2.9%/18.8% ± 2.6%) compared to healthy individuals (22.6% ± 3.2%/19.6% ± 2.9%/17.1% ± 2.6%) and AS (20.5% ± 2.8%/17.7% ± 2.5%/14.0% ± 5.6%), P < .001. All 3 groups exhibited a similar LSS pattern with highest values in the endocardial and lowest values in the epicardial layer. The epicardial-endocardial strain ratio was lower in AS (0.72 ± 0.04) than in MR (0.75 ± 0.04, P = .04). Global longitudinal strain (GLS) correlated significantly with LV wall stress (r = .39, P = .0003) but not with LV stroke work or contractility. CONCLUSION: Layer-specific myocardial strain (LSS) patterns differed in patients with severe AS, significant MR, and healthy individuals with highest values in MR. Strain irrespective of layer assessed was associated with LV wall stress but seemed less related to contractility and unrelated to stroke work in the setting of normal LVEF.

Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve.

BACKGROUND: Heart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserve in these patients. METHODS: A total of 155 patients with HF with reduced ejection fraction underwent a low-dose dobutamine echocardiography and blood sampling for biomarker measurements. Patients were classified according to history of DM and an oral glucose tolerance test (OGTT) as: normal glucose tolerance (NGT) (n = 70), impaired glucose tolerance (IGT) (n = 25) and DM (n = 60). RESULTS: Galectin-3 levels were elevated in DM patients as compared to non-diabetic patients (P = 0.02), while higher fibulin-1 levels were observed in HF patients with IGF and DM (P = 0.07). Reduced LV contractile reserve was associated with increasing Gal-3 levels (ß = -0.19, P = 0.03) although, this association was attenuated after adjustment for estimated glomerular filtration rate (P = 0.66). Fibulin-1 was not associated with LV contractile reserve (P = 0.71). CONCLUSIONS: Galectin-3 and fibulin-1 levels were elevated in HF patients with impaired glucose metabolism. However, reduced LV contractile reserve among HF patients with DM does not to have an independent impact on plasma Gal-3 and fibulin-1 levels.

Impact of chronic obstructive pulmonary disease on survival and symptoms of severe aortic valve stenosis.

BACKGROUND: As patients with severe aortic valve stenosis (AS) develop symptoms their survival decreases rapidly, if treated conservatively. Transcatheter aortic valve implantation (TAVI) has been introduced as a less invasive treatment alternative, especially in inoperable patients, who often have severe comorbidities, including chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Since the beginning of our TAVI program in March 2008, data on all 131 TAVI patients were prospectively and consecutively collected in this registry with complete follow-up. COPD was present in 37 patients. By January 2012 survival data were collected from the Danish Civil Registration System. Median follow-up duration was 559 days. RESULTS: Overall survival and survival from cardiac death was equivalent in both patients with and without COPD (p = 0.98 and p = 0.26) in the follow-up period. Further, patients with COPD had higher New York Heart Association (NYHA) class prior to intervention compared with those without (3.1 ± 0.5 vs. 2.9 ± 0.5, p = 0.02). In multivariate regression analysis COPD was associated with 30-day postoperative NYHA class (0.43; 95% confidence interval (CI): 0.10-0.75; p = 0.01), but not to NYHA class improvement from pre- to postintervention (0.25; 95% CI: - 0.12 to -0.63; p = 0.18). CONCLUSIONS: In patients with symptomatic severe AS treated with TAVI, the presence of COPD neither affects overall survival nor survival from cardiac death. Patients with COPD had, however, both higher pre- and postoperative NYHA class compared with patients without COPD, but NYHA class improvement from pre- to postintervention was equivalent in both groups.

Cardiac Damage in Early Aortic Stenosis: Is the Valve to Blame?

BACKGROUND: Despite the close association between aortic stenosis (AS) and cardiac damage (CD), it is unclear if CD is limited to patients with moderate and severe AS and which factors affect its progression. Although altered valvular hemodynamic status may drive the development of CD in AS, commonly occurring comorbidities may contribute. OBJECTIVES: The aim of this study was to determine the prevalence of and factors associated with CD in mild AS. METHODS: This retrospective study included 9,611 patients with mild AS (peak aortic valve velocity [Vmax] 2-3 m/s and description of abnormal aortic valve) from 2010 through 2021. CD was staged using the Genereux classification. RESULTS: All but 20% (n = 1,901; stage 0) of patients with mild AS demonstrated CD: 1,613 (17%) stage 1, 4,843 (50%) stage 2, 891 (9%) stage 3, and 363 (4%) stage 4. Patients with higher stages had more comorbidities (hypertension, heart failure, ischemic heart disease, stroke, peripheral arterial disease, chronic kidney disease, chronic pulmonary disease, and diabetes mellitus) but had valvular hemodynamic status similar to those without CD. CD stage did not worsen with higher Vmax range (stage >1 in 64% with Vmax <2.5 m/s vs 61% with Vmax ≥2.5 m/s) but increased with the number of comorbidities, with stage >1 occurring in 50%, 53%, 60%, 66%, 72%, and 73% in the presence of 0, 1, 2, 3, 4, and 5 or more comorbidities, respectively. CONCLUSIONS: CD was highly prevalent in patients with mild AS. Among patients with mild AS, there was no relationship between the degree of CD and AS severity; instead, CD was highly associated with comorbidities.

Impact of Blood Pressure Targets in Patients With Heart Failure Undergoing Postresuscitation Care: A Subgroup Analysis From a Randomized Controlled Trial.

BACKGROUND: To assess the effect of targeting higher or lower blood pressure during postresucitation intensive care among comatose patients with out-of-hospital cardiac arrest with a history of heart failure. METHODS: The BOX trial (Blood Pressure and Oxygenation Targets After Out-of-Hospital Cardiac Arrest) was a randomized, controlled, double-blinded, multicenter study comparing titration of vasopressors toward a mean arterial pressure (MAP) of 63 versus 77 mm Hg during postresuscitation intensive care. Patients with a history of heart failure were included in this substudy. Pulmonary artery catheters were inserted shortly after admission. History of heart failure was assessed through chart review of all included patients. The primary outcome was cardiac index during the first 72 hours. Secondary outcomes were left ventricular ejection fraction, heart rate, stroke volume, renal replacement therapy and all-cause mortality at 365 days. RESULTS: A total of 134 patients (17% of the BOX cohort) had a history of heart failure (patients with left ventricular ejection fraction, ≤40%: 103 [77%]) of which 71 (53%) were allocated to a MAP of 77 mm Hg. Cardiac index at intensive care unit arrival was 1.77±0.11 L/min·m-2 in the MAP63-group and 1.78±0.17 L/min·m-2 in the MAP77, P=0.92. During the next 72 hours, the mean difference was 0.15 (95% CI, -0.04 to 0.35) L/min·m-2; Pgroup=0.22. Left ventricular ejection fraction and stroke volume was similar between the groups. Patients allocated to MAP77 had significantly elevated heart rate (mean difference 6 [1-12] beats/min, Pgroup=0.03). Vasopressor usage was also significantly increased (P=0.006). At 365 days, 69 (51%) of the patients had died. The adjusted hazard ratio for 365 day mortality was 1.38 (0.84-2.27), P=0.20 and adjusted odds ratio for renal replacement therapy was 2.73 (0.84-8.89; P=0.09). CONCLUSIONS: In resuscitated patients with out-of-hospital cardiac arrest with a history of heart failure, allocation to a higher blood pressure target resulted in significantly increased heart rate in the higher blood pressure-target group. However, no certain differences was found for cardiac index, left ventricular ejection fraction or stroke volume. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03141099.

Angiotensin II Receptor Blockers Are Associated With Reduced Valvular Fibrosis in Women With Aortic Stenosis.

BACKGROUND: Angiotensin receptor blockers (ARBs) may slow down the progression of aortic stenosis (AS) through their antifibrotic effect. Women present more valvular fibrosis than men, so ARBs may have more effect in females. Our aim was to assess the impact of ARBs on the remodelling of the aortic valve in men and women. METHODS: We included patients who had an aortic valve replacement with or without coronary bypass grafting from 2006 to 2013. Patients with missing echocardiographic or histologic data were excluded. Warren-Yong and fibrosis scores of the explanted valves were performed. Patients were divided into 4 phenotypes according to their Warren-Yong and fibrosis scores: mild calcification/fibrosis, severe calcification/fibrosis group, predominant fibrosis group, predominant calcification group. RESULTS: Among the 1321 included patients, the vast majority (89%) has severe AS. Patients in the predominant fibrosis group, compared with the predominant calcium group, were more often female (39% vs 31%; P = 0.008) with bicuspid valves (44% vs 34%; P = 0.002), and less often used ARBs (25% vs 30%; P = 0.046). Female sex was independently associated with being in the predominant fibrosis group (odds ratio 1.45, 95% confidence interval 1.08-1.95; P = 0.01), with a significant interaction between female sex and ARBs. Women taking ARBs compared with women not taking ARBs had significantly lower fibrosis scores (P < 0.001). This difference was not seen in men. CONCLUSIONS: In this large series of patients with moderate-severe AS, among the women there was a negative association between intake of ARBs and valvular fibrosis. Thus, the possible effects of ARBs may be sex specific, with a larger therapeutic role in women.

Haemodynamic implications of VA-ECMO vs. VA-ECMO plus Impella CP for cardiogenic shock in a large animal model.

AIMS: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with profound left ventricular (LV) failure is associated with inadequate LV emptying. To unload the LV, VA-ECMO can be combined with Impella CP (ECMELLA). We hypothesized that ECMELLA improves cardiac energetics compared with VA-ECMO in a porcine model of cardiogenic shock (CS). METHODS AND RESULTS: Land-race pigs (weight 70 kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. CS was induced with embolization in the left main coronary artery. CS was defined as reduction of ≥50% in cardiac output or mixed oxygen saturation (SvO2) or a SvO2 < 30%. At CS VA-ECMO was initiated and embolization was continued until arterial pulse pressure was <10 mmHg. At this point, Impella CP was placed in the ECMELLA arm. Support was maintained for 4 h. CS was induced in 15 pigs (VA-ECMO n = 7, ECMELLA n = 8). At time of CS MAP was <45 mmHg in both groups, with no difference at 4 h (VA-ECMO 64 mmHg ± 11 vs. ECMELLA 55 mmHg ± 21, P = 0.08). Carotid blood flow and arterial lactate increased from CS and was similar in VA-ECMO and ECMELLA [239 mL/min ± 97 vs. 213 mL/min ± 133 (P = 0.6) and 5.2 ± 3.3 vs. 4.2 ± 2.9 mmol/ (P = 0.5)]. Pressure-volume area (PVA) was significantly higher with VA-ECMO compared with ECMELLA (9567 ± 1733 vs. 6921 ± 5036 mmHg × mL/min × 10-3, P = 0.014). Total diureses was found to be lower in VA-ECMO compared with ECMELLA [248 mL (179-930) vs. 506 mL (418-2190); P = 0.005]. CONCLUSIONS: In a porcine model of CS, we found lower PVA, with the ECMELLA configuration compared with VA-ECMO, indicating better cardiac energetics without compromising systemic perfusion.

Impact of blood pressure targets on central hemodynamics during intensive care after out-of-hospital cardiac arrest.

OBJECTIVES: The aim was to investigate the advanced hemodynamic effects of the two MAP-targets during intensive care on systemic hemodynamics in comatose patients after cardiac arrest. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Primary vasopressor used was per protocol norepinephrine. Hemodynamic monitoring was done with pulmonary artery catheters (PAC) and measurements were made on predefined time points. The primary endpoint of this substudy was the difference in cardiac index within 48 h from a repeated measurements-mixed model. Secondary endpoints included systemic vascular resistance index (SVRI), heart rate, and stroke volume index. PATIENTS: Comatose survivors after out-of-hospital cardiac arrest. INTERVENTIONS: The "Blood pressure and oxygenations targets after out-of-hospital cardiac arrest (BOX)"-trial was a randomized, controlled, double-blinded, multicenter-study comparing targeted mean arterial pressure (MAP) of 63 mmHg (MAP63) vs 77 mmHg (MAP77). MEASUREMENTS AND MAIN RESULTS: Among 789 randomized patients, 730 (93%) patients were included in the hemodynamic substudy. From PAC-insertion (median 1 hours after ICU-admission) and the next 48 hours, the MAP77-group received significantly higher doses of norepinephrine (mean difference 0.09 µg/kg/min, 95% confidence interval (CI) 0.07-0.11, pgroup < 0.0001). Cardiac index was significantly increased (0.20 L/min/m2 (CI 0.12-0.28), pgroup < 0.0001) as was SVRI with an overall difference of (43 dynes m2/s/cm5 (CI 7-79); pgroup = 0.02). Heart rate was increased in the MAP77-group (4 beats/minute; CI 2-6, pgroup < 0.003), but stroke volume index was not (pgroup = 0.10). CONCLUSIONS: Targeted MAP at 77 mmHg compared to 63 mmHg resulted in a higher dose of norepinephrine, increased cardiac index and SVRI. Heart rate was also increased, but stroke volume index was not affected by a higher blood pressure target.