Recombinant human placental growth factor-2 in post-infarction left ventricular dysfunction: a randomized, placebo-controlled, preclinical study.

Placental growth factor (PlGF)-2 induces angio- and arteriogenesis in rodents but its therapeutic potential in a clinically representative post-infarction left ventricular (LV) dysfunction model remains unclear. We, therefore, investigated the safety and efficacy of recombinant human (rh)PlGF-2 in the infarcted porcine heart in a randomized, placebo-controlled blinded study. We induced myocardial infarction (MI) in pigs using 75 min mid-LAD balloon occlusion followed by reperfusion. After 4 w, we randomized pigs with marked LV dysfunction (LVEF < 40%) to receive continuous intravenous infusion of 5, 15, 45 µg/kg/day rhPlGF-2 or PBS (CON) for 2 w using osmotic pumps. We evaluated the treatment effect at 8 w using comprehensive MRI and immunohistochemistry and measured myocardial PlGF-2 receptor transcript levels. At 4 w after MI, infarct size was 16-18 ± 4% of LV mass, resulting in significantly impaired systolic function (LVEF 34 ± 4%). In the pilot study (3 pigs/dose), PIGF administration showed sustained dose-dependent increases in plasma concentrations for 14 days without systemic toxicity and was associated with favorable post-infarct remodeling. In the second phase (n = 42), we detected no significant differences at 8 w between CON and PlGF-treated pigs in infarct size, capillary or arteriolar density, global LV function and regional myocardial blood flow at rest or during stress. Molecular analysis showed significant downregulation of the main PlGF-2 receptor, pVEGFR-1, in dysfunctional myocardium. Chronic rhPIGF-2 infusion was safe but failed to induce therapeutic neovascularization and improve global cardiac function after myocardial infarction in pigs. Our data emphasize the critical need for properly designed trials in representative large animal models before translating presumed promising therapies to patients.

Nurse-led diuretic titration via a point-of-care urinary sodium sensor in patients with acute decompensated heart failure (EASY-HF): A single-centre, randomized, open-label study.

AIMS: Early evaluation of the natriuretic response is recommended to guide diuretic therapy in acute decompensated heart failure (ADHF). However, its implementation in daily practice is hampered by implementation barriers and increased time constraints. The Readily Available Urinary Sodium Analysis in Patients with Acute Decompensated Heart Failure (EASY-HF) study assessed the feasibility, efficacy and safety of a nurse-led urinary sodium-based diuretic titration protocol with the use of a point-of-care urinary sodium sensor. METHODS AND RESULTS: The EASY-HF study was a single-centre, randomized, open-label study comparing diuretic management at the treating physician's discretion as standard of care (SOC) with a nurse-led natriuresis-guided protocol in patients with ADHF. The LAQUAtwin Sodium Meter (HORIBA) was used as point-of-care sensor to measure urine sodium concentration. The primary endpoint was natriuresis after 48 h. Secondary endpoints included safety profile and user-friendliness of both the protocol and the point-of-care sensor. Sixty patients were randomized towards SOC (n = 30) versus protocolized care (n = 30). The mean age was 80 ± 8 years, 25% were women and median N-terminal pro-B-type natriuretic peptide was 4667 (2667-7709) ng/L. Natriuresis after 48 h was significantly higher in the protocolized versus SOC group (820 ± 279 vs. 657 ± 273 mmol; p = 0.027). Pre-defined safety endpoints were similar among both groups. The sensor-based protocol was evaluated as easy to use by the nursing staff, and preferred over urinary collections. CONCLUSION: A nurse-led diuretic titration protocol via a point-of-care urinary sodium sensor was feasible, safe and resulted in an increased natriuresis in ADHF compared to SOC.

Characteristics and Management of Patients With Cancer and Atrial Fibrillation: The BLITZ-AF Cancer Registry.

Background: Atrial fibrillation (AF) is a frequent cardiovascular (CV) comorbidity in cancer. Objectives: The purpose of this study was to examine clinical characteristics and contemporary management of patients with AF and cancer with a specific focus on antithrombotic treatments. Methods: This was a prospective, multicenter, observational study of patients with a recent cancer diagnosis and electrocardiographically confirmed AF (the BLITZ-AF Cancer Registry). CHA2DS2VASc scores were calculated for study participants. Results: Overall, 1,514 individuals were enrolled from June 2019 to September 2021 (mean age 74 ± 9 years, 47.5% of participants >75 years of age; 63.5% males). CV diseases were common: 20.9% had heart failure, 18.1% had coronary artery disease, 38.5% had valvular heart disease, and 9.8% had peripheral artery disease. Previous thromboembolic and hemorrhagic events occurred in 13.9% and 10.4% of subjects, respectively. The most common cancer types were lung (14.9%), colorectal (14.1%), prostate (8.8%), and non-Hodgkin lymphoma (8.1%). In total, 41.5% of the patients had a CHA2DS2VASc score ≥4. Before admission or prior to cardiologist consultation, 16.6% of subjects were not taking any antithrombotic therapy and 22.7% were receiving antiplatelet agents and/or low-molecular-weight heparin. At discharge or after cardiologic assessment, these percentages dropped to 7.7% and 16.6%, respectively. This trend was paralleled by an increase in the use of direct-acting oral anticoagulant, while the proportion of vitamin K antagonist declined. Conclusions: This study demonstrates that there is underuse of appropriate antithrombotic therapy for AF in cancer patients highlighting the need to integrate early CV assessment in the management of these patients. (Non-interventional Study on Patients With Atrial Fibrillation and Cancer [BLITZ-AF Cancer]; NCT03909386).

Corrigendum: Progression of functional and structural glaucomatous damage in relation to diurnal and nocturnal dips in mean arterial pressure.

[This corrects the article DOI: 10.3389/fcvm.2022.1024044.].

Geographical variation in patient characteristics and outcomes in heart failure with mildly reduced and preserved ejection fraction.

AIMS: Compared to heart failure (HF) with reduced ejection fraction, HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) are increasing in prevalence, yet little is known about the geographic variation in patient characteristics, treatments and outcomes among these two HF phenotypes. The aim of this study was to investigate geographic differences in HFpEF and HFmrEF. METHODS AND RESULTS: We conducted an individual patient analysis of five clinical trials enrolling patients with HFpEF or HFmrEF from North America (NA), Latin America (LA), Western Europe (WE), Central/Eastern Europe and Russia (CEER), and Asia-Pacific (AP). We compared regions using descriptive statistics and multivariable regression models. Among the 19 959 patients included, 4066 (23.1%) had HFmrEF and 15 353 (76.9%) HFpEF. Regardless of HF phenotype, patients from WE were oldest, and those in CEER youngest. LA had the largest portion of females and NA most black patients. Obesity and diabetes were most prevalent in NA and hypertension and coronary heart disease most common in CEER. Self-reported health status varied strikingly and was the worst in NA and best in AP. Among patients with HFmrEF, rates of the primary composite endpoint (cardiovascular death or HF hospitalization) were: NA 12.56 per 100 patient-years (/100py), AP 11.67/100py, CEER 10.12/100py, LA 8.90/100py, and WE 8.43/100py, driven by differences in the rate of HF hospitalization. The corresponding values in HFpEF were 11.47/100py, 7.80/100py, 5.47/100py, 5.92/100py, and 7.80/100py, respectively. CONCLUSIONS: There is substantial geographic variation in patient characteristics, treatment and outcomes among patients with HFpEF and HFmrEF. These findings have implications for interpretation and generalizability of trial results, design and conduct of future trials, and optimization of care for these patients.

Call for Action to Target Interhospital Variation in Cardiovascular Mortality, Readmissions, and Length-of-Stay: Results of a National Population Analysis.

BACKGROUND: Excessive interhospital variation threatens healthcare quality. Data on variation in patient outcomes across the whole cardiovascular spectrum are lacking. We aimed to examine interhospital variability for 28 cardiovascular All Patient Refined-Diagnosis-related Groups (APR-DRGs). METHODS: We studied 103,299 cardiovascular admissions in 99 (98%) Belgian acute-care hospitals between 2012 and 2018. Using generalized linear mixed models, we estimated hospital-specific and APR-DRG-specific risk-standardized rates for in-hospital mortality, 30-day readmissions, and length-of-stay above the APR-DRG-specific 90th percentile. Interhospital variation was assessed based on estimated variance components and time trends between the 2012-2014 and 2016-2018 periods were examined. RESULTS: There was strong evidence of interhospital variation, with statistically significant variation across the 3 outcomes for 5 APR-DRGs after accounting for patient and hospital factors: percutaneous cardiovascular procedures with acute myocardial infarction, heart failure, hypertension, angina pectoris, and arrhythmia. Medical diagnoses, with in particular hypertension, heart failure, angina pectoris, and cardiac arrest, showed strongest variability, with hypertension displaying the largest median odds ratio for mortality (2.51). Overall, hospitals performing at the upper-quartile level should achieve improvements to the median level, and an annual 633 deaths, 322 readmissions, and 1578 extended hospital stays could potentially be avoided. CONCLUSIONS: Analysis of interhospital variation highlights important outcome differences that are not explained by known patient or hospital characteristics. Targeting variation is therefore a promising strategy to improve cardiovascular care. Considering their treatment in multidisciplinary teams, policy makers, and managers should prioritize heart failure, hypertension, cardiac arrest, and angina pectoris improvements by targeting guideline implementation outside the cardiology department.

Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial.

OBJECTIVE: Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine understanding of the antifibrotic action of spironolactone. METHODS: In this substudy (n=290) to the Heart 'Omics' in Ageing Study trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/day and followed for 9 months. The analysis included 1498 sequenced urinary peptides detectable in ≥30% of patients and carboxyterminal propeptide of procollagen I (PICP) and PICP/carboxyterminal telopeptide of collagen I (CITP) as serum biomarkers of COL1A1 synthesis. After rank normalisation of biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted mixed model analysis of variance. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher's Z transform. RESULTS: Multivariable-adjusted between-group differences in the urinary peptides with error 1 rate correction were limited to 27 collagen fragments, of which 16 were upregulated (7 COL1A1 fragments) on spironolactone and 11 downregulated (4 COL1A1 fragments). Over 9 months of follow-up, spironolactone decreased serum PICP from 81 (IQR 66-95) to 75 (61-90) µg/L and PICP/CITP from 22 (17-28) to 18 (13-26), whereas no changes occurred in the control group, resulting in a difference (spironolactone minus control) expressed in standardised units of -0.321 (95% CI 0.0007). Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and in PICP or the PICP/CITP ratio. CONCLUSIONS: Spironolactone decreased serum markers of collagen synthesis and predominantly downregulated urinary collagen-derived peptides, but upregulated others. The interpretation of these opposite UPP trends might be due to shrinking the body-wide pool of collagens, explaining downregulation, while some degree of collagen synthesis must be maintained to sustain vital organ functions, explaining upregulation. Combining urinary and serum fibrosis markers opens new avenues for the understanding of the action of antifibrotic drugs. TRIAL REGISTRATION NUMBER: NCT02556450.

Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence.

Inhaled nitric oxide (NO) has been used in pediatric and adult perioperative cardiac intensive care for over three decades. NO is a cellular signaling molecule that induces smooth muscle relaxation in the mammalian vasculature. Inhaled NO has the unique ability to exert its vasodilatory effects in the pulmonary vasculature without any hypotensive side-effects in the systemic circulation. In patients undergoing cardiac surgery, NO has been reported in numerous studies to exert beneficial effects on acutely lowering pulmonary artery pressure and reversing right ventricular dysfunction and/or failure. Yet, various investigations failed to demonstrate significant differences in long-term clinical outcomes. The authors, serving as an advisory board of international experts in the field of inhaled NO within pediatric and adult cardiac surgery, will discuss how the existing scientific evidence can be further improved. We will summarize the basic mechanisms underlying the clinical applications of inhaled NO and how this translates into the mandate for inhaled NO in cardiac surgery. We will move on to the popular use of inhaled NO and will talk about the evidence base of the use of this selective pulmonary vasodilator. This review will elucidate what kind of clinical and biological barriers and gaps in knowledge need to be solved and how this has impacted in the development of clinical trials. The authors will elaborate on how the optimization of inhaled NO therapy, the development of biomarkers to identify the target population and the definition of response can improve the design of future large clinical trials. We will explain why it is mandatory to gain an international consensus for the state of the art of NO therapy far beyond this expert advisory board by including the different major players in the field, such as the different medical societies and the pharma industry to improve our understanding of the real-life effects of inhaled NO in large scale observational studies. The design for future innovative randomized controlled trials on inhaled NO therapy in cardiac surgery, adequately powered and based on enhanced biological phenotyping, will be crucial to eventually provide scientific evidence of its clinical efficacy beyond its beneficial hemodynamic properties.

[BLITZ-AF Cancer study: an international observational research project on patients with atrial fibrillation and cancer]. / Studio BLITZ-AF Cancer: un progetto di ricerca osservazionale internazionale sui pazienti con fibrillazione atriale e cancro.

BACKGROUND: Cancer is an important condition associated with the development of atrial fibrillation (AF). The objectives of the BLITZ-AF Cancer study were to collect real-life information on the clinical profile and use of antithrombotic drugs in patients with AF and cancer to improve clinical management, as well as the evaluation of the association between different antithrombotic treatments (or their absence) and the main clinical events. METHODS: European multinational, multicenter, prospective, non-interventional study conducted in patients with AF (electrocardiographically confirmed) and cancer occurring within 3 years. The CHA2DS2-VASc and the HAS-BLED scores were calculated in all enrolled patients. RESULTS: From June 2019 to July 2021, 1514 patients were enrolled, 36.5% women, from 112 cardiology departments in 6 European countries (Italy, Belgium, the Netherlands, Spain, Portugal and Ireland). Italy enrolled 971 patients in 77 centers. Average age of patients was 74 ± 9 years, of which 20.9% affected by heart failure, 18.1% by ischemic heart disease, 9.8% by peripheral arterial disease and 38.5% by valvular diseases; 41.5% of patients had a CHA2DS2-VASc score ≥4. The most represented cancer sites were lung (14.9%), colorectal tract (14.1%), prostate (8.8%), or non-Hodgkin's lymphoma (8.1%). Before enrollment, 16.6% of patients were not taking antithrombotic therapy, while 22.7% were on therapy with antiplatelet agents and/or low molecular weight heparin. After enrollment these percentages decreased to 7.7% and 16.6%, respectively and, at the same time, the percentage of patients on direct oral anticoagulant (DOAC) therapy increased from 48.4% to 68.4%, also to the detriment of those on vitamin K antagonist therapy. CONCLUSIONS: The BLITZ-AF Cancer study, which enrolled patients diagnosed with AF and cancer, highlights that the use of DOACs by cardiologists in this clinical context has increased, even though the guidelines on AF do not give accurate indications about oral anticoagulant therapy in patients with cancer.

Remotely Triggered LAD Occlusion Using a Balloon Catheter in Spontaneously Breathing Mice.

Acute myocardial infarction (AMI) is a prevalent and high-mortality cardiovascular condition. Despite advancements in revascularization strategies for AMI, it frequently leads to myocardial ischemia-reperfusion injury (IRI), amplifying cardiac damage. Murine models serve as vital tools for investigating both acute injury and chronic myocardial remodeling in vivo. This study presents a unique closed-chest technique for remotely inducing myocardial IRI in mice, enabling the investigation of the very early phase of occlusion and reperfusion using in-vivo imaging such as MRI or PET. The protocol utilizes a remote occlusion method, allowing precise control over ischemia initiation after chest closure. It reduces surgical trauma, enables spontaneous breathing, and enhances experimental consistency. What sets this technique apart is its potential for simultaneous noninvasive imaging, including ultrasound and magnetic resonance imaging (MRI), during occlusion and reperfusion events. It offers a unique opportunity to analyze tissue responses in almost real-time, providing critical insights into processes during ischemia and reperfusion. Extensive systematic testing of this innovative approach was conducted, measuring cardiac necrosis markers for infarction, assessing the area at risk using contrast-enhanced MRI, and staining infarcts at the scar maturation stage. Through these investigations, emphasis was placed on the value of the proposed tool in advancing research approaches to myocardial ischemia-reperfusion injury and accelerating the development of targeted interventions. Preliminary findings demonstrating the feasibility of combining the proposed innovative experimental protocol with noninvasive imaging techniques are presented herein. These initial results highlight the benefit of utilizing the purpose-built animal cradle to remotely induce myocardial ischemia while simultaneously conducting MRI scans.

How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education.

Physician-oriented online education could be a pathway to improve care for patients with heart failure, however, it is difficult to measure the impact of such education. Self-efficacy is a potential outcome measure. In this article, we develop a methodology for analyzing an educational intervention for general practitioners (GPs) using self-efficacy as a concept. This study was partly conducted within the setting of an observational study, IMPACT-B, where we developed online education for GPs. We designed and refined a 24-item questionnaire using item analysis, and exploratory and confirmatory factor analysis. Ninety-one GPs completed the questionnaire before and after the online education. Follow-up data after 6 months was available for 13 GPs. Item analysis revealed a high degree of internal consistency (coefficient alpha 0.95) and validity. Each additional year of experience was associated with an average baseline self-efficacy score of 0.50 points (95% CI [0.21-0.80]), and each additional patient in HF follow-up with an average score of 2.0 points (95% CI [0.48-3.5]). Items that differentiated most between GPs with high and low self-efficacy were the treatment of congestion as well as titrating medication and MRA in heart failure with reduced ejection fraction. Factor analysis reduced the number of questions to 14, mapping to three factors (diagnosis, treatment, and follow-up), and improved the model fit as measured by the goodness-of-fit indicator comparative-fit-index (from 0.83 to 0.91). We demonstrated a method to assess the impact of online education on general practitioners. This led to a questionnaire that was reliable, valid, and convenient to use in an implementation context.

OSTEO18, a novel urinary proteomic signature, associated with osteoporosis in heart transplant recipients.

Background: Immunosuppressive treatment in heart transplant (HTx) recipient causes osteoporosis. The urinary proteomic profile (UPP) includes peptide fragments derived from the bone extracellular matrix. Study aims were to develop and validate a multidimensional UPP biomarker for osteoporosis in HTx patients from single sequenced urinary peptides identifying the parent proteins. Methods: A single-center HTx cohort was analyzed. Urine samples were measured by capillary electrophoresis coupled with mass spectrometry. Cases with osteoporosis and matching controls were randomly selected from all available 389 patients. In derivation case-control dataset, 1576 sequenced peptides detectable in ≥30 % of patients. Applying statistical analysis on these, an 18-peptide multidimensional osteoporosis UPP biomarker (OSTEO18) was generated by support vector modeling. The 2 replication datasets included 118 and 94 patients. For further validation, the whole cohort was analyzed. Statistical methods included logistic regression and receiver operating characteristic curve (ROC) analysis. Results: In derivation dataset, the AUC, sensitivity and specificity of OSTEO18 were 0.83 (95 % CI: 0.76-0.90), 74.3 % and 87.1 %, respectively. In replication datasets, results were confirmatory. In the whole cohort (154 osteoporotic patients [39.6 %]), the ORs for osteoporosis increased (p < 0.0001) across OSTEO18 quartiles from 0.39 (95 % CI: 0.25-0.61) to 3.14 (2.08-4.75). With full adjustment for known osteoporosis risk factors, OSTEO18 improved AUC from 0.708 to 0.786 (p = 0.0003) for OSTEO18 categorized (optimized threshold: 0.095) and to 0.784 (p = 0.0004) for OSTEO18 as continuously distributed classifier. Conclusion: OSTEO18 is a clinically meaningful novel biomarker indicative of osteoporosis in HTx recipients and is being certified as in-vitro diagnostic.

Sodium loading in ambulatory patients with heart failure with reduced ejection fraction: Mechanistic insights into sodium handling.

AIMS: Sodium restriction was not associated with improved outcomes in heart failure patients in recent trials. The skin might act as a sodium buffer, potentially explaining tolerance to fluctuations in sodium intake without volume overload, but this is insufficiently understood. Therefore, we studied the handling of an increased sodium load in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Twenty-one ambulatory, stable HFrEF patients and 10 healthy controls underwent a 2-week run-in phase, followed by a 4-week period of daily 1.2 g (51 mmol) sodium intake increment. Clinical, echocardiographic, 24-h urine collection, and bioelectrical impedance data were collected every 2 weeks. Blood volume, skin sodium content, and skin glycosaminoglycan content were assessed before and after sodium loading. Sodium loading did not significantly affect weight, blood pressure, congestion score, N-terminal pro-brain natriuretic peptide, echocardiographic indices of congestion, or total body water in HFrEF (all p > 0.09). There was no change in total blood volume (4748 ml vs. 4885 ml; p = 0.327). Natriuresis increased from 150 mmol/24 h to 173 mmol/24 h (p = 0.024), while plasma renin decreased from 286 to 88 µU/L (p = 0.002). There were no significant changes in skin sodium content, total glycosaminoglycan content, or sulfated glycosaminoglycan content (all p > 0.265). Healthy controls had no change in volume status, but a higher increase in natriuresis without any change in renin. CONCLUSIONS: Selected HFrEF patients can tolerate sodium loading, with increased renal sodium excretion and decreased neurohormonal activation.

Artificial intelligence electrocardiogram as a novel screening tool to detect a newly abnormal left ventricular ejection fraction after anthracycline-based cancer therapy.

AIMS: Cardiotoxicity is a serious side effect of anthracycline treatment, most commonly manifesting as a reduction in left ventricular ejection fraction (EF). Early recognition and treatment have been advocated, but robust, convenient, and cost-effective alternatives to cardiac imaging are missing. Recent developments in artificial intelligence (AI) techniques applied to electrocardiograms (ECGs) may fill this gap, but no study so far has demonstrated its merit for the detection of an abnormal EF after anthracycline therapy. METHODS AND RESULTS: Single centre consecutive cohort study of all breast cancer patients with ECG and transthoracic echocardiography (TTE) evaluation before and after (neo)adjuvant anthracycline chemotherapy. Patients with HER2-directed therapy, metastatic disease, second primary malignancy, or pre-existing cardiovascular disease were excluded from the analyses as were patients with EF decline for reasons other than anthracycline-induced cardiotoxicity. Primary readout was the diagnostic performance of AI-ECG by area under the curve (AUC) for EFs < 50%. Of 989 consecutive female breast cancer patients, 22 developed a decline in EF attributed to anthracycline therapy over a follow-up time of 9.8 ± 4.2 years. After exclusion of patients who did not have ECGs within 90 days of a TTE, 20 cases and 683 controls remained. The AI-ECG model detected an EF < 50% and ≤ 35% after anthracycline therapy with an AUC of 0.93 and 0.94, respectively. CONCLUSION: These data support the use of AI-ECG for cardiotoxicity screening after anthracycline-based chemotherapy. This technology could serve as a gatekeeper to more costly cardiac imaging and could enable patients to monitor themselves over long periods of time.

Artificial intelligence electrocardiogram can be used to screen for an abnormal heart function after anthracycline chemotherapy, opening the door to new ways of cost-effective screening of cancer survivors at risk of cardiotoxicity over long periods of time.

Pheochromocytoma leading to Takotsubo and Ogilvie syndrome, a pathophysiological triad.

Takotsubo syndrome (TTS) is a transient left ventricle dysfunction usually caused by a stressful trigger (emotional or physical). We report the case of a 77 year-old female patient who presented with TTS caused by a pheochromocytoma, a catecholamine-producing neuroendocrine tumour. Diagnosis was facilitated by acute kidney injury prompting renal ultrasound, recurrence of TTS and symptoms of episodic palpitations, profuse sweating and labile blood pressure. Furthermore, during her hospitalisation the patient also developed an Ogilvie syndrome, an acute colonic pseudo-obstruction, due to the catecholamine-excess. Treatment consisted of betablocker and angiotensin-converting enzyme inhibitor for TTS, neostigmine for Ogilvie syndrome, in combination with alpha-blocker and surgical removal of the tumour after recuperation of left ventricular function and colonic pseudo-obstruction. To our knowledge, this is the first case report of the pathophysiological triad of pheochromocytoma leading to Takotsubo and Ogilvie syndrome in a single patient.

Heparin dosing in patients with Impella-supported cardiogenic shock.

BACKGROUND: Impella™ is increasingly used in cardiogenic shock. However, thromboembolic and bleeding events are frequent during percutaneous mechanical circulatory support (pMCS). OBJECTIVE: Therefore, we aimed to explore the optimal anticoagulation regime for pMCS to prevent thromboembolism and bleedings. METHODS: This hypothesis-generating multi-center cohort study investigated 170 patients with left-Impella™ support. We (A) compared bleeding/thrombotic events in two centers with therapeutic range (TR-aPTT) activated partial thromboplastin time (60-80s) and (B) compared events of these centers with one center with intermediate range aPTT (40-60s). RESULTS: After matching, there were no differences in patients' characteristics. In centers aiming at TR-aPTT, major bleeding was numerically lower with aPTT <60s within 48 h of left-Impella™ support, versus patients that achieved the aimed aPTT of ≥60s [aPTT ≥60s: 22 (37.3%) vs. aPTT<60s 14 (23.7%); Hazard ratio [HR], 0.62 (95%) CI, 0.28-1.38; p = 0.234]. Major cardiovascular and cerebrovascular adverse events (MACCE) did not differ between groups. In comparison of centers, TR-aPTT strategy showed higher major bleeding rates [TR: 8 (47.1%) vs. intermediate range: 1 (5.9%); HR, 0.06 (95%) CI, 0.01-0.45; p = 0.006]. MACCE were lower in the intermediate range aPTT group as well [TR 12 (70.6%) vs. intermediate range 5 (29.4%) HR, 0.32 (95%) CI, 0.11-0.92; p = 0.034]. CONCLUSION: This pilot analysis showed that lowering UFH-targets in left-Impella™ supported CS patients seems to be a safe and promising strategy for reducing major bleedings without increasing MACCE. This needs to be validated in larger, randomized clinical trials.

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).

Effect of 24-h blood pressure dysregulations and reduced ocular perfusion pressure in open-angle glaucoma progression.

BACKGROUND: Low ocular perfusion pressure (OPP), which depends on the mean arterial pressure (MAP) and intraocular pressure (IOP), is associated with glaucoma. We studied 24-h MAP dysregulations and OPP in relation to the progression of glaucoma damage. METHODS: We retrospectively analyzed 155 normal-tension glaucoma (NTG) and 110 primary open-angle glaucoma (POAG) patients aged 18 years old followed at the University Hospital Leuven with repeated visual field tests ( n  = 7000 measures, including both eyes) who underwent 24-h ambulatory blood pressure monitoring. Twenty-four-hour MAP dysregulations were variability independent of the mean (VIM), and the five lowest dips in MAP readings over 24 h. OPP was the difference between 2/3 of the MAP and IOP. Glaucoma progression was the deterioration of the visual field, expressed as decibel (dB) changes in mean deviation analyzed by applying multivariable linear mixed regression models. RESULTS: The mean age was 68 years (53% were women). High 24-h VIMmap was associated with glaucoma progression in POAG ( P  < 0.001) independently of the 24-h MAP level. The estimated changes in mean deviation in relation to dip MAP measures ranged from -2.84 dB [95% confidence interval (CI) -4.12 to -1.57] to -2.16 dB (95% CI -3.46 to -0.85) in POAG. Reduced OPP along with high variability and dips in MAP resulted in worse mean deviation deterioration. CONCLUSION: The progression of glaucoma damage associates with repetitive and extreme dips in MAP caused by high variability in MAP throughout 24 h. This progression exacerbates if 24-h MAP dysregulations occur along with reduced OPP.

Management of Bleeding and Hemolysis During Percutaneous Microaxial Flow Pump Support: A Practical Approach.

Percutaneous ventricular assist devices (pVADs) are increasingly being used because of improved experience and availability. The Impella (Abiomed), a percutaneous microaxial, continuous-flow, short-term ventricular assist device, requires meticulous postimplantation management to avoid the 2 most frequent complications, namely, bleeding and hemolysis. A standardized approach to the prevention, detection, and treatment of these complications is mandatory to improve outcomes. The risk for hemolysis is mostly influenced by pump instability, resulting from patient- or device-related factors. Upfront echocardiographic assessment, frequent monitoring, and prompt intervention are essential. The precarious hemostatic balance during pVAD support results from the combination of a procoagulant state, due to critical illness and contact pathway activation, together with a variety of factors aggravating bleeding risk. Preventive strategies and appropriate management, adapted to the impact of the bleeding, are crucial. This review offers a guide to physicians to tackle these device-related complications in this critically ill pVAD-supported patient population.