The prognostic role of advanced hemodynamic variables in patients with left ventricular assist devices.

BACKGROUND: Invasive hemodynamic variables obtained from right heart catheterization have been used for risk-stratifying patients with advanced heart failure (HF). However, there is a paucity of data on the prognostic value of invasive hemodynamic variables in patients with left ventricular assist devices (LVAD). We hypothesized that cardiac power output (CPO), cardiac power efficiency (CPE), and left ventricular stroke work index (LVSWI) can serve as prognostic markers in patients with LVADs. METHODS: Baseline hemodynamic data from patients who had LVAD ramp studies at our institution from 4/2014 to 7/2018 were prospectively collected, from which advanced hemodynamic variables (CPO, CPE, and LVSWI) were retrospectively analyzed. Univariate and multivariable analyses were performed for hemocompatibility-related adverse events (HRAE), HF admissions, and mortality. RESULTS: Ninety-one participants (age 61 ± 11 years, 34% women, 40% Black or African American, and 38% ischemic cardiomyopathy) were analyzed. Low CPE was significantly associated with mortality (HR 2.42, 95% CI 1.02-5.74, p = 0.045) in univariate analysis and Kaplan-Meier analysis (p = 0.04). Low LVSWI was significantly associated with mortality (HR 2.13, 95% CI 1.09-4.17, p = 0.03) in univariate analysis and Kaplan-Meier analysis (p = 0.02). CPO was not associated with mortality. CPO, CPE, and LVSWI were not associated with HRAE or HF admissions. CONCLUSIONS: Advanced hemodynamic variables can serve as prognostic indicators for patients with LVADs. Low CPE and LVSWI are prognostic for higher mortality, but no variables were associated with HF admissions or HRAEs.

Structural insights into inhibition of lipid I production in bacterial cell wall synthesis.

Antibiotic-resistant bacterial infection is a serious threat to public health. Peptidoglycan biosynthesis is a well-established target for antibiotic development. MraY (phospho-MurNAc-pentapeptide translocase) catalyses the first and an essential membrane step of peptidoglycan biosynthesis. It is considered a very promising target for the development of new antibiotics, as many naturally occurring nucleoside inhibitors with antibacterial activity target this enzyme. However, antibiotics targeting MraY have not been developed for clinical use, mainly owing to a lack of structural insight into inhibition of this enzyme. Here we present the crystal structure of MraY from Aquifex aeolicus (MraYAA) in complex with its naturally occurring inhibitor, muraymycin D2 (MD2). We show that after binding MD2, MraYAA undergoes remarkably large conformational rearrangements near the active site, which lead to the formation of a nucleoside-binding pocket and a peptide-binding site. MD2 binds the nucleoside-binding pocket like a two-pronged plug inserting into a socket. Further interactions it makes in the adjacent peptide-binding site anchor MD2 to and enhance its affinity for MraYAA. Surprisingly, MD2 does not interact with three acidic residues or the Mg(2+) cofactor required for catalysis, suggesting that MD2 binds to MraYAA in a manner that overlaps with, but is distinct from, its natural substrate, UDP-MurNAc-pentapeptide. We have determined the principles of MD2 binding to MraYAA, including how it avoids the need for pyrophosphate and sugar moieties, which are essential features for substrate binding. The conformational plasticity of MraY could be the reason that it is the target of many structurally distinct inhibitors. These findings can inform the design of new inhibitors targeting MraY as well as its paralogues, WecA and TarO.

Postoperative tolvaptan use in left ventricular assist device patients: The TOLVAD randomized pilot study.

PURPOSE: Tolvaptan, a selective vasopressin type-2 antagonist, has been shown to increase serum sodium (Na) and urine output in hyponatremic left ventricular assist device (LVAD) patients in retrospective studies. In this prospective randomized pilot study, we aimed to assess the efficacy of tolvaptan in this population. METHODS: We conducted a prospective, randomized, non-blinded pilot study of LVAD recipients with post-operative hyponatremia (Na < 135 mEq/L) (NCT05408104). Eligible participants were randomized to receive tolvaptan 15 mg daily in addition to usual care versus usual care alone. The primary outcome was a change in Na level and estimated glomerular filtration rate (eGFR), from the first post-operative day of hyponatremia (the day of randomization) to discharge. RESULTS: A total of 33 participants were enrolled, and 28 underwent randomization (median age 55 [IQR 50-62]), 21% women, 54% Black, 32% ischemic cardiomyopathy, median baseline Na 135 (IQR 134-138). Fifteen participants were randomized to tolvaptan (TLV) and 13 were randomized to usual care alone (No-TLV). Mean change in Na from randomization to discharge in the TLV group was 2.7 mEq/L (95%CI 0.7-4.7, p = 0.013) and 1.8 (95%CI 0.5-4.0, p = 0.11) in the No-TLV group, though baseline and final Na levels were similar between groups. The mean change in eGFR was 2.6 ml/min/1.73 m2 (95%CI 10.1-15.3, p = 0.59) in TLV versus 7.5 ml/min/1.73 m2 (95%CI 5.2-20.2, p = 0.15) in No-TLV. TLV participants had significantly more urine output than No-TLV patients during their first 24 h after randomization (3294 vs 2155 ml, p = 0.043). CONCLUSION: TLV significantly increases urine output, with nominal improvement in Na level, in hyponatremic post-operative LVAD patients without adversely impacting renal function.

Aortic Pulsatility Index: A Novel Hemodynamic Variable for Evaluation of Decompensated Heart Failure.

BACKGROUND: Right heart catheterization for invasive hemodynamics has shown only modest correlation with clinical outcomes. We designed a novel hemodynamic variable that incorporates ventricular output and filling pressure. We anticipated that the aortic pulsatility index (API) would correlate with clinical outcomes in patients with heart failure. METHODS AND RESULTS: We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (February 2013 to November 2019). The API was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure. The primary outcome was freedom from advanced therapies, defined as the need for inotropes, temporary mechanical circulatory support, a left ventricular assist device, or orthotopic heart transplantation, or death at 30 days. A total of 224 patient encounters, age 57 years (48-66 years; 34% women; 31% ischemic cardiomyopathy) were included. In univariable analysis, lower baseline API was significantly associated with progression to advanced therapies or death at 30-days (odds ratio 0.43, 95% confidence interval 0.30-0.61; P < .001) compared with those on continued medical management. Receiver operator characteristic analysis specified an optimal cutpoint of 1.45 for API. A Kaplan-Meier analysis indicated an association of API with the primary outcome (79% for API ≥ 1.45 vs 48% for API < 1.45). In multivariable analysis, higher API was strongly associated with freedom from advanced therapies or death (odds ratio 0.38, 95% confidence interval 0.22-0.65, P ≤ .001), even when adjusted for baseline characteristics and routine right heart catheterization measurements. CONCLUSIONS: The API is a novel invasive hemodynamic measurement that is associated independently with freedom from advanced therapies or death at 30-day follow-up.

Early experience of COVID-19 in 2 heart transplant recipients: Case reports and review of treatment options.

The coronavirus disease 2019 (COVID-19) pandemic poses special challenges to immunocompromised transplant patients. Given the paucity of proven data in treating COVID-19, management of these patients is difficult, rapidly evolving, and mainly based on anecdotal experience. We report 2 cases of heart transplant (HT) recipients with COVID-19. The first is a 59-year-old female with HT in 2012 who presented on March 20, 2020 with fever, hypoxia, and ground-glass opacities on chest X-ray. She quickly progressed to acute hypoxic respiratory failure and vasoplegic shock. Despite reduction in immunosuppression and treatment with tocilizumab, intravenous immunoglobulin, hydroxychloroquine, lopinavir/ritonavir, and broad-spectrum antibiotics, she ultimately died from multiorgan failure. The second case is a 75-year-old man with HT in 2000 who presented on April 2, 2020 after curbside testing revealed positive COVID-19. Given a milder presentation compared to the first patient, antimetabolite was discontinued and only hydroxychloroquine was started. Because of a lack of clinical improvement several days later, tocilizumab, methylprednisolone, and therapeutic anticoagulation were initiated. The patient clinically improved with decreasing oxygen requirements and was discharged home. These 2 cases highlight the wide range of different presentations of COVID-19 in HT recipients and the rapidity with which the management of these patients is evolving.

Discordance Between Clinical Assessment and Invasive Hemodynamics in Patients With Advanced Heart Failure.

BACKGROUND: Historically, invasive hemodynamic guidance was not superior compared to clinical assessment in patients admitted with acute decompensated heart failure (ADHF). This study assessed the accuracy of clinical assessment vs invasive hemodynamics in patients with ADHF. METHODS AND RESULTS: We conducted a prospective cohort study of patients admitted with ADHF. Prior to right-heart catheterization (RHC), physicians categorically predicted right atrial pressure, pulmonary capillary wedge pressure, cardiac index and hemodynamic profile (wet/dry, warm/cold) based on physical examination and clinical data evaluation (warm = cardiac index > 2.2 L/min/m2; wet = pulmonary capillary wedge pressure > 18 mmHg). We collected 218 surveys (of 83 cardiology fellows, 55 attending cardiologists, 45 residents, 35 interns) evaluating 97 patients. Of those patients, 46% were receiving inotropes prior to RHC. The positive and negative predictive values of clinical assessment compared to RHC for the cold and wet subgroups were 74.7% and 50.4%. The accuracy of categorical prediction was 43.6% for right atrial pressure, 34.4% for pulmonary capillary wedge pressure and 49.1% for cardiac index, and accuracy did not differ by clinician (P > 0.05 for all). Interprovider agreement was 44.4%. Therapeutic changes following RHC occurred in 71.1% overall (P < 0.001). CONCLUSIONS: Clinical assessment of patients with advanced heart failure presenting with ADHF has low accuracy across all training levels, with exaggerated rates of misrecognition of the most high-risk patients.

Heart transplantation in patients with localized prostate cancer-Are we denying a life-saving therapy due to an indolent tumor?

BACKGROUND: Prostate cancer (PC) is the most common non-cutaneous cancer in men. Approximately 90% of these cancers are localized (LPC) with a cancer-specific survival rate of 99% at 10 years. Some heart transplant centers (HTCs) regard PC as an absolute contraindication to heart transplantation (HT). This study aims to understand the current status of HT in patients with advanced heart failure (AHF) and concurrent LPC in the United States. METHODS: Adult HTCs in the United States were asked to fill out an email questionnaire addressing their current approach to HT in AHF patients with concurrent LPC. RESULTS: Fifty of the 90 HTCs that received the questionnaire responded. Only 16% of HTCs had a formal policy regarding HT in patients with LPC, while only 10% had patients with LPC on the HT waitlist at the time of the survey. Overall, 84% of the HTCs had never performed HT in a patient with LPC in the history of their transplant program. CONCLUSION: An overwhelming majority of HTCs in the United States do not consider HT an option for AHF patients with concurrent LPC and lack a formal policy regarding the same.

Hemodynamics of concomitant tricuspid valve procedures at LVAD implantation.

BACKGROUND: Tricuspid regurgitation (TR) is common in patients receiving left ventricular assist device (LVAD) implantation. The current literature is conflicting regarding the effects of concomitant tricuspid valve repair (TVR) at LVAD implantation. We investigated the hemodynamic effects of concomitant TVR at LVAD implantation. METHODS: Consecutive clinically stable LVAD outpatients who underwent hemodynamic ramp testings were enrolled in this study, and they were stratified by concomitant TVR. Results of hemodynamic ramp tests were compared between the TVR group and the non-TVR group. RESULTS: Among 65 LVAD patients undergoing ramp tests, 34 patients had received TVR, and 31 had not. There were no significant differences in baseline characteristics between two groups except for higher degree of TR and lower pulmonary artery pulsatility index in the TVR group (P < .05 for both). Following LVAD implantation, the degree of TR improved significantly in the TVR group down to the comparable level with the non-TVR group. During ramp tests, the TVR group had steeper cardiac index slope (0.14 ± 0.12 vs 0.07 ± 0.07 L/min/m2 /step, P = .002) and higher cardiac index at set LVAD speed (2.99 ± 0.84 vs 2.52 ± 0.42 L/min/m2 , P = .007). CONCLUSIONS: Concomitant TVR improves cardiac output and its response to LVAD speed change following LVAD implantation. Longitudinal clinical implications of such hemodynamic changes are unknown.

Long-Acting Octreotide Reduces the Recurrence of Gastrointestinal Bleeding in Patients With a Continuous-Flow Left Ventricular Assist Device.

BACKGROUND: Recurrent gastrointestinal bleeding is one of the most significant adverse events in patients with left ventricular assist devices (LVADs). METHODS: We enrolled LVAD patients who had received an intramuscular injection of 20 mg octreotide every 4 weeks as secondary prevention for recurrent gastrointestinal bleeding despite conventional medical therapies and repeated transfusions. The frequency of gastrointestinal bleeding and other associated clinical outcomes before and during octreotide therapy were compared. RESULTS: Thirty LVAD patients (66.4 ± 8.8 years old, 16 men [53%]) received octreotide therapy for 498.8 ± 356.0 days without any octreotide-associated adverse events. The frequency of gastrointestinal bleeding was decreased significantly during octreotide therapy (from 3.4 ± 3.1 to 0.7 ± 1.3 events/year; P < .001), accompanied by significant reductions in red blood cell and flesh frozen plasma transfusions, days in hospital, and need for endoscopic procedures (P < .05 for all). CONCLUSIONS: Octreotide therapy reduced the frequency of recurrent gastrointestinal bleeding and may be considered for secondary prevention.

Cannula and Pump Positions Are Associated With Left Ventricular Unloading and Clinical Outcome in Patients With HeartWare Left Ventricular Assist Device.

BACKGROUND: Cannula and pump positions are associated with clinical outcomes such as device thrombosis in patients with HeartMate II; however, clinical implications of HVAD (HeartWare International, Framingham, Massachusetts) cannula position are unknown. This study aims to assess the relationship among cannula position, left ventricular (LV) unloading, and patient prognosis. METHODS AND RESULTS: Twenty-seven HVAD patients (60.0 ± 12.6 years of age and 19 males [70%]) underwent ramp test. Device position was quantified from chest X-ray parameters obtained at the time of the hemodyamic ramp test: (1) cannula coronal angle, (2) pump depth, (3) cannula sagittal angle, and (4) pump area. Lower cannula coronal angle was associated with LV unloading (as measured by smaller LV diastolic dimension and lower pulmonary capillary wedge pressure). Smaller pump area was associated with LV dynamic unloading, as assessed by steeper negative slopes of LV diastolic dimension and pulmonary capillary wedge pressure during incremental rotational speed change. Cannula coronal angle ≤65° was associated with reduced heart failure readmission rate (hazard ratio, 10.33; P = .007 by log-rank test). CONCLUSION: HVAD cannula and pump positions are associated with LV unloading and improved clinical outcomes. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on clinical outcomes are warranted.

Decoupling Between Diastolic Pulmonary Arterial Pressure and Pulmonary Arterial Wedge Pressure at Incremental Left Ventricular Assist Device (LVAD) Speeds Is Associated With Worse Prognosis After LVAD Implantation.

BACKGROUND: Decoupling between diastolic pulmonary arterial pressure (dPAP) and pulmonary arterial wedge pressure (PAWP) is an index of pulmonary vasculature remodeling and provides prognostic information. Furthermore, decoupling may change during incremental left ventricular assist device (LVAD) speed changes. METHODS AND RESULTS: In this prospective study, patients underwent an echocardiographic and hemodynamic ramp test after LVAD implantation and were followed for 1 year. The change in decoupling (dPAP - PAWP) between the lowest and highest LVAD speeds during the ramp test was calculated. Survival and heart failure admission rates were assessed by means of Kaplan-Meier analysis. Eighty-seven patients were enrolled in the study: 54 had a Heartmate II LVAD (60.8 ± 9.3 years of age and 34 male) and 33 had an HVAD LVAD (58.6 ± 13.2 years of age and 20 male). Patients who experienced greater changes in decoupling (Δdecoupling >3 mm Hg) had a persistently elevated dPAP at incremental LVAD speed and had worse 1-year heart failure readmission-free survival compared with the group without significant changes in the degree of decoupling (41% vs 75%; P = .001). CONCLUSIONS: An increase in decoupling between dPAP and PAWP at incremental LVAD speed changes was associated with worse prognosis in LVAD patients.

New-Onset Neurosarcoidosis Following Heart Transplant for Cardiac Sarcoidosis.

A 63-year-old woman who underwent heart transplantation for cardiac sarcoidosis developed new headache and vision changes. Extensive workup resulted in a diagnosis of neurosarcoidosis treated with pulse dose steroids and infliximab. Recurrence of sarcoidosis after transplantation for isolated cardiac sarcoidosis occurs, but optimal surveillance methods remain unknown.

The Seattle Heart Failure Model in Kidney Transplant Recipients.

Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function. We applied the SHFM to patients with end-stage renal disease (ESRD) who were being evaluated for kidney transplantation to determine if the model was associated with post-transplant mortality. This retrospective single-center study analyzed survival among 360 adult deceased-donor kidney transplant recipients. Cox regression was used to model post-transplant patient survival. Our findings indicated that a 1.0-point increase in the adapted SHFM score was significantly associated with post-transplant mortality (HR 1.76, 95% CI = 1.10-2.83, p = 0.02), independently of the Kidney Donor Profile Index and Estimated Post-Transplant Survival. Individual covariates of the SHFM were evaluated in univariate analyses, and age, sodium, cholesterol, and lymphocyte count were significantly related to mortality. This study provides preliminary evidence that an adapted SHFM score could be a useful tool in evaluating mortality risk post-transplant in patients with ESRD.

The feasibility of endovascular aortic repair strategy in treating infected aortic aneurysms.

BACKGROUND: Open surgical treatment for an infected aortic aneurysm has a high rate of surgical morbidity and mortality and does not guarantee eradication of the infected nidus. The use of endovascular aortic repair (EVAR) might simplify the procedure and provide a good alternative for this critical condition, but this remains to be proved. This study assessed the efficacy and outcome of EVAR with an adjunctive antibiotic treatment strategy. METHODS: We focused on the experiences and results of the management of infected aortic aneurysms with positive blood cultures. We drew the blood for culture study, immediately prescribed broad-spectrum antibiotics, performed EVAR procedures, and followed this with sensitive antibiotics and adjunctive procedures. RESULTS: Twelve consecutive patients (mean age, 70 years) were included in this EVAR strategy. Three patients had thoracic, two thoracoabdominal, and the remaining seven had infected abdominal aneurysms. Ten Salmonella, one Staphylococcus, and one Streptococcus spp were identified. There was no hospital death. Three patients underwent computed tomography (CT)-guided drainage, and one underwent open laparotomy debridement. Mean follow-up was 24 months. One late death occurred but was unrelated to reinfection. All patients seemed well, with no evidence of EVAR graft infection at a mean follow-up of 23.6 months. CONCLUSIONS: This small multi-institutional study summarizing the experiences of patients with an infected aortic aneurysm managed by EVAR and an aggressive antibiotic strategy revealed that this EVAR strategy might be a suitable approach to treating this disease. These favorable results may be typical for Salmonella infection, which was present in most of the patients. Further experience is needed to assess whether this therapeutic strategy works equally well in aneurysm infection caused by other organisms.

Extensive pulmonary venous stenoses as a complication of radiofrequency catheter ablation for atrial fibrillation.

Although pulmonary veins stenosis (PVS) is a well documented complication of radiofrequency-catheter ablation (RFCA) of atrial fibrillation (AF), simultaneous involvement of multiple PVs is extremely rare. We present the case of a 69 years-old male patient, with prior medical history of persistent AF, who had been treated with RFCA two years ago. After RFCA, he started with shortness of breath and needed hospitalization for bilateral pneumonia. One year after the procedure, he was on home oxygen, but still referred dyspnea, cough and hemoptysis. A transthoracic echocardiogram showed moderate right ventricular (RV) systolic dysfunction and elevated RV systolic pressure. Dedicated cardiac tomography for PV assessment revealed severe narrowing and pre-stenotic engorgement of all 5 PVs, with subtotal ostial occlusion of both the left lower and right middle PVs. PV angiography confirmed the diagnosis. Only the left and right upper PV were able to be wire-crossed and stented, with substantial reductions in stenosis from 90 % to 10 %. After 3 months of follow-up, the patient improved substantially, and home O2 was withdrawn.

Discordance between lactic acidemia and hemodynamics in patients with advanced heart failure.

BACKGROUND: Elevated lactic acid (LA) levels carry a poor prognosis in patients with shock. Data are lacking on the significance of LA levels in patients with acute decompensated heart failure (ADHF). HYPOTHESIS: This study assessed the relationship between LA levels, hemodynamics and clinical outcomes. METHODS: This was a retrospective analysis of registry data of 100 advanced heart failure patients presenting for right heart catheterization (RHC) for concern of ADHF. LA levels (normal ≤2.1 mmol/L) were obtained prior to RHC; no significant changes in therapy were made between LA collection and RHC. RESULTS: Median age was 58 (47.3, 64.8) years; 57% were receiving inotropes prior to RHC. Median pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were 28 (21, 35) mmHg and 2.0 (1.7, 2.5) L/min/m2 , respectively. Eighty patients had normal LA prior to RHC. There was no correlation between LA levels and PCWP (R = 0.09, p = .38); 63% of the normal LA group had a PCWP >24 mmHg. There was a moderate inverse correlation between LA and CI (R = - 0.40; p < .001); 58% of the normal LA group had a CI <2.2 L/min/m2 . Thirty-day survival free of death/hospice, inotrope dependence, progression to heart transplant/left-ventricular assist device implant was comparable between the normal and elevated LA groups (28% vs. 20%; p = .17). CONCLUSION: In patients presenting with ADHF, normal LA levels do not exclude the presence of depressed CI (a hemodynamic criteria for cardiogenic shock) and may not offer accurate risk stratification. Invasive hemodynamics should not be delayed based on normal LA levels alone.

Biventricular Pacing Versus Right Ventricular Pacing in Patients Supported With LVAD.

OBJECTIVES: This study sought to evaluate the effects of right ventricular (RV) pacing versus biventricular (BiV) pacing on quality of life, functional status, and arrhythmias in LVAD patients. BACKGROUND: Cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVADs) independently improve outcomes in heart failure patients, but the effects of combining these therapies remains unknown. We present the first prospective randomized study evaluating the effects of RV versus BiV pacing on quality of life, functional status, and arrhythmias in LVAD patients. METHODS: In this prospective randomized crossover study, LVAD patients with prior CRT devices were alternated on RV and BiV pacing for planned 7-14-day periods. Ambulatory step count, 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire scores, arrhythmia burden, CRT lead function, and echocardiographic data were collected with each pacing mode. RESULTS: Thirty patients were enrolled, with a median age of 65 years, 67% male, and mean duration of LVAD support of 309 days. Compared with BiV pacing, RV-only pacing resulted in 29% higher mean daily step count, 11% higher 6-minute walk test distance, and 7% improved KCCQ-12 score (all p < 0.03). LV end-diastolic volume was significantly lower with RV pacing (220 vs. 250 mL; p = 0.03). Fewer patients had ventricular tachyarrhythmia episodes during RV pacing (p = 0.03). RV lead impedance was lower with RV pacing (p = 0.047), but no significant differences were observed in impedance across other CRT leads. CONCLUSIONS: In the first prospective randomized study comparing variable pacing in LVAD patients, RV pacing was associated with significantly improved functional status, quality of life, fewer ventricular tachyarrhythmias, and stable lead impedance compared with BiV pacing. This study supports turning off LV lead pacing in LVAD patients with CRT.

Aortic pulsatility index predicts clinical outcomes in heart failure: a sub-analysis of the ESCAPE trial.

AIMS: Aortic pulsatility index (API), calculated as (systolic-diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel haemodynamic measurement representing both cardiac filling pressures and contractility. We hypothesized that API would better predict clinical outcomes than traditional haemodynamic metrics of cardiac function. METHODS AND RESULTS: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual-level data were used. Routine haemodynamic measurements, including Fick cardiac index (CI), and the advanced haemodynamic metrics of API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated after final haemodynamic-monitored optimization. The primary outcome was a composite endpoint of death or need for orthotopic heart transplant (OHT) or left ventricular assist device (LVAD) at 6 months. A total of 433 participants were enrolled in the ESCAPE trial of which 145 had final haemodynamic data. Final API measurements predicted the primary outcome, OR 0.47 (95% CI 0.32-0.70, P < 0.001), while CI, CPO, and PAPI did not. Receiver operator characteristic analyses of final advanced haemodynamic measurements indicated API best predicted the primary outcome with a cutoff of 2.9 (sensitivity 76.2%, specificity 55.3%, correctly classified 61.4%, area-under-the-curve 0.71), compared with CPO, CI, and PAPI. Kaplan-Meier analyses indicated API ≥ 2.9 was associated with greater freedom from the primary outcome (83.5%), compared with API < 2.9 (58.4%), P = 0.001. While PAPI was also significantly associated, CI and CPO were not. CONCLUSIONS: The novel haemodynamic measurement API better predicted clinical outcomes in the ESCAPE trial when compared with traditional invasive haemodynamic metrics of cardiac function.

Increased expression of glucose transporter 3 in gerbil brains following magnesium sulfate treatment and focal cerebral ischemic injury.

Glucose is the primary energy substrate for neurons. Glucose transporter 3 (Glut3) localizes at the neuronal cellular membrane, which transports glucose from the extracelluar space into neurons. Ischemia results in an increased energy demand that is associated with profound changes in brain energy metabolism. Magnesium sulfate (MgSO(4)) ameliorates ischemia-induced neuronal death in the rat and gerbil model. We investigated the effects of MgSO(4) administration on the expression of Glut3 in cortex and hippocampus of gerbils during ischemia. The focal cerebral ischemia was produced by unilateral occlusion of the right common carotid artery and right middle cerebral artery. Following ischemia, Glut3 expression increased significantly versus non-ischemic (contra-lateral) cortex and hippocampus. MgSO(4) treatment significantly increased the level of Glut3 expression in the non-ischemic and ischemic cortex and hippocampus. We found that the MgSO(4)-induced increase in Glut3 expression was not reversed by administration of U0126, a MEK kinase inhibitor. These results suggest that other factors may function to modulate the MgSO(4)-induced Glut3 response. In all, our data showed that MgSO(4) increases the expression of Glut3 in the cortex and hippocampus of gerbil brains both in non-ischemia and ischemia status. However, the MEK signaling pathway might not be involved in MgSO(4)-induced Glut3 expression following focal ischemia.