Guideline-based and restricted fluid resuscitation strategy in sepsis patients with heart failure: A systematic review and meta-analysis.

OBJECTIVES: To examine whether a fluid resuscitation strategy based on guidelines (at least 30 mL/kg IV crystalloids) vs. a restrictive approach with <30 mL/kg within three hours affects in-hospital mortality in patients with sepsis and a history of heart failure (HF). DATA SOURCES: On 03/07/2023, we searched Embase, PubMed, and Scopus for peer-reviewed papers and abstracts using the PRISMA guidelines. STUDY SELECTION: The language was limited to English. Studies published since 2016 included if they had sepsis patients with a history of HF, or a subgroup of patients with HF, and in-hospital mortality data on these patients that did or did not meet the 30 mL/kg by 3 h (30 × 3) goal. Duplicate studies, studies that focused on a broader period than 3 h from the diagnosis of sepsis or without mortality breakdown for HF patients or with unrelated title/abstract, or without an IRB approval were excluded. DATA EXTRACTION: In-hospital mortality data was taken from the final studies for HF patients with sepsis who did or did not meet the 30 × 3 goal. DATA SYNTHESIS: The meta-analysis was performed using the Review Manager 5.4 program with ORs as the effect measure. The ProMeta program version 3.0 was used to evaluate the publication bias. Egger's linear regression and Berg and Mazumdar's rank correlation was used to evaluate the publication bias. The result was visually represented by a funnel plot. To estimate the proportion of variance attributable to heterogeneity, the I2 statistic was calculated. RESULTS: The search yielded 26,069 records, which were narrowed down to 4 studies. Compared to those who met the 30 × 3 goal, the <30 × 3 group had a significantly higher risk of in-hospital mortality (OR = 1.81, 95% CI = 1.13-2.89, P = 0.01). CONCLUSIONS: Restrictive fluid resuscitation increased the risk of in-hospital mortality in HF patients with sepsis. More rigorous research is required to determine the optimal fluid resuscitation strategy for this population.

ModelHeart: a resident-led implementation of metrics to reduce 30-day heart failure readmissions.

Hospitals have been penalised for excessive 30-day readmissions via Medicare payment penalties. As such there has been keen interest in finding ways of reducing readmissions. The basis for the study was a retrospective review of heart failure (HF) admissions at Cleveland Clinic Florida from 1 January 2010 to 31 December 2010. The result of this was a set of metrics associated with >30 day span between admissions: N-terminal pro-brain natriuretic peptide by at least 23%, fluid balance of ≤-1.3 L and sodium ≥135 mEq/L on discharge. The ModelHeart trial was a prospective resident-led validation of these criteria that consisted of education about and implementation of these metrics. A total of 200 patients carrying a diagnosis of HF, admitted between 1 November 2012 and 14 January 2014 were included in the trial. Of the 200 enrolled patients, 94% of discharged patients met at least one criteria, 58% met at least two criteria and 20% met all three. There were forty-eight all-cause 30-day readmissions. 30-day readmission rates between themore than equal to two criteria cohort and the remaining patients were not significantly different (p=0.71). Overall readmission rates were higher in the 2011-2012 retrospective patient pool (19%) versus the ModelHeart cohort (11%), and proportional differences were significant, (p<0.001). This may suggest that education provided sufficient awareness to alter discharge practices outside of the measured metrics. However, the lack of significant differences between groups with respect to discharge metrics suggests that further study is needed to refine the metrics and that reducing HF readmissions involves a continuum of care that spans the inpatient and outpatient setting.

Increased levels of retinol binding protein 4 in patients with advanced heart failure correct after hemodynamic improvement through ventricular assist device placement.

BACKGROUND: Chronic heart failure is associated with higher risk for developing diabetes mellitus. Secretory products from adipocytes may contribute to the deterioration in glycemic control and increased insulin resistance (IR). Retinol binding protein 4 (RBP4) is an adipose tissue-derived protein with pro-diabetogenic effects. The aim of the present study was to investigate the relationship of RBP4 in patients with heart failure. METHODS AND RESULTS: Serum levels of RBP4, insulin, and fasting glucose were assessed in 58 patients with severe heart failure at the time of left ventricular assist device (LVAD) implantation and in 44 patients at the time of explantation, as well as in 10 normal control subjects. Serum RBP4 levels were measured by specific enzyme-linked immunosorbent assay, and IR was assessed using the homeostatic model of IR (HOMA-IR). Fasting glucose, insulin and HOMA-IR were significantly higher in patients at the time of LVAD implantation compared to controls (all P<0.01). RBP-4 and HOMA-IR significantly decreased after LVAD implantation (21.7 ± 8.8 mg/dl to 16.0 ± 3.8 mg/dl, P<0.05; 4.2 ± 2.7 to 2.5 ± 2.0, P<0.01). CONCLUSIONS: Patients with advanced heart failure have increased levels of RBP4, and LVAD implantation reduces RBP4. These findings implicate RBP4 in the cascade of reversible metabolic derangements in advanced heart failure.

Vascular inflammation and abnormal aortic histomorphometry in patients after pulsatile- and continuous-flow left ventricular assist device placement.

BACKGROUND: Left ventricular assist devices are increasingly being used in patients with advanced heart failure as both destination therapy and bridge to transplant. We aimed to identify histomorphometric, structural and inflammatory changes after pulsatile- and continuous-flow left ventricular assist device placement. METHODS: Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by Western blot. RESULTS: Decellularization of the aortic tunica media was observed in patients receiving continuous-flow support. Both device types showed an increased inflammatory response after left ventricular assist device placement with variable T-cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. CONCLUSIONS: Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous-flow left ventricular assist and associated with aortic media decellularization. The present findings help to explain the progressive aortic root dilation and vascular dysfunction in patients after continuous-flow device placement.

Value of peak exercise oxygen consumption combined with B-type natriuretic peptide levels for optimal timing of cardiac transplantation.

BACKGROUND: Peak exercise oxygen consumption (VO(2)) is widely used to select candidates for heart transplantation (HTx). However, the prognosis of patients with advanced heart failure and peak VO(2) of 10 to 14 mL/min per kg in the era of modern medical therapy for heart failure is not fully elucidated. B-type natriuretic peptide (BNP) is a useful prognostic marker in patients with heart failure. METHODS AND RESULTS: A total of 424 patients undergoing HTx evaluation were classified according to peak VO(2) during cardiopulmonary exercise testing (>14, 10-14, and <10 mL/min per kg). Survival after cardiopulmonary exercise testing without HTx or ventricular assist device (VAD) support was compared with survival of 743 de novo HTx recipients. Multivariable analysis revealed that high BNP and low peak VO(2) were independently associated with death, HTx, or VAD requirements (hazard ratio, 3.5 and 0.6; 95% CI, 1.24-9.23 and 0.03-0.71; P=0.02 and <0.0001, respectively). VAD-free or HTx-free survival of patients with peak VO(2) 10 to 14 mL/min per kg was identical to post-HTx survival. When patients with peak VO(2) 10 to 14 mL/min per kg were dichotomized by a cutoff value of BNP of 506 pg/mL, those with BNP<506 pg/mL was equivalent to post-HTx survival (1 year: 90.8% versus 87.2%; P=0.61), whereas those with BNP≥506 showed worse VAD-free or HTx-free survival (1 year: 79.7%; P<0.001 versus post-HTx). Patients with peak VO(2) <10 mL/min per kg showed worse survival compared with post-HTx survival, and there was a survival difference between those with BNP≥506 and <506 pg/mL (1 year: 77.2% versus 56.1%; P=0.01). CONCLUSIONS: Patients with peak VO(2) 10 to 14 mL/min per kg and low BNP levels have a VAD-free or HTx-free survival similar to post-HTx survival in heart recipients, whereas high BNP levels indicate worse outcome in this group of patients.

Hepatic dysfunction and survival after orthotopic heart transplantation: application of the MELD scoring system for outcome prediction.

BACKGROUND: The prevalence of heart failure (HF) is rising and the only corrective treatment is cardiac transplantation. Advanced HF is associated with congestive hepatopathy and progressive functional and ultrastructural changes of the liver. We hypothesized that hepatic dysfunction is associated with impaired clinical outcome after heart transplantation. METHODS: Data of 617 adult patients (75% men, mean age 53 ± 12 years, mean BMI 25 ± 4, mean ejection fraction 19 ± 9%) undergoing orthotopic heart transplantation (OHT) were analyzed retrospectively. Deviation from institutional normal ranges was used to define abnormal liver function. Standard Model for End-stage Liver Disease (MELD) scores were calculated and a modified MELD score with albumin replacing INR (modMELD) was created to eliminate the confounding effects of anti-coagulation. RESULTS: Before OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the population, respectively. Total protein and albumin were decreased in 25% and 52% of the population, respectively. By 2 months post-transplantation, percentages of individuals with pathologic values decreased significantly, except for ALT, total protein and albumin, all of which took longer to normalize. Individuals with a higher pre-transplantation MELD or modMELD score had worse outcome 30 days post-transplant and reduced long-term survival over a 10-year follow-up. CONCLUSIONS: In this large, single-center retrospective study, we demonstrated the dynamics of liver dysfunction after cardiac transplantation and that elevated MELD scores indicating impaired liver function are associated with poor clinical outcome after OHT. Thus, pre-operative liver dysfunction has a significant impact on survival of patients after cardiac transplantation.