Membrane bending and sphingomyelinase-associated, sulfatide-dependent hypoxic adhesion of sickle mature erythrocytes.

Abnormal erythrocyte adhesion owing to polymerization of sickle hemoglobin is central to the pathophysiology of sickle cell disease (SCD). Mature erythrocytes constitute >80% of all erythrocytes in SCD; however, the relative contributions of erythrocytes to acute and chronic vasculopathy in SCD are not well understood. Here, we showed that bending stress exerted on the erythrocyte plasma membrane by polymerization of sickle hemoglobin under hypoxia, enhances sulfatide-mediated abnormal mature erythrocyte adhesion. We hypothesized that sphingomyelinase (SMase) activity, which is upregulated by accumulated bending energy, leads to elevated membrane sulfatide availability, and thus, hypoxic mature erythrocyte adhesion. We found that mature erythrocyte adhesion to laminin in controlled microfluidic experiments is significantly greater under hypoxia than under normoxia (1856 ± 481 vs 78 ± 23, mean ± SEM), whereas sickle reticulocyte (early erythrocyte) adhesion, high to begin with, does not change (1281 ± 299 vs 1258 ± 328, mean ± SEM). We showed that greater mean accumulated bending energy of adhered mature erythrocytes was associated with higher acid SMase activity and increased mature erythrocyte adhesion (P = .022, for acid SMase activity and P = .002 for the increase in mature erythrocyte adhesion with hypoxia, N = 5). In addition, hypoxia results in sulfatide exposure of the erythrocyte membrane, and an increase in SMase, whereas anti-sulfatide inhibits enhanced adhesion of erythrocytes. These results suggest that the lipid components of the plasma membrane contribute to SCD complications. Therefore, sulfatide and the components of its upregulation pathway, particularly SMase, should be further explored as potential therapeutic targets for inhibiting sickle erythrocyte adhesion.

Donor heart selection: Evidence-based guidelines for providers.

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review.

LVAD Vasculitis Case Series: Suggestion of a New Fatal LVAD-Related Phenomenon.

Left ventricular assist devices (LVADs) are surgically implanted mechanical devices indicated for patients with advanced heart failure and are known to come with several complications. Here we present a case series, and review 1 documented report, of LVAD vasculitis, a presumed new LVAD immune/humoral related phenomenon. (Level of Difficulty: Advanced.).

PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure: Results of the PRIME-HF Trial.

BACKGROUND: Ivabradine is guideline-recommended to reduce heart failure (HF) hospitalization in patients with stable chronic HF with reduced ejection fraction (EF). Ivabradine initiation following acute HF has had limited evaluation, and there are few randomized data in US patients. The PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) study was conducted to address predischarge ivabradine initiation in stabilized acute HF patients. METHODS: PRIME-HF was an investigator-initiated, randomized, open-label study of predischarge initiation of ivabradine versus usual care. Eligible patients were hospitalized for acute HF but stabilized, with EF ≤35%, on maximally tolerated ß-blocker and in sinus rhythm with heart rate ≥70 beats/min. Ivabradine was acquired per routine care. The primary end point was the proportion of patients on ivabradine at 180 days. Additional end points included heart rate change, patient-reported outcomes, ß-blocker use/dose, and safety events (symptomatic bradycardia and hypotension). RESULTS: Overall, 104 patients (36% women, 64% African American) were randomized, and the study was terminated early because of funding limitations. At 180 days, 21 of 52 (40.4%) of patients randomized to predischarge initiation were treated with ivabradine compared with 6 of 52 (11.5%) randomized to usual care (odds ratio 5.19, 95% CI 1.88-14.33, P = .002). The predischarge initiation group experienced greater reduction in heart rate through 180 days (mean -10.0 beats/min, 95% CI -15.7 to -4.3 vs 0.7 beats/min, 95% CI -5.4 to 6.7, P = .011). Patient-reported outcomes, ß-blocker use/dose, and safety events were similar (all P > .05). CONCLUSIONS: Ivabradine initiation prior to discharge among stabilized HF patients increased ivabradine use at 180 days and lowered heart rates without reducing ß-blockers or increasing adverse events. As the trial did not achieve the planned enrollment, additional studies are needed.

Association of Acute Venous Thromboembolism With In-Hospital Outcomes of Coronary Artery Bypass Graft Surgery.

Background While venous thromboembolism (VTE) prophylaxis is a strong recommendation after most surgeries, it is controversial in cardiac surgeries such as coronary artery bypass grafting (CABG), because of perceived low VTE incidence and increased bleeding risk. Prior studies may not have been adequately powered to study outcomes of VTE in this population. We sought to investigate the postoperative incidence and outcomes of CABG patients using a large national inpatient database. Methods and Results We utilized the 2013 to 2014 National Inpatient Sample to identify all patients >18 years of age who underwent CABG (without concomitant valvular procedures), and had VTE during the hospital stay. We then compared clinically relevant outcomes in patients with and without VTE. We identified 331 950 CABG procedures. Of these, 1.3% (n=4205) had VTE. Patients with VTE were more likely to be older (mean 67.2±10.4 years versus 65.2±10.4 years, P<0.001). VTE was associated with higher incidence of inpatient mortality (6.8% versus 1.7%; adjusted odds ratio 1.92 [95% CI 1.40-2.65]; P<0.001) and complications. VTE was also associated with higher cost (mean±SE $81 995±$923 versus $48 909±$55) and longer length of stay (mean±SE 17.06±0.16 days versus 8.52±0.01 days). Conclusions Our analysis of >330 000 CABG procedures suggests that while postoperative VTE after CABG is rare, it is associated with increased morbidity and mortality. Randomized controlled trials are needed to identify optimal strategies for VTE prophylaxis in these patients.

Waitlist Mortality of Patients With Amyloid Cardiomyopathy who Are Listed for Heart Transplantation and Implications for Organ Allocation.

BACKGROUND: Outcomes of patients with amyloid cardiomyopathy (ACM) undergoing heart transplantation have been reported, but there are scant data concerning the waitlist mortality (WLM) of these patients. AIM: The aim of this study was to investigate whether patients with ACM have higher waitlist mortality compared to those with other types of cardiomyopathies. METHODS: We queried the United Network for Organ Sharing registry for all patients (age ≥ 18 years) listed for heart transplantation between 2008 and 2015. We compared patients with ACM to those with dilated cardiomyopathy (DCM) or idiopathic restrictive cardiomyopathy (RCM) for WLM and waitlist mortality or delisting for deterioration (WLM/D). We identified 306 patients with ACM, 183 with RCM and 8416 with DCM. Patients with ACM were older (ACM 61 vs RCM 49 vs DCM 51 years, P < .001), were more likely to be male (82% vs 60% vs 73%, P < .001) but less likely to be listed as status 1A (16% vs 18% vs 23%, P< .001). After adjusting for baseline characteristics, ACM was associated with increased risk of mortality and mortality/delisting compared with DCM (HR 2.03 [1.36-3.04], P = .001 for WLM; HR 2.07 [1.55-2.78], P < .001 for WLM/D) but not with other RCMs (HR 1.28 [0.54-3.02], P = .58 for WLM; HR 0.97 [0.56-1.69], P = .91 for WLM/D). RESULTS: Patients with ACM are listed with lower acuity and have higher waitlist mortality compared with those with dilated cardiomyopathies. Further studies are needed to identify whether special prioritization should be considered for patients with ACM listed for heart transplantation.

Relation of Concomitant Heart Failure to Outcomes in Patients Hospitalized With Influenza.

Influenza is a major public health challenge. Patients hospitalized with influenza who also have heart failure (HF) may be at risk for worse outcomes compared with patients without HF. There is a lack of large studies examining this issue. We queried the 2013 to 2014 National Inpatient Sample for all adult patients (aged ≥ 18 years) admitted with influenza with and without concomitant HF. Using propensity score matching, patients were matched across demographics, discharge weights, and comorbidities. Outcomes included in-hospital mortality, complications, length of stay, and average hospital costs. Of 218,540 influenza hospitalizations, 45,460 (20.8%) had concomitant HF. Patients with HF had higher in-hospital mortality (6.1% vs 3.8%, adjusted odds ratio [aOR] 1.66 [95% confidence interval [CI] 1.44 to 1.91]; p <0.001), acute kidney injury (29.5% vs 22.2%, aOR 1.47 [95% CI 1.37 to 1.57]; p <0.001), acute kidney injury requiring dialysis (2.0% vs 1.0%, aOR 2.08 [1.62 to 2.67], acute respiratory failure (36.2% vs 23.5%, aOR 1.85 [1.73 to 1.97]; p <0.001), and acute respiratory failure requiring mechanical ventilation (17.1% vs 9.3%, OR 2.01 [1.84 to 2.21]; p <0.001), longer length of stay (5.70 ± 0.02 days vs 4.60 ± 0.01 days, p <0.001) and higher average hospital costs ($11,609 ± $52 vs $9,003 ± $38, p <0.001). In conclusion, in patients hospitalized with influenza, HF is associated with increased risk of in-hospital mortality and complications. Our results highlight a need for early recognition and aggressive treatment of HF in these patients to try to improve outcomes.

Effect of Influenza on Outcomes in Patients With Heart Failure.

OBJECTIVES: This study sought to determine whether influenza infection increases morbidity and mortality in patients hospitalized with heart failure (HF). BACKGROUND: Patients with HF may be at increased risk of morbidity and mortality from influenza infection. However, there are limited data for the associated hazards of influenza infection in patients with HF. METHODS: We queried the 2013 to 2014 National Inpatient Sample database for all adult patients (18 years of age or older) admitted with HF with and without concomitant influenza infection. Propensity score matching was used to match patients across age, race, sex, and comorbidities. Outcomes included in-hospital mortality, in-hospital complications, length of stay, and average hospital costs. RESULTS: Of 8,189,119 all-cause hospitalizations in patients with HF, 54,590 (0.67%) had concomitant influenza infection. Patients with concomitant influenza had higher incidence of in-hospital mortality (6.2% vs. 5.4%, respectively; odds ratio [OR]: 1.15 [95% confidence interval [CI]: 1.03 to 1.30]; p = 0.02), acute respiratory failure (36.9% vs. 23.1%, respectively; OR: 1.95 [95% CI: 1.83 to 2.07]; p < 0.001), acute respiratory failure requiring mechanical ventilation (18.2% vs. 11.3%, respectively; OR: 1.75 [95% CI: 1.62 to 1.89]; p < 0.001), acute kidney injury (AKI) (30.3% vs. 28.7%, respectively; OR: 1.08 [95% CI: 1.02 to 1.15]; p = 0.01), and AKI requiring dialysis (2.4% vs. 1.8%, respectively; OR: 1.37 [95% CI: 1.14 to 1.65]; p = 0.001). Patients with influenza had longer mean lengths of stay (5.9 days vs. 5.2 days, respectively; p <0.001) but similar average hospital costs ($12,137 vs. $12,003, respectively; p = 0.40). CONCLUSIONS: Influenza infection is associated with increased in-hospital morbidity and mortality in patients with HF. Our results emphasize the need for efforts to mitigate the incidence of influenza, specifically in this high-risk patient cohort.

Risk of Myocardial Infarction in Inflammatory Bowel Disease: A Population-based National Study.

BACKGROUND & OBJECTIVE: Chronic inflammation is linked to increased cardiovascular risk. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and elevated pro-inflammatory markers. The association between IBD and myocardial infarction (MI) is not well understood. We sought to elucidate this risk using a large database. METHODS: We reviewed data from a large commercial database (Explorys, IBM Watson) that aggregates electronic medical records from 26 nationwide health care systems. Using systemized nomenclature of medicine-clinical terms, we identified adult patients (20 to 65 years) with a diagnosis of IBD-ulcerative colitis (UC) or Crohn's disease (CD)-who had active records between August 2013 and August 2018. We then examined the risk of MI in patients with or without IBD. RESULTS: Out of 29,090,220 patients, 131,680 (0.45%) had UC, and 158,750 (0.55%) had CD. Prevalence of MI was higher in patients with UC and CD versus non-IBD patients (UC 6.7% vs CD 8.8% vs non-IBD 3.3%, odds ratio [OR] for UC 2.09 [2.04 -2.13], and CD 2.79 [2.74-2.85]. The odds of MI in IBD patients overall were highest in younger patients and decreased with age (age 30-34 years: OR 12.05 [11.16-13.01], age 65+ years: OR 2.08 [2.04-2.11]). After adjusting for age, race, sex, and traditional cardiovascular risk factor, IBD conferred greater odds of MI (adjusted odds ratio [aOR] 1.25 [1.24-1.27]). CONCLUSION: In this large cohort, IBD is associated with significantly increased MI compared with non-IBD patients. The relative risk of MI was highest in younger patients and decreased with age. These findings emphasize the need for aggressive risk factor reduction in IBD.

Current Status of Inotropes in Heart Failure.

Inotropes are medications that improve the contractility of the heart and are used in patients with low cardiac output or evidence of end-organ dysfunction. Since their initial discovery, inotropes have held promise in alleviating symptoms and potentially increasing longevity in such patients. Decades of intensive study have further elucidated the benefits and risks of using inotropes. In this article, the authors discuss the history of inotropes, their indications, mechanism of action, and current guidelines pertaining to their use in heart failure. The authors provide insight into their appropriate use and related shortcomings and the practical aspects of inotrope use.

Left Ventricular Assist Devices or Inotropes for Decreasing Pulmonary Vascular Resistance in Patients with Pulmonary Hypertension Listed for Heart Transplantation.

BACKGROUND: Fixed pulmonary hypertension is common in patients with advanced heart failure and is a contraindication for heart transplantation. Left ventricular assist devices (LVAD) and inotropes have been used to reduce pulmonary vascular resistance (PVR) and allow transplantation. However, little is known about the efficacy of this strategy. METHODS: We queried the United Network for Organ Sharing registry for all adult patients (age ≥18 years) listed for primary heart transplantation (2008-2014) with PVR of >5 wood units (WU) or transpulmonary gradient >16 mmHg who were treated with LVAD or IV inotropes as status 1a, 1b, or 7. We compared waitlist mortality/delisting and absolute changes in hemodynamics between listing and transplantation. RESULTS: Of 18,009 patients listed during the study period, 1016 were included in the analysis (393 LVAD, 623 inotropes), with a mean age of 52.9 ± 11.6 years, 74% male, and 38% had ischemic etiology. Mean PVR was 5.7 ± 2.4 WU and transpulmonary pressure gradient 19.3 ± 5.3 mmHg. Compared with the inotrope group, LVAD patients were more likely listed as status 1A (32.8% vs 18.1%, P < .001), had lower PVR (5.3 WU vs 5.9 WU, P = .001), and higher cardiac output (4.1 vs 3.6 L/min, P < .001). After a mean of 239 days, PVR decreased by 1.71 WU in the LVAD group vs 1.85 WU in the inotrope group (P = .52). PVR normalization (<2.5 WU) occurred at similar rates among those treated with inotropes and LVAD (30.7% vs 35.6%, P = .228). Waitlist mortality was similar between LVAD and inotropes (adjusted P = .837). Absolute PVR and transpulmonary pressure gradient reductions correlated with time on the waitlist (P < .001 for both comparisons). CONCLUSION: Only about one-third of patients with fixed pulmonary hypertension achieve normalization of PVR before transplant with either LVAD or inotropes. Similar waitlist mortality was observed among patients bridged with either strategy.