Peri-operative fever and LVAD: SIRS or impaired right ventricular strain?

BACKGROUND: An inflammatory milieu after left ventricular assist device (LVAD) implantation is associated with multi-organ dysfunction and pre-operative heightened inflammatory state is associated with right ventricular failure after LVAD implantation. METHODS: We performed a retrospective analysis of 30 LVAD patients in our institution within the last 2 years for the development of fever and compared them to 30 non-LVAD open-heart surgery patients. RESULTS: Our results suggest that patients undergoing LVAD implantation are more likely to develop fever in the immediate post-operative period compared to other open-heart surgeries. This is independent of pharmacological treatment, age, or ethnical background. Females and obese patients were more likely to develop fever. CONCLUSION: Patients with right ventricular dysfunction, as demonstrated by elevated central venous pressure (CVP), had the strongest correlation with fever development. These results pose the question if there is a systemic inflammatory response-like phenomenon driven by increased right ventricular dysfunction.

Outcomes of outflow graft stenting in HeartMate 3 left ventricular assist devices: A systematic review and individual patient data meta-analysis.

PURPOSE: LVAD outflow graft stenosis continues to remain prevalent with a high complication rate. We sought to pool the existing evidence on indications, utilization patterns, and outcomes of transcatheter interventions for outflow graft stenosis in the HeartMate 3 LVAD. METHODS: An electronic search was performed to identify all studies in the English literature reporting on HeartMate 3 LVAD outflow graft stenting. Patient-level data were extracted for analysis. RESULTS: Thirteen published reports and one unpublished case comprising a total of 28 patients were included. Median patient age was 68.5 years [Interquartile range: 58, 71] and 25.9% (7/27) were female. Dyspnea [60.7% (17/28)] was the most common presenting symptom. Low flow alarms were present in 60% (15/25) of patients. Findings included external compression [35.7% (10/28)], graft twist [21.4% (6/28)], graft twist and external compression [14.3% (4.28)], intraluminal thrombus [10.7% (3/28)], graft twist and intraluminal thrombus [3.6% (1/28)], and pseudoaneurysm of outflow graft [3.6% (1/28)]. Median time from LVAD implantation to stenting was 2.1 years [1.4, 3]. Immediate flow normalization after stenting was observed in 85.7% (24/28). The 30-day mortality was 12% (3/25). Overall mortality was 12% (3/25) at a median follow-up of 3.9 months [1, 17]. CONCLUSION: Outflow graft stenting in the HeartMate 3 LVAD appears to be a reasonable treatment option for outflow graft stenosis, with low overall rates of complications and mortality. Further refinement of indications and approaches may improve outcomes.

The impact of the OPTN policy change on patients with a durable left ventricular assist device and chronic kidney disease: Analysis of the UNOS database.

BACKGROUND: The Organ Procurement and Transplantation Network (OPTN) implemented modifications in 2018 to the adult heart transplant allocation system to better stratify the most medically urgent transplant candidates. We evaluated the impact of these changes on patients supported by a durable left ventricular assist device (LVAD) with chronic kidney disease (CKD). OBJECTIVE: To evaluate the impact of the OPTN policy change on patients supported by durable left ventricular assist devices (LVAD) with chronic kidney disease (CKD). METHODS: We performed an analysis of patients from the United Network of Organ Sharing Database supported by durable LVAD listed for a heart transplant (HT) between October 17, 2016 and September 30, 2021. Patients were divided into two groups: pre- and postpolicy, depending on whether they were listed on or prior to October 17, 2018. Patients who were on dialysis prior to surgery or discharge were excluded from the analysis. Patients with simultaneous heart and kidney transplants were excluded. Patients who were listed for transplant prepolicy change but transplanted postpolicy change were excluded. This cohort was then subdivided into degrees of CKD based on estimated glomerular filtration rate (eGFR), which resulted in 678 patients (23.7%) in Stage 1 (GFR ≥89.499) (Prepolicy: 345, Postpolicy: 333), 1233 (43.1%) in Stage 2 (89.499 > GFR ≥ 59.499) (Prepolicy: 618, Postpolicy: 615), 613 (21.4%) in Stage 3a (59.499 > GFR ≥ 44.499) (Prepolicy: 291, Postpolicy: 322), 294 (10.3%) in Stage 3b (44.499 > GFR ≥ 29.499) (Prepolicy: 143, Postpolicy: 151), 36 (1.3%) in Stage 4 (29.499 > GFR ≥ 15) (Prepolicy: 21, Postpolicy: 15), and 9 (0.3%) in Stage 5 (15 > GFR) (Prepolicy: 4, Postpolicy: 5). The primary outcome was 1-year and 2-year post-HT survival. RESULTS: There were 2863 patients who met the study criteria (1422 prepolicy, 1441 postpolicy). Overall survival, regardless of CKD stage, was lower following the policy change (p < 0.01). There was a similar risk of primary graft failure (PGF) in the pre- and postpolicy period (1.8% vs. 1.2%, p = 0.26). 1-year overall survival was 93% (91, 94) and 89% (87, 91) in the pre- and postpolicy periods, respectively. 2-year overall survival was 89% (88, 91) and 85% (82, 87) in the pre- and postpolicy periods, respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 1 -year survival was 93% (91, 95), 92% (90,93), 89% (86, 91), 89% (86, 93), 80% (68, 94), and 100% (100, 100), respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 2-year survival was 91% (88, 93), 88% (86, 90), 84% (81, 88), 84% (80, 89), 73% (59, 90), and 100% (100, 100), respectively. Patients with CKD 1 and 2 had better survival compared to those with CKD 3 (p < 0.01) and CKD 4 and 5 (p = 0.03) in the pre- and postpolicy periods. Patients with CKD 3 did not have a survival advantage over those with CKD 4 and 5 (p = 0.25). On cox regression analysis, advancing degrees of CKD were associated with an increased risk of mortality. CONCLUSIONS: Patients with LVAD support had decreased overall survival after the OPTN policy change. Patients with more advanced CKD had lower survival than patients without advanced CKD, though they were not impacted by the OPTN policy change.

COVID-19 associated development of antibody mediated rejection in orthotopic heart transplantation patients.

Solid organ transplant candidates encountered increased wait times and mortality rates during the coronavirus 2019 (COVID-19) pandemic. Despite improvement in medical management and vaccination efficacy, this patient population remains at increased risk for complications post COVID-19 including organ rejection. We describe the development of antibody mediated rejection with or without cellular rejection in heart transplant (HT) recipients and previous COVID-19 infection or vaccination. Although centers have changed their management of outpatient follow-up for orthotopic heart transplant patients, little is known on surveillance of rejection and management of HT recipients after COVID-19 infection. We recommend frequent surveillance for rejection or allograft dysfunction after COVID-19 infection. We have adopted a transplant surveillance protocol for HT recipients with COVID-19 infection, given our recent experience with transplanted patients affected of COVID-19.

PCI for acute myocardial infarction in patients with a pre-existing LVAD, does it improve survival?

BACKGROUND: It is well established that percutaneous coronary intervention (PCI) is a life-saving procedure for acute myocardial infarction (AMI) in the general population and is guideline-recommended for both STEMI and NSTEMI. There is little literature regarding its use in patients with a pre-implanted Left Ventricular Assist Device (LVAD). METHODS: We retrospectively analyzed data from the National Inpatient Sample (NIS) Database to select all US adult patients (>18 years) with an LVAD diagnosed with an AMI divided into two groups; those who received PCI during the hospitalization and those who did not. RESULTS: A total of 3722 LVAD patients with AMI were identified, of these 17% of patients received PCI and 83% did not. After propensity matching of LVAD patients with AMI, there were 626 patients who received PCI and 623 who did not. Of patients receiving PCI, 37.5% had a STEMI while 29.7% of patients who did not receive PCI had STEMI. Rates of kidney injury (36.5% vs. 43.3%, OR 0.75, 95% CI 0.60-0.94, p = 0.016), sepsis (3.2% vs. 11.4%, OR 0.26, 95% CI 0.15-0.43, p < 0.001), cardiogenic shock (44.1% vs. 50.4%, OR 0.78, 95% CI 0.62-0.97, p = 0.03) and mortality (17.4% vs. 28.9%, OR 0.52, 95% CI 0.40-0.68, p < 0.001) were all better for patients receiving PCI. Vascular complications (1.4% vs. 0%, p = 0.008) and intracerebral hemorrhage (ICH) (1.6% vs. 0, p = 0.004) were both more common in the group receiving PCI. CONCLUSIONS: In this study, patients supported by LVAD with AMI had an elevated risk of mortality compared to generally accepted mortality rates of patients without LVAD. In this analysis PCI was associated with a decreased risk of mortality, cardiogenic shock, and kidney injury while increasing the risk for vascular complications and intracranial hemorrhage.

Association of Heart Transplant Volume with Presence of Lung Transplant Programs and Heart Transplant's SRTR One-year Survival Rating.

BACKGROUND: Several factors affect heart transplant (HTx) and lung transplant (LTx) program outcomes. Variabilities in institutional and community characteristics have been shown to influence survival. At present, half of HTx centers in the United States do not possess a concomitant LTx program. This study sought to better understand the characteristics of HTx with and without LTx programs. METHODS: Nationwide transplant data were collected from the Scientific Registry of Transplant Recipients (SRTR) in August 2020. SRTR star rating ranges from tier 1 (lowest) to tier 5 (highest). HTx volumes and SRTR star ratings for survival were compared between the centers with heart-only (H0) programs and the centers with heart-lung (HL) programs. RESULTS: SRTR star ratings were available for 117 transplant centers with one or more HTx reported. The median number of HTx performed over 1 year was 16 (interquartile range [IQR]: 2-29). The number of HL centers (n = 67, 57.3%) were comparable to H0 centers (n = 50, 42.7%; p = 0.14). The HTx volume at the HL centers (28 [IQR: 17-41]) exceeded the HTx volume at the H0 centers (13 [IQR: 9-23]; p < 0.01), but were comparable to the LTx volume at the HL centers (31 [IQR: 16-46]; p = 0.25). The median HTx one-year survival rating was 3 (IQR: 2-4) at both the H0 and HL centers (p = 0.85). The HTx and LTx volumes were positively associated with the respective 1-year survivals (p < 0.01). CONCLUSION: While the presence of an LTx program is not directly associated with HTx survival, it has a positive association with the HTx volume. The HTx and LTx volumes are positively associated with the 1-year survival.

Assessing donor-recipient size metrics for heart transplant outcomes: UNOS database analysis.

STUDY: There is no widely accepted donor to recipient size-match metric to predict outcomes in cardiac transplant. The predictive ability of size-match metrics has not been studied when recipients are stratified by heart failure etiology. We sought to assess the performance of commonly used size metrics to predict survival after heart transplant, accounting for restrictive versus non-restrictive pathology. METHODS: The UNOS registry was queried from 2000 to 2017 for all primary isolated heart transplants. Donor-recipient ratios were calculated for commonly used size metrics and their association with survival was assessed using continuous, nonlinear analysis. RESULTS: 29 817 patients were identified. Height (P < .001), predicted heart mass (PHM) (P = .003), ideal body weight (IBW) (P < .001) and body mass index (BMI) (P = .003) ratios were significantly associated with survival, while weight and body surface area (BSA) ratios were not. When stratified, only BMI ratio retained significance for both restrictive (P = .051) and non-restrictive (P = .003) subsets. Recipients with restrictive etiology had increased risk of mortality with both a lower and higher BMI ratio. CONCLUSIONS: While many metrics show association with survival in the non-restrictive subset, BMI is the only metric that retains significance in the restrictive subset. Recipients with restrictive and non-restrictive etiologies of heart failure tolerate size mismatch differently.

Cardiac transplantation after heparin-induced thrombocytopenia: A systematic review.

PURPOSE: Heparin-induced thrombocytopenia (HIT) presents a unique challenge in patients requiring orthotopic heart transplantation (OHT). We sought to pool the existing evidence in a systematic review. METHODS: Electronic search was performed to identify all relevant studies on OHT in patients with HIT. Patient-level data for 33 patients from 21 studies were extracted for statistical analysis. RESULTS: Median patient age was 51 [IQR 41, 55] years, with 75.8% (25/33) males. All patients had a clinical diagnosis of HIT, and anti-PF4/Heparin antibodies were positive in 87.9% (29/33). Median lowest reported platelet count was 46 × 109 /L [27.2, 73.5]. Intraoperatively, 61% (20/33) of patients were given unfractionated heparin (UFH), while 39% (13/33) were given alternative anticoagulants. The alternative agent subgroup required more antifibrinolytics [54% (7/13) vs 10% (2/20), P = .02] and clotting factors [69.2% (9/13) vs 15.0% (3/20), P < .01]. Perioperative thrombosis occurred more [53.8% (7/13) vs 0% (0/20, P < .01) in alternate agent subgroup. More patients in the alternate agent subgroup required post-operative transfusions [54% (7/13) vs 0% (0/20), P < .01]. Thirty-day mortality of 15.2% (5/33) was comparable between the subgroups. CONCLUSION: Heparin use during OHT may be associated with less adverse effects compared to use of other anticoagulants with no difference in 30-day mortality.

Impact of ventricular arrhythmia on LVAD implantation admission outcomes.

INTRODUCTION: Ventricular arrhythmias (VAs) are common after left ventricular assist device (LVAD) implantation though data are mixed on whether these events have an impact on mortality. METHODS: The National Inpatient Sample (NIS) database from 2002-2019 was queried for LVAD implantation admissions. Secondary ICD codes were analyzed to assess for the occurrence of VAs during this admission. Propensity score matching (PSM) was used to control for confounding variables between those with versus without VAs. RESULTS: The NIS database from 2002-2019 contained 43 936 admissions with LVAD implantation. VAs occurred in 19 985 (45.4%) patients. After PSM, the study cohort consisted of 39 989 patients, 19 985 (50.0%) of which had a secondary diagnosis of VA during the admission. When compared to those without VA, those with VA were at no higher risk for in-hospital mortality (adjusted odds ratio 1.011, 99.9% CI 0.956-1.069, p = 0.699). Those with a VA were at higher risk for cardiogenic shock and requiring mechanical ventilation, tracheostomy, and percutaneous endoscopic gastrostomy placement. Patients with a VA were also at lower risk for device thrombosis. Conversely, the VA group was at no higher risk for stroke. In comparing trends from 2002 to 2019, the incidence of VAs has increased, while the mortality rate of those with and without VAs has decreased during this same period. CONCLUSION: In this retrospective study of the NIS database, VAs were common (45.4%) during the LVAD implantation admission. However, the occurrence of VAs during the implantation admission did not alter in-hospital mortality. More longitudinal studies are required to assess the long-term impact of VAs on mortality. In comparing trends from 2002-2019, the incidence of VAs has increased, while the mortality rate of those with and without VAs has decreased.

Continuous-flow LVAD exchange to a different pump model: Systematic review and meta-analysis of the outcomes.

Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.

Safety and efficacy of RNAi therapy for transthyretin amyloidosis.

BACKGROUND: Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS: We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS: Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS: ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).

Clinical characteristics and in hospital outcomes of heart transplant recipients with allograft vasculopathy undergoing percutaneous coronary intervention: Insights from the National Cardiovascular Data Registry.

BACKGROUND: Cardiac allograft vasculopathy is a major cause of morbidity and mortality following heart transplantation. Large multicenter studies evaluating the clinical characteristics and inhospital outcomes of heart transplant recipients undergoing percutaneous coronary intervention (PCI) are lacking. OBJECTIVE: To evaluate the clinical characteristics, treatment patterns and inhospital outcomes of heart transplant recipients undergoing PCI compared to general population. METHODS: We analyzed 1,897,328 patients from the National Cardiovascular Data Registry CathPCI registry who underwent PCI of at least 1 native vessel between July 2009 and December 2013 from 1,477 centers, of which 542 patients (0.03%) were heart transplant recipients. Clinical characteristics were evaluated and, after 1:4 propensity matching, inhospital outcomes were compared between 538 heart transplant patients and 2,128 non-transplant patients. RESULTS: Transplant recipients undergoing PCI had a higher prevalence of diabetes, dyslipidemia and peripheral vascular disease; lower prevalence of angina, acute coronary syndrome, abnormal noninvasive functional study, and type C coronary lesions compared to the non-transplant PCI population. After propensity matching, all-cause inhospital mortality was similar between transplant and non-transplant groups (1.3% vs 1.0%; OR, 1.21; 95% CI, 0.54-2.67). CONCLUSION: This is the largest series to date outlining the characteristics of heart transplant recipients undergoing PCI. Similar inhospital outcomes were noted in heart transplant recipients compared to the general population. Further studies evaluating long-term outcomes are warranted.

Determinants of pulmonary hypertension in patients with end-stage kidney disease and arteriovenous access.

BACKGROUND: Pulmonary Hypertension (PH) is a sequela of arteriovenous (AV) fistulas (AVF) or AV grafts (AVG) in patients with end-stage kidney disease (ESKD) due to the creation of shunt physiology and increased pulmonary blood flow. PH has been consistently associated with increased mortality but there is a paucity of data regarding management. RESEARCH QUESTION: The objective of this study was to identify risk factors and outcomes in patients who develop PH after AVF or AVG creation for hemodialysis access. METHODS: Using the United States Renal Data System, we identified all patients over age 18 initiated on dialysis from 2012-2019 who did not receive renal transplant. We identified a) the predictors of PH in patients with ESKD on hemodialysis; b) the independent mortality risk associated with development of PH. RESULTS: We identified 478,896 patients initiated on dialysis from 2012-2019 of whom 27,787 (5.8 %) had a diagnosis of PH. The median age was 65 (IQR: 55-74) years and 59.1 % were male. Reduced ejection fraction, any congestive heart failure, obstructive sleep apnea, and female sex were the strongest predictors of PH diagnosis. Both AVG and AVF were also associated with an increased rate of PH diagnosis compared to catheter-based dialysis (p < 0.001). PH portended a poor prognosis and was associated with significantly increased mortality (p < 0.001). CONCLUSIONS: Patients with AVF or AVG should be screened using echocardiography prior to creation and monitored with serial echocardiography for the development of PH, and if present, considered for revision of the AVA. This is also the first study to identify that AVG are a risk factor for PH in dialysis patients.

Characterizing Adaptive Changes and Patient Survival After 2018 Donor Allocation Restructuring: A UNOS Database Analysis.

PURPOSE: We sought to characterize adaptive changes to the revised United Network for Organ Sharing donor heart allocation policy and estimate long-term survival trends for heart transplant (HTx) recipients. METHODS: Patients listed for HTx between October 17, 2013 and September 30, 2021 were identified from the United Network for Organ Sharing database, and stratified into pre- and postpolicy revision groups. Subanalyses were performed to examine trends in device utilization for extracorporeal membranous oxygenation (ECMO), durable left ventricular assist device (LVAD), intra-aortic balloon pump (IABP), microaxial support (Impella), and no mechanical circulatory support (non-MCS). Survival data post-HTx were fitted to parametric distributions and extrapolated to 5 years. RESULTS: We identified 27,523 HTx waitlist candidates during the study period, most of whom (n = 16,376) were waitlisted in the prepolicy change period. Overall, 19,554 patients underwent HTx during the study period (pre: 12,037 and post: 7517). Listings increased after the policy change for ECMO ( P < 0.01), Impella ( P < 0.01), and IABP ( P < 0.01) patients. Listings for LVAD ( P < 0.01) and non-MCS ( P < 0.01) patients decreased. HTx increased for ECMO ( P < 0.01), Impella ( P < 0.01), and IABP ( P < 0.01) patients after the policy change and decreased for LVAD ( P < 0.01) and non-MCS ( P < 0.01) patients. Waitlist survival increased for the overall ( P < 0.01), ECMO ( P < 0.01), IABP ( P < 0.01), and non-MCS ( P < 0.01) groups. Waitlist survival did not differ for the LVAD ( P = 0.8) and Impella ( P = 0.1) groups. Post-transplant survival decreased for the overall ( P < 0.01), LVAD ( P < 0.01), and non-MCS ( P < 0.01) populations. CONCLUSIONS: Allocation policy revisions have contributed to greater utilization of ECMO, Impella, and IABP, decreased utilization of LVADs and non-MCS, increased waitlist survival, and decreased post-HTx survival.

Clinical Outcomes of Transcatheter Aortic Valve Replacement (TAVR) vs Surgical Aortic Valve Replacement (SAVR) in Patients With Sarcoidosis.

Introduction Data regarding clinical outcomes after transcatheter aortic valve replacement (TAVR) vs surgical aortic valve replacement (SAVR) in patients with sarcoidosis is lacking. This study aims to clarify the clinical outcomes of TAVR vs SAVR in patients with sarcoidosis. Methods Data was collected from the National Inpatient Sample database from 2016-2019 using validated ICD-10-CM codes for sarcoidosis, TAVR, and SAVR. Patients were divided into two cohorts: those who underwent TAVR and those who underwent SAVR. Statistical analysis was performed using Pearson's chi-squared test to determine clinical outcomes of TAVR vs SAVR in patients with sarcoidosis. Results The prevalence of sarcoidosis was 0.23% among total study patients (n=142,420,378). After exclusions, the prevalence of TAVR was 650 (49%) and SAVR was 675 (51%) in patients with sarcoidosis. Patients who underwent TAVR were on average older (74 vs 65 years old, p=0.001), and more likely to be female (57 vs 40%, p<0.001) compared to patients who underwent SAVR. The TAVR cohort had higher rates of congestive heart failure (CHF) (77.7 vs 42.2%, p=0.001), chronic kidney disease (CKD) (42.3 vs 24.4% p=0.001), anemia (5.4 vs 2.2%, p=0.004), percutaneous coronary intervention (PCI) (1.5 vs 0%, p=0.004), and hypothyroidism (31.5 vs 16.3%, p=0.001) compared to the SAVR cohort. Inpatient mortality post-procedure was higher in the SAVR cohort compared to the TAVR cohort (15 vs 0, p=0.001). Regarding post-procedure complications, respiratory complications were more common in the SAVR cohort (4.4 vs 0%, p=0.001), while TAVR was associated with a higher incidence of permanent pacemaker (PPM) insertion (2.15 vs 0.8%, p=0.001). There was no statistical difference in the development of acute kidney injury (AKI) (0.8 vs 1.5%, p=0.33), AKI requiring hemodialysis (0 vs. 0.7%, p=0.08), or stroke (0.8 vs 0.7, p=1) post-procedure between the two cohorts. Conclusion This study found that in the sarcoidosis population, TAVR was associated with reduced mortality, shorter hospital length of stay, and lower hospitalization costs in comparison to SAVR.

Antimicrobial activity of nanoemulsion in combination with cetylpyridinium chloride in multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii has emerged as a serious problematic pathogen due to the ever-increasing presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria, enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion preparations against four Acinetobacter baumannii isolates to identify the most suitable preparation for further evaluation. Among them, N5, which contains 10% (vol/vol) Triton X-100, 25% (vol/vol) soybean oil, and 1% (wt/vol) cetylpyridinium chloride (CPC), showed the best efficacy against A. baumannii in both its planktonic and biofilm forms and was selected for further study. Our data demonstrate that, while the killing of planktonic forms of A. baumannii was due to the 1% CPC component of our nanoemulsions, the breakdown of biofilms was achieved via the emulsified oil and detergent fractions. Furthermore, we documented the effect of ethanol and NaCl in combination with N5 on planktonic A. baumannii. In killing curves of N5 combined with other agents (ethanol or NaCl), a synergistic effect of a ≥ 2-log decrease in CFU/ml was observed. The antibiofilm activity of N5 was confirmed via a cell proliferation test and scanning electron microscopy. The effects of exposure to severe environmental conditions, which simulates the field conditions in Iraq and Afghanistan, were evaluated, and this exposure did not affect the overall antimicrobial activity of N5. These studies lay a solid foundation for the utilization of nanoemulsions against the antibiotic-resistant forms of A. baumannii.

Lipid-like materials for low-dose, in vivo gene silencing.

Significant effort has been applied to discover and develop vehicles which can guide small interfering RNAs (siRNA) through the many barriers guarding the interior of target cells. While studies have demonstrated the potential of gene silencing in vivo, improvements in delivery efficacy are required to fulfill the broadest potential of RNA interference therapeutics. Through the combinatorial synthesis and screening of a different class of materials, a formulation has been identified that enables siRNA-directed liver gene silencing in mice at doses below 0.01 mg/kg. This formulation was also shown to specifically inhibit expression of five hepatic genes simultaneously, after a single injection. The potential of this formulation was further validated in nonhuman primates, where high levels of knockdown of the clinically relevant gene transthyretin was observed at doses as low as 0.03 mg/kg. To our knowledge, this formulation facilitates gene silencing at orders-of-magnitude lower doses than required by any previously described siRNA liver delivery system.

Aldosterone antagonists in heart failure.

BACKGROUND: Chronic, systolic heart failure is an increasing and costly health problem, and treatments based on pathophysiology have evolved that include the use of aldosterone antagonists. PURPOSE: Advances in the understanding of neurohormonal responses to heart failure have led to better pharmacologic treatments. The steroid hormone aldosterone has been associated with detrimental effects on the cardiovascular system, such as ventricular remodeling and endothelial dysfunction. This article will review the literature and guidelines that support the use of aldosterone antagonists in the treatment of chronic, systolic heart failure. CONCLUSIONS: Aldosterone antagonists are life-saving drugs that have been shown to decrease mortality in patients with New York Heart Association class III to IV heart failure and in patients with heart failure after an acute myocardial infarction. Additional studies are being conducted to determine if the role of aldosterone antagonists can be expanded to patients with less severe forms of heart failure. CLINICAL IMPLICATIONS: Aldosterone antagonists are an important pharmacologic therapy in the neurohormonal blockade necessary in the treatment of systolic heart failure. These drugs have been shown to decrease mortality and reduce hospital readmission rates. The major complication of aldosterone antagonists is hyperkalemia, which can be avoided with appropriate patient selection and diligent monitoring.

Human Metapneumovirus: lessons learned over the first decade.

It has been 10 years since human metapneumovirus (HMPV) was identified as a causative agent of respiratory illness in humans. Since then, numerous studies have contributed to a substantial body of knowledge on many aspects of HMPV. This review summarizes our current knowledge on HMPV, HMPV disease pathogenesis, and disease intervention strategies and identifies a number of areas with key questions to be addressed in the future.