Isolated left ventricular assist device implantation produces variable changes to patient body mass index.

BACKGROUND: Body mass index (BMI) is an important consideration for transplant-eligible left ventricular assist device (LVAD) recipients. LVAD therapy's impact on BMI is unclear. We evaluated BMI changes in patients who underwent LVAD implantation. The association between these patients' BMI and the transplant was studied. METHODS: This was a retrospective cohort study of patients who underwent LVAD implantation between January 1, 2012 and December 31, 2018 at our institution. Patients were stratified by preoperative BMI (kg/m2 ) into four groups: <30, 30-34.9, 34.9-39.9, and ≥40. BMI data were collected at 12 and 6 months prior to implantation, time of implantation, and 3- and 6- months postimplantation. RESULTS: A total of 107 patients underwent LVAD implantation at our institution. Data were available for 80 patients. Baseline characteristics included a mean age of 56.0 years, 69% male, and a mean implant BMI of 29.9 ± 6.8 kg/m2 . The mean BMI (kg/m2 ) for each of the BMI (kg/m2 ) groups <30, 30-34.9, 35-39.9, and ≥40 (n = 60, 25, 12, and 10, respectively) was 25.1, 32.5, 36.8, and 43.8, respectively. There was no consistent pattern with weight change across differing implant BMIs. No patient with a BMI of <30 gained sufficient weight to impact transplant candidacy. Twenty-three percent of patients with a BMI of 30-34.9 kg/m2 , 60% of patients with a BMI of 35-39.9 kg/m2 , and 87.5% of patients with a BMI of ≥40 kg/m2 had a 6-month BMI potentially affecting transplant. CONCLUSIONS: Associated weight changes during LVAD support may significantly impact transplant candidacy. Higher BMI groups may benefit from multimodal and multidisciplinary targeted weight-loss interventions.

The Neutrophil-Lymphocyte Ratio and Survival During Left Ventricular Assist Device Support.

BACKGROUND: Systolic heart failure (HF) is a low-grade systemic inflammatory state. Neutrophil-lymphocyte ratio (NLR) is a nonspecific inflammatory marker with prognostic value in HF. We aimed to determine the relationship between NLR and mortality during left ventricular assist device (LVAD) support. METHODS AND RESULTS: We retrospectively reviewed LVAD recipients implanted in the years 2010-2018. NLR was recorded before LVAD implantation and at intervals during LVAD support; pre-LVAD and 90-day LVAD NLRs were compared. Cox proportional hazard models were constructed to study the impact of NLR, both before LVAD implantation and at 90 days with LVAD, on mortality during subsequent LVAD support. Among 301 subjects, the median pre-LVAD NLR was 4.7 (interquartile range 3.0-8.0). Higher pre-LVAD NLR was independently associated with increased mortality during a median 324 days of LVAD support (adjusted hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.01-1.06; P = .012, adjusted for pre-LVAD age, HF etiology, white blood count, hemoglobin, blood urea nitrogen, and sodium). After LVAD implantation, the NLR rose initially and then plateaued lower by day 90. Despite the mean decrease, higher 90-day LVAD NLR remained independently associated with increased mortality (adjusted HR 1.06, 95% CI 1.01-1.13; P = .033, stratified by early infection events). CONCLUSIONS: Higher pre-LVAD NLR is independently associated with mortality during LVAD support. NLR improves during LVAD support, but even accounting for early infections, a higher NLR at day 90 remains associated with subsequent mortality.

A fast and sensitive alternative for ß-galactosidase detection in mouse embryos.

The bacterial lacZ gene is widely used as a reporter in a myriad of mouse transgenic experiments. ß-Galactosidase, encoded by lacZ, is usually detected using X-gal in combination with ferric and ferrous ions. This assay produces a blue indole precipitate that is easy to detect visually. Here, we show that Salmon-gal in combination with tetrazolium salts provides a more sensitive and faster staining reaction than the traditional ß-galactosidase assay in mouse embryos. Using a combination of Salmon-gal and tetranitroblue tetrazolium, we were able to visualize the activity of ß-galactosidase in embryos at stages when the customary X-gal reaction failed to detect staining. Our studies provide an enhanced alternative for ß-galactosidase detection in expression and cell fate studies that use lacZ-based transgenic mouse lines.

The histone gene activator HINFP is a nonredundant cyclin E/CDK2 effector during early embryonic cell cycles.

Competency for DNA replication is functionally coupled to the activation of histone gene expression at the onset of S phase to form chromatin. Human histone nuclear factor P (HiNF-P; gene symbol HINFP) bound to its cyclin E/cyclin-dependent kinase 2 (CDK2) responsive coactivator p220(NPAT) is a key regulator of multiple human histone H4 genes that encode a major subunit of the nucleosome. Induction of the histone H4 transcription factor (HINFP)/p220(NPAT) coactivation complex occurs in parallel with the CDK-dependent release of pRB from E2F at the restriction point. Here, we show that the downstream CDK-dependent cell cycle effector HINFP is genetically required and, in contrast to the CDK2/cyclin E complex, cannot be compensated. We constructed a mouse Hinfp-null mutation and found that heterozygous Hinfp mice survive, indicating that 1 allele suffices for embryogenesis. Homozygous loss-of-function causes embryonic lethality: No homozygous Hinfp-null mice are obtained at or beyond embryonic day (E) 6.5. In blastocyst cultures, Hinfp-null embryos exhibit a delay in hatching, abnormal growth, and loss of histone H4 gene expression. Our data indicate that the CDK2/cyclin E/p220(NPAT)/HINFP/histone gene signaling pathway at the G1/S phase transition is an essential, nonredundant cell cycle regulatory mechanism that is established early in embryogenesis.

Sustained Use of the Impella 5.0 Heart Pump Enables Bridge to Clinical Decisions in 34 Patients.

We studied whether sustained hemodynamic support (>7 d) with the Impella 5.0 heart pump can be used as a bridge to clinical decisions in patients who present with cardiogenic shock, and whether such support can improve their outcomes. We retrospectively reviewed cases of patients who had Impella 5.0 support at our hospital from August 2017 through May 2019. Thirty-four patients (23 with cardiogenic shock and 11 with severely decompensated heart failure) underwent sustained support for a mean duration of 11.7 ± 9.3 days (range, ≤48 d). Of 29 patients (85.3%) who survived to next therapy, 15 were weaned from the Impella, 8 underwent durable left ventricular assist device placement, 4 were escalated to venoarterial extracorporeal membrane oxygenation support, and 2 underwent heart transplantation. The 30-day survival rate was 76.5% (26 of 34 patients). Only 2 patients had a major adverse event: one each had an ischemic stroke and flail mitral leaflet. None of the devices malfunctioned. Sustained hemodynamic support with the Impella 5.0 not only improved outcomes in patients who presented with cardiogenic shock, but also provided time for multidisciplinary evaluation of potential cardiac recovery, or the need for durable left ventricular assist device implantation or heart transplantation. Our study shows the value of using the Impella 5.0 as a bridge to clinical decisions.

COVID-19 Experience in a Wisconsin Academic Medical Center.

BACKGROUND: Several studies describing Coronavirus disease 2019 (COVID-19) have been reported; however, to our knowledge, no case series has been published from the Midwest. OBJECTIVE: To describe demographic characteristics and outcomes of patients admitted with COVID-19 to a Wisconsin academic medical center. METHODS: We performed a retrospective analysis of data obtained for COVID-19 patients admitted from March 14, 2020, through April 19, 2020. RESULTS: One hundred sixty-eight patients were admitted. Outcomes measured include time in the intensive care unit (53%), mechanical ventilation (18%), and death (19%). ICU patients had higher rates of diabetes, obesity, and higher inflammatory markers. The majority of patients admitted were African American (68%). CONCLUSION: This case series highlights demographic similarities and differences, as well as outcomes, among COVID-19 patients in a Wisconsin Academic Medical Center compared to those reported in other geographic regions.

Burden of arrhythmia and electrophysiologic procedures in alcoholic cardiomyopathy hospitalizations.

BACKGROUND: Limited national US data are available regarding the prevalence of and trends in different arrhythmias and the use of electrophysiological procedures in patients with alcoholic cardiomyopathy. METHODS: This was a cross-sectional study that used the Nationwide Inpatient Sample database (2007-2014). Hospitalizations of adults with alcoholic CMP were identified with the ICD-9 code (425.5). CAD and other causes of cardiomyopathy were excluded. Chi-square test, t-test, mixed-effect logistic regression and quantile regression were used. RESULTS: Among 75,430 hospitalizations, 48% had arrhythmias. Individuals with a co-diagnosis of arrhythmia tended to be older (56.9 vs 53.2-year-old) and male (89.5% vs 81.9%). The most prevalent arrhythmias were atrial fibrillation/flutter (31.5%), followed by ventricular tachycardia (7.9%). The prevalence of arrhythmias increased from 44% to 50% (2007-2014) (p < 0.001) and this increase was mainly secondary to the increasing prevalence AFib/AFL. Excluding cardiac arrest, arrhythmias were not associated with increased in-hospital mortality. The median length of stay and total charges for arrhythmia vs no-arrhythmia hospitalizations were 5 vs 4 days (p < 0.001) and $31,127 vs $24,199 respectively (p < 0.001). EP procedures were performed in 5.6% of all hospitalizations and it increased from 5.2% to 6% (2007-2014) (p = 0.2). The most common procedures were cardioversion (2.7%), ICD placement (2.2%) and PPM placement (1.1%). CONCLUSION: Arrhythmias were reported in 48% of hospitalizations. There was an increasing burden of arrhythmias secondary to increasing atrial fibrillation. Excluding cardiac arrest, arrhythmias were not associated with increased in-hospital mortality but were associated with longer hospital stays and higher total charges.

A Dual-Lumen Percutaneous Cannula for Managing Refractory Right Ventricular Failure.

A right ventricular assist device (RVAD) using a dual-lumen percutaneous cannula inserted through the right internal jugular vein (IJV) might improve weaning in patients with refractory right ventricular (RV) failure. However, the reported experience with this cannula is limited. We reviewed the records of all patients receiving RVAD support with this new dual-lumen cannula at our institution between April 2017 and February 2019. We recorded data on weaning, mortality, and device-specific complications. We compared outcomes among three subgroups based on the indications for RVAD support (postcardiotomy, cardiogenic shock, and primary respiratory failure) and against similar results in the literature. Mean (standard deviation [SD]) age of the 40 patients (29 men) was 53 (15.5) years. Indications for implantation were postcardiotomy support in 18 patients, cardiogenic shock in 12, and respiratory failure in 10. In all, 17 (94%) patients in the postcardiotomy group were weaned from RVAD support, five (42%) in the cardiogenic shock group, and seven (70%) in the respiratory failure group, overall higher than those reported in the literature (49% to 59%) for surgically placed RVADs. Whereas published in-hospital mortality rates range from 42% to 50% for surgically placed RVADs and from 41% to 50% for RVADs with percutaneous cannulas implanted through the right IJV, mortality was 11%, 58%, and 40% in our subgroups, respectively. There were no major device-related complications. This percutaneous dual-lumen cannula appears to be safe and effective for managing refractory RV failure, with improved weaning and mortality profile, and with limited device-specific adverse events.

Association of preoperative duration of inotropy on prevalence of right ventricular failure following LVAD implantation.

AIMS: 20% to 40% of left ventricular assist device (LVAD) device implantations are complicated by right ventricular (RV) failure that results in significant morbidity and mortality. We hypothesized that the duration on milrinone infusion is an independent risk factor for RV failure following LVAD implantation. METHODS AND RESULTS: Retrospective demographic, clinical and hemodynamic data were collected on all adults with ACC/AHA stage D heart failure on intravenous milrinone who underwent LVAD implantation between 2012 and 2019. Patients (n = 104) were divided into two groups, those on milrinone <30 days (STM, n = 55) vs. ≥30 (LTM, n = 49). The primary endpoint was the prevalence of RV failure (need for inotropic support for more than 14 days or RV assist device) within 30 days post-LVAD implantation. There were no significant differences between STM and LTM patients with respect to demographic, echocardiographic, right heart catheterization data, or baseline medications. The mean age of patients was 55.6 ± 12 years (70% male patients). Mean duration on milrinone was 13.7 vs. 81.0 days in STM and LTM, respectively. Forty-five (43.3%) patients developed RV failure. LTM had higher prevalence of RV failure with odds ratio (OR) = 5.04 (95% CI 2.18-11.68, P = 0.0002). After adjusting for age, gender, and co-morbidity count, the OR was 6.33 (95% CI 2.51-15.93), P < 0.0001. CONCLUSIONS: In this retrospective study of ACC/AHA stage D HF patients, longer duration of milrinone infusion was associated with higher prevalence of RV failure after LVAD implantation.

Testing the obesity paradox in patients on long-term milrinone infusion for end-stage heart failure.

BACKGROUND: Obese patients with chronic HF have a lower mortality than do non-obese patients with heart failure (HF) i.e. "obesity paradox". We sought to determine the relationship between obesity (defined by body-mass index; BMI) and survival in inotrope-dependent patients with Stage D HF. METHODS AND RESULTS: We screened the medical records of adults with ACC/AHA stage D HF who were admitted to our institution between January, 2010 and July, 2018 who were both initiated and discharged on continuous intravenous milrinone. Patients were divided into three groups: non-obese patients (Nob-BMI < 30 kg/m2), Class 1 obese patients (Ob1-BMI 30 to 34.9 kg/m2), and class 2/3 obese patients (Ob2/3-BMI ≥ 35 kg/m2). The primary endpoint was all-cause mortality. Of the 233 patients included in the study, 154 were NOb, 39 were Ob1, and 40 were OB2/3. Age and baseline comorbidities did not differ significantly among the groups. Mean follow up was 21.8 months (Median: 12.4, IQ range: 3.6-31.3). Compared to the NOb, relative mortality (HR) was 0.68 for Ob1 patients and 1.21 for Ob2/3 patients (P = 0.30). Adjusting for age, sex, race, and medical comorbidities, relative mortality was 0.85 in the Ob1 and 1.77 in the Ob2/3 (P = 0.08). CONCLUSION: In this retrospective study of stage D inotrope-dependent HF patients, there was trend of an "obesity paradox" with higher survival in the Ob1 group patients compared to NOb and Ob2/3 patients. Ob2/3 patients had the worst survival.