Publications by authors named "Emmanuel Akintoye"

100 Publications

Outcomes of diabetic patients with end-stage heart failure listed for heart transplantation: A propensity-matched analysis.

Clin Transplant 2022 Jan 12:e14590. Epub 2022 Jan 12.

Division of Heart Failure and Transplant, University of Iowa Hospitals and Clinics, Iowa, Iowa, USA.

Background: We investigated the current trends and outcomes of diabetic patients listed for heart transplants in the U.S. and provided a method for risk-stratification.

Methods: Using data from the United Network for Organ Sharing (UNOS), we identified heart failure patients listed for heart transplants between 2010 and 2019. Diabetic patients were propensity-matched with non-diabetics, and waitlist mortality as well as post-transplant graft survival were compared between the two groups. Further risk-stratification of diabetic patients was done based on the risk factors that independently predict graft failure.

Results: 28,928 adult patients (30% diabetic) with end-stage heart failure were added to the waitlist over the study period. In the propensity-matched cohort, waitlist mortality was higher in diabetic patients compared to non-diabetics (HR = 1.13 (95% CI = 1.04-1.22, P = .002). Over the study period, 5739 patients with diabetes were transplanted. In the propensity-matched cohorts of transplant recipients, the rate of graft failure was significantly higher for diabetic patients (23.3%) compared to non-diabetics (20.4%); HR = 1.17, 95% CI = 1.08-1.26, P < .001. We identified 12 risk factors of graft failure among diabetic patients and developed a risk score that further risk-stratify these patients. Diabetic patients at low risk (score≤4) had similar graft survival as patients without diabetes (HR = .91, 95% CI = .82-1.01, P = .06). On the other hand, high-risk diabetic patients had worse graft survival compared to non-diabetics (HR = 1.52, 95% CI = 1.38-1.67, P < .001).

Conclusion: Among patients with end-stage heart failure, pre-existing diabetes was associated with higher waitlist mortality and worse graft survival. However, with careful patient selection, graft survival is similar to those without diabetes.
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http://dx.doi.org/10.1111/ctr.14590DOI Listing
January 2022

Rilonacept for the treatment of recurrent pericarditis.

Expert Opin Biol Ther 2021 Nov 10. Epub 2021 Nov 10.

Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic. Cleveland, OH 44195.

Introduction: Recurrent pericarditis (RP) is a debilitating disease that has an underlying autoinflammatory pathophysiology mediated by cytokine interleukin (IL)-1. Rilonacept, a recombinant dimeric fusion protein that blocks IL-1α and IL-1β signaling has emerged as a valuable therapeutic option of RP. Rilonacept has been evaluated in Phase 2 and 3 clinic trials and was recently approved for RP treatment.

Areas Covered: This article reviews available clinical trials assessing the efficacy and safety of rilonacept for the treatment of RP.

Expert Opinion: Findings from Rhapsody (Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes stuDY) phase 2 and 3 trials suggest that rilonacept represents a promising new therapy for those patients with colchicine resistant or glucocorticoid-dependence disease. Treatment leads to rapid clinical response, with a median resolution of symptoms in 5 days, normalization of C-reactive protein (CRP) in a median of 7 days, and successful weaning from glucocorticoids. This novel therapy also reduces recurrence rates compared with placebo. Rilonacept has also demonstrated a good safety profile, with the most common adverse events including injection-site reactions and upper respiratory tract infections. This anti-IL 1 agent has emerged as an efficacious treatment for RP, with potential use for glucocorticoid-free regimens and as monotherapy. Future trials are needed to explore these treatment options and to clarify the appropriate therapy duration.
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http://dx.doi.org/10.1080/14712598.2022.2005024DOI Listing
November 2021

Changing Demographics, Temporal Trends in Waitlist, and Posttransplant Outcomes After Heart Transplantation in the United States: Analysis of the UNOS Database 1991-2019.

Circ Heart Fail 2021 11 25;14(11):e008764. Epub 2021 Oct 25.

Division of Heart Failure and Transplant (A.B.), University of Iowa Hospitals and Clinics, Iowa City.

Background: We sought to investigate temporal trends in patient characteristics, waitlist, and posttransplant outcomes after heart transplantation in the United States.

Methods: Using data from the United Network of Organ Sharing, we identified adults listed for heart transplantation between 1991 and 2019. Patients were divided into 4 eras based on the 3 time points in which changes were made to the patient selection/allocation policy (Era 1=January 1991-January 1999; Era 2=January 1999-July 2006; Era 3=July 2006-October 2018; and Era 4=October 2018-March 2020), and patient characteristics, waitlist, and posttransplant outcomes were evaluated for each era.

Results: Between 1991 and 2019, 95 179 patients were added to the heart transplantation waitlist. Compared with Era 1, patients listed in Era 4 were older (mean age: 50 versus 52 years) and with higher risk comorbidities (eg, 10% versus 28.8% diabetes, 23.3% versus 35.6% obese). Over the study period, 22 738 patients died or were permanently delisted for deterioration on the waitlist while 61 687 were transplanted. Compared with the preceding era, there was significant decrease in death or deterioration in the last 2 eras (sub-hazard ratio, 0.67 [95% CI, 0.65-0.70] for Era 3 versus Era 2 and sub-hazard ratio, 0.65 [95% CI, 0.58-0.73] for Era 4 versus 3). Across the years, 27.1% to 40.5% of those on the waitlist were transplanted. Among those transplanted, there was increase in the rates of in-hospital stroke (2.8% in Era 1 to 3.7% in Era 4), renal failure requiring dialysis (7.2%-17.1%), and length-of-stay (14-17days), <0.001. However, this did not negatively impact short-term survival when compared with the preceding era (1-year graft survival from Era 1 to Era 4=84.1%, 86.4%, 90.4%, and 89.7%, respectively).

Conclusions: There have been significant changes in the characteristics of patients listed for heart transplantation. Although transplant volume has increased, the wide supply-demand gap persisted. The last two changes in the allocation policy achieved their primary objective of reducing waitlist mortality.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.008764DOI Listing
November 2021

Prognostic Implications of Ambulatory N-Terminal Pro-B-Type Natriuretic Peptide Changes in Patients with Continuous-Flow Left Ventricular Assist Devices.

ASAIO J 2021 Aug 3. Epub 2021 Aug 3.

From the Department of Medicine, University of Iowa Health Care, Carver College of Medicine, Iowa, Iowa Department of Medicine, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York Department of Surgery, University of Iowa Health Care, Carver College of Medicine, Iowa, Iowa.

Data regarding the role of N-terminal Pro-B-type natriuretic peptide (NT-pro BNP) in patients with a continuous-flow left ventricular assist device (CFLVAD) is scarce. To evaluate the prognostic implications of measuring both absolute values and changes in NT-pro BNP concentrations in ambulatory patients with a CFLVAD, we performed a retrospective study of 168 consecutive patients who had an LVAD implantation at our institution and survived beyond their index hospitalization. Of these, 127 patients (56.2 ± 12.5 years, 21.2% female) had NT-pro BNP measured at 1 and 3 months postdischarge in ambulatory settings. Compared to the NT-pro BNP concentration at 1 month, 94 patients (74%) had a decline, and 33 patients (26%) had an increase in concentrations, from their 1 month baseline. After a median follow-up of 17 months, a total of 53 (41.7%) adverse events occurred. Of these, 37 (69.8%) were heart failure (HF) hospitalizations, and 16 (30.2%) were deaths. For each 1,000 unit increase in NT-pro BNP concentration at 3 months, there was a 17% increase in the risk of HF hospitalization or death (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.04-1.32, p = 0.007). Conversely, each 1000 unit decline during the same time, was associated with an 11% decrease in the risk of HF hospitalization or death (HR = 0.89, 95% CI = 0.77-0.98, p = 0.04). In conclusion, in patients with a CFLAD, an increase in NT-pro BNP concentration from 1 to 3 months is associated with an increased risk of HF hospitalization and death. In contrast, a decline is associated with a reduction in the risk of HF hospitalization and death.
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http://dx.doi.org/10.1097/MAT.0000000000001524DOI Listing
August 2021

Prognostic Utility of Risk Enhancers and Coronary Artery Calcium Score Recommended in the 2018 ACC/AHA Multisociety Cholesterol Treatment Guidelines Over the Pooled Cohort Equation: Insights From 3 Large Prospective Cohorts.

J Am Heart Assoc 2021 06 7;10(12):e019589. Epub 2021 Jun 7.

Division of Cardiology University of Iowa Hospital and Clinics Iowa City IA.

Background Limited data exist on the incremental value of the risk enhancers recommended in the 2018 American Heart Association/American College of Cardiology (ACC/AHA) cholesterol treatment guidelines in addition to the pooled cohort equation. Methods and Results Using pooled individual-level data from 3 epidemiological cohorts involving 22 942 participants (56% women, mean age 59 years), we evaluated the predictive ability of the risk enhancers and coronary artery calcium (CAC) score for atherosclerotic cardiovascular disease, and determined their incremental utility using the C statistic, net reclassification index, and integrated discrimination index. A total of 1960 (8.5%) atherosclerotic cardiovascular disease events were accrued over 10 years. Of the 10 risk enhancers evaluated, only 6 predicted atherosclerotic cardiovascular disease independent of the pooled cohort equation. However, the individual enhancers demonstrated little or no incremental benefit. There was more incremental value from combining the 6 enhancers into an aggregate score (hazard ratio [HR], 1.21; 95% CI, 1.08-1.37 for each additional enhancer), and having ≥3 enhancers represents an optimum threshold for incremental prediction (C statistic, 0.766; net reclassification index, 0.041; integrated discrimination index, 0.010; ≤0.007). On the other hand, CAC was superior to individual enhancers (C statistic, 0.774; net reclassification index, 0.073; integrated discrimination index, 0.010; <0.001), reliably reclassifies intermediate-risk participants with <3 risk enhancers (event rate, 3.5% if no CAC and 9.8% if positive CAC), but offered no reclassification among participants with ≥3 enhancers. Conclusions The individual risk enhancers evaluated in this study provided no or only marginal incremental information added to the pooled cohort equation. However, the presence of ≥3 risk enhancers reliably identified intermediate-risk patients that will benefit from statin therapy, and further CAC testing may be considered among those with <3 risk enhancers.
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http://dx.doi.org/10.1161/JAHA.120.019589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477885PMC
June 2021

Cardiac magnetic resonance imaging findings in primary arrhythmogenic left ventricular cardiomyopathy with cardiocutaneous phenotype-Carvajal syndrome.

HeartRhythm Case Rep 2021 May 10;7(5):312-315. Epub 2021 Feb 10.

Division of Cardiovascular Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

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http://dx.doi.org/10.1016/j.hrcr.2021.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134784PMC
May 2021

Top ten takeaways from #ASNC2020: FITs' perspective.

J Nucl Cardiol 2021 Jun 2;28(3):1068-1071. Epub 2021 Mar 2.

Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, Iowa City, USA.

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http://dx.doi.org/10.1007/s12350-021-02559-0DOI Listing
June 2021

Longitudinal trends and outcomes of adult heart transplantation in the U.S.

Eur J Intern Med 2021 04 22;86:115-117. Epub 2021 Jan 22.

Division of Cardiovascular Diseases, Section of Heart Failure and Transplant, University of Iowa Hospitals and Clinics, Iowa City, IA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ejim.2021.01.001DOI Listing
April 2021

State-Level Variation in Waitlist Mortality and Transplant Outcomes Among Patients Listed for Heart Transplantation in the US From 2011 to 2016.

JAMA Netw Open 2020 12 1;3(12):e2028459. Epub 2020 Dec 1.

Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, Iowa City.

Importance: Little is known about geographic variation in the outcomes of adult patients listed for heart transplantation in the US. Identifying the patterns and extent of variation is important to minimize disparity in outcomes.

Objective: To evaluate the geographic patterns, extent, and factors associated with state-level variation in outcomes of adult patients listed for heart transplantation in the US.

Design, Setting, And Participants: This nationwide retrospective cohort study used data from the United Network for Organ Sharing database to identify adult patients listed for heart transplantation at status 1A between January 1, 2011, and December 31, 2016. Patients were followed up until March 31, 2018. Data were analyzed from November 1, 2019, to September 19, 2020.

Main Outcomes And Measures: The study evaluated state-level variation in the 3 main organ transplant measures: waitlist mortality, transplant rate, and risk-adjusted 1-year graft survival. The rate of death while on the waitlist and the rate of transplant were calculated for each state per 1000 waitlist person-days listed at status 1A over the study period. Risk-adjusted 1-year graft survival was calculated based on the Scientific Registry of Transplant Recipients risk-adjustment model. State-level variation in each outcome measure was evaluated via multivariable-adjusted models.

Results: Across 50 states and the District of Columbia, a total of 15 036 patients (mean [SD] age, 52 [13] years; 3531 women [24%]; 9626 White [64%]) were listed at status 1A for adult heart transplantation between 2011 and 2016. Of those, 2146 patients (14.3%) died while on the waitlist, and 10 982 patients (73.0%) received transplants. Among those who received transplants, the median time on the waitlist was 31 days (interquartile range, 13-61 days). State-level outcomes ranged from 1.0 to 7.8 deaths per 1000 waitlist person-days for waitlist mortality, 5.6 to 34.5 transplants per 1000 waitlist person-days for transplant rate, and 87% to 92% for risk-adjusted 1-year graft survival. In a comparison of the highest and lowest quartiles, significant state-level variation was found in waitlist mortality (hazard ratio [HR], 1.53; 95% CI, 1.27-1.86), transplant rate (HR, 1.57; 95% CI, 1.31-1.87), and 1-year graft survival (odds ratio, 2.07; 95% CI, 1.64-2.62).

Conclusions And Relevance: The study's findings indicate that significant state-level variation exists in the outcomes of patients listed for heart transplantation in the US. Identifying and addressing the factors associated with these geographic variations in outcomes is important to ensure a fair allocation system.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.28459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726636PMC
December 2020

Intermediate and Late Outcomes With PCI vs CABG for Left Main Disease - Landmark Meta-Analysis of Randomized Trials.

Cardiovasc Revasc Med 2021 02 2;23:114-118. Epub 2020 Sep 2.

Department of Cardiothoracic Surgery, Alpert Medical School, Brown University, RI, USA.

PCI to improve survival is currently recommended as a reasonable alternative to CABG in patients with unprotected left main disease. However, RCTs to support this recommendation has generated mixed results and recently published EXCEL trial has sparked debate about differences in late mortality. To address this point, we performed landmark meta-analysis of 4 RCTs with 5 year follow up data - EXCEL, NOBLE, PRECOMBAT and SYNTAX LEFT MAIN. Overall, there was no significant difference in all-cause mortality between PCI and CABG at 5 years (RR = 1.03 [95% CI = 0.79-1.33]). However, there was apparent change in the direction of association before and after the 1 year landmark that underscores the need for long term follow up in these trials. In addition, we found that PCI was associated with significantly lower rate of intermediate stroke at 1 year (RR = 0.44 [0.24-0.82]) but higher rate of late MI after 1 year (3.31 [2.11-5.18]) compared to CABG.
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http://dx.doi.org/10.1016/j.carrev.2020.08.040DOI Listing
February 2021

Characteristics and Outcomes of Patients Undergoing Combined Organ Transplantation (from the United Network for Organ Sharing).

Am J Cardiol 2020 08 24;129:42-45. Epub 2020 May 24.

Division of Cardiovascular Diseases, Section of Heart Failure and Transplant, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

Studies have shown that highly selected patients who underwent combined heart-kidney (HK) and heart-liver transplants (HLv) have short- and long-term outcomes comparable to those observed in primary heart transplantation (HT). Adults patients with stage D heart failure that underwent combined HK, HLv, and heart-lung (HL) were identified in the United Network for Organ Sharing registry from 1991 to 2016, with follow-up through March 2018. We conducted inverse probability of treatment weighting survival analysis of long-term survival stratified by type of combined organ transplant, accounting for donor, recipient, and operative characteristics. We identified 2,300 patients who underwent combined organ transplant (HK 1,257, HLv 212, HL 831). HL recipients were more likely white (77%), women (58%), with congenital heart disease (44.5%), and longer waiting list time (median 195 days). HK transplant increased significantly during the study period where as HL decreased significantly. Median survival was 12.2 years for HK (95% confidence intervals [CI] 10.8 to 12.8), 12 for HLv (95% CI 8.6 to 17.6) but significantly lower at 4.5 years for HL (95% CI 3.6 to 5.8). Combined HK and HLv transplantation rates are increasing and long-term survival is comparable to primary HT, unlike HL which is associated with decreasing trends and significantly lower survival.
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http://dx.doi.org/10.1016/j.amjcard.2020.05.034DOI Listing
August 2020

Effect of Concurrent Dementia on Heart Failure Hospital Outcomes: Nationwide Inpatient Sample (2007-2014).

J Card Fail 2021 02 5;27(2):258-260. Epub 2020 Jun 5.

Division of Nuclear Medicine, Department of Radiology, Brigham and Women's Hospital; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA; Cardiac Amyloidosis Program, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA. Electronic address:

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http://dx.doi.org/10.1016/j.cardfail.2020.05.020DOI Listing
February 2021

Incidence and clinical outcomes of bleeding complications and acute limb ischemia in STEMI and cardiogenic shock.

Catheter Cardiovasc Interv 2021 05 30;97(6):1129-1138. Epub 2020 May 30.

Division of Cardiology, Department of Internal Medicine, Tuft University Medical Center, Boston, Massachusetts, USA.

Background: Bleeding complications and acute limb ischemia (ALI) are devastating vascular complications in patients with ST-segment elevation myocardial infarction (STEMI). Cardiogenic shock (CS) can further increase this risk due to multiorgan failure. In the contemporary era, percutaneous mechanical circulatory support is commonly used for management of CS. We hypothesized that vascular complications may be an important determinant of clinical outcomes for CS due to STEMI (CS-STEMI).

Objective: We evaluated 10-year national trends, resource utilization and outcomes of bleeding complications, and ALI in CS-STEMI.

Methods: We performed a retrospective cohort study of CS-STEMI patients from a large U.S. national database (National Inpatient Sample) between 2005 and 2014. Events were then divided into four different groups: no MCS, with intra-aortic balloon pump, percutaneous ventricular assist device includes Impella or Tandem Heart or extracorporeal membrane oxygenation.

Results: Bleeding complications and ALI were observed in 31,389 (18.2%) and 1,628 (0.9%) out of 172,491 admissions with CS-STEMI, respectively. Between 2005 and 2014, overall trends increased for ALI; however, the number of bleeding events decreased. ALI was associated with increased in-hospital mortality in comparison to those without any ALI. However, bleeding complications were not associated with increased in-hospital mortality. Compared to patients without complications, both bleeding and ALI were associated with increased length of stay (LOS) and hospitalization costs.

Conclusions: Bleeding and ALI are common complications associated with CS-STEMI in the contemporary era. Both complications are associated with increased hospital costs and LOS. These findings highlight the need to develop algorithms focused on vascular safety in CS-STEMI.
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http://dx.doi.org/10.1002/ccd.29003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344361PMC
May 2021

Aortic Valve Replacement for Severe Aortic Stenosis Before and During the Era of Transcatheter Aortic Valve Implantation.

Am J Cardiol 2020 07 9;126:73-81. Epub 2020 Apr 9.

Center for Heart Valve Disease, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.

Recent positive results of transcatheter aortic valve replacement (TAVI) in clinical trials have sparked debate on whether TAVI should be first line for all patients with aortic stenosis. However, limited evidence exists on the clinical impact of TAVI on a national level. Using the national inpatient sample (NIS) of hospital discharges in the United States from 2001 to 2016, we evaluated the rate of AVR and associated in-hospital outcomes in pre-TAVI and TAVI era. Hierarchical mixed effect modeling was used to assess for trend and calculate risk adjusted estimates. Annual volume of AVR increased from 49,357 in 2001 to 100,050 in 2016 (103% increase). Compared with the pre-TAVI era, mean annual change in volume of AVR was higher in the TAVI era (+2.9% vs +9.4%, respectively, p <0.001). In contrast, rate of in-hospital mortality decreased from 5.4% in 2001 to 2.7% in 2016 (50% decrease). Compared with the pre-TAVI era, magnitude of mean annual change in mortality was higher in TAVI era (-4.0% vs -6.7%, respectively, p = 0.04). Unlike SAVR for which risk-adjusted rate for most outcomes seems to have plateaued, TAVI demonstrated significant improvement from 2012 to 2016 for mortality (4.6% to 1.8%), acute kidney injury (15.1% to 2.6%) and nonroutine home discharge (63.6% to 44.6%). However, no significant change in the rate of stroke (2.4% to 2.1%) and pacemaker implantation remained high (8.1% to 9.4%). Lastly, median length of stay was shorter for TAVI compared with isolated SAVR (3 vs 8 days, respectively). In conclusion, the adoption of TAVI has led to increase in volume of AVR for severe aortic stenosis in the United States with favorable short-term outcome.
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http://dx.doi.org/10.1016/j.amjcard.2020.03.038DOI Listing
July 2020

Palliative Care in Ruptured Aortic Aneurysm in the United States: A Retrospective Analysis of Nationwide Inpatient Sample Database.

Angiology 2020 08 6;71(7):633-640. Epub 2020 Apr 6.

Shizuoka Medical Center, Shizuoka, Japan.

We assessed the trend of palliative care (PC) referrals and its effect on hospitalization cost and length of stay (LOS) in ruptured aortic aneurysm (rAA). The Nationwide Inpatient Sample from 2005 to 2014 was used to identify admissions with age ≥50 and rAA. A total of 54 134 rAA admissions were identified and 5019 (9.3%) had PC referrals. During the study period, PC referral rate increased from 0.97% to 15.3% ( trend < .0001). Length of stay (1.7 vs 2.8 days, adjusted mean ratio [aMR] = 0.62, 95% confidence interval [CI]: 0.58-0.66), and cost (US$7778 vs US$13 575, aMR = 0.57, 95% CI: 0.52-0.63) were significantly lower in rAA admissions that did not undergo interventions. In the percutaneous repair group, LOS was similar but the cost was higher (US$61 759 vs US$52 260, aMR = 1.18, 95% CI: 1.05-1.30), whereas in surgical repair group, LOS was shorter (4.6 vs 5.9 days, aMR = 0.77, 95% CI: 0.73-0.82) but the cost was higher (US$59 755 vs US$52 523, aMR = 1.14, 95% CI: 1.02-1.28). Palliative care could shorten LOS and save hospitalization cost in rAA admissions not a candidate for repair. Further studies are required to investigate the variable effects of PC on rAA.
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http://dx.doi.org/10.1177/0003319720917239DOI Listing
August 2020

Rural-Urban Disparities in Intracerebral Hemorrhage Mortality in the USA: Preliminary Findings from the National Inpatient Sample.

Neurocrit Care 2020 06;32(3):715-724

Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Objectives: To compare in-hospital mortality between intracerebral hemorrhage (ICH) patients in rural hospitals to those in urban hospitals of the USA.

Methods: We used the National Inpatient Sample to retrospectively identify all cases of ICH in the USA over the period 2004-2014. We used multivariable-adjusted models to compare odds of mortality between rural and urban hospitals. Joinpoint regression was used to evaluate trends in age- and sex-adjusted mortality in rural and urban hospitals over time.

Results: From 2004 to 2014, 5.8% of ICH patients were admitted in rural hospitals. Rural patients were older (mean [SE] 76.0 [0.44] years vs. 68.8 [0.11] years in urban), more likely to be white and have Medicare insurance. Age- and sex-adjusted mortality was greater in rural hospitals (32.2%) compared to urban patients (26.5%) (p value < 0.001). After multivariable adjustment, patients hospitalized in rural hospitals had two times the odds of in-hospital death compared to patients in urban hospitals (OR 2.07, 95% CI 1.77-2.41. p value < 0.001). After joinpoint regression, mortality declined in urban hospitals by an average of 2.8% per year (average annual percentage change, [AAPC] - 2.8%, 95% CI - 3.7 to - 1.8%), but rates in rural hospitals remained unchanged (AAPC - 0.54%, 95% CI - 1.66 to 0.58%).

Conclusions: Despite current efforts to reduce disparity in stroke care, ICH patients hospitalized in rural hospitals had two times the odds of dying compared to those in urban hospitals. In addition, the ICH mortality gap between rural and urban centers is increasing. Further studies are needed to identify and reverse the causes of this disparity.
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http://dx.doi.org/10.1007/s12028-020-00950-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223184PMC
June 2020

Temporal trends and outcomes of patients waiting on left ventricular assist devices and inotropes for heart transplantation.

Clin Transplant 2020 06 10;34(6):e13857. Epub 2020 Apr 10.

Section of Heart Failure and Transplant, Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.

We sought to evaluate the trends and outcomes of patients with left ventricular assist devices (LVADs) and inotropes at the time of listing for heart transplantation. Adults with an LVAD implanted and listed with 1A status were identified in the United Network for Organ Sharing (UNOS) registry between 2010 and 2017. Patients were grouped according to the presence or absence of inotropes at the time of listing and transplantation. A total of 2714 patients were included in the study including 664 patients on inotropes at the time of listing, 235 at the time of transplantation, and 118 on inotropes both at listing and at the time of transplantation. Patients on LVAD and inotropes at the time of listing were more frequently supported with a right ventricular assist device (RVAD) (P < .001), had higher risk of death in the waiting list (sub-hazard ratio [SHR] = 1.48, 95% CI 1.14-1.90, P = .002), and were less likely to be transplanted (SHR = 0.70, 95% CI 0.63-0.78, P < .001) compared with those not on inotropes, after adjusting for described confounders. Approximately 1 in 10 LVAD recipients listed as status 1A are on inotropic therapy at the time of heart transplantation. Patients on LVAD and inotropes have worse outcomes in terms of survival and lower rates of transplantation.
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http://dx.doi.org/10.1111/ctr.13857DOI Listing
June 2020

The impact of insurance type on listing status and wait-list mortality of patients with left ventricular assist devices as bridge to transplantation.

ESC Heart Fail 2020 06 5;7(3):804-810. Epub 2020 Mar 5.

Division of Cardiovascular Diseases, Section of Heart Failure and Transplant, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

Aims: Adequate health insurance coverage is necessary for heart transplantation (HT) candidates. Prior studies have suggested inferior outcomes post HT with public health insurance. We sought to evaluate the effects of insurance type on transplantation rates, listing status and mortality prior to HT.

Methods And Results: Patients ≥18 years old with a left ventricular assist device implanted and listed with 1A status were identified in the United Network for Organ Sharing registry between January 2010 and December 2017, with follow-up through March 2018. Patients were grouped based on the type of insurance private/self-pay (PV), Medicare (MC), and Medicaid (MA) at the time of listing. We conducted multivariable competing risks regression analysis on listing status and mortality on the waiting list, stratified by insurance type at the time of listing. We identified 2604 patients listed in status 1A (PV: 51.4%, MC: 32.1%, and MA: 16.5%). MA patients were younger (43.5 vs. 56.4 for MC vs. 51.5 for PV, P < 0.001) and less frequently White (P < 0.001). The cumulative incidence of HT did not differ among the three insurance types (PV: 74.8%, MC 76.3%, and MA 71.1%, P = 0.14). The cumulative mortality on the waiting list prior to HT was not different among groups (PV: 29.3%, MC 26.3%, and MA 21.8%, P = 0.94). Μore patients with MA were removed from the list because of improvement of their condition (MA 40.3% vs. MC 28.3% and PV 32.8%).

Conclusions: We did not detect any disparities in listing status and mortality among different insurance types.
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http://dx.doi.org/10.1002/ehf2.12655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261523PMC
June 2020

Association between Hospital volume of cardiopulmonary resuscitation for in-hospital cardiac arrest and survival to Hospital discharge.

Resuscitation 2020 03 13;148:25-31. Epub 2020 Jan 13.

Division of Cardiovascular Medicine, University of Iowa Hospital and Clinics, Iowa, IA, United States.

Background: Prior studies have shown that hospital case volume is not associated with survival in patients with out-of-hospital cardiac arrest (OHCA). However, how case volume impact on survival for in-hospital cardiac arrest (IHCA) is unknown.

Methods: We queried the National Inpatient Sample (NIS) in the U.S. 2005-2011 to identify cases in which in-hospital CPR was performed for IHCA. Restricted cubic spine was used to evaluate the association between hospital annual CPR volume and survival to hospital discharge.

Results: Across more than 1000 hospitals in NIS, we identified 125,082 cases (mean age 67, 45% female) of IHCA for which CPR was performed over the study period. Median [Q1, Q3] case volume was 60 [34, 99]. Compared to those in the 1 st quartile of case volume, hospitals in the 4th quartile tends to have younger patients (mean = 66 vs 68 yrs), higher comorbidities (median Elixhauser score = 4 vs 3), and in low income areas (37 vs 30%). Overall, 23% of the patients survived to hospital discharge. There was a non-linear association between CPR volume and survival: a non-significant trend towards better survival was observed with increasing annual CPR volume that reached a plateau at 51-55 cases per year, after which survival began to drop and became significantly lower after 75 cases per year (p for non-linearity<0.001). Compared to those in first quartile of case volume, hospitals in 4 quartile had higher length of stay (median = 8 vs 10 days, respectively) and higher rate of non-routine home discharge (64% vs 67%) among those who survived.

Conclusion: Unlike OHCA, low CPR volume is an indicator of good performing hospitals and increasing CPR case volume does not translate to improve survival for IHCA.
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http://dx.doi.org/10.1016/j.resuscitation.2019.12.037DOI Listing
March 2020

Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis.

Can J Cardiol 2019 12 8;35(12):1784-1790. Epub 2019 Aug 8.

Department of Cardiovascular Medicine Mayo Clinic, Rochester, Minnesota, USA.

Background: Although there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.

Methods: We used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Of the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).

Conclusions: LV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.
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http://dx.doi.org/10.1016/j.cjca.2019.07.634DOI Listing
December 2019

Palliative care referral in ST-segment elevation myocardial infarction complicated with cardiogenic shock in the United States.

Heart Lung 2020 Jan - Feb;49(1):25-29. Epub 2019 Nov 6.

University of Iowa Hospitals and Clinics, Iowa, Iowa, United States.

Background: ST-segment elevation myocardial infarction complicated with cardiogenic shock (STEMI-CS) is associated with high mortality but the trends of utilization and predictors of palliative care (PC) referral in this population have not been well described.

Objectives: To investigate the utilization trends and predictors of PC referral in STEMI-CS.

Methods: Nationwide inpatient sample from 2005-2014 was queried to identify patients with STEMI-CS of age ≥18. PC referral was identified International Classification of Diseases, Ninth Edition Clinical Modification, V66.7.

Results: A total of 33,294 admissions were identified and 1,878 (5.6%) had PC encounter. PC referral group were older and had higher comorbidities. PC consultation increased approximately 10 times over the study period in those who died (from 2.3% to 27.4%) and in those who survived (from 0.21% to 2.83%). In multivariable analysis, age, higher Exlixhauser score, no revascularization, teaching hospital, large bed hospital, mechanical circulatory support use, and lower income status were associated with increased PC referral whereas coronary artery bypass graft was associated with lower PC referral rates. Patients under PC group were more often discharged to an extended care facility and less likely discharged home.

Conclusion: PC utilization increased substantially during the 10-years study period in the United States in STEMI-CS. Several baseline, procedural, hospital, and socioeconomic factors were associated with PC referral in the setting STEMI-CS.
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http://dx.doi.org/10.1016/j.hrtlng.2019.10.005DOI Listing
November 2020

Do the Bare Minimum During Percutaneous Revascularization of Myocardial Infarction in Cardiogenic Shock.

Cardiovasc Revasc Med 2019 11 7;20(11):935-936. Epub 2019 Sep 7.

University of Iowa Healthcare, Iowa City, IA, United States.

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http://dx.doi.org/10.1016/j.carrev.2019.09.004DOI Listing
November 2019

Gender Differences in Outcomes After Implantation of Left Ventricular Assist Devices.

Ann Thorac Surg 2020 03 31;109(3):780-786. Epub 2019 Aug 31.

Section of Heart Failure and Transplant, Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, Iowa City, Iowa. Electronic address:

Background: Left ventricular assist device (LVAD) implantation has historically been underutilized in women compared with men. It was hypothesized that the introduction of continuous-flow LVADs would lead to more LVAD implantations in women and possibly narrow the gender gap.

Methods: Patients who underwent LVAD implantation between 2009 and 2014 were identified using the national inpatient sample.

Results: A total of 3511 patients (17,251 when weighted) underwent LVAD implantation in the United States between 2009 and 2014. Mean age was 56 years and there were 817 women in the study sample (23.32%). LVAD implantations in women doubled from 2009 to 2014, but men continued to receive LVAD 3 times more than women. Inpatient mortality after LVAD placement was similar between men and women (13.42% women vs 12.85% men; odds ratio, 1.05; P = .16). Most common complications after LVAD implantation in both genders included acute kidney injury, bleeding requiring blood transfusion, and postoperative sepsis. There were no gender-specific differences in the incidence of periprocedural complications, including postoperative cardiac tamponade, postoperative thromboembolism, or sepsis. In addition, no significant difference was found in length of stay and median hospitalization cost. The use of extracorporeal membrane oxygenation did not differ between men and women. Subgroup analysis in patients older than 65 years of age showed higher in-hospital mortality but no differences between genders.

Conclusions: The number of women undergoing LVAD implantation has increased with the introduction of continuous-flow LVADs, but a gender gap still exists. Most major in-hospital outcomes after LVAD implantation are similar between genders.
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http://dx.doi.org/10.1016/j.athoracsur.2019.07.032DOI Listing
March 2020

The impact of safety-net burden on in-hospital outcomes after surgical aortic valve replacement.

J Card Surg 2019 Nov 23;34(11):1178-1184. Epub 2019 Aug 23.

Division of Cardiovascular Surgery, Department of Surgery, Shizuoka Medical Center, Shizuoka, Japan.

Background And Aim: Surgical aortic valve replacement (SAVR) is the most common valvular surgery and thus needs to be widely available including minorities and socially disadvantaged patients. SAVR outcomes at safety-net hospitals, which serve a high percentage of these patients, are limited. We aimed to compare the outcomes of SAVR at different safety-net burden hospitals.

Methods: Nationwide Inpatient Sample from 2005 to 2011 was queried to identify SAVR performed for over the age of 50. The safety-net burden of hospitals was calculated as the number of admission to a hospital in a year who were uninsured or insured by Medicaid divided by the total number of admissions for the respective year. Hospitals were categorized into quintiles of safety-net rate and then into three categories based on the safety-net burden (low burden hospitals [LBHs], lowest quintile, medium burden hospitals [MBHs], 2nd-4th quintiles; and high burden hospitals [HBHs], highest quintile).

Results: A total of 85 441 SAVR were included. In unadjusted models, in-hospital mortality was higher in HBHs compared with LBHs but became nonsignificant after adjustments for patient and hospital-level characteristics. Major perioperative complications and hospital costs were similar, but hospital stay was longer at HBHs compared with LBHs. At MBHs, acute kidney injury requiring dialysis and bleeding requiring transfusion was lower compared with LBHs. Length of stay and cost were shorter and lower at MBHs compared with LBHs. Nonroutine discharge was similar for HBHs and MBHs compared with LBHs.

Conclusion: SAVR outcomes are reassuring at MBHs and HBHs.
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http://dx.doi.org/10.1111/jocs.14187DOI Listing
November 2019

Clinical Impact of Atrial Fibrillation on Short-Term Outcomes and In-Hospital Mortality in Patients with Takotsubo Syndrome: A Propensity-Matched National Study.

Cardiovasc Revasc Med 2020 04 23;21(4):522-526. Epub 2019 Jul 23.

Division of Cardiology, Department of Internal Medicine, Detroit Medical Center/Wayne State University School of Medicine, Detroit, MI, USA.

Introduction: Takotsubo Syndrome (TS) patients are at high risk of developing atrial fibrillation. We sought to investigate the outcomes and economic impact of atrial fibrillation on TS patients utilizing the National Inpatient Sample.

Methods: Patients with TS were identified in the National Inpatient Sample (NIS) database between 2010 and 2014 using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), and subsequently were divided into two groups, those with and without atrial fibrillation. The primary outcome was all-cause in-hospital mortality in the two groups. Secondary outcomes were in-hospital complications. We also evaluated the length of hospital stay and the cost of hospitalization. Propensity score-matched analysis was performed to address potential confounding factors.

Results: Among the study population, the prevalence of atrial fibrillation was 17.57%. After matching, the atrial fibrillation group had no significant increase of in-hospital mortality (OR: 1.13; 95% CI: 0.94-1.35, p = 0.211). However, atrial fibrillation patients were more likely to develop cardiac arrest and ventricular arrhythmias (OR: 1.51, 95% CI: 1.26-1.80, p < 0.0001), have higher rate of major cardiac complications when combined as a single endpoint in-hospital complication (OR: 1.16, 95% CI: 1.04-1.29, p: 0.006), also they were more likely to stay longer in hospital (OR: 1.13, 95% CI: 1.08-1.19, p < 0.0001), and have increased cost of hospitalization (OR: 1.13, 95% CI 1.07-1.20, p < 0.0001).

Conclusion: Atrial fibrillation does not increase in-hospital mortality in patients presenting with TS. However atrial fibrillation is associated with an increased risk of ventricular arrhythmias, length of stay, non-routine discharges and cost of hospitalization.
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http://dx.doi.org/10.1016/j.carrev.2019.07.022DOI Listing
April 2020

Reducing substance abuse in patients receiving prescription opioids for chronic non-cancer pain: a quality improvement and patient safety study in a primary care setting.

J Community Hosp Intern Med Perspect 2019 19;9(3):175-180. Epub 2019 Jun 19.

Division of Cardiovascular Disease, University of Iowa Hospitals and Clinics, Iowa City, USA.

: Chronic non-cancer pain is a common cause of primary care physicians' office visits. : To determine the impact of adopting screening and monitoring measures in primary care settings on the illicit substance use behavior of patients receiving opioid analgesic prescriptions. : This was a retrospective analysis of data on patients who were prescribed opioid analgesics for chronic non-cancer pain between 2014 and 2017 Q1 (i.e., first quarter of 2017). Study participants were patients who sought medical care at our academic primary care clinic practice that is part of an internal medicine residency program. Participants were adults (>18 years) who were considered eligible for opioid analgesics for chronic non-cancer pain. : (1) Rolling out of the chronic non-cancer pain management policy to clinic staff; (2) pain medication contracts with patients; (3) random urine drug screen (UDS) testing performed on patients during their clinic visits; 4) a didactics curriculum for internal medicine residents to highlight the key elements in utilizing and interpreting UDS results; (5) adding alerts to the electronic medical record that notifies clinic staff of discrepancy between patients' prescribed medications and UDS findings, as well as for quick identification of patients who had violated a stipulation of the contract; (6) mandatory regular utilization of Michigan State's online prescription monitoring records; and (7) employment of an on-site behavioral specialist for patients with mental illness or at risk of drug abuse. : The main endpoint was the percentage of illicit drug use detected per year. : A total of 8096 UDS samples were collected over the study period. Mean (SD) participant age was 52 (SD 12) and 51% were male. Urine samples which had at least one illicit substance constituted 41% of the samples in 2014 prior to intervention. We found a significant decrease in the percentage of illicit substances after initiation of the intervention to 37% in 2015, 19% in 2016, and 12% in 2017Q1 ( < 0.001). : Adopting a system-wide screening and monitoring measures in a primary care setting can significantly reduce the amount of illicit drug use among patients receiving an opioid prescription for non-cancer pain. This has important implications for patient safety and the current opioid epidemic in the USA. Further studies are needed to evaluate similar interventions in other settings such as a pain clinic.
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http://dx.doi.org/10.1080/20009666.2019.1622377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586083PMC
June 2019

In-Hospital Outcomes of ST-Segment Elevation Myocardial Infarction Complicated With Cardiogenic Shock at Safety-Net Hospitals in the United States (from the Nationwide Inpatient Sample).

Am J Cardiol 2019 08 28;124(4):485-490. Epub 2019 May 28.

University of Iowa Hospitals and Clinics, Iowa, Iowa.

Safety-net hospitals (SNHs) are hospitals that serve a higher proportion of patients insured by Medicaid or uninsured and have been reported to have poor outcomes compared with non-SNHs. Procedural and clinical outcomes of ST-segment elevation myocardial infarction complicated by cardiogenic shock (STEMI-CS) at SNHs have not been well described. Nationwide Inpatient Sample from 2005 to 2011 was queried to identify STEMI-CS and age ≥18. SNHs were defined as hospitals with the highest number of inpatient stays that were paid by Medicaid or were uninsured (the top quartile). A total of 23,229 STEMI-CS of which 3,639 (15.7%) were treated at SNHs. Admissions to SNHs were younger (mean age 66.0 vs 67.2, p < 0.001), more likely men (64.0% vs 62.2%, p = 0.04), more frequently ethnic minorities (Black; 11.0% vs 6.0%, Hispanic 20.4% vs 5.8%, p < 0.001), and had higher Elixhauser ≥4 (25.8% vs 21.9%, respectively, p < 0.001). Percutaneous coronary interventions were less performed (60.4% vs 65.8%, p < 0.001) whereas administrations of thrombolysis (2.9% vs 2.1%, p = 0.001) were more frequent at SNHs. Coronary artery bypass and the use of mechanical circulatory support was similar. In-hospital mortality was significantly elevated at SNHs (36.6% vs 32.7%, adjusted odds ratio 1.24, 95% confidence interval 1.10 to 1.39) whereas new dialysis, stroke, and fatal arrhythmias were similar. The median length of stay was similar (6 vs 7 days, p = 0.58) but the median cost was higher (40,175 vs 38,012 US dollars, p = 0.01) at SNHs. SNHs had lower utilization of percutaneous coronary intervention and higher in-hospital mortality compared with non-SNHs in STEMI-CS. Further cause analysis is warranted to improve outcomes of STEMI-CS admitted at SNHs.
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http://dx.doi.org/10.1016/j.amjcard.2019.05.037DOI Listing
August 2019

Trends, Outcomes, and Readmissions Among Left Ventricular Assist Device Recipients with Acute Kidney Injury Requiring Hemodialysis.

ASAIO J 2020 05;66(5):507-512

From the Division of Cardiovascular Medicine, University of Iowa, Iowa City, Iowa.

Although renal function may improve after left ventricular assist devices (LVAD) implantation, acute kidney injury (AKI) requiring hemodialysis (HD) therapy can occur postoperatively. We used data from the National Readmissions Database to calculate annual rates of in-hospital outcomes and readmissions among patients who underwent implantation and developed acute kidney injury (AKI) requiring hemodialysis (HD) for years 2012-2015. We identified 178 (weighted 469) patients with AKI requiring HD after LVAD implantation. In-hospital mortality was significantly higher among LVAD recipients who required HD for AKI compared with those who did not (42.38% vs. 8.38%, p < 0.001). Rates of in-hospital mortality (from 52.1% in 2012 to 33.9% in 2014, p = 0.046) and length of stay (from 60.3 days in 2012 to 47.1 days in 2014, p = 0.003) decreased significantly, whereas there was a trend toward reduced hospital cost (from $320,414 in 2012 to $267,285 in 2014, p = 0.076) during the study period. However, postoperative bleeding increased significantly (p = 0.01). Acute kidney injury requiring HD after implantation was not associated with significantly higher rates of readmissions compared with LVAD recipients without AKI on HD, after adjustment for clinical and hospital characteristics (41.4% vs. 30.5%; odds ratio 1.28; 95% confidence interval [CI]: 0.85-1.95; P = 0.239). However, 5.42% of these patients required maintenance hemodialysis in readmissions. In-hospital mortality and length of stay are decreasing but remain unacceptably high in patients requiring HD for AKI after LVAD implantation but remain higher than LVAD recipients without AKI on HD. A minority of these patients who survive hospital discharge require maintenance hemodialysis.
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http://dx.doi.org/10.1097/MAT.0000000000001036DOI Listing
May 2020

Trends and Outcomes of Infective Endocarditis in Adults With Tetralogy of Fallot: A Review of the National Inpatient Sample Database.

Can J Cardiol 2019 06 16;35(6):721-726. Epub 2019 Feb 16.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Background: Lesion complexity and prosthetic valves are known risk factors for infective endocarditis in patients with congenital heart disease. Tetralogy of Fallot (TOF) is the most common complex/cyanotic congenital heart disease and often requires prosthetic valve implantation. Population-based risk of endocarditis in TOF patients is unknown.

Methods: We reviewed the National Inpatient Sample (NIS) and identified admissions in TOF patients (>18 years), 2000 to 2014. The primary outcome was to describe incidence of endocarditis-related admissions. To assess trends, we divided the study period into tertiles: early (2000 to 2004), mid (2005 to 2009) and late (2010 to 2014) eras. The secondary outcome was to compare in-hospital mortality, complications, and health care resource utilization between admissions with and without endocarditis.

Results: There were 393 (2.1%) endocarditis-related admissions among 18,353 admissions, and the incidence of endocarditis-related admissions increased over time: 1.9% (early era) vs 2.2% (mid-era) vs 2.4% (late era), P < 0.001. Overall in-hospital mortality was 6%. In addition to previously described risk factors for endocarditis, such as previous pacemaker/defibrillator or prosthetic valve implantation, we observed an association between endocarditis-related admissions and male gender, black race, and lower socioeconomic class. In comparison with admissions without endocarditis, the endocarditis-related admissions had higher in-hospital mortality, complications, and health care resource utilization measured by length of stay, inflation-adjusted hospitalization cost, and type of hospital discharge.

Conclusions: Incidence of endocarditis-related admissions increased over time and was associated with higher mortality, complications, and health care resource utilization. Further studies are required to investigate the observed temporal increase in incidence of endocarditis and explore new strategies to improve outcomes.
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http://dx.doi.org/10.1016/j.cjca.2019.02.006DOI Listing
June 2019
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