Dunlay, Shannon M.

Introduction: Axial and centrifugal-flow left ventricular assist devices (LVAD) have varied response to changes in loading conditions. Whether ventricular size modulates the response to LVAD therapy between the axial flow Heartmate II (HMII) and centrifugal flow Heartware (HVAD) is unknown. Hypothesis: Adverse event and survival rates between devices are affected by recipient pre-op left ventricular end-diastolic diameter (LVEDD). Methods: Data on 1,149 continuous-flow LVAD recipients from May 2004 to May 2015 was pooled from the Mechanical Circulatory Support Research Network (MCSRN). The effect of pre-op LVEDD on the instantaneous hazard of death and adverse events was evaluated between HMII (n=864) and HVAD (n=283). Results: The average LVEDD was 7.0cm and did not differ between the device recipients. Patients with a smaller LVEDD (≤ 6.3cm) were more likely female 39% v. 24% (p < 0.0001) and to have an ischemic cardiomyopathy (30% v. 24%, p = 0.045). For every 1cm increase in pre-op LVEDD, the adjusted hazard ratio (HR) for mortality increased with HVAD (HR 1.31, 95% CI 0.94-1.82, p = 0.005) and decreased with HMII (HR 0.78, 95% CI 0.67-0.92, p = 0.005), Figure 1a. Other predictors of mortality included age (HR 1.31, 95% CI 1.12 - 1.53 per 10y, p < 0.001) and bilirubin (HR 1.15, 95% CI 0.94-1.42 per mg/dL, p = 0.027). LVEDD by device type interaction was not a significant predictor of gastrointestinal bleeding or pump thrombosis. The risk of stroke increased with LVEDD for HVAD and decreased for HMII, but this did not reach statistical significance, Figure 1b. Ischemic etiology of heart failure (HR 1.7 95% CI 1.14 - 2.55, p = 0.01) and HVAD device use (HR 1.47 95% CI 1.00 - 2.17, p = 0.03) were significant predictors of stroke. Conclusions: Our data suggest important differences exist in patient outcomes between HMII and HVAD based on pre-op ventricular size. Studies are needed to determine if these differences in outcome are due to device or flow-specific differences in patient support.

Background: Whether age alone explains the comorbidity burden in heart failure (HF) is unclear. In particular, differences in the burden of co-morbid conditions in HF patients compared to population controls has not been well documented. Methods: The prevalence of 17 chronic conditions defined by the US Department of Health and Human Services were obtained in 1746 incident HF patients from 2000-2010 and controls matched 1:1 on sex and age from Olmsted County, MN. Conditions were ascertained requiring 2 occurrences of a diagnostic code. Logistic regression determined associations of each condition with HF. Results: Among the 1746 matched pairs (mean age 76.2 years, 43.5% men), the prevalence was higher in HF cases for all conditions (p<0.05) except dementia and osteoporosis. After adjusting for all conditions, hypertension, coronary artery disease, arrhythmia, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hepatitis, and substance abuse were significantly more common in HF (figure). More than a 2-fold increased odds of hepatitis, arrhythmia, and coronary artery disease was observed among HF cases. Arrhythmia (34.2%), hypertension (31.1%), and coronary artery disease (27.8%) had the largest attributable risk of HF; for example, assuming a causal relationship, if arrhythmias were eliminated, 34% of HF would be avoided. Conclusions: Compared to age- and sex-matched controls, HF patients have a higher prevalence of many chronic conditions, indicating the excess comorbidity in HF is not due to age alone. Some cardiovascular conditions, including arrhythmia, coronary artery disease, and hypertension were more common in HF. Of the non-cardiovascular conditions, hepatitis had the strongest association with HF and was an unanticipated finding that deserves additional investigation. It is important to understand comorbidities as they play a key role in the excess mortality and healthcare utilization experienced by HF patients.

Introduction: Mortality among patients with heart failure (HF) is high. Though individual biomarkers have been studied to determine their value in risk prediction, the role of a multimarker strategy in predicting mortality above established risk indicators requires evaluation in a relevant cohort using robust analytical methods. Objective: To determine whether adding C-reactive protein (CRP), B-type natriuretic peptide (BNP), and troponin T (TnT) to established risk indicators improved HF mortality risk prediction. Methods: Olmsted County residents presenting with HF from July 2004 to September 2007 were prospectively recruited to undergo biomarker measurement. We investigated whether addition of CRP, BNP, and TnT to a model including established risk indicators improved 6-month mortality risk prediction using multiple methods ( c statistic, net reclassification index, integrated discrimination improvement). Results: Of 566 participants (mean age 77±13 years, 48% male), 87(15%) patients died after 6 months follow-up. Patients with CRP (<12.1mg/L), BNP (<341pg/mL), and TnT (≥0.01ng/mL) below the median (n=112) had the lowest mortality (3%), those with one or two biomarkers above the median had intermediate mortality, and those with all biomarkers above the median (n=105) had markedly increased 6-month mortality (33%). After adjustment for other predictors, higher CRP, BNP, and TnT were each associated with increased mortality, with odds ratios (95% confidence intervals) of 1.66(1.24 –2.24), 2.06(1.42–3.07), and 1.45(1.12–1.87), respectively. While adding CRP, BNP, and TnT individually to the model improved mortality risk prediction, the combination of two or more biomarkers offered greater incremental benefit. Using all biomarkers resulted in an increase in the c statistic from 0.747 to 0.832 (p<0.001), a net reclassification index of 0.33 (p<0.001), and a 100% relative improvement in risk discrimination (integrated discrimination improvement 0.097, p<0.001). Conclusions: The combined use of CRP, BNP, and TnT markedly improved the prediction of 6-month mortality in HF beyond established risk indicators. Implementation of a multimarker strategy including CRP, BNP, and TnT for risk prediction in HF should be considered. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

Background: Contemporary data on survival after incident acute coronary syndrome (ACS), including both myocardial infarction (MI) and unstable angina (UA), are limited. Objective: To describe survival after incident ACS, to determine if it differs by ACS type (MI or UA) and to determine whether it has improved over time. Methods: Olmsted County, MN residents hospitalized between 1/1/2005-12/31/2010 were screened for incident ACS. ACS was defined as either MI validated by standard epidemiological criteria or UA validated by the Braunwald classification. Patients were followed for death from any cause. Cox proportional hazards regression was used to determine whether survival differed by ACS type, while adjusting for year of diagnosis, age, sex and comorbidities. Results: Among 1,160 incident ACS cases (mean±SD age 66.9±14.8, 60% male), 35% were UA and 65% were MI. After a mean (SD) follow up of 3.7 (2.1) years, 274 deaths occurred. The 3-year Kaplan-Meier survival estimate for MI was 79.6% (95% CI: 76.7%-82.6%) and for UA was 84.9% (95% CI: 81.3%-88.6%) (log-rank p=0.011). The association of ACS type with survival differed by age (p=0.056). After adjustment for year of diagnosis, sex and comorbidities, no difference in survival was observed between ACS types among those aged <60 (HR for MI vs. UA: 0.64, 95% 0.29-1.42). By contrast, among patients aged 60-79, those with an MI had 2 times the risk of death compared to those with UA (HR: 2.04, 95% CI: 1.24-3.37). Patients aged 80 or older who had an MI had a 40% increased risk of death compared to patients of the same age who had UA (HR: 1.42, 95% CI: 1.02-1.98). There was no difference in survival over time (HR for 2010 vs. 2005: 0.91, 95% CI: 0.61-1.36). Conclusions: Survival did not differ between UA and MI patients younger than 60, however among patients 60 or older, survival was worse among those with an MI. Survival after ACS did not change over the study period.

Background: In July 2015, the FDA approved the use of sacubitril/ valsartan in patients with heart failure (HF) and reduced ejection fraction. It was shown in a large clinical trial to reduce the risk of both hospitalization and death compared with enalapril, and has since received a class I recommendation for use in the 2016 ACC/ AHA HF guidelines. However, the use of sacubitril/ valsartan in a clinical practice has not been described. We aimed to assess the uptake and cost of sacubitril/ valsartan in its first year following FDA approval. Methods: Using a large U.S. insurance database, we identified privately insured and Medicare Advantage (MA) patients who filled a first prescription for sacubitril/ valsartan between July 1, 2015 and July 31, 2016. We restricted to persons with medical and pharmacy enrollment for 6 months prior to first fill. For reference, we identified all individuals with a diagnosis of HF on a billing claim (ICD9 428.X or ICD-10 I50.X) in the same time period. Results: There were 314,410 individuals with a diagnosis of HF in the study period. In total, 972 filled a new prescription for sacubitril/ valsartan, and the number of new users steadily increased over time (Figure). The mean age of sacubitril/ valsartan users was 68.1±12.3 years, 32.5% were women, 61.1% were white, and 77% were enrolled in MA plans. Most prescribing clinicians were cardiologists (82.5%). A majority of prescription costs were covered by the health plan (mean $324.05, median $335.38, interquartile range [IQR] $266.56-$370.10). Out-of-pocket (OOP) costs per 30-day prescription filled were variable (mean $101.53, median $45.00, IQR $7.40-$97.49), and were similar in beneficiaries enrolled in MA and commercial plans. By comparison, median OOP costs were $2-4 for lisinopril, losartan, carvedilol, and spironolactone per 30-day prescription. Discussion: These finding suggest that the uptake of sacubitril/ valsartan has been slow in the first year after FDA approval. While the majority of prescription costs are covered by the health plan, OOP costs are still much higher than other guideline-recommended HF medications. Further studies are needed to determine if uptake of sacubril/ valsartan continues to rise and if the higher prescription cost is associated with lower downstream costs of hospitalization and mortality benefit.

Abstract Aims This study aims to evaluate the impact of the combination of cardiogenic shock (CS) and cardiac arrest (CA) complicating non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results Adult (&gt;18 years) NSTEMI admissions using the National Inpatient Sample database (2000 to 2017) were stratified by the presence of CA and/or CS. Outcomes of interest included in-hospital mortality, early coronary angiography, hospitalization costs, and length of stay. Of the 7 302 447 hospitalizations due to NSTEMI, 147 795 (2.0%) had CS only, 155 522 (2.1%) had CA only, and 41 360 (0.6%) had both CS and CA. Compared with 2000, the adjusted odds ratios (ORs) and 95% confidence interval (CIs) for CS, CA, and both CS and CA in 2017 were 3.75 (3.58–3.92), 1.46 (1.42–1.50), and 4.52 (4.16–4.87), respectively (all P &lt; 0.001). The CS + CA (61.2%) cohort had higher multiorgan failure than CS (42.3%) and CA only (32.0%) cohorts, P &lt; 0.001. The CA only cohort had lower rates of overall (52% vs. 59–60%) and early (17% vs. 18–27%) angiography compared with the other groups (all P &lt; 0.001). CS + CA admissions had higher in-hospital mortality compared with those with CS alone (aOR 4.12 [95% CI 4.00–4.24]), CA alone (aOR 1.69 [95% CI 1.65–1.74]), or without CS/CA (aOR 22.66 [95% CI 22.06–23.27]). The presence of CS, either alone or with CA, was associated with higher hospitalization costs and longer hospital length of stay. Conclusions The combination of CS and CA is associated with higher rates of acute non-cardiac organ failure and in-hospital mortality in NSTEMI admissions as compared with those with either CS or CA alone.

Abstract Aims There are limited contemporary data on the use of initial fibrinolysis in ST-segment elevation myocardial infarction cardiogenic shock (STEMI-CS). This study sought to compare the outcomes of STEMI-CS receiving initial fibrinolysis vs. primary percutaneous coronary intervention (PPCI). Methods Using the National (Nationwide) Inpatient Sample from 2009 to 2017, a comparative effectiveness study of adult (&gt;18 years) STEMI-CS admissions receiving pre-hospital/in-hospital fibrinolysis were compared with those receiving PPCI. Admissions with alternate indications for fibrinolysis and STEMI-CS managed medically or with surgical revascularization (without fibrinolysis) were excluded. Outcomes of interest included in-hospital mortality, development of non-cardiac organ failure, complications, hospital length of stay, hospitalization costs, use of palliative care, and do-not-resuscitate status. Results During 2009–2017, 5297 and 110 452 admissions received initial fibrinolysis and PPCI, respectively. Compared with those receiving PPCI, the fibrinolysis group was more often non-White, with lower co-morbidity, and admitted on weekends and to small rural hospitals (all P &lt; 0.001). In the fibrinolysis group, 95.3%, 77.4%, and 15.7% received angiography, PCI, and coronary artery bypass grafting, respectively. The fibrinolysis group had higher rates of haemorrhagic complications (13.5% vs. 9.9%; P &lt; 0.001). The fibrinolysis group had comparable all-cause in-hospital mortality [logistic regression analysis: 28.8% vs. 28.5%; propensity-matched analysis: 30.8% vs. 30.3%; adjusted odds ratio 0.97 (95% confidence interval 0.90–1.05); P = 0.50]. The fibrinolysis group had comparable rates of acute organ failure, hospital length of stay, rates of palliative care referrals, do-not-resuscitate status use, and lesser hospitalization costs. Conclusions The use of initial fibrinolysis had comparable in-hospital mortality than those receiving PPCI in STEMI-CS in the contemporary era in this large national observational study.

Background: There are limited data on the epidemiology and timing of in-hospital death (IHD) in patients with acute myocardial infarction-cardiogenic shock (AMI-CS). Methods: Adult admissions with AMI-CS with IHDs were identified using the National Inpatient Sample (2000–2016) and were classified as early (≤2 days), mid-term (3–7 days), and late (>7 days). Inter-hospital transfers and those with do-not-resuscitate statuses were excluded. The outcomes of interest included the epidemiology, temporal trends and predictors for IHD timing. Results: IHD was noted in 113,349 AMI-CS admissions (median time to IHD 3 (interquartile range 1–7) days), with early, mid-term and late IHD in 44%, 32% and 24%, respectively. Compared to the mid-term and late groups, the early IHD group had higher rates of ST-segment-elevation AMI-CS (74%, 63%, 60%) and cardiac arrest (37%, 33%, 29%), but lower rates of acute organ failure (68%, 79%, 89%), use of coronary angiography (45%, 56%, 67%), percutaneous coronary intervention (33%, 36%, 42%), and mechanical circulatory support (31%, 39%, 50%) (all p < 0.001). There was a temporal increase in the early (adjusted odds ratio (aOR) for 2016 vs. 2000 2.50 (95% confidence interval (CI) 2.22–2.78)) and a decrease in mid-term (aOR 0.75 (95% CI 0.71–0.79)) and late (aOR 0.34 (95% CI 0.31–0.37)) IHD. ST-segment-elevation AMI-CS and cardiac arrest were associated with the increased risk of early IHD, whereas advanced comorbidity and acute organ failure were associated with late IHD. Conclusions: Early IHD after AMI-CS has increased between 2000 and 2016. The populations with early vs. late IHD were systematically different.

Background. Despite demonstrated efficacy, patient decision aids (DAs) are rarely used in clinical practice in the absence of coverage mandates. Deciding whether to pursue a left ventricular assist device (LVAD) is a major, preference-sensitive decision—ideal for exploring implementation of a DA. Methods. We conducted a type II effectiveness-implementation hybrid trial at 6 LVAD programs using a stepped-wedge cluster-randomized design. Using the RE-AIM framework, we collected both quantitative and qualitative outcomes, including a checklist collected by study staff for each enrolled patient regarding DA use and interviews with LVAD program clinicians preintervention, 6 months postintervention, and at the conclusion of the study. Results. From June 2015 to January 2017, 248 patients and their caregivers were enrolled. A total of 69 interviews were conducted with 48 clinicians at 3 time points. The DA reached 95% of eligible patients. Adoption was 100%, as all sites approached agreed to participate in the trial. Interviews revealed several themes related to the implementation of the DA: clinicians had a strong desire to ensure patients were informed and embraced the DA. Despite this, they reported communication challenges among their team that impeded implementation. Five of the 6 sites have maintained use of the DA following the trial; 1 site reported concerns about decreased procedural volume with use of the DA as a reason for discontinuation. Conclusions. In this hybrid trial, a DA for patients considering LVADs and their caregivers demonstrated high reach. Adoption and implementation were facilitated by a strong desire to ensure that patients were well informed. Future dissemination research and practice should attend to concerns about procedure volume and coverage mandates and facilitate ongoing communication at sites using the DA.