Puza P. Sharma

In-Hospital Worsening Heart Failure and Associations With Mortality, Readmission, and Healthcare Utilization

Background A subset of patients hospitalized with acute heart failure experiences worsening clinical status and requires escalation of therapy. Worsening heart failure is an end point in many clinical trials, but little is known about its prevalence in clinical practice and its associated outcomes. Methods and Results We analyzed inpatient data from the Acute Decompensated Heart Failure National Registry linked to Medicare claims to examine the prevalence and outcomes of patients with worsening heart failure, defined as the need for escalation of therapy at least 12 hours after hospital presentation. We compared patients with worsening heart failure to patients with an uncomplicated hospital course and patients with a complicated presentation. Of 63 727 patients hospitalized with acute heart failure, 11% developed worsening heart failure. These patients had the highest observed rates of mortality, all‐cause readmission, and Medicare payments at 30 days and 1 year after hospitalization (P < 0.001 for all comparisons). The adjusted hazards of 30‐day mortality were 2.56 (99% CI, 2.34 to 2.80) compared with an uncomplicated course and 1.29 (99% CI, 1.17 to 1.42) compared with a complicated presentation. The adjusted cost ratios for postdischarge Medicare payments at 30 days were 1.35 (99% CI, 1.24 to 1.46) compared with an uncomplicated course and 1.11 (99% CI, 1.02 to 1.22) compared with a complicated presentation. Conclusions In‐hospital worsening heart failure was common and was associated with higher rates of mortality, all‐cause readmission, and postdischarge Medicare payments. Prevention and treatment of in‐hospital worsening heart failure represents an important goal for patients hospitalized with acute heart failure.

Transient and persistent worsening renal function during hospitalization for acute heart failure

BACKGROUND Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF. METHODS We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (< 0.3 mg/dL) or persistent WRF (≥ 0.3 mg/dL). We examined unadjusted rates and adjusted associations between 90-day outcomes and WRF status. RESULTS Among 27,309 patients, 18,568 (68.0%) had no WRF, 3,205 (11.7%) had transient WRF, and 5,536 (20.3%) had persistent WRF. Patients with WRF had higher observed rates of 90-day postdischarge all-cause readmission and 90-day postadmission mortality (P < .001). After multivariable adjustment, transient WRF (hazard ratio [HR] 1.19, 99% CI 1.05-1.35) and persistent WRF (HR 1.73, 99% CI 1.57-1.91) were associated with higher risks of 90-day postadmission mortality (P < .001 for both). Compared with transient WRF, persistent WRF was associated with a higher risk of 90-day postadmission mortality (HR 1.46, 99% CI 1.28-1.66, P < .001). CONCLUSIONS Transient and persistent WRF during hospitalization for acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes.

Development and validation of a risk model for in-hospital worsening heart failure from the Acute Decompensated Heart Failure National Registry (ADHERE)

BACKGROUND A subset of patients hospitalized with acute heart failure experiences in-hospital worsening heart failure, defined as persistent or worsening signs or symptoms requiring an escalation of therapy. METHODS We analyzed data from the Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims to develop and validate a risk model for in-hospital worsening heart failure. Our definition of in-hospital worsening heart failure included events such as escalation of medical therapy (eg, inotropic medications) >12hours after admission. We considered candidate risk prediction variables routinely assessed at admission, including age, medical history, biomarkers, and renal function. We used logistic regression with robust standard errors to generate a risk model in a 66% random derivation sample; we validated the model in the remaining 34%. We evaluated the calibration and discrimination of the model in both samples. RESULTS We evaluated 23,696 patients hospitalized with acute heart failure. Baseline characteristics were well matched in the derivation and validation samples, and the occurrence of in-hospital worsening heart failure was similar in both samples (15.4% and 15.6%, respectively). In the multivariable model, the strongest predictors of in-hospital worsening heart failure were increased troponin and creatinine. The model was well calibrated and had good discrimination in the derivation sample (c statistic, 0.74) and validation sample (c statistic, 0.72). CONCLUSIONS The ADHERE worsening heart failure risk model is a clinical tool with good discrimination for use in patients hospitalized with acute heart failure to identify those at increased risk for in-hospital worsening heart failure. This tool may be useful to target treatment strategies for patients at high risk for in-hospital worsening heart failure.

Differences in health care use and outcomes by the timing of in-hospital worsening heart failure

BACKGROUND Patients hospitalized with acute heart failure may experience worsening symptoms requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and postdischarge outcomes, but associations between the timing of worsening heart failure and outcomes are unknown. METHODS Using data from a large clinical registry linked to Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for acute heart failure. We defined in-hospital worsening heart failure by the use of inotropes or intravenous vasodilators or initiation of mechanical circulatory support, hemodialysis, or ventilation. The study groups were early worsening heart failure (n = 1,990), late worsening heart failure (n = 4,223), complicated presentation (n = 15,361), and uncomplicated hospital course (n = 41,334). RESULTS Among 62,908 patients, those with late in-hospital worsening heart failure had higher in-hospital and postdischarge mortality than patients with early worsening heart failure or complicated presentation. Those with early or late worsening heart failure had more frequent all-cause and heart failure readmissions at 30 days and 1 year, with resultant higher costs, compared with patients with an uncomplicated hospital course. CONCLUSION Although late worsening heart failure was associated with the highest mortality, both early and late worsening heart failures were associated with more frequent readmissions and higher health care costs compared to uncomplicated hospital course. Prevention of worsening heart failure may be an important focus in the care of hospitalized patients with acute heart failure.

Health Status Disparities by Sex, Race/Ethnicity, and Socioeconomic Status in Outpatients With Heart Failure

OBJECTIVES This study sought to describe the health status of outpatients with heart failure and reduced ejection fraction (HFrEF) by sex, race/ethnicity, and socioeconomic status (SES). BACKGROUND Although a primary goal in treating patients with HFrEF is to optimize health status, whether disparities by sex, race/ethnicity, and SES exist is unknown. METHODS In the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, the associations among sex, race, and SES and health status, as measured by the Kansas City Cardiomyopathy Questionnaire-overall summary (KCCQ-os) score (range 0 to 100; higher scores indicate better health status) was compared among 3,494 patients from 140 U.S. clinics. SES was categorized by total household income. Hierarchical multivariate linear regression estimated differences in KCCQ-os score after adjusting for 31 patient characteristics and 10 medications. RESULTS Overall mean KCCQ-os scores were 64.2 ± 24.0 but lower for women (29% of sample; 60.3 ± 24.0 vs. 65.9 ± 24.0, respectively; p < 0.001), for blacks (60.5 ± 25.0 vs. 64.9 ± 23.0, respectively; p < 0.001), for Hispanics (59.1 ± 21.0 vs. 64.9 ± 23.0, respectively; p < 0.001), and for those with the lowest income (<

Health Status Variation Across Practices in Outpatients With Heart Failure: Insights From the CHAMP-HF (Change the Management of Patients With Heart Failure) Registry

25,000; mean: 57.1 vs. 63.1 to 74.7 for other income categories; p < 0.001). Fully adjusted KCCQ-os scores were 2.2 points lower for women (95% confidence interval [CI]: −3.8 to −0.6; p = 0.007), no different for blacks (p = 0.74), 4.0 points lower for Hispanics (95% CI: −6.6 to −1.3; p = 0.003), and lowest in the poorest patients (4.7 points lower than those with the highest income (95% CI: 0.1 to 9.2; p = 0.045; p for trend = 0.003). CONCLUSIONS Among outpatients with HFrEF, women, blacks, Hispanics, and poorer patients had worse health status, which remained significant for women, Hispanics, and poorer patients in fully adjusted analyses. This suggests an opportunity to further optimize treatment to reduce these observed disparities.

Retrospective Study of the Prevalence, Predictors, and Consequences of Nonadherence With Lapatinib in Women With Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab

Background: Although a key treatment goal for patients with heart failure with reduced ejection fraction is to optimize their health status (their symptoms, function, and quality of life), the variability across outpatient practices in achieving this goal is unknown. Methods and Results: In the CHAMP-HF (Change the Management of Patients With Heart Failure) registry, associations between baseline practice characteristics and Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary (OS) and Symptom Frequency (SF) scores were assessed in 3494 patients across 140 US practices using hierarchical regression after accounting for 23 patient and 11 treatment characteristics. We then calculated an adjusted median odds ratio to quantify the average difference in likelihood that a patient would have excellent (KCCQ-OS, ≥75) health status or minimal (monthly or fewer) symptoms (KCCQ-SF, ≥75) when treated at one practice versus another, at random. The mean (±SD) KCCQ-OS and KCCQ-SF were 64.2±24 and 68.9±25.6, with 40% (n=1380) and 50% (n=1760) having KCCQ scores ≥75, respectively. The adjusted median odds ratio across practices, for KCCQ-OS ≥75, was 1.70 (95% confidence interval, 1.54–1.99; P<0.001) indicating a median 70% higher odds of a patient having good-to-excellent health status when treated at one random practice versus another. In regard to KCCQ-SF, the adjusted median odds ratio for KCCQ-SF ≥75 was 1.54 (95% confidence interval, 1.41–1.76; P=0.001). Conclusions: In a large, contemporary registry of outpatients with chronic heart failure with reduced ejection fraction, we observed significant practice-level variability in patients’ health status. Quantifying patients’ health status as a measure of quality should be explored as a foundation for improving care. Clinical Trial Registration: URL: https://www.centerwatch.com. Unique identifier: TX144901.Background While a key treatment goal for patients with heart failure and reduced ejection fraction (HFrEF) is to optimize their health status (their symptoms, function, and quality of life), the variability across outpatient practices in achieving this goal is unknown.

Characteristics and Treatments of Patients Enrolled in the CHAMP‐HF Registry Compared With Patients Enrolled in the PARADIGM‐HF Trial

Background. Lapatinib is an oral small molecule dual tyrosine kinase inhibitor that has been shown to improve time to progression versus capecitabine in women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab. Objective. To describe extent, predictors, and consequences of nonadherence with lapatinib in women with MBC who were previously treated with trastuzumab. Methods. This was a retrospective observational study using data from a large health insurance claims databases spanning January 2000 to March 2010. Measures of lapatinib adherence included medication possession ratio (MPR), time to discontinuation (end of supply), time to first treatment interruption (gap during treatment of 30 days without supply), and duration of continuous therapy (time to gap of 30 days without supply or end of supply). Predictors of nonadherence to lapatinib and the association between nonadherence and outcomes, utilization, and costs were examined using multiple regression analysis. Results. A total of 666 patients met all inclusion criteria. Mean initial lapatinib dosage was 1161 mg daily; 63% received index lapatinib in combination with capecitabine. Mean MPR was 87%; 22% of patients had MPR < 80%. Median time to lapatinib discontinuation was 9.1 months (95% confidence interval = 8.0-10.2). Twenty-seven percent of patients had one or more treatment interruptions during follow-up. Median duration of continuous therapy was 5.9 months (95% confidence interval = 5.1-6.1). Concomitant therapy with a taxane was a predictor of nonadherence (odds ratio for MPR < 80% = 10.30; P < .001). There was a statistically significant association between nonadherence to lapatinib and greater number of outpatient visits (P = .028). Conclusions. In women with MBC who were previously treated with trastuzumab, mean adherence to lapatinib in typical clinical practice is relatively high overall, although there is a small group of patients with high nonadherence. Targeted efforts to improve adherence to lapatinib in this subgroup may be warranted.

High-sensitivity C-reactive protein elevation in patients with prior myocardial infarction in the United States

Background The US Food and Drug Administration approved sacubitril/valsartan for patients with chronic heart failure (HF) with reduced ejection fraction in 2015 on the basis of the results of the PARADIGM‐HF (Prospective Comparison of ARNI [Angiotensin Receptor Neprilysin Inhibitor] With ACEI [Angiotensin‐Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. There are limited data assessing the generalizability of PARADIGM‐HF trial participants to a broader population of patients with HF with reduced ejection fraction routinely encountered in outpatient clinical practice. Methods and Results We compared the baseline characteristics of patients in the PARADIGM‐HF trial with those in the CHAMP‐HF (Change the Management of Patients With Heart Failure) study a large US outpatient registry of patients with HF with reduced ejection fraction. Patients in the PARADIGM‐HF trial (n=8442) were similar to those in the CHAMP‐HF registry (n=3497) in terms of age (mean, 64 versus 66 years), sex (22% versus 29% women), New York Heart Association class III to IV (25% versus 32%), systolic blood pressure (mean, 121 versus 121 mm Hg), left ventricular ejection fraction (mean, 29% versus 29%), and other key baseline characteristics. The median (25th–75th percentile) Meta‐Analysis Global Group in Chronic Heart Failure risk scores were similar for the 2 studies (20 [16–24] versus 22 [8–27]). Despite this, only 13% of patients in the CHAMP‐HF registry were prescribed sacubitril/valsartan at baseline. Conclusions These data suggest participants randomized in the PARADIGM‐HF trial have similar baseline characteristics to those encountered in routine outpatient clinical practice, but there is a substantial lag in the adoption of sacubitril/valsartan for patients with chronic HF with reduced ejection fraction.

All-Cause and Acute Pancreatitis Health Care Costs in Patients With Severe Hypertriglyceridemia.

Importance The extent to which levels of high‐sensitivity C‐reactive protein (hs‐CRP), a known marker of increased cardiovascular risk, are elevated and are associated with standard cardiovascular risk factors in patients with a history of myocardial infarction (MI) is unknown. Objectives To determine the pattern and determinants of the distribution of hs‐CRP in those with a prior MI in the United States using a nationally representative sample. Design and Participants Adults with hs‐CRP data in the National Health and Nutrition Examination Surveys from 1999–2010. Results Among 1296 individuals in our cohort, the median age was 65 years and the median hs‐CRP level was 2.69 mg/L, measured an average of 7.1 years after the MI. Among these patients, 22% had hs‐CRP levels of <1 mg/L, 61% had ≥2 mg/L, and 48% had ≥3 mg/L. Increasing hs‐CRP was associated in a multivariable model with increasing body mass index (partial R2 [pR2] 0.113, P < .001), increasing non‐high‐density lipoprotein [HDL] (pR2 0.030, P < .001), increasing age (pR2 0.008, P = .017), and decreasing HDL (pR2 0.005, P = .046). Adjusted mean hs‐CRP was also higher in women (3.6 vs 2.7 mg/L; P < .001), in people with hypertension (3.5 vs. 2.8, P = .030), and among smokers (4.2 vs 2.3 mg/L; P < .001), and lower in people with hyperlipidemia (2.8 vs. 3.5, P = .007). Standard cardiovascular risk factors accounted for only 22% of the variability in hs‐CRP levels. Conclusions and Relevance Among patients with prior MI, elevated hs‐CRP is prevalent several years after the MI, and standard cardiovascular risk factors explain only a small proportion of hs‐CRP variability. In light of emerging evidence on the importance of inflammation in the pathogenesis of cardiovascular disease, the high prevalence of elevated hs‐CRP in patients with prior MI in the United States may have public health implications.