IV Diuresis in Alternative Treatment Settings for the Management of Heart Failure: Implications for Mortality, Hospitalizations and Cost.

BACKGROUND: Recent advances in heart failure (HF) care have sought to shift management from inpatient to outpatient and observation settings. We evaluated the association among HF treatment in the (1) inpatient; (2) observation; (3) emergency department (ED); and (4) outpatient settings with 30-day mortality, hospitalizations and cost. METHODS: Using 100% Medicare inpatient, outpatient and Part B files from 2011-2018, 1,534,708 unique patient encounters in which intravenous (IV) diuretics were received for a primary diagnosis of HF were identified. Encounters were sorted into mutually exclusive settings: (1) inpatient; (2) observation; (3) ED; or (4) outpatient IV diuretic clinic. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 30-day hospitalization and total 30-day costs. Multivariable logistic and linear regression were used to examine the association between treatment location and the primary and secondary outcomes. RESULTS: Patients treated in observation and outpatient settings had lower 30-day mortality rates (observation OR 0.67, 95% CI 0.66-0.69; P < 0.001; outpatient OR 0.53, 95% CI 0.51-0.55; P < 0.001) compared to those treated in inpatient settings. Observation and outpatient treatment were also associated with decreased 30-day total cost compared to inpatient treatment. Observation relative cost -$5528.77, 95% CI -$5613.63 to -$5443.92; outpatient relative cost -$7005.95; 95% CI -$7103.94 to -$6907.96). Patients treated in the emergency department and discharged had increased mortality rates (OR 1.15, 95% CI 1.13-1.17; P < 0.001) and increased rates of hospitalization (OR 1.72, 95% CI 1.70-1.73; P < 0.001) compared to patients treated as inpatients. CONCLUSIONS: Medicare beneficiaries who received IV diuresis for acute HF in the outpatient and observation settings had lower mortality rates and decreased costs of care compared to patients treated as inpatients. Outpatient and observation management of acute decompensated HF, when available, is a safe and cost-effective strategy in certain populations of patients with HF.

Medicaid Expansion Under the Affordable Care Act and Association With Cardiac Care: A Systematic Review.

BACKGROUND: The goal of the Affordable Care Act was to improve health outcomes through expanding insurance, including through Medicaid expansion. We systematically reviewed the available literature on the association of Affordable Care Act Medicaid expansion with cardiac outcomes. METHODS: Consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we performed systematic searches in PubMed, the Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature using the keywords such as Medicaid expansion and cardiac, cardiovascular, or heart to identify titles published from 1/2014 to 7/2022 that evaluated the association between Medicaid expansion and cardiac outcomes. RESULTS: A total of 30 studies met inclusion and exclusion criteria. Of these, 14 studies (47%) used a difference-in-difference study design and 10 (33%) used a multiple time series design. The median number of postexpansion years evaluated was 2 (range, 0.5-6) and the median number of expansion states included was 23 (range, 1-33). Commonly assessed outcomes included insurance coverage of and utilization of cardiac treatments (25.0%), morbidity/mortality (19.6%), disparities in care (14.3%), and preventive care (41.1%). Medicaid expansion was generally associated with increased insurance coverage, reduction in overall cardiac morbidity/mortality outside of acute care settings, and some increase in screening for and treatment of cardiac comorbidities. CONCLUSIONS: Current literature demonstrates that Medicaid expansion was generally associated with increased insurance coverage of cardiac treatments, improvement in cardiac outcomes outside of acute care settings, and some improvements in cardiac-focused prevention and screening. Conclusions are limited because quasi-experimental comparisons of expansion and nonexpansion states cannot account for unmeasured state-level confounders.

Mitral Regurgitation and Mortality Risk in Medicare Beneficiaries With Heart Failure and Preserved Ejection Fraction.

The association of mitral regurgitation (MR) severity and mortality in heart failure with preserved ejection fraction (HFpEF) is uncertain. We sought to evaluate the relation between MR severity on transthoracic echocardiography (TTE) and subsequent all-cause mortality in Medicare beneficiaries with HFpEF. We linked 57,608 patients referred for TTE at Beth Israel Deaconess Medical Center to Medicare inpatient claims from 2003 to 2017. In those with a history of HF and a physician-reported left ventricular ejection fraction ≥50%, we evaluated the relation of MR severity and time to the primary end point of all-cause mortality using Kaplan-Meier methods. A total of 7,778 individuals (14.5%) met inclusion criteria (mean age 75.5 years ± 11.9, 55.9% female). Over a median follow-up of 8.1 years, 2,016 (25.9%) died at a median (interquartile range) of 1.7 (0.3 to 4.1) years. At 1 year, 15.8% with 3 to 4+ MR had died versus 10.5% with 0 to 2+ MR (hazard ratio 1.54, 95% confidence interval 1.22 to 1.95, p <0.001). After multivariable adjustment, 3 to 4+ MR continued to be associated with increased all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.14 to 1.94, p = 0.004) except in the subset with atrial fibrillation (interaction p = 0.03) or recent (<3 months) HF hospitalization (p = 0.54). In conclusion, in this large, single-institution retrospective study of Medicare beneficiaries with HFpEF who underwent TTE, moderate-to-severe and severe MR were significantly associated with an increased risk of all-cause mortality after multivariable adjustment, except in those with atrial fibrillation or recent HF. Prospective studies are needed to assess the role of MR reduction in mitigating this risk.

Fulminant cardiac sarcoidosis resembling giant cell myocarditis: a case report.

BACKGROUND: Severe cardiac sarcoidosis (CS) can share clinical and histopathologic features with giant cell myocarditis (GCM). CASE SUMMARY: A 56-year-old female presented with 1 week of exertional chest pressure and dyspnoea. Echocardiogram demonstrated extensive regional dysfunction with left ventricular ejection fraction (LVEF) 38%. Cardiac catheterization revealed no obstructive coronary artery disease and cardiac index 1.5 L/min/m2. Cardiac magnetic resonance imaging (MRI) demonstrated diffuse late gadolinium enhancement. Positron emission tomography with fluorodeoxyglucose (FDG) (FDG-PET) computed tomography showed FDG uptake in the anteroseptal and anterior wall and no extracardiac activity. Endomyocardial biopsy (EMB) demonstrated fragments of endocardial fibrosis with mixed inflammatory infiltrate including histiocytic giant cells, which could be due to CS or GCM. She was initially treated for GCM with high dose steroids, tacrolimus, and mycophenolate mofetil. Repeat EMB was pursued and demonstrated multiple granulomas with sharp demarcation from adjacent uninvolved myocardium consistent with CS. A dual-chamber implantable cardioverter-defibrillator was placed, and immunosuppression was changed to prednisone alone with plan for infliximab. DISCUSSION: This case illustrates a rare presentation of fulminant isolated CS. Endomyocardial biopsy with sufficient tissue was critical to establish a diagnosis and initiate appropriate immunosuppression.

Performance in Federal Value-Based Programs of Hospitals Recognized by the American Heart Association and American College of Cardiology for High-Quality Heart Failure and Acute Myocardial Infarction Care.

Importance: The US Centers for Medicare & Medicaid Services have implemented national value-based programs that incentivize hospitals to deliver better cardiovascular care. However, it is unclear how hospitals recognized for high-quality cardiovascular care by American Heart Association (AHA) and American College of Cardiology (ACC) national quality improvement initiatives (termed award hospitals) have performed under value-based programs. Objective: To determine if hospitals that received awards for high-quality cardiovascular care from the AHA/ACC were less likely to be penalized under the Hospital Readmissions Reduction Program (HRRP) and the Hospital Value-Based Purchasing Program (VBP) compared with other hospitals. Design, Setting, and Participants: This national cross-sectional study included data from short-term acute care hospitals in the United States that were participating in the HRRP or VBP in fiscal year 2018. Exposures: Recognition awards for high-quality care from the AHA's Get With The Guidelines-Heart Failure and ACC's Chest Pain-MI (myocardial infarction) Registry national quality improvement initiatives. Main Outcomes and Measures: Proportion of hospitals that received a financial penalty or financial reward under the HRRP or VBP, median payment adjustments, and hospital-level 30-day mortality rates. Results: This study included 3175 hospitals participating in the HRRP and 2781 hospitals participating in the VBP in fiscal year 2018. Under the HRRP, a higher proportion of award hospitals received financial penalties compared with other hospitals (419 [85.5%] vs 2112 [78.7%]; P < .001), although payment reductions were similar (median, 0.39% [interquartile range (IQR), 0.08%-0.84%] vs 0.33% [IQR, 0.03%-0.89%]; P = .17). Under the VBP, a higher proportion of award hospitals received penalties compared with other hospitals (250 [51.7%] vs 950 [41.4%]; P < .001), and fewer award hospitals received financial rewards (234 [48.4%] vs 1347 [58.6%]; P < .001). Median payment reductions were higher for award hospitals than other hospitals (0.01% [IQR, 0.00%-0.38%] vs 0.0% [IQR, 0.00%-0.28%]; P < .001), and median payment increases were lower (0.0% [IQR, 0.00%-0.34%] vs 0.13% [IQR, 0.00%-0.60%]; P < .001). Thirty-day mortality at award hospitals was similar (acute myocardial infarction, 13.2% vs 13.2%; P = .76) or slightly lower (heart failure, 11.3% vs 11.7%; P = .001) compared with other hospitals. Conclusions and Relevance: Hospitals that received awards for high-quality cardiovascular care from the AHA/ACC were more likely to be penalized and less likely to be financially rewarded by federal value-based programs. These findings highlight the potential need to standardize measurement of cardiovascular care quality.

Disparities in Care and Mortality Among Homeless Adults Hospitalized for Cardiovascular Conditions.

Importance: Cardiovascular disease is a major cause of death among homeless adults, with mortality rates that are substantially higher than in the general population. It is unknown whether differences in hospitalization-related care contribute to these disparities in cardiovascular outcomes. Objective: To evaluate differences in intensity of care and mortality between homeless and nonhomeless individuals hospitalized for cardiovascular conditions (ie, acute myocardial infarction, stroke, cardiac arrest, or heart failure). Design, Setting, and Participants: This retrospective cross-sectional study included all hospitalizations for cardiovascular conditions among homeless adults (n = 24 890) and nonhomeless adults (n = 1 827 900) 18 years or older in New York, Massachusetts, and Florida from January 1, 2010, to September 30, 2015. Statistical analysis was performed from February 6 to July 16, 2019. Main Outcomes and Measures: Risk-standardized diagnostic and therapeutic procedure rates and in-hospital mortality rates. Results: Of the 1 852 790 total hospitalizations for cardiovascular conditions across 525 hospitals, 24 890 occurred among patients who were homeless (11 452 women and 13 438 men; mean [SD] age, 65.1 [14.8] years) and 1 827 900 occurred among patients who were not homeless (850 660 women and 977 240 men; mean [SD] age, 72.1 [14.6] years). Most hospitalizations among homeless individuals were primarily concentrated among 11 hospitals. Homeless adults were more likely than nonhomeless adults to be black (38.6% vs 15.6%) and insured by Medicaid (49.3% vs 8.5%). After accounting for differences in demographics (age, sex, and race/ethnicity), insurance payer, and clinical comorbidities, homeless adults hospitalized for acute myocardial infarction were less likely to undergo coronary angiography compared with nonhomeless adults (39.5% vs 70.9%; P < .001), percutaneous coronary intervention (24.8% vs 47.4%; P < .001), and coronary artery bypass graft (2.5% vs 7.0%; P < .001). Among adults hospitalized with stroke, those who were homeless were less likely than nonhomeless individuals to undergo cerebral angiography (2.9% vs 9.5%; P < .001) but were as likely to receive thrombolytic therapy (4.8% vs 5.2%; P = .28). In the cardiac arrest cohort, homeless adults were less likely than nonhomeless adults to undergo coronary angiography (10.1% vs 17.6%; P < .001) and percutaneous coronary intervention (0.0% vs 4.7%; P < .001). Risk-standardized mortality was higher for homeless persons with ST-elevation myocardial infarction compared with nonhomeless persons (8.3% vs 6.2%; P = .04). Mortality rates were also higher for homeless persons than for nonhomeless persons hospitalized with stroke (8.9% vs 6.3%; P < .001) or cardiac arrest (76.1% vs 57.4%; P < .001) but did not differ for heart failure (1.6% vs 1.6%; P = .83). Conclusions and Relevance: There are significant disparities in in-hospital care and mortality between homeless and nonhomeless adults with cardiovascular conditions. There is a need for public health and policy efforts to support hospitals that care for homeless persons to reduce disparities in hospital-based care and improve health outcomes for this population.

Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases.

BACKGROUND: Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)-positive NSCLC. Alectinib has demonstrated robust CNS activity in both crizotinib-naive and crizotinib-resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases. METHODS: In this retrospective study, patients were eligible if they had advanced ALK-positive NSCLC with large (defined as ≥1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Of the 19 patients, 15 (79%) had measurable CNS disease at baseline and were evaluable for response. The CNS objective response rate in these patients was 73.3% (95% confidence interval [CI]: 44.9%-92.2%), the CNS disease control rate was 100.0% (95% CI: 78.2%-100.0%), and the median CNS duration of response was 19.3 months (95% CI: 14.3 months-not evaluable). In 18 evaluable patients with measurable and/or nonmeasurable baseline CNS disease, the CNS objective response rate was 72.2% (95% CI: 46.5%-90.3%), the CNS disease control rate was 100.0% (95% CI: 81.5%-100.0%), and the median CNS duration of response was 17.1 months (95% CI: 14.3 months-not evaluable). All eight patients with symptoms attributable to CNS metastases had clinical improvement upon starting alectinib therapy. Six patients (32%) eventually required salvage brain radiotherapy. CONCLUSIONS: Alectinib demonstrated meaningful CNS efficacy in patients with ALK-positive NSCLC with untreated symptomatic or large brain metastases.

Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer.

PURPOSE: Targeted therapy is the cornerstone of treatment of advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS), the preferred method for genotyping, typically requires several weeks. Here, we assessed workflows designed to rapidly identify patients with actionable EGFR mutations and reduce time to initiation (TTI) of epidermal growth factor receptor (EGFR)-directed therapy. PATIENTS AND METHODS: We performed rapid testing for EGFR L858R mutations and exon 19 deletions on paraffin-embedded or frozen section biopsy specimens from newly diagnosed patients with metastatic NSCLC by using an EGFR-specific assay (rapid test). To determine clinical utility, we assessed concordance with NGS results, turnaround time, and TTI of EGFR therapy, and we evaluated reimbursement data. RESULTS: Between January 2015 and September 2017, we performed 243 rapid EGFR tests and identified EGFR mutations in 43 patients (18%). With NGS results as a reference, sensitivity and specificity of the rapid EGFR polymerase chain reaction assay were 98% and 100%, respectively. The median turnaround time for NGS was 14 days, compared with 7 days for rapid testing (P < .001). In the rapid group, 95% of patients received an EGFR inhibitor in the first-line setting. The median TTI of EGFR therapy was significantly shorter in the rapid cohort when compared with 121 historical cases (22 v 37 days; P = .01). Escalation of the initiative into an interdisciplinary ultra-rapid next-day frozen-section workflow for highly symptomatic patients (n = 8) resulted in a reduction in the median (± standard deviation) turnaround time to 1 ± 0.4 days and allowed several patients to initiate therapy within 1 week of biopsy. An extended 9-month clinical evaluation phase confirmed operational sustainability (turnaround times: ultra-rapid, 0.81 ± 0.4 days; rapid, 3 ± 1.5 days), and a 63% reimbursement rate indicated financial sustainability. CONCLUSION: Rapid genotyping facilitates earlier initiation of EGFR-directed therapies without compromising NGS workflows.

Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer.

Purpose Advanced anaplastic lymphoma kinase ( ALK) fusion-positive non-small-cell lung cancers (NSCLCs) are effectively treated with ALK tyrosine kinase inhibitors (TKIs). However, clinical outcomes in these patients vary, and the benefit of TKIs is limited as a result of acquired resistance. Emerging data suggest that the ALK fusion variant may affect clinical outcome, but the molecular basis for this association is unknown. Patients and Methods We identified 129 patients with ALK-positive NSCLC with known ALK variants. ALK resistance mutations and clinical outcomes on ALK TKIs were retrospectively evaluated according to ALK variant. A Foundation Medicine data set of 577 patients with ALK-positive NSCLC was also examined. Results The most frequent ALK variants were EML4-ALK variant 1 in 55 patients (43%) and variant 3 in 51 patients (40%). We analyzed 77 tumor biopsy specimens from patients with variants 1 and 3 who had progressed on an ALK TKI. ALK resistance mutations were significantly more common in variant 3 than in variant 1 (57% v 30%; P = .023). In particular, ALK G1202R was more common in variant 3 than in variant 1 (32% v 0%; P < .001). Analysis of the Foundation Medicine database revealed similar associations of variant 3 with ALK resistance mutation and with G1202R ( P = .010 and .015, respectively). Among patients treated with the third-generation ALK TKI lorlatinib, variant 3 was associated with a significantly longer progression-free survival than variant 1 (hazard ratio, 0.31; 95% CI, 0.12 to 0.79; P = .011). Conclusion Specific ALK variants may be associated with the development of ALK resistance mutations, particularly G1202R, and provide a molecular link between variant and clinical outcome. ALK variant thus represents a potentially important factor in the selection of next-generation ALK inhibitors.

Palliative Radiation Therapy for Recurrent Ovarian Cancer: Efficacy and Predictors of Clinical Response.

OBJECTIVE: This study aimed to report response rates and predictors of response to palliative radiotherapy (RT) for recurrent ovarian cancer. METHODS/MATERIALS: Database review identified 64 patients with symptomatic ovarian cancer recurrence who received a total of 76 courses of RT for 103 indications from March 2003 to August 2014. Radiotherapy indications were pain (44%), bleeding (32%), obstruction (15%), and other (9%). Responses were categorized as complete, partial, or none; all response (AR) was the sum of complete and partial responses. Response rates were compared using a χ test. Multivariate analysis was performed using logistic regression. Patients were followed up for symptom recurrence and death. RESULTS: Response rates were significantly higher for pain (AR, 87%) and bleeding (93%) than for obstruction (62%) and other (60%; P < 0.01). Patients treated for pain at nonbony sites had higher response rates (AR 96%) compared with those treated at bony sites (75%; P = 0.04). Patients with clear cell histology had the lowest response rates (AR, 60%) compared with those with serous (82%), endometrioid (95%), or other Müllerian histology (85%; P = 0.01). Platinum status at diagnosis or the time of RT was not associated with response, nor was tumor size or number of prior chemotherapy regimens. On multivariate analysis, histology, RT indication, and RT dose were independent predictors of response (all P < 0.01). CONCLUSIONS: Palliative RT provides relief of pain and bleeding in most patients with ovarian cancer recurrence. Patients with symptomatic obstruction, bony involvement, and clear cell histology may experience lower clinical response rates.

Palliative head and neck radiotherapy with the RTOG 8502 regimen for incurable primary or metastatic cancers.

OBJECTIVES: To report on our institutional experience of palliative radiotherapy (RT) of cancers in the head and neck by the RTOG 8502 'QUAD SHOT' regimen. METHODS: Seventy-five patients completed at least 1 cycle of palliative RT to the head and neck for primary or metastatic disease based on the RTOG 8502 regimen (3.7 Gy twice daily over 2 consecutive days at 4 week intervals per cycle) between 2/2005 and 7/2014. RESULTS: Median patient age was 76 years (range 23-97). The most common histologies were squamous cell carcinoma (55%), non-anaplastic thyroid carcinoma (10%) and salivary gland carcinoma (9%). Thirty patients (40%) received prior RT at the palliative site. Twenty-eight patients (37%) completed at least three RTOG 8502 cycles. Sixty-five percent of all patients had a palliative response. Median overall survival was 5.67 months (range, 0.20-34.5). Grade 3 toxicity in 4 patients (5%) consisted of acute dermatitis and functional mucositis. Palliative response was significantly correlated with increasing number of RTOG 8502 cycles (p = 0.012), but not KPS, prior RT, palliative chemotherapy, prior surgery, histology or stage. On survival analysis, palliative response (p < 0.001), KPS ⩾ 70 (p = 0.001), and greater number of RTOG 8502 cycles (p = 0.022) remained independent predictors of improved survival. CONCLUSIONS: For patients with incurable malignant disease in the head and neck, the palliative RTOG 8502 'QUAD SHOT' regimen provides excellent rates of palliative response with minimal associated toxicity. Patients who are able to complete greater number of RT cycles have higher rates of palliative response and overall survival.

Learning and memory depend on fibroblast growth factor receptor 2 functioning in hippocampus.

BACKGROUND: Fibroblast growth factor (FGF) signaling controls self-renewal of neural stem cells during embryonic telencephalic development. FGF receptor 2 (FGFR2) has a significant role in the production of cortical neurons during embryogenesis, but its role in the hippocampus during development and in adulthood has not been described. METHODS: Here we dissociate the role of FGFR2 in the hippocampus during development and during adulthood with the use of embryonic knockout and inducible knockout mice. RESULTS: Embryonic knockout of FGFR2 causes a reduction of hippocampal volume and impairment in adult spatial memory in mice. Spatial reference memory, as assessed by performance on the water maze probe trial, was correlated with reduced hippocampal parvalbumin+ cells, whereas short-term learning was correlated with reduction in immature neurons in the dentate gyrus. Furthermore, short-term learning and newly generated neurons in the dentate gyrus were deficient even when FGFR2 was lacking only in adulthood. CONCLUSIONS: Taken together, these findings support a dual role for FGFR2 in hippocampal short-term learning and long-term reference memory, which appear to depend on the abundance of two separate cellular components, parvalbumin interneurons and newly generated granule cells in the hippocampus.