A retrospective longitudinal evaluation of new overactive bladder patients in an FPMRS urologist practice: Are patients following up and utilizing third-line therapies?

AIMS: Third-line therapies are efficacious in improving overactive bladder (OAB) symptoms; however, OAB patients have poor follow-up and rarely progress to these therapies. Clinical care pathways (CCP) may improve OAB follow-up rates and third-line therapy use. We sought to determine how new OAB patients follow up and utilize third-line therapies with the implementation of an OAB CCP in a fellowship Female Pelvic Medicine and Reconstructive Surgery (FPMRS) trained urologist's academic practice. METHODS: We identified new OAB patients using ICD-9 and 10 codes. They were placed into two groups: pre- and post-CCP use. Basic demographic data were collected. Patients were evaluated in a retrospective longitudinal fashion over 12 months to determine follow-up and third-line therapy utilization. RESULTS: A total of 769 new OAB patients (261 pre-CCP and 508 post-CCP) were identified. The mean number of follow-up visits increased significantly at 6 months (0.94 vs. 1.64 visits, p = .001) and 12 months (1.26 vs. 2.46 visits, p < .003). Follow-up rates increased significantly at 3 months (38.7% vs. 50.2%, p = .002). Mean time to third-line therapy decreased significantly (280 days vs. 160 days, p = .016). Third-line therapy utilization therapy rates increased at 6 months (7.7% vs. 13.4%, p = .018) and at 12 months (11.1% vs. 16.5%, p = .044). CONCLUSIONS: New OAB patients follow-up and progress to third-line therapies faster and more frequently with the use of a CCP in an FPMRS-trained urologist practice. However, many OAB patients still fail to follow up and overall utilization of third-line therapies remains low. Future studies are warranted to identify factors to why overall OAB compliance remains low.

Association between Nonalcoholic Fatty Liver Disease at CT and Coronary Microvascular Dysfunction at Myocardial Perfusion PET/CT.

Background Cardiovascular disease is a major cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). However, the association of NAFLD with coronary microvascular dysfunction is, to our knowledge, unknown. Purpose To determine whether coronary microvascular dysfunction is more prevalent in patients with NAFLD and to determine whether coronary microvascular dysfunction predicts major adverse cardiac events (MACE) independently of NAFLD. Materials and Methods This retrospective study (2006-2014) included patients without evidence of obstructive epicardial coronary artery disease and healthy left ventricular ejection fraction (≥40%) at a clinical rest and stress myocardial perfusion PET/CT. NAFLD was defined by a mean hepatic attenuation of less than 40 HU at CT and coronary microvascular dysfunction as a coronary flow reserve (CFR) of less than 2.0. A composite of all-cause mortality, myocardial infarction, coronary revascularization, and hospitalization because of heart failure comprised MACE (130 of 886 patients; 14.7%). The relation between NAFLD and MACE was assessed by using multivariable Cox regression analysis. Results Among 886 patients (mean age, 62 years ± 12 [standard deviation]; 631 women [mean age, 62 years ± 12 years] and 255 men [mean age, 61 years ± 12]; and ejection fraction, 63% ± 9), 125 patients (14.1%) had NAFLD and 411 patients (46.4%) had coronary microvascular dysfunction. Coronary microvascular dysfunction was more prevalent (64.8% vs 43.4%; P < .001) and CFR was lower (1.9 ± 1.1 vs 2.2 ± 0.7; P < .001) in patients with NAFLD compared with those without NAFLD. NAFLD independently predicted coronary microvascular dysfunction (P = .01). The interaction of NAFLD and male sex predicted MACE (hazard ratio, 1.45; 95% confidence interval: 1.08, 1.69; P = .008) and coronary microvascular dysfunction remained associated with MACE (adjusted hazard ratio, 1.46; 95% confidence interval: 1.02, 2.07; P = .04). Conclusion Coronary microvascular dysfunction was more prevalent in patients with nonalcoholic fatty liver disease and predicted major adverse cardiac events independently of nonalcoholic fatty liver disease. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Ambale-Venkatesh and Lima in this issue.

Mortality From Heart Failure and Dementia in the United States: CDC WONDER 1999-2016.

BACKGROUND: Heart failure and dementia are diseases of the elderly that result in billions of dollars in annual health care expenditure. With the aging of the United States population and increasing evidence of shared risk factors, there is a need to understand the conditions' shared contributions to nationwide mortality. The objectives of this study were to estimate the burden of mortality from heart failure and dementia and characterize the demographics of affected individuals. METHODS AND RESULTS: This retrospective study used National Vital Statistics Data from 1999 to 2016 provided by the Centers for Disease Control and International Classification of Diseases (10th edition) codes for heart failure and dementia as defined by the Medicare Chronic Conditions Data Warehouse. From 1999 to 2016, deaths contributed to by both heart failure and dementia totaled 214,706 and constituted 4.00% of all heart failure deaths and 9.04% of all dementia deaths. Women were more affected than men, with higher age-adjusted mortality rates (per 1,000,000 person-years): 38.67 (95% confidence interval [CI] 38.47-38.87) versus 32.90 (95% CI 32.65-33.15; P < .001). Whites were affected more than blacks, with age-adjusted mortality rates (per 1,000,000 person-years) of 38.00 (95% CI 37.83-38.16) versus 31.06 (95% CI 30.54-31.59; P < .001). However, under the age of 65 years, higher crude mortality rates (per 1,000,000 person-years) were reported in men (0.20, 95% CI 0.18-0.22) compared with women (0.15, 95% CI 0.13-0.16; P < .001). CONCLUSIONS: This study provides insight into temporal trends and nationwide mortality rates reported for heart failure and dementia. Our results suggest a disproportionate burden on populations over 85 years of age, whites, and women.

Early Detection of Multiorgan Light-Chain Amyloidosis by Whole-Body 18F-Florbetapir PET/CT.

Immunoglobulin light-chain (AL) amyloidosis affects multiple systemic organs. However, determination of the precise extent of organ involvement remains challenging. Targeted amyloid imaging with 18F-florbetapir PET/CT offers the potential to detect AL deposits in multiple organs. The primary aim of this study was to determine the distribution and frequency of AL deposits in the various organs of subjects with systemic AL amyloidosis using 18F-florbetapir PET/CT. Methods: This prospective study included 40 subjects with biopsy-proven AL amyloidosis including active AL amyloidosis (n = 30) or AL amyloidosis in hematologic remission for more than 1 y (n = 10). All subjects underwent 18F-florbetapir PET/CT, skull base to below the kidney scan field, from 60 to 90 min after injection of radiotracer. Volume-of-interest measurements of SUVmax were obtained using Hermes software for the parotid gland, tongue, thyroid, lung, gastric wall, pancreas, spleen, kidney, muscle, abdominal fat, lower thoracic spine, vertebral body, and humeral head. Uptake in each organ was visually compared with that in spine bone marrow. An SUVmax of at least 2.5 was considered abnormal in all organs other than the liver. Results: Compared with the international consensus definition of organ involvement, 18F-florbetapir PET/CT identified amyloid deposits in substantially higher percentages of subjects for several organ systems, including parotid gland (50% vs. 3%), tongue (53% vs. 10%), and lung (35% vs. 10%). In several organ systems, including kidney (13% vs. 28%) and abdominal wall fat (10% vs. 13%), PET identified involvement in fewer subjects than did international consensus. Quantitative analysis of 18F-florbetapir PET/CT revealed more frequent organ involvement than did visual analysis in the tongue, thyroid, lung, pancreas, kidney, muscle, and humeral head. Extensive organ amyloid deposits were observed in active AL as well as in AL remission cohorts, and in both cardiac and noncardiac AL cohorts. Conclusion:18F-florbetapir PET/CT detected widespread organ amyloid deposition in subjects with both active AL and AL hematologic remission. In most instances, amyloid deposits in the various organs were not associated with clinical symptoms and, thus, were unrecognized. Early recognition of systemic organ involvement may help tailor treatment, and noninvasive monitoring of organ-level disease may guide management with novel fibril-resorbing therapies.

Relative Apical Sparing of Myocardial Longitudinal Strain Is Explained by Regional Differences in Total Amyloid Mass Rather Than the Proportion of Amyloid Deposits.

OBJECTIVES: This study sought to test whether relative apical sparing (RELAPS) of left ventricular (LV) longitudinal strain (LS) in cardiac amyloidosis (CA) is explained by regional differences in markers of amyloid burden (18F-florbetapir uptake by positron emission tomography [PET] and/or extracellular volume fraction [ECV] by cardiac magnetic resonance (CMR)]. BACKGROUND: Further knowledge of the pathophysiological basis for RELAPS can help understand the adverse outcomes associated with apical LS impairment. METHODS: This was a prospective study of 32 subjects (age 62 ± 7 years; 50% males) with light chain CA. All subjects underwent two-dimensional echocardiography for LS estimation and 18F-florbetapir PET for quantification of LV florbetapir retention index (RI). A subset also underwent CMR (n = 22) for ECV quantification. Extracellular LV mass (LV mass*ECV) and total florbetapir binding (extracellular LV mass*florbetapir RI) were also calculated. All parameters were measured globally and regionally (base, mid, and apex). RESULTS: There was a significant base-to-apex gradient in LS (-7.4 ± 3.2% vs. -8.6 ± 4.0% vs. -20.8 ± 6.6%; p < 0.0001), maximal LV wall thickness (15.7 ± 1.9 cm vs. 15.4 ± 2.9 cm vs. 10.1 ± 2.4 cm; p < 0.0001), and LV mass (74.8 ± 21.2 g vs. 60.8 ± 17.3 g vs. 23.4 ± 6.2 g; p < 0.0001). In contrast, florbetapir RI (0.089 ± 0.03 µmol/min/g vs. 0.097 ± 0.03 µmol/min/g vs. 0.085 ± 0.03 µmol/min/g; p = 0.45) and ECV (0.53 ± 0.08 vs. 0.49 ± 0.08 vs. 0.49 ± 0.07; p = 0.15) showed no significant base-to-apex gradient in the tissue concentration or proportion of amyloid infiltration, whereas markers of total amyloid load, such as total florbetapir binding (3.4 ± 1.7 µmol/min vs. 2.8 ± 1.5 µmol/min vs. 0.93 ± 0.49 µmol/min; p < 0.0001) and extracellular LV mass (40.0 ± 15.6 g vs. 30.2 ± 10.9 g vs. 11.6 ± 3.9 g; p < 0.0001), did show a marked base-to-apex gradient. CONCLUSIONS: Segmental differences in the distribution of the total amyloid mass, rather than the proportion of amyloid deposits, appear to explain the marked regional differences in LS in CA. Although these 2 matrices are clearly related concepts, they should not be used interchangeably.

Geographic Disparities in Reported US Amyloidosis Mortality From 1979 to 2015: Potential Underdetection of Cardiac Amyloidosis.

Importance: Cardiac amyloidosis is an underdiagnosed disease and is highly fatal when untreated. Early diagnosis and treatment with the emerging novel therapies significantly improve survival. A comprehensive analysis of amyloidosis-related mortality is critical to appreciate the nature and distribution of underdiagnosis and improve disease detection. Objective: To evaluate the temporal and regional trends in age-adjusted amyloidosis-related mortality among men and women of various races/ethnicities in the United States. Design, Setting, and Participants: In this observational cohort study, death certificate information from the Centers for Disease Control and Prevention's Wide-ranging ONline Data for Epidemiologic Research database and the National Vital Statistics System from 1979 to 2015 was analyzed. A total of 30 764 individuals in the United States with amyloidosis listed as the underlying cause of death and 26 591 individuals with amyloidosis listed as a contributing cause of death were analyzed. Exposures: Region of residence. Main Outcomes and Measures: Age-adjusted mortality rate from amyloidosis per 1 000 000 population stratified by year, sex, race/ethnicity, and state and county of residence. Results: Of the 30 764 individuals with amyloidosis listed as the underlying cause of death, 17 421 (56.6%) were men and 27 312 (88.8%) were 55 years or older. From 1979 to 2015, the reported overall mean age-adjusted mortality rate from amyloidosis as the underlying cause of death doubled from 1.77 to 3.96 per 1 000 000 population (2.32 to 5.43 in men and 1.35 to 2.80 in women). Black men had the highest mortality rate (12.36 per 1 000 000), followed by black women (6.48 per 1 000 000). Amyloidosis contributed to age-adjusted mortality rates as high as 31.73 per 1 000 000 in certain counties. Most southern states reported the lowest US mortality rates despite having the highest proportions of black individuals. Conclusions and Relevance: The increased reported mortality over time and in proximity to amyloidosis centers more likely reflects an overall increase in disease diagnosis rather than increased lethality. The reported amyloidosis mortality is highly variable in different US regions. The lack of higher reported mortality rates in states with a greater proportion of black residents suggests underdiagnosis of amyloidosis, including cardiac forms of the disease, in many areas of the United States. Better understanding of the determinants of geographic and racial disparity in the reporting of amyloidosis deaths are warranted.

Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.

Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This clonal hematopoiesis correlates with an increased risk of atherosclerotic cardiovascular disease. We studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr-/-) mice. We found that partial bone marrow reconstitution with TET2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size. TET2-deficient macrophages exhibited an increase in NLRP3 inflammasome-mediated interleukin-1ß secretion. An NLRP3 inhibitor showed greater atheroprotective activity in chimeric mice reconstituted with TET2-deficient cells than in nonchimeric mice. These results support the hypothesis that somatic TET2 mutations in blood cells play a causal role in atherosclerosis.