Atypical cardiac amyloidosis phenotypes identified at transplant: a case series.

Background: Transthyretin amyloidosis (TTR) is increasingly implicated as an aetiology of advanced cardiomyopathy. Typically, both genetic variant (TTRv) and wild-type (TTRwt) amyloidosis present with a restrictive phenotype. We present a series of three patients who were found to have cardiac amyloidosis on explant following heart transplant (HT) who had atypical, non-restrictive phenotypes. Case Summary: All three patients were men, three were Black, and only one had an alternative pre-HT explanation for their advanced, dilated cardiomyopathy. Pre-HT transthoracic echocardiograms were notable for left ventricular (LV) dilation (>95th percentile for height and gender), low EF, and normal LV wall thickness. Explants showed varying amounts of amyloid deposition, ranging from diffuse biventricular patterns to perivascular involvement. Mass spectrometry confirmed the presence of TTRv (two cases) and TTRwt (one case). Discussion: Patients with dilated cardiomyopathy may harbour cardiac amyloidosis. Uncertainty remains regarding the contribution of amyloidosis to the development of a dilated phenotype. The pathogenic Val142Ile variant seen in two of these patients, a variant common in Black patients, suggests a need for further investigation into the potential relationship between TTRv amyloidosis and dilated cardiomyopathy.

Incidence, Risk Factors, and Outcomes of COVID-19 Infection in a Large Cohort of Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTr) are at increased risk for severe disease from coronavirus disease 2019 (COVID-19) compared with non-SOTr. METHODS: We performed a retrospective cohort study between March 1, 2020, and March, 30, 2021, in an integrated healthcare system with 4.3 million members aged ≥18 y including 5126 SOTr. Comparisons in COVID-19 mortality, hospitalization, and incidence were made between SOTr and non-SOTr, and between different SOTr organs. Multivariate analysis was performed to identify risk factors for COVID-19 mortality and hospitalization. RESULTS: There were 600 SOTr (kidney, liver, heart, and lung) with COVID-19. Per person-year incidence of COVID-19 among SOTr was 10.0% versus 7.6% among non-SOTr (P < 0.0001). Compared with uninfected SOTr, infected SOTr were older (57.1 ± 14.0 versus 45.7 ± 17.9 y, P < 0.001), predominantly Hispanic/Latino (58.8% versus 38.6%, P < 0.0001), hypertensive (77.0% versus 23.8%; P < 0.0001), and diabetic (49.6% versus 13.0%; P = 0.0009). Compared with non-SOTr, infected SOTr had higher hospitalization (39.5% versus 6.0%; P < 0.0001), intensive care unit admission (29.1% versus 15.5%; P < 0.0001), and mortality (14.7% versus 1.8%; P < 0.0001) from COVID-19. Older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.05-1.10), male gender (HR, 1.79; 95% CI, 1.11-2.86), and higher body mass index (HR, 1.04; 95% CI, 1.00-1.09; P = 0.047) were associated with increased mortality from COVID-19, whereas race, diabetes, and number/type of immunosuppressive medications were not. Among the different SOTr, COVID-19 mortality risk was lowest in liver recipients (HR, 0.34; 95% CI, 0.16-0.73) and highest in lung recipients (HR, 1.74; 95% CI, 0.68-4.42). CONCLUSIONS: SOTr have higher rates of hospitalization and mortality from COVID-19 compared with the general population. Among the SOTr, the incidence and outcomes were distinct among different transplantation types.

Real-world use patterns of angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) among patients with heart failure within a large integrated health system.

BACKGROUND: Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that is now preferred in guidelines over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with heart failure with reduced ejection fraction (HFrEF). However, it has not been broadly adopted in clinical practice. OBJECTIVE: To characterize ARNI use within a large diverse real-world population and assess for any racial disparities. METHODS: We conducted a cross-sectional study within Kaiser Permanente Southern California. Adult patients with HFrEF who received ARNIs, ACEIs, or ARBs between January 1, 2014, and November 30, 2020, were identified. The prevalence of ARNI use among the cohort and patient characteristics by ARNIs vs ACEIs/ARBs use were described. Multivariable regression was performed to estimate odds ratios and 95% CIs of receiving ARNI by race and ethnicity. RESULTS: Among 12,250 patients with HFrEF receiving ACEIs, ARBs, or ARNIs, 556 (4.54%) patients received ARNIs. ARNI use among this cohort increased from 0.02% in 2015 to 7.48% in 2020. Patients receiving ARNIs were younger (aged 62 vs 69 years) and had a lower median ejection fraction (27% vs 32%) compared with patients receiving ACEIs/ARBs. They also had higher use of mineralocorticoid antagonists (24.1% vs 19.8%) and automatic implantable cardioverterdefibrillators (17.4% vs 13.3%). There were no significant differences in rate of ARNI use by race and ethnicity. CONCLUSIONS: Within a large diverse integrated health system in Southern California, the rate of ARNI use has risen over time. Patients given ARNIs were younger with fewer comorbidities, while having worse ejection fraction. Racial minorities were no less likely to receive ARNIs compared with White patients. DISCLOSURES: Dr Huang had stock ownership in Gilead and Pfizer. Dr Liang received support for article processing and medical writing.

ß-Blocker Use and Risk of Mortality in Heart Failure Patients Initiating Maintenance Dialysis.

RATIONAL & OBJECTIVE: Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether ß-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included. EXPOSURES: Patients were considered treated with ß-blockers if they had a quantity of drug dispensed covering the dialysis transition date. OUTCOMES: All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis. ANALYTICAL APPROACH: Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between ß-blocker use and study outcomes. RESULTS: 3,503 patients were included in the study. There were 2,115 (60.4%) patients using ß-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any ß-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization. LIMITATIONS: The observational nature of our study could not fully account for residual confounding. CONCLUSIONS: Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Marijuana and Listing for Heart Transplant: A Survey of Transplant Providers.

BACKGROUND: There is no consensus within the heart transplant community about whether patients who use marijuana should be eligible for transplant listing, but several states have passed legislation prohibiting marijuana-using patients from being denied transplant listing based on their use of the substance. METHODS AND RESULTS: We conducted an independent, voluntary, web-based survey of heart and lung transplant providers to assess current practice patterns and attitudes toward marijuana use in patients with advanced heart failure being considered for transplant. A total of 360 heart transplant providers responded from 26 countries. Nearly two thirds of respondents (n=222, 64.4%) supported listing patients with advanced, end-stage heart failure for transplant who use legal medical marijuana. Significantly, fewer respondents (n=96, 27.5%) supported transplant listing for patients using legal recreational marijuana. The majority of providers currently make patients eligible for transplantation after a period of abstinence from marijuana (n=241, 68.3%). There were no differences between the proportion of respondents supporting transplant listing after stratification by profession or country/region. Most (78.4%) survey respondents from states with laws prohibiting marijuana-using patients from being denied transplant listing reported denying all marijuana-using patients or mandating abstinence before transplant listing. CONCLUSIONS: The majority of heart and lung transplant providers in our study sample supports the listing of patients who use medical marijuana for transplant after a period of abstinence. Communication and collaboration between the medical community and legislative groups about marijuana use in transplant candidates is needed to ensure the best patient outcomes with the use of scarce donor organs.

Echocardiographic parameters associated with right ventricular failure after left ventricular assist device: A review.

Left ventricular assist devices improve functional class and survival in selected patients with advanced heart failure, but right ventricular failure after surgery remains common and challenging to predict. Pre-operative echocardiography provides important information in the evaluation of patients before device implant. This review summarizes the data on this complex topic.

Association of long-term air pollution with ventricular conduction and repolarization abnormalities.

BACKGROUND: Short-term exposure to air pollution may affect ventricular repolarization, but there is limited information on how long-term exposures might affect the surface ventricular electrocardiographic (ECG) abnormalities associated with cardiovascular events. We carried out a study to determine whether long-term air pollution exposure is associated with abnormalities of ventricular repolarization and conduction in adults without known cardiovascular disease. METHODS: A total of 4783 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis underwent 12-lead ECG examinations, cardiac-computed tomography, and calcium scoring, as well as estimation of air pollution exposure using a finely resolved spatiotemporal model to determine long-term average individual exposure to fine particulate matter (PM(2.5)) and proximity to major roadways. We assessed ventricular electrical abnormalities including presence of QT prolongation (Rautaharju QTrr criteria) and intraventricular conduction delay (QRS duration >120 milliseconds). We used logistic regression to determine the adjusted relationship between air pollution exposures and ECG abnormalities. RESULTS: A 10-µg/m³ increase in estimated residential PM(2.5) was associated with an increased odds of prevalent QT prolongation (adjusted odds ratio [OR] = 1.6 [95% confidence interval (CI) = 1.2-2.2]) and intraventricular conduction delay (1.7 [1.0-2.6]), independent of coronary-artery calcium score. Living near major roadways was not associated with ventricular electrical abnormalities. No evidence of effect modification by traditional risk factors or study site was observed. CONCLUSIONS: This study demonstrates an association between long-term exposure to air pollution and ventricular repolarization and conduction abnormalities in adults without clinical cardiovascular disease, independent of subclinical coronary arterial calcification.

Racial/ethnic and socioeconomic disparities in health-related quality of life among people with coronary heart disease, 2007.

INTRODUCTION: Health-related quality of life (HRQOL) refers to a person's or group's perceived physical and mental health over time. Coronary heart disease (CHD) affects HRQOL and likely varies among groups. This study examined disparities in HRQOL among adults with self-reported CHD. METHODS: We examined disparities in HRQOL by using the unhealthy days measurements among adults who self-reported CHD in the 2007 Behavioral Risk Factor Surveillance System state-based telephone survey. CHD was based on self-reported medical history of heart attack, angina, or coronary heart disease. We assessed differences in fair/poor health status, 14 or more physically unhealthy days, 14 or more mentally unhealthy days, 14 or more total unhealthy days (total of physically and mentally unhealthy days), and 14 or more activity-limited days. Multivariate logistic regression models included age, race/ethnicity, sex, education, annual household income, household size, and health insurance coverage. RESULTS: Of the population surveyed, 35,378 (6.1%) self-reported CHD. Compared with non-Hispanic whites, Native Americans were more likely to report fair/poor health status (adjusted odds ratio [AOR], 1.7), 14 or more total unhealthy days (AOR, 1.6), 14 or more physically unhealthy days (AOR, 1.7), and 14 or more activity-limited days (AOR, 1.9). Hispanics were more likely than non-Hispanic whites to report fair/poor health status (AOR, 1.5) and less likely to report 14 or more activity-limited days (AOR, 0.5), and Asians were less likely to report 14 or more activity-limited days (AOR, 0.2). Non-Hispanic blacks did not differ in unhealthy days measurements from non-Hispanic whites. The proportion reporting 14 or more total unhealthy days increased with increasing age, was higher among women than men, and was lower with increasing levels of education and income. CONCLUSION: There are sex, racial/ethnic, and socioeconomic disparities in HRQOL among people with CHD. Tailoring interventions to people who have both with CHD and poor HRQOL may assist in the overall management of CHD.

Use of molecular testing to identify a cluster of patients with polycythemia vera in eastern Pennsylvania.

BACKGROUND: The role of the environment in the origin of polycythemia vera has not been well documented. Recently, molecular diagnostic tools have been developed to facilitate the diagnosis of polycythemia vera. A cluster of patients with polycythemia vera was suspected in three countries in eastern Pennsylvania where there have long been a concern about environment hazards. METHODS: Rigorous clinical criteria and JAK2 617V>F testing were used to confirm the diagnosis of polycythemia vera in patients in this area. Participants included cases of polycythemia vera from the 2001 to 2005 state cancer registry as well as self- and physician-referred cases. FINDING: A diagnosis of polycythemia vera was confirmed in 53% of 62 participants using WHO criteria, which includes JAK2 617V>F testing. A statistically significant cluster of cases (P < 0.001) was identified where the incidence of polycythemia vera was 4.3 times that of the rest of the study area. The area of the cluster contained numerous sources of hazardous material including waste-coal power plants and U.S. Environmental Protection Agency Superfund sites. INTERPRETATION: The diagnosis of polycythemia vera based solely on clinical criteria is frequently erroneous, suggesting that our prior knowledge of the epidemiology of this disease might be inaccurate. The JAK2 617V>F mutational analysis provides diagnostic clarity and permitted the confirmation of a cluster of polycythemia vera cases not identified by traditional clinical and pathologic diagnostic criteria. The close proximity of this cluster to known areas of hazardous material exposure raises concern that such environmental factors might play a role in the origin of polycythemia vera.

A comparison of anion-exchange and steric-exclusion HPLC assays of mouse plasma lipoproteins.

We compared two HPLC methods (anion exchange [AE] and steric exclusion [SE]) for analysis of mouse lipoprotein profiles by determining coefficients of variability (CVs) under varying conditions. CVs for AE and SE were comparable on fresh samples. There was an inverse relationship between subfraction curve area and CV [r = -0.65 (AE) and -0.50 (SE)], consistent with the interpretation that as curve area decreased, error variance increased and signal-to-noise ratio decreased. Sample storage did not affect SE. In contrast, with AE, alterations in measured lipoproteins were apparent after storage, including a decrease in the HDL subfraction [66.8% (baseline) vs. 15.9% (1 week); P < 0.01] and an increase in areas under LDL and VLDL peaks. Concomitant with decreasing HDL area, reproducibility deteriorated with the duration of storage. Analysis of the effects of decreasing sample injectate volume to <25 microl on SE lipoprotein subfractions revealed that areas under LDL and VLDL peaks decreased and persisted as volume was decreased further. Areas under all lipoprotein subfractions measured with either AE or SE were linearly correlated with the amount of cholesterol [r = 0.69 (AE) and 0.87 (SE)]. Both AE and SE yield reproducible, accurate, and rapid measurements of lipoproteins from small amounts of serum. AE yields more sensitive, high-amplitude, well-defined peaks that can be easily distinguished and necessitates the use of smaller sample volumes compared with SE, but sample storage causes alterations in the chromatogram. SE appears better suited to serial analyses involving stored samples.