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.

Donor hyperoxia is a novel risk factor for severe cardiac primary graft dysfunction.

BACKGROUND: Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT. METHODS: A cohort of HT recipients from 2 transplant centers between 1/1/12 and 12/31/19 was linked to their respective donors in the United Network for Organ Sharing (UNOS) DMG Registry (n = 1,079). PGD was defined according to modified ISHLT criteria. Variables were subject to univariate and multivariable multinomial modeling with development of mild/moderate or severe PGD as the outcome variable. A second multicenter cohort of 4,010 donors from the DMG Registry was used for validation. RESULTS: Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO2), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO2 ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort. CONCLUSIONS: Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management.

HLA Homozygosity and Likelihood of Sensitization in Kidney Transplant Candidates.

Background: Homozygosity for HLAs has been associated with adverse outcomes after viral infection as well as pregnancy-induced HLA sensitization. We sought to assess the relationship between HLA locus homozygosity and the level of HLA antibody sensitization. Methods: We measured sensitization using the calculated panel reactive antibody value for a large cohort of 147 461 patients added to the US OPTN/United Network for Organ Sharing kidney transplant waitlist between December 2014 and December 2019. We used multinomial logistic modeling to compare 62 510 sensitized patients to 84 955 unsensitized controls. Results: We found that the number of homozygous HLA loci was strongly associated with the level of sensitization. Within mildly, highly, or extremely sensitized candidates, women displayed a higher relative abundance of HLA homozygosity at multiple HLA loci as compared with men, with attenuation of this effect in Black candidates. In a multivariable logistic model, the number of homozygous HLA loci interacted with female sex but not with other factors associated with sensitization, including recipient ethnicity and a history of prior kidney transplant. Conclusions: This study shows that HLA homozygosity is an innate genetic factor that affects the likelihood of HLA sensitization. Further research is needed to identify the immunologic mechanisms that underlie this observation.

Heart Transplant in Older Adults.

Purpose of Review: Older adults with end-stage heart failure may be candidates for heart transplantation (HT) and changing guidelines and institutional policies have increased the availability of HT for septuagenarians. This review explores historical, pre-HT evaluation, and post-HT outcomes for older adult HT recipients. Recent Findings: Rates of HT in older adults have increased in the past decade and more than 800 septuagenarians have undergone HT. Older adult HT recipients have similar survival, rehospitalization, and graft failure rates when compared to younger patients despite additional comorbidities and higher risk donors. Summary: HT is feasible in carefully selected older adults. As the number of older adults who are considered for HT increases, additional research into population-specific assessment tools will be needed. Furthermore, age-related immune changes warrant population-specific studies on immunosuppressive regimens.

Heterogeneity of liver fibrosis in patients with congestive hepatopathy: A biopsy and explant comparison series.

PURPOSE: Patients with end-stage heart failure and concomitant irreversible liver injury may be candidates for combined heart liver transplant (CHLT). Determining appropriate candidates for CHLT is essential given organ scarcity. Transjugular liver biopsy (TJLB) is used to evaluate the severity of parenchymal liver injury in transplant candidates. In patients with congestive hepatopathy (CH), the fibrosis pattern may be heterogenous. METHODS: We reviewed all CHLT cases between 2007 and 2017, as well as lone-heart transplant cases with post-mortem autopsy. Pre-transplant TJLB was compared to explant to assess the performance of biopsy fibrosis staging. RESULTS: 12 patients were included. Median age at time of transplant was 58 and the cohort was predominantly male (75%). Seven (64%) TJLB were predominantly stage 4 fibrosis and 4 (36%) were stage 1. Advanced fibrosis was the dominant pattern in 7 (70%) explants and 5 (50%) explants had heterogenous fibrosis. In 50% of CH cases, there was discordance between the TJLB and explant. In the autopsy cases, the TJLB and autopsy findings differed. CONCLUSIONS: In this series of matched TJLB and explanted livers, we found variable performance of TJLB in predicting the predominant fibrosis stage present in the liver.

Recipient and surgical factors trigger severe primary graft dysfunction after heart transplant.

BACKGROUND: Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). The International Society for Heart and Lung Transplantation (ISHLT) subdivides PGD into 3 grades of increasing severity. Most studies have assessed risk factors for PGD without distinguishing between PGD severity grade. We sought to identify recipient, donor and surgical risk factors specifically associated with mild/moderate or severe PGD. METHODS: We identified 734 heart transplant recipients at our institution transplanted between January 1, 2012 and December 31, 2018. PGD was defined according to modified ISHLT criteria. Recipient, donor and surgical variables were analyzed by multinomial logistic regression with mild/moderate or severe PGD as the response. Variables significant in single variable modeling were subject to multivariable analysis via penalized logistic regression. RESULTS: PGD occurred in 24% of the cohort (n = 178) of whom 6% (n = 44) had severe PGD. One-year survival was reduced in recipients with severe PGD but not in those with mild or moderate PGD. Multivariable analysis identified 3 recipient factors: prior cardiac surgery, recipient treatment with ACEI/ARB/ARNI plus MRA, recipient treatment with amiodarone plus beta-blocker, and 3 surgical factors: longer ischemic time, more red blood cell transfusions, and more platelet transfusions, that were associated with severe PGD. We developed a clinical risk score, ABCE, which provided acceptable discrimination and calibration for severe PGD. CONCLUSIONS: Risk factors for mild/moderate PGD were largely distinct from those for severe PGD, suggesting a differing pathophysiology involving several biological pathways. Further research into mechanisms underlying the development of PGD is urgently needed.

A case of a pregnant patient with COVID-19 infection treated with emergency c-section and extracorporeal membrane oxygenation.

Coronavirus disease 2019 (COVID-19) causes the development of severe acute respiratory distress syndrome. Pregnant women may be at increased risk for the development of severe disease. We present the case of a pregnant patient who developed respiratory failure due to COVID-19 and rapidly decompensated requiring intubation. Despite mechanical ventilation, the patient's respiratory status continued to worsen. At bedside, cardiothoracic surgeons, obstetricians, intensivists, and neonatologists discussed balancing the risk of COVID-19 and respiratory failure to the patient, premature delivery to the neonate, potential coagulopathy associated with COVID-19, and the need for anticoagulation with mechanical circulatory support. Ultimately, the decision was to proceed with emergency cesarean section delivery in the intensive care unit followed by peri-partum veno-venous extracorporeal membrane oxygenation initiation. The patient and neonate were both discharged home in stable condition.

Corrigendum to "Evaluation of Healthy2Go: A country store transformation project to improve the food environment and consumer choices in Appalachian Kentucky" [Prev. Med. Rep. 7 (2017) 187-192].

[This corrects the article DOI: 10.1016/j.pmedr.2017.06.009.].

The Association Between Secondhand Smoke Exposure and Survival for Patients With Heart Failure.

BACKGROUND: The effect of secondhand tobacco smoke (SHS) exposure on patients with heart failure (HF) is uncertain. We investigated the association of mortality with SHS exposure for patients with HF. METHODS: Nonsmokers with clinical HF were enrolled from 2003 to 2008 in a single-center longitudinal cohort study. The effect of SHS exposure determined by high-sensitivity urinary cotinine on mortality was estimated by multivariable proportional hazards modeling. RESULTS: Mortality was assessed after median 4.3 years. Of 202 patients, enrollment urinary cotinine levels were below the limit of detection for 106 (52%) considered unexposed to SHS. The median detectable cotinine was 0.47 ng/mL (interquartile range: [0.28, 1.28]). Participants were 41% female, 65 ± 17 years old, and 57% white race. Elevated cotinine was associated with increased mortality after multivariate adjustment: hazard ratio (HR) per 1 ng/mL increase in urinary cotinine: 1.15, 95% confidence interval (CI): 1.08-1.23, P < .001. Higher age (HR per 5-year increase: 1.32, 95% CI: 1.22-1.43, P < .001), male sex (HR vs female: 1.52, 95% CI: 1.02-2.28, P = .040), and New York Heart Association class (HR for class III vs I: 2.91, 95% CI: 1.71-4.99, P < .001) were also associated with mortality. CONCLUSIONS: SHS exposure is associated with a dose-dependent increase in mortality for patients with HF.

A social-network behavioral health program on sustained long-term body weight and glycemic outcomes: 2-year follow-up of a 4-month Microclinic Health Program in Jordan.

The burden of chronic diseases like diabetes and obesity is rapidly increasing in low and lower-middle income countries. This work assesses the long-term efficacy of a social-network based community health program for the management and prevention of type 2 diabetes. METHODS: The 4-month Microclinic Social Network Behavioral Health Program in Jordan (J-MCP) was an intervention for obesity and diabetes prevention and management conducted in the Kingdom of Jordan. Weight and HbA1c were collected at baseline, end of the 4-month program, and then 12 and 24 months after baseline. Multi-level longitudinal repeated measures analysis estimated the long-term change in metabolic outcomes, and estimated the intra-class correlations (ICCs) for assessing the degree of clustering that different social network levels, of microclinic group vs. classroom group vs. clinic geographic location vs. cohort temporal wave, contributed to body weight and glycemic changes. RESULTS: Of 315 participants, 83.2% completed the J-MCP program, with 90% followup at 12-months, and 70% at 24-months. At the end of the 4-month program, participants experienced a -2.8 kg (95% CI: -3.6 to -2.1) mean body weight decrease, a corresponding -1.1 kg/m2 (-1.3 to -0.8) BMI decrease, and a -0.5% reduction in HbA1c (-0.6 to -0.3). At year 1, we observed significant mean weight reduction of -1.8 kg (-2.7 to -0.9), a corresponding -0.7 kg/m2 (-1.0 to -0.4) reduction in BMI, as well as a -0.4% (-0.6 to -0.3) sustained reduction in HbA1c. At 2 years, participants sustained mean weight loss of -1.6 kg (-2.6 to -0.5), a -0.42 kg/m2 (-0.8 to -0.04) reduction in BMI, and an absolute -1.0% (-1.1 to -0.8) sustained reduction in HbA1c. Analyzing different social network levels, classroom group explained ~50% of total clustering of total weight loss and 22% of HbA1c trajectories during the short 4 month intervention. However, during 12 and 24 month followup, microclinic social group clustering explained ~75% to 92% of long-term weight loss trajectories, and 55% of long-term HbA1c trajectories. The pattern of 1-2 year sustainability of the weight and HbA1c decreases was largely attributed to the microclinic social network clusters. CONCLUSION: Results demonstrate that the 4-month J-MCP behavioral intervention yielded important 2-year sustained weight and HbA1c reductions, which were mostly attributed to microclinic social groups.

Development and Implementation of a Subcutaneous Insulin Pen Label Bar Code Scanning Protocol to Prevent Wrong-Patient Insulin Pen Errors.

PROBLEM DEFINITION: Insulin, a high-alert medication, is regularly prescribed in the inpatient setting for hyperglycemia and diabetes mellitus. Although convenient, insulin pens carry a risk of blood-borne pathogens if the same pen is used on multiple patients. At the University of California, San Francisco (UCSF), a new nursing protocol for insulin pen administration was developed to ensure that insulin was quickly available and to identify and move to eliminate wrong-patient insulin pen errors. This protocol involved unit-based automated dispensing machines and an electronic health record (EHR)-integrated patient-specific bar code label work flow. APPROACH: After piloting on three hospital units, this new patient-specific bar code label process was expanded hospitalwide. "Print Label For Insulin Pen" and "Scan Insulin Pen" buttons were programmed into the EHR to enable nurses to print patient-specific bar code labels. In addition, a "wrong-patient pen alert" was activated to prevent wrong-pen insulin pen administration. OUTCOMES: For the 162,075 inpatient insulin pen administrations during the study period (April 2017-March 2018), monthly errors (rates) ranged from 13 (0.12%) to 36 (0.23%). In total, 296 near-miss events (0.18% of all insulin pen administrations) were observed and prevented. CONCLUSION: Insulin pen work flow and EHR changes implemented at UCSF enable subcutaneous insulin to remain a time-critical medication and ensure patient safety. The wide adoption of EHRs offers an opportunity to integrate patient safety improvements directly into the electronic medication administration record systems to maximize patient safety.

Evaluation of Healthy2Go: A country store transformation project to improve the food environment and consumer choices in Appalachian Kentucky.

Rates of obesity and type 2 diabetes in Kentucky's Cumberland Valley region are among the highest in the United States and limited access to healthy food contributes to these epidemics. The aim of Healthy2Go (H2G), a country store transformation project launched by Spread the Health Appalachia (STHA), was to improve awareness and availability of healthy options in small, rural stores. Ten country stores participated in H2G and received training and technical assistance to increase availability and awareness of healthy foods. Stores made inventory changes; installed point-of-purchase educational and in-store marketing materials directing shoppers to healthier options; provided nutrition education such as healthy recipes; and altered the display and location of healthy items. To measure changes within stores and the potential impact on resident eating and purchasing habits, STHA used four instruments: a modified version of the Nutrition Environs Measures Survey - Corner Stores at baseline and follow-up, a bimonthly store inventory assessment, a final store owner survey, and a Community Nutrition Survey at baseline (n = 287) and follow-up (n = 281). The stores in the H2G program (n = 10) had a 40% increase in stocking fresh produce, a 20% increase in produce variety, and trends towards increasing healthy inventory. During the same period, surveyed residents reported a statistically significant increase in the frequency of healthy food consumption. Small store transformation programs can improve availability of and access to healthy food in rural settings and influence local purchasing patterns.

Remote Monitoring and Consultation of Inpatient Populations with Diabetes.

PURPOSE OF REVIEW: Inpatient hyperglycemia is common and is linked to increased morbidity and mortality. We review current and innovative ways diabetes specialists consult in the management of inpatient diabetes. RECENT FINDINGS: With electronic medical records (EMRs), remote monitoring and intervention may improve the management of inpatient hyperglycemia. Automated reports allow monitoring of glucose levels and allow diabetes teams to intervene through formal or remote consultation. Following a 2-year transition of our complex paper-based insulin order sets to be EMR based, we leveraged this change by developing new daily glycemic reports and a virtual glucose management service (vGMS). Based on a daily report identifying patients with two or more glucoses over 225 mg/dl and/or a glucose <70 mg/dl in the past 24 h, a vGMS note with management recommendations was placed in the chart. Following the introduction of the vGMS, the proportion of hyperglycemic patients decreased 39% from a baseline of 6.5 per 100 patient-days to 4.0 per 100 patient-days The hypoglycemia proportion decreased by 36%. Ninety-nine percent of surveyed medical and surgical residents said the vGMS was both important and helpful.