Longitudinal Change and Predictors of Myocardial Flow Reserve by Positron Emission Tomography for the Evaluation of Cardiac Allograft Vasculopathy Following Heart Transplantation.

BACKGROUND: Positron emission tomography (PET) myocardial flow reserve (MFR) is a noninvasive method of detecting cardiac allograft vasculopathy in recipients of heart transplants (HTs). There are limited data on longitudinal change and predictors of MFR following HT. METHODS: We conducted a retrospective analysis of HT recipients undergoing PET myocardial perfusion imaging at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors and the prognostic value of MFR after HT. RESULTS: Of HT recipients, 183 underwent 658 PET studies. The average MFR was 2.34 ± 0.70. MFR initially increased during the first 3 years following HT (+ 0.12 per year; P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P < 0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mammalian target of rapamycin (mTOR) inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (P < 0.001), hypertension (P < 0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4-13.4; P < 0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4-3.9; P < 0.001) were associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization. CONCLUSION: MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk-factor modification and treatment with higher-intensity statin therapy and mechanistic target of rapamycin inhibitors are associated with a higher MFR.

Characteristics of Heart Failure Patients With or Without Hypotension When Transitioning From Nitroprusside to Sacubitril-Valsartan.

BACKGROUND: Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction (HFrEF). Little is known about outcomes of HFrEF patients transitioned from sodium nitroprusside (SNP) to sacubitril-valsartan during an admission for acute decompensated heart failure. We sought to describe characteristics of patients initiated on sacubitril-valsartan while receiving SNP and, in particular, those patients who did and did not experience hypotension requiring interruption or discontinuation of sacubitril-valsartan. METHODS: We performed a retrospective case series of adult patients (>18 years) with HFrEF (left ventricular ejection fraction ≤40%) admitted to the University of Michigan cardiac intensive care unit between July 2018 to September 2020 who received sacubitril-valsartan while on SNP. RESULTS: A total of 15 patients with acute decompensated heart failure were initiated on sacubitril-valsartan while on SNP. The mean age was 57 ± 15.9 years. Seven (46.7%) patients experienced hypotension. The patients in the cohort who experienced hypotension were numerically older (60 ± 17 vs. 55 ± 15.5), and the majority were white (86%). Patients with hypotension had a numerically lower left ventricular ejection fraction (13 ± 4.2 vs. 18 ± 8.2) and higher serum creatinine (1.4 ± 0.54 vs. 0.88 ± 0.25). Seven (100%) patients received a diuretic on the day of sacubitril-valsartan initiation in those who experienced hypotension compared with 2 (25%) in those who did not experience hypotension. CONCLUSIONS: In almost half of patients admitted to the cardiac intensive care unit with acutely decompensated HFrEF, significant hypotension was seen when initiating sacubitril-valsartan while on SNP. Future studies should evaluate appropriate patients for this transition and delineate appropriate titration parameters.

Assessing the utility of pre-operative first pass radionuclide angiography to predict right ventricular failure post left ventricular assist device implantation.

INTRODUCTION: Right ventricular failure (RVF) after left ventricular assist device (LVAD) placement is associated with worse outcomes. We hypothesized that decreased right ventricular (RV) ejection fraction (EF) as well as qualitative assessments of RV function and dilation, as assessed by first pass radionuclide angiography (FPRNA), are associated with an increased risk of RVF following LVAD implantation. METHODS: We retrospectively identified 46 patients from 1/2008 to 11/2017 that underwent FPRNA and LVAD implantation. RVF was defined as requiring inotropes for greater than 14 days after LVAD implantation or requiring a right ventricular assist device. FPRNA-derived variables of RV performance and structure were compared between those that did and did not have RVF post implant. Statistical analyses were performed with Mann-Whitney U tests for ordinal and continuous variables. Fisher's exact tests and Pearson's χ2 tests were used for categorical variables. RESULTS: Eight patients developed RVF after device implantation. The average RV EF on FPRNA was 41.45% in those that did not develop RVF and 40.13% in those that did (P = 0.787). RV dilation (P = 0.896) and global RV function (P = 0.827) by FPRNA were not statistically different between the two groups. CONCLUSION: In patients that required FPRNA for further assessment of RV function prior to LVAD implantation, decreased RV EF, RV dilation and global RV function on FPRNA were not associated with an increased risk of RVF.

Imaging Coronary Allograft Vasculopathy with Cardiac PET and Cardiac MRI.

PURPOSE OF REVIEW: Coronary allograft vasculopathy (CAV) is a leading cause of morbidity and mortality in heart transplant patients. It presents a diagnostic challenge as early CAV is often clinically silent, and it affects both epicardial coronary arteries and microvasculature. This review outlines the role of cardiac positron emission tomography (PET) and cardiac magnetic resonance imaging (CMR) in the diagnosis and prognosis of CAV. RECENT FINDINGS: Relative myocardial perfusion imaging (MPI) and quantitative myocardial blood flow using cardiac PET are useful in the diagnosis and prognosis of CAV. Late gadolinium enhancement (LGE) and quantitative measures including myocardial perfusion reserve and mean diastolic rate using CMR are useful in the diagnosis and prognosis of CAV. Cardiac PET is now established as a non-invasive imaging modality for screening and monitoring for CAV, and CMR has demonstrated promise in this application. Further investigation of these modalities is needed with larger, multicenter studies that follow patients serially to demonstrate the clinical implications of using these modalities to detect early CAV and alter therapies to improve patient outcomes.

Coronavirus Disease-2019 in Heart Transplant Recipients in Southeastern Michigan: A Case Series.

BACKGROUND: Since coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019, the number of cases has risen exponentially. Clinical characteristics and outcomes among patients with orthotopic heart transplant (OHT) with COVID-19 remain poorly described. METHODS: We performed a retrospective case series of patients with OHT with COVID-19 admitted to 1 of 2 hospitals in Southeastern Michigan between March 21 and April 22, 2020. Clinical data were obtained through review of the electronic medical record. Final date of follow-up was May 7, 2020. Demographic, clinical, laboratory, radiologic, treatment, and mortality data were collected and analyzed. RESULTS: We identified 13 patients with OHT admitted with COVID-19. The mean age of patients was 61 ± 12 years, 100% were black males, and symptoms began 6 ± 4 days before admission. The most common symptoms included subjective fever (92%), shortness of breath (85%), and cough (77%). Six patients (46%) required admission to the intensive care unit. Two patients (15%) died during hospitalization. CONCLUSIONS: Black men may be at increased risk for COVID-19 among patients with OHT. Presenting signs and symptoms in this cohort are similar to those in the general population. Elevated inflammatory markers on presentation appear to be associated with more severe illness.

Safety of regadenoson positron emission tomography stress testing in orthotopic heart transplant patients.

OBJECTIVES: We sought to determine the safety of regadenoson (REG) stress testing in patients who have undergone orthotopic heart transplantation (OHT). BACKGROUND: Routine screening for cardiac allograft vasculopathy (CAV) is necessary after OHT. Adenosine stress is contraindicated after heart transplantation due to supersensitivity in denervated hearts. Safety of regadenoson stress following OHT has not been well studied. METHODS: We retrospectively reviewed data from OHT patients (N = 123) who were referred to REG stress testing. Medical records were reviewed to determine hemodynamic and ECG response to regadenoson and to identify adverse reactions. RESULTS: No serious adverse events occurred. No life-threatening arrhythmias or hemodynamic changes occurred. Common side-effects related to regadenoson were observed, dyspnea being the most frequent (66.7%). On average the heart rate rose from 82.8 ± 12 to 95.7 ± 13.4 bpm (P < 0.001), systolic blood pressure decreased from 138.7 ± 20.9 to 115.9 ± 23.9 mmHg (P < 0.001) and mean arterial pressure decreased from 103.5 ± 14.1 to 84.72 ± 15.90 mmHg (P < 0.001) during stress protocol. There was no sustained ventricular tachycardia, ventricular fibrillation, or second-or third-degree atrioventricular block. CONCLUSION: Regadenoson stress testing appears to be well tolerated and safe in OHT patients.

Lower Extremity Function Is Independently Associated With Hospitalization Burden in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Frailty reflects decreased resilience to physiological stressors; its prevalence and prognosis are not fully defined in heart failure with preserved ejection fraction (HFpEF). METHODS: The Short Physical Performance Battery (SPPB) was prospectively obtained in 114 outpatients with HFpEF. The SPPB tests gait speed, tandem balance, and timed chair rises, each scored from 0 to 4 points. Severe and mild frailty were respectively defined as an SPPB score ≤6 and 7-9 points. We used risk-adjusted logistic, Poisson, and negative binominal regression, respectively, to assess the relationship between SPPB score and risk of death or all-cause hospitalization, number of hospitalizations, and days hospitalized or dead longer than 6 months. RESULTS: Patients were similar to other HFpEF cohorts (age 68 ± 13 years, 58% female, body mass index 36 ± 8 kg/m2, multiple comorbidities). Mean SPPB score was 6.9 ± 3.2, and 80% of patients were at least mildly frail. Over a 6-month period, the SPPB score independently predicted death or all-cause hospitalization (odds ratio 0.81 per point, 95% confidence interval [CI] 0.69-0.94, P = .006), number of hospitalizations (incidence rate ratio 0.92 per point, 95% CI 0.86-0.97, P = .006), and days hospitalized or dead (incidence rate ratio 0.85 per point, 95% CI 0.73-0.99, P = .04). CONCLUSIONS: Lower extremity function, as measured by the SPPB, independently predicts hospitalization burden in outpatients with HFpEF. Additional studies are warranted to explore shared mechanisms and treatment implications of frailty in HFpEF.

Reduced Myocardial Flow Reserve Is Associated With Diastolic Dysfunction and Decreased Left Atrial Strain in Patients With Normal Ejection Fraction and Epicardial Perfusion.

INTRODUCTION: Coronary microvascular dysfunction (MVD) may contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Using myocardial flow reserve (MFR) measured by positron emission tomography (PET) as an assessment of microvascular function, we hypothesized that abnormal MFR is associated with LV diastolic dysfunction (DD) and reduced LV and LA strain in patients with risk factors for HFpEF and normal epicardial perfusion on cardiac PET. METHODS AND RESULTS: Retrospective study of patients without heart failure who underwent cardiac rubidium-82 PET and echocardiography. Global MFR was calculated as the ratio of global stress to rest myocardial blood flow. Echocardiographic measures of diastolic function were recorded. Global longitudinal LA and LV strain were measured with a 2-dimensional speckle-tracking technique. Relationships among MFR and echocardiographic measures were assessed with linear regression, analysis of variance, and test for trend. Seventy-three patients (age 64 ± 11 years, 52% male) were identified with no epicardial perfusion defect on cardiac PET and an ejection fraction ≥50%. Decreased MFR was associated with LV DD (P = .02) and increased E/e', an estimation of LV filling pressure (low E/e' [<8] vs. high E/e' [>15], P < .001). MFR was associated with LA strain independent of age, gender, and common comorbidities (adjusted ß = 2.6% per unit MFR, P = 0.046); however, MFR was only marginally related to LV strain. CONCLUSIONS: In patients with risk factors for HFpEF, MVD assessed with MFR was associated with DD, increased estimated LV filling pressure, and abnormal LA strain.

Current Perspectives on Systemic Hypertension in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

Cytomegalovirus infection is associated with impaired myocardial flow reserve after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation (HT). This study evaluates the relationship between clinically significant cytomegalovirus infection (CS-CMVi) and CAV using cardiac positron emission tomography (PET). METHODS: We retrospectively evaluated HT patients from 2005 to 2019 who underwent cardiac PET for CAV evaluation. Multivariable linear and logistic regression models were used to evaluate the association between CS-CMVi and myocardial flow reserve (MFR). Kaplan-Meier and Cox regression analyses were used to assess the relationship between CS-CMV, MFR, and clinical outcomes. RESULTS: Thirty-two (31.1%) of 103 HT patients developed CS-CMVi at a median 9 months after HT. Patients with CS-CMVi had a significantly lower MFR at year 1 and 3, driven by reduction in stress myocardial blood flow. Patients with CS-CMVi had a faster rate of decline in MFR compared to those without infection (-0.10 vs -0.06 per year, p < 0.001). CS-CMVi was an independent predictor of abnormal MFR (<2.0) (odds ratio: 3.8, 95% confidence intervals (CI): 1.4-10.7, p = 0.001) and a lower MFR (ß = -0.39, 95% CI: -0.63 to -0.16, p = 0.001) at year 3. In adjusted survival analyses, both abnormal MFR (log-rank p < 0.001; hazard ratio [HR]: 5.7, 95% CI: 4.2-7.2) and CS-CMVi (log-rank p = 0.028; HR: 3.3, 95% CI: 1.8-4.8) were significant predictors of the primary outcome of all-cause mortality, retransplantation, heart failure hospitalization, and acute coronary syndrome. CONCLUSIONS: CS-CMVi is an independent predictor of reduced MFR following HT. These findings suggest that CMV infection is an important risk factor in the development and progression of CAV.

Post-intensive cardiac care outpatient long-term outreach clinic (PICCOLO clinic): Defining health care needs and outcomes among coronary care unit survivors.

Objective: Patients who survive critical illness endure complex physical and mental health conditions, referred to as post-intensive care syndrome (PICS). The University of Michigan's post-intensive cardiac care outpatient long-term outreach (PICCOLO) clinic is designed for patients recently admitted to the coronary care unit (CCU). The long-term goal of this clinic is to understand post-CCU patients' needs and design targeted interventions to reduce their morbidity and mortality post-discharge. As a first step toward this goal, we aimed to define the post-discharge needs of CCU survivors. Design setting particpants: We retrospectively reviewed case-mix data (including rates of depression, PTSD, disability, and cognitive abnormalities) and health outcomes for patients referred to the PICCOLO clinic from July 1, 2018, through June 30, 2021 at Michigan Medicine. Results: Of the 134 referred patients meeting inclusion criteria, 74 (55 %) patients were seen in the PICCOLO clinic within 30 days of discharge. Patients seen in the clinic frequently screened positive for depression (PHQ-2 score ≥3, 21.4 %) and cognitive impairment (MOCA <26, 38.8 %). Further, patients also reported high rates of physical difficulty (mean WHODAS 2.0 score 28.4 %, consistent with moderate physical difficulty). Consistent with medical intensive care unit (ICU) patients, CCU survivors experience PICS. Conclusion: This work highlights the feasibility of an outpatient care model and the need to leverage information gathered from this care model to develop treatment strategies and pathways to address symptoms of PICS in CCU survivors, including depression, cognitive impairment, and physical disability.

Short-term outcomes after sodium-glucose cotransporter-2 inhibitor initiation in a cohort of heart failure patients.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease mortality and risk of hospitalization in patients with heart failure with reduced ejection fraction (HFrEF). SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate rates of acute kidney injury (AKI) and therapy discontinuation with SGLT2i initiation in a real-world cohort of HFrEF patients. METHODS AND RESULTS: We abstracted data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting at the University of Michigan (between 1 July 2016 and 2 July 2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. A total of 200 patients were included. The majority of patients were male (64%) with a mean left ventricular ejection fraction (LVEF) of 27%. One hundred and four (52%) patients had diabetes mellitus. Most patients exhibited New York Heart Association class II (51.5%) or III (33.5%) symptoms. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3 mg. AKI occurred in 22 patients and 18 patients discontinued their SGLT2i. Yeast infection (n = 6), hypotension (n = 5), and AKI (n = 4) were the most common reasons for discontinuation. Using receiver operating characteristic curve analysis, the strongest models for AKI were A1C [area underneath its curve (AUC) = 75.8, empirical confidence interval (ECI) 66.5-83.5]; baseline serum creatinine (SCr) (AUC = 72.0, ECI 65.7-78.7); LVEF (AUC = 67.6, ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC = 66.0, ECI 57.5-74.6). Similarly, the strongest positive models for SGLT2i discontinuation were A1C (AUC = 81.1, ECI 74.8-87.2); baseline SCr (AUC = 67.4, ECI 58.7-75.5); LVEF (AUC = 68.7, ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC = 67.2, ECI 58.2-76.0). CONCLUSIONS: A1C was the strongest model of AKI, and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. Patients with higher baseline SCr on higher doses of loop diuretics may be at greater risk of these outcomes. Future prospective studies will be needed to further evaluate these findings and other models of AKI and SGLT2i discontinuation to guide clinical use of SGLT2 inhibitors.

Malnutrition in heart failure with preserved ejection fraction.

BACKGROUND: Malnutrition may be an important geriatric condition in adults with heart failure with preserved ejection fraction (HFpEF), but studies on its prevalence and associated clinical outcomes are limited. The aim of this study was to determine if malnutrition is associated with short-term morbidity and mortality in ambulatory patients with HFpEF. METHODS: We examined 231 patients with a clinical diagnosis of HFpEF seen at two dedicated academic HFpEF programs (Weill Cornell Medicine and Michigan Medicine) from June 2018 to April 2022. Malnutrition was defined by Mini-Nutritional Assessment Short Form (MNA-SF) scores ≤11. The primary endpoint was a 6-month composite of all-cause mortality and all-cause hospitalization. A Cox proportional-hazard models was used to examine the association between malnutrition and the primary endpoint, adjusting for race, prior hospitalization history, and the validated Meta-Analysis Global Group in Chronic (MAGGIC) heart failure prognostic risk score. RESULTS: The median age of the cohort was 73 years (interquartile range 64-81). The most common comorbid conditions included hypertension (prevalence 81%), atrial fibrillation (43%), and obesity (63%). The prevalence of malnutrition was 42% (n = 97), and MNA-SF scores did not significantly correlate with body mass index (R = -0.02, p = 0.71). At the 6-month follow-up, 62 patients (26.8%) were hospitalized and four patients died (1.7%). In a fully-adjusted analysis, malnutrition was independently associated with the composite outcome of all-cause mortality and all-cause hospitalization (HR 1.94 [95% CI: 1.17-3.20], p = 0.01). CONCLUSION: Despite a high prevalence of obesity, two out of five ambulatory adults with HFpEF are malnourished. Malnutrition was independently associated with adverse outcomes at 6 months. Future work is necessary to develop interventions that can address malnutrition.

Epidemiology, Diagnosis, Pathophysiology, and Initial Approach to Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is common and increasing in prevalence. Despite this, HFpEF is challenging to diagnose due in part to its shared clinical features with other comorbid conditions. HFpEF is now understood as a systemic syndrome, often driven by pro-inflammatory comorbidities, rather than solely a cardiac disease. This review summarizes the epidemiology, diagnostic criteria, and pathophysiology of HFpEF and proposes a clinical approach for patients suspected of having or diagnosed with HFpEF.

Impact of a pharmacist in an interdisciplinary post-cardiac intensive care unit clinic.

BACKGROUND: The complex needs of cardiac patients shortly after discharge from a cardiac intensive care unit (CICU) provides a unique opportunity for a pharmacist to help optimize medication management and guideline-directed medical therapy (GDMT). OBJECTIVE: This study describes the impact of a pharmacist in a multidisciplinary post-CICU clinic. METHODS: We performed a retrospective cohort study of patients ≥18 years of age who completed a visit in the University of Michigan Post Intensive Cardiac Care Outpatient Long-Term Outreach (PICCOLO) Clinic from July 2018 to May 2020. RESULTS: One hundred and six CICU survivors were referred. Of these 12 chose to follow-up with long term care providers. A total of 70 of the remaining 94 (74%) completed a visit. The median age was 65 (54-72) years, 71.4% were male, and 85.7% were Caucasian. The median number of pharmacist interventions at each visit was 4 (3-5), all patients had at least 1 intervention. Interventions included medication dose adjustment (n = 46); GDMT optimization (n = 42); medication change (n = 18); medication addition (n = 23) and cessation (n = 21); lab monitoring (n = 97); refill assistance (n = 16); pillbox provision (n = 8); and medication cost assistance (n = 8). CONCLUSIONS: Pharmacist led interventions in a post CICU clinic resulted in medication changes to optimize therapy, increased laboratory monitoring, medication cost savings for patients, and interventions to facilitate GDMT adherence.

Tacrolimus time in therapeutic range and long-term outcomes in heart transplant recipients.

STUDY OBJECTIVE: Little is known about the association between tacrolimus time in therapeutic range (TTR) within the guideline-recommended targets and heart transplant (HT) patient outcomes. This study evaluated the association of early tacrolimus TTR with rejection and other clinical outcomes during an extended follow-up after HT. DESIGN: This was a single-center retrospective cohort study. SETTING: The study was conducted at Michigan Medicine (1/1/2006-12/31/2017). PATIENTS: HT recipients ≥18 years of age were included. MEASUREMENT: The primary end point was the effect of tacrolimus TTR on time to rejection over the entire follow-up period. MAIN RESULTS: A total of 137 patients were included with a median follow-up of 53 months. Based on the median TTR of 58%, the patients were divided into the low tacrolimus TTR (n = 68) and high tacrolimus TTR (n = 69) cohort. The high tacrolimus TTR was associated with a significantly lower risk of rejection compared to the low tacrolimus TTR cohort (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.41-0.98; p = 0.04). A post hoc analysis revealed associations between rejection and TTR when high and low TTR groups were created at different levels. TTR <30% was associated with a 7-fold higher risk of rejection (HR 7.56; 95% CI 1.76-37.6; p < 0.01) and TTR >75% was associated with a 77% lower risk of rejection (HR 0.23; 95% CI 0.08-0.627; p < 0.01). CONCLUSIONS: Patients in the higher tacrolimus TTR cohort had a lower risk of rejection. We observed correlations between higher risk of rejection with TTR <30% and lower risk of rejection with TTR >75%. Future studies should focus on validating the optimal TTR cutoff while also exploring a cutoff to delineate high-risk patients for which early interventions to improve tacrolimus TTR may be beneficial.

Health of the Food Environment Is Associated With Heart Failure Mortality in the United States.

BACKGROUND: Food environment factors contribute to cardiovascular disease, but their effect on population-level heart failure (HF) mortality is unclear. METHODS: We utilized the National Vital Statistics System and USDA Food Environment Atlas to collect HF mortality rates (MR) and 2 county food environment indices: (1) food insecurity percentage (FI%) and (2) food environment index (FEI), a scaled index (0-10, 10 best) incorporating FI% and access to healthy food. We used linear regression to estimate the association between food environment and HF MR Results: Mean county FI% and FEI were 13% and 7.8 in 2956 included counties. Counties with FI% above the national median had significantly higher HF MR (30.7 versus 26.7 per 100 000; P<0.001) compared with FI% below the national median. Counties with HF MR above the national median had higher FI%, lower FEI, lower density of grocery stores, poorer access to stores among older adults, and lower Supplemental Nutrition Assistance Program participation rate (P<0.001 for all). Lower county FI% (ß=-1.3% per 1% decrease) and higher county FEI (ß=-3.6% per 1-unit increase in FEI) were significantly associated with lower HF MR after adjustment for county demographic, socioeconomic, and health factors. This association was stronger for HF MR compared with non-HF cardiovascular disease MR and all-cause MR The relationship between food environment and HF MR was stronger in counties with the highest income inequity and poverty rate. CONCLUSIONS: Healthier food environment is significantly associated with lower HF mortality at the county level. This reinforces the role of food security on cardiovascular outcomes.

Atypical Antipsychotic Safety in the CICU.

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

High-circulating gut microbiota-dependent metabolite trimethylamine N-oxide is associated with poor prognosis in pulmonary arterial hypertension.

Aims: We aimed to examine the hypothesis that circulating trimethylamine-N-oxide (TMAO) levels serve as a biomarker in pulmonary arterial hypertension (PAH), and to determine whether 3,3-dimethyl-1-butanol (DMB), a TMAO inhibitor, exerted a protective effect in monocrotaline (MCT)-induced PAH rats. Methods and results: In-patients with PAH were prospectively recruited from the Fuwai Hospital. Fasting blood samples were obtained to assess the TMAO levels and other laboratory values during the initial and second hospitalization. In a MCT-induced PAH rat, a normal diet and water supplemented with or without 1% DMB were administered for 4 weeks. The TMAO levels, haemodynamic examinations, changes in organ-tissue, and molecular levels were evaluated. In total, 124 patients with PAH were enrolled in this study. High TMAO levels were correlated with increased disease severity and poor prognosis even after adjusting for confounders. The TMAO levels in the rats decreased in the MCT + DMB group, accompanied by improved haemodynamic parameters, decreased right ventricular hypertrophy, and amelioration of pulmonary vascular remodelling. The decrease in abnormal apoptosis, excessive cell proliferation, transforming growth factor-ß expression, and restoration of endothelial nitric oxide synthase after DMB treatment further explained the amelioration of PAH. Conclusion: Increased TMAO levels were associated with poor prognosis in patients with PAH, and DMB played a protective effect in MCT-induced PAH rat.