Citations

Background: Pulmonary hypertension is common in HFpEF and is associated with increased mortality. Pulmonary hypertension can lead to right ventricular systolic dysfunction. However, the magnitude and prognostic significance of RV dysfunction in the HFpEF population are unclear. Hypothesis: RV systolic dysfunction is common in HFpEF and is associated with increased mortality. Methods: RV size and systolic function were assessed qualitatively (as normal or abnormal) and pulmonary artery systolic pressure (PASP) was estimated using echocardiography in 548 consecutive HFpEF subjects (Framingham criteria and EF ≥50%) from a prospective population based study (Olmsted County, Minnesota). Control group was a retrospectively identified random sample of age and sex matched hypertensive (N=360) and normotensive subjects (N=168) from Olmsted County. HFpEF group was followed for up to 5 years (median follow up 4.4 years). Results: See table and figure. RV enlargement and systolic dysfunction were more prevalent in HFpEF compared with age and sex matched hypertensive and normotensive controls. In HFpEF subjects with PASP above the median, RV systolic dysfunction was associated with poor survival compared with normal RV function. RV systolic dysfunction was a significant predictor of mortality even after adjustment for age and PASP in a Cox regression model (Hazard Ratio=1.4, p=0.02). Conclusions: In the community, RV systolic dysfunction is common in HFpEF and is associated with higher mortality. Although quantitative assessment of RV function is difficult owing to its complex geometry, qualitative assessment is feasible on the majority of subjects and provides significant prognostic information.

Objective : Practice analysis of cardiac surgical service lines suggested that, for patients having routine cardiac surgery, standardization of care processes in the ICU could reduce cost and improve outcomes. We tested this hypothesis in a large surgical practice. Methods : Patients eligible for a standardized care pathway were prospectively identified preoperatively. ICU protocol development and practice redesign occurred in 2009 with implementation in 2010. In the ICU, all major process steps to recovery were managed by tiered and integrated protocols whereby care advancement is the default if clinical criteria are met. We compared outcomes of patients managed by protocol to those managed by standard care. ICU metrics (time intubated, drip weaning, length of stay) were benchmarked against a sample of 65 CABG patients from 2008. Return to ICU and to OR for standardized care patients were compared to concurrent patients under routine care. We report on all patients having cardiac surgery for 12 months beginning March 2010. Findings : Over 12 months, the ICU care of 1289 patients followed standardized tiered protocols, while 1309 patients were managed by standard care. After implementation of standardized protocols, ICU metrics improved in protocol patients relative to 2008 (2010 versus 2008): mean intubation time in hours (7.4 vs 11.6), mean time on hemodynamic drips in hours (16.2 vs 25.3), average ICU length of stay in hours (25.1 vs 35.9). The safety of protocol based care is demonstrated by lower rates of return to ICU and to OR among patients under protocol vs non-protocol: return to OR (1.8% vs 8.9%), return to ICU (1.6% vs 6.2%). Conclusions: With proper patient selection and rigorous protocols that make care advancement the default, cardiac surgical care in the ICU can be standardized and clinical metrics improved. The safety of this strategy is demonstrated by very low rates of return to OR or ICU. This practice model is translatable to other ICU practices.

Objective: To determine if the implementation of smoke-free workplace laws reduced the incidence of the acute coronary events including myocardial infarction (MI) and sudden cardiac death (SCD). Background: Nonsmokers chronically exposed to second-hand smoke (SHS) are at increased risk of death from heart disease. However, a nonlinear dose relationship exists between SHS exposure and coronary heart disease (CHD) such that the relative risk of CHD is 1.31 for nonsmokers and 1.78 for smokers. Reductions in admissions for MI in locales where smoke-free workplace laws have been implemented have been observed, but none have assessed SCD. On January 1, 2002, a smoke-free restaurant law (Ordinance #1) was implemented in Olmsted County, Minnesota, and on October 1, 2007, all workplaces became smoke-free (Ordinance #2). Methods: Under the auspices of the Rochester Epidemiology Project, we measured the incidence of MI and SCD during the 18-month calendar period before and after implementation of each smoke-free ordinance. All MI were validated using biomarkers, cardiac pain, and Minnesota coding of the ECG. SCD was defined as out-of-hospital deaths assigned to CHD (ICD-9 codes 410 through 414). Results: For the overall study period of the 18 months before the implementation of the smoke-free restaurant ordinance and 18 months after the implementation of the smoke-free workplace ordinance, we observed a 45% decline in the incidence for MI (p <0.01) and a 50% decline in the incidence for SCD (p <0.01). See Table. During this same period, the prevalence of hypertension, diabetes, hypercholesterolemia, and obesity either remained constant or increased while the prevalence of smoking among adults declined by 23% (22% to 17%). Conclusion: In the Olmsted County population, substantial declines in the incidence of MI and SCD were observed after smoke-free laws were implemented. Smoke-free workplace laws may not only be associated with a decrease in MI but SCD as well.

Abstract Background Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health‐related quality of life in patients with HF is not well understood. Methods Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF‐related prescription drugs from four U.S. institutions were mailed a survey to measure patient‐centric factors including functional status (activities of daily living [ADLs]) and health‐related quality of life (PROMIS‐29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non‐cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS‐29 sub‐scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. Results A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66–4.45), depression (OR: 3.11, 95% CI: 2.39–4.06), and fatigue (OR: 4.19, 95% CI: 3.25–5.40); worse sleep (OR: 2.14, 95% CI: 1.69–2.72) and pain (OR: 6.73, 95% CI: 5.15–8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19–12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. Conclusion Patients with only functional limitation have similar poor health‐related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well‐being of patients with HF.

Background Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low‐density lipoprotein cholesterol (VLDL‐C) and lipid discordance could be contributors to the residual risk of ASCVD. Methods and Results Cardiovascular disease–free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low‐density lipoprotein cholesterol (LDL‐C) and VLDL‐C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow‐up. The association of LDL‐C and VLDL‐C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL‐C and VLDL‐C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL‐C (per 10‐mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05–1.09]; P <0.001]) after adjustment for traditional risk factors. The interaction between LDL‐C and VLDL‐C was not statistically significant ( P =0.11). Discordant individuals with high VLDL‐C and low LDL‐C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person‐years, during follow‐up. Conclusions VLDL‐C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.

Here, we used digital spatial profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways with progressively decreased expression in response to increasing pathology scores, including signal recognition particle–dependent cotranslational protein targeting to membrane and selenocysteine synthesis pathways. We also identified a distinct signature of upregulated and downregulated genes common to all the diseases investigated when compared with nondiseased tissue from nephrectomies. These analyses using DSP at the single-glomerulus level could help to increase insight into the pathophysiology of kidney disease and possibly the identification of biomarkers of disease progression in glomerulopathies.

AbstractObjectivesEosinophilic esophagitis (EoE) is often diagnosed in school‐age children between 6‐ and 9‐year‐old. There is less known about those who are diagnosed with EoE that are younger than 6 years old. The objective of this study is to compare clinical presentation, comorbidities, and outcomes based on age at diagnosis of EoE.MethodsSingle‐center retrospective chart review of children (<18 years) diagnosed with EoE between 2005 and 2020. We recorded demographics, clinical presentation, family history, past medical history, treatment, and endoscopic findings. Children in this cohort were classified based on age into three age groups: <2 years, 2−<6 years, and 6−<18 years.ResultsWe identified 256 children with EoE, the mean age (SD) at the time of diagnosis was 9 (5.2) years and 184 (72%) were male. We had 164 (64%) patients with available follow‐up esophagogastroduodenoscopies (EGDs) data (495 EGDs in total) of those 99/164 (60%) reached mucosal remission. In the very young children (<2 years) vomiting was the most common presentation, while poor weight gain was seen more in the 2−<6‐year group in comparison to the >6‐years. Food impaction and abdominal pain were most likely to present in older children 6−18 years. Combination therapy, as opposed to a single therapy, induced remission at a higher frequency in the <6‐year group in comparison to the 6−<18‐year group (85% vs. 66%).ConclusionEoE should be considered in younger children presenting with feeding difficulty and poor weight gain. Combination therapy seems to be more effective in younger children with EoE, but further studies with bigger sample size are needed to study the efficacy of the different combination therapies.

Abstract Background Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. Aim The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m‐amph). Methods Wistar rats were given 14 days of m‐amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low‐frequency stimulation (LFS) or continuous high‐frequency stimulation (HFS). Immediately after DBS, manic‐like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open‐field tests and fast‐scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. Results M‐amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M‐amph increased DA reuptake time post‐sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. Conclusion These results demonstrate that both VTA LFS and HFS DBS exert anti‐manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti‐manic effects.

Background Frailty is common in heart failure (HF) and is associated with death but not routinely captured clinically. Frailty is linked with inflammation and malnutrition, which can be assessed by a novel plasma multimarker score: the metabolic vulnerability index (MVX). We sought to evaluate the associations between frailty and MVX and their prognostic impact. Methods and Results In an HF community cohort (2003–2012), we measured frailty as a proportion of deficits present out of 32 physical limitations and comorbidities, MVX by nuclear magnetic resonance spectroscopy, and collected extensive longitudinal clinical data. Patients were categorized by frailty score (≤0.14, >0.14 and ≤0.27, >0.27) and MVX score (≤50, >50 and ≤60, >60 and ≤70, >70). Cox models estimated associations of frailty and MVX with death, adjusted for Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide). Uno's C‐statistic measured the incremental value of MVX beyond frailty and clinical factors. Weibull's accelerated failure time regression assessed whether MVX mediated the association between frailty and death. We studied 985 patients (median age, 77; 48% women). Frailty and MVX were weakly correlated (Spearman's ρ=0.21). The highest frailty group experienced an increased rate of death, independent of MVX, MAGGIC score, and NT‐proBNP (hazard ratio, 3.3 [95% CI, 2.5–4.2]). Frailty improved Uno's c‐statistic beyond MAGGIC score and NT‐proBNP (0.69–0.73). MVX only mediated 3.3% and 4.5% of the association between high and medium frailty groups and death, respectively. Conclusions In this HF cohort, frailty and MVX are weakly correlated. Both independently contribute to stratifying the risk of death, suggesting that they capture distinct domains of vulnerability in HF.