Eileen Hsich

Vascular effects following homozygous disruption of p47(phox) : An essential component of NADPH oxidase.

BACKGROUNDnEvidence suggests that the vessel wall contains an oxidase similar, if not identical, to phagocytic NADPH oxidase. We tested the contribution of this specific oxidase to the progression of atherosclerosis and the regulation of blood pressure.nnnMETHODS AND RESULTSnAn examination of aortic rings from wild-type mice and mice with homozygous targeted disruptions in p47(phox) revealed that p47(phox) knockout mice had a reduction in vascular superoxide production. However, analyses of apoE -/- p47(phox)+/+ and apoE -/- p47(phox) -/- strains of mice demonstrated no significant differences in atherosclerotic lesion sizes. Similarly, analyses of wild-type and p47(phox) knockout mice revealed no differences in either basal blood pressure or the rise in blood pressure seen after the pharmacological inhibition of nitric oxide synthase.nnnCONCLUSIONSnNADPH oxidase contributes to basal vascular superoxide production. However, the absence of a functional oxidase does not significantly affect the progression of atherosclerosis in the standard mouse apoE -/- model, nor does it significantly influence basal blood pressure.

Heart Failure in Women: A Need for Prospective Data

Heart failure affects 5 million Americans, and nearly 50% of these are women. Sex differences have been noted regarding the underlying etiology, pathophysiology, and prognosis. Women are less likely to have coronary artery disease and more likely than men to have hypertension and valvular disease as the underlying etiology. They often present at an older age with better systolic function than men. For both sexes, there is significant morbidity, but age-adjusted data reveal that women have a better survival. Despite these known sex differences, medical management recommendations are the same for women and men, because prospective sex-specific clinical trials have not been performed. However, our review raises some concerns that women might respond differently to therapy.

Identifying Important Risk Factors for Survival in Patient With Systolic Heart Failure Using Random Survival Forests

Background— Heart failure survival models typically are constructed using Cox proportional hazards regression. Regression modeling suffers from a number of limitations, including bias introduced by commonly used variable selection methods. We illustrate the value of an intuitive, robust approach to variable selection, random survival forests (RSF), in a large clinical cohort. RSF are a potentially powerful extensions of classification and regression trees, with lower variance and bias. Methods and Results— We studied 2231 adult patients with systolic heart failure who underwent cardiopulmonary stress testing. During a mean follow-up of 5 years, 742 patients died. Thirty-nine demographic, cardiac and noncardiac comorbidity, and stress testing variables were analyzed as potential predictors of all-cause mortality. An RSF of 2000 trees was constructed, with each tree constructed on a bootstrap sample from the original cohort. The most predictive variables were defined as those near the tree trunks (averaged over the forest). The RSF identified peak oxygen consumption, serum urea nitrogen, and treadmill exercise time as the 3 most important predictors of survival. The RSF predicted survival similarly to a conventional Cox proportional hazards model (out-of-bag C-index of 0.705 for RSF versus 0.698 for Cox proportional hazards model). Conclusions— An RSF model in a cohort of patients with heart failure performed as well as a traditional Cox proportional hazard model and may serve as a more intuitive approach for clinicians to identify important risk factors for all-cause mortality.

Importance of Treadmill Exercise Time as an Initial Prognostic Screening Tool in Patients With Systolic Left Ventricular Dysfunction

Background— We sought to determine whether treadmill exercise time may be of value as an initial prognostic screening tool in ambulatory patients with impaired systolic function who are referred for cardiopulmonary exercise testing. Methods and Results— We studied 2231 adult systolic heart failure patients (27% of whom were women) who underwent cardiopulmonary stress testing using a modified Naughton protocol. We assessed the value of treadmill exercise time for prediction of all-cause death and a composite of death or United Network for Organ Sharing status 1 heart transplantation. During a mean follow-up of 5 years, 742 patients (33%) died. There were 249 United Network for Organ Sharing status 1 heart transplants (11%). Treadmill exercise time was predictive of death and the composite outcome in both women and men, even after accounting for peak oxygen consumption and other clinical covariates (adjusted hazard ratio of lowest versus high sex-specific quartile for prediction of death 1.70, 95% confidence interval 1.05 to 2.75, P=0.03; for prediction of the composite outcome, 1.75, 95% confidence interval 1.15 to 2.66, P=0.009). For a 1-minute change in exercise time, there was a 7% increased hazard of death (eg, comparing 480 to 540 seconds, hazard ratio =1.07, 95% confidence interval 1.02 to 1.12, P=0.004). Conclusions— Because cardiopulmonary stress testing is not available in every hospital, treadmill exercise time with a modified Naughton protocol may be of value as an initial prognostic screening tool.

Should Women Receive Left Ventricular Assist Device Support?Clinical Perspective

Background—Small studies have reported women to have worse outcomes and more adverse events after implantation of mechanical circulatory support device compared with men. To further evaluate sex differences in outcome, we used the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Methods and Results—There were 401 women (pulsatile devices=78) and 1535 men (pulsatile devices=402) from 89 institutions who were prospectively enrolled into the INTERMACS database for primary implantation of a left ventricular assist device (LVAD) between June 23, 2006, and March 31, 2010. Extensive preimplantation and outcome data were collected on all patients. With a mean follow-up of 7 months, 67 females (17%) died and 250 males (16%) died. There was no statistically significant sex difference in mortality for either pulsatile-flow (P=0.82) or continuous-flow (P=0.95) devices in adjusted and unadjusted models. There were also no statistically significant sex differences with time to first infection, bleeding, or device malfunction. However, female sex was associated with an increased hazard of first neurological event (adjusted hazard ratio, 1.44; 95% CI, 1.05–1.96; P=0.020). Conclusions—There were no significant sex differences in mortality, time to first infection, bleeding, or device malfunction with either pulsatile- or continuous-flow LVADs. However, women had an increased risk of first neurological event. For urgent/emergent mechanical support, the benefit of LVAD support likely outweighs the risk, but it remains less clear for women undergoing elective LVAD implantation.

Mini-Cog PerformanceCLINICAL PERSPECTIVE

Background—Heart failure (HF) guidelines recommend screening for cognitive impairment (CI) but do not identify how. The Mini-Cog is an ultrashort cognitive “vital signs” measure that has not been studied in patients hospitalized for HF. The purpose of this study was to evaluate whether CI as assessed by the Mini-Cog is associated with increased readmission or mortality risk after hospitalization for HF. Methods and Results—We analyzed 720 consecutive patients who completed the Mini-Cog as a part of routine clinical care during hospitalization for HF. Our primary outcome was time between hospital discharge and first occurrence of readmission or mortality. There was a high prevalence of CI as quantified by Mini-Cog performance (23% of cohort). During a mean follow-up time of 6 months, 342 (48%) patients were readmitted, and 24 (3%) died. Poor Mini-Cog performance was an independent predictor of composite outcome (adjusted hazard ratio, 1.90; 95% confidence interval, 1.47–2.44; P<0.0001) and was identified as the most important predictor among 55 variables by random survival forest analysis. Inclusion of Mini-Cog performance in risk models improved accuracy (bootstrapped c-index, 0.602 versus 0.624) and risk reclassification (category-free net reclassification improvement, 27%; 95% confidence interval, 14%–40%; P<0.001). Secondary analysis of initial 30 days post discharge showed effect modification by venue of discharge, whereby patients with CI discharged to a facility had longer time to outcome as compared with those discharged home. Conclusions—Mini-Cog performance is a novel marker of posthospitalization risk. Discharge to facility rather than home may be protective for those patients with HF and CI. It is unknown whether structured in-home support would yield similar outcomes.Background— Heart failure (HF) guidelines recommend screening for cognitive impairment (CI) but do not identify how. The Mini-Cog is an ultrashort cognitive “vital signs” measure that has not been studied in patients hospitalized for HF. The purpose of this study was to evaluate whether CI as assessed by the Mini-Cog is associated with increased readmission or mortality risk after hospitalization for HF.nnMethods and Results— We analyzed 720 consecutive patients who completed the Mini-Cog as a part of routine clinical care during hospitalization for HF. Our primary outcome was time between hospital discharge and first occurrence of readmission or mortality. There was a high prevalence of CI as quantified by Mini-Cog performance (23% of cohort). During a mean follow-up time of 6 months, 342 (48%) patients were readmitted, and 24 (3%) died. Poor Mini-Cog performance was an independent predictor of composite outcome (adjusted hazard ratio, 1.90; 95% confidence interval, 1.47–2.44; P <0.0001) and was identified as the most important predictor among 55 variables by random survival forest analysis. Inclusion of Mini-Cog performance in risk models improved accuracy (bootstrapped c -index, 0.602 versus 0.624) and risk reclassification (category-free net reclassification improvement, 27%; 95% confidence interval, 14%–40%; P <0.001). Secondary analysis of initial 30 days post discharge showed effect modification by venue of discharge, whereby patients with CI discharged to a facility had longer time to outcome as compared with those discharged home.nnConclusions— Mini-Cog performance is a novel marker of posthospitalization risk. Discharge to facility rather than home may be protective for those patients with HF and CI. It is unknown whether structured in-home support would yield similar outcomes.

Mini-Cog Performance Novel Marker of Post Discharge Risk Among Patients Hospitalized for Heart Failure

Background—Heart failure (HF) guidelines recommend screening for cognitive impairment (CI) but do not identify how. The Mini-Cog is an ultrashort cognitive “vital signs” measure that has not been studied in patients hospitalized for HF. The purpose of this study was to evaluate whether CI as assessed by the Mini-Cog is associated with increased readmission or mortality risk after hospitalization for HF. Methods and Results—We analyzed 720 consecutive patients who completed the Mini-Cog as a part of routine clinical care during hospitalization for HF. Our primary outcome was time between hospital discharge and first occurrence of readmission or mortality. There was a high prevalence of CI as quantified by Mini-Cog performance (23% of cohort). During a mean follow-up time of 6 months, 342 (48%) patients were readmitted, and 24 (3%) died. Poor Mini-Cog performance was an independent predictor of composite outcome (adjusted hazard ratio, 1.90; 95% confidence interval, 1.47–2.44; P<0.0001) and was identified as the most important predictor among 55 variables by random survival forest analysis. Inclusion of Mini-Cog performance in risk models improved accuracy (bootstrapped c-index, 0.602 versus 0.624) and risk reclassification (category-free net reclassification improvement, 27%; 95% confidence interval, 14%–40%; P<0.001). Secondary analysis of initial 30 days post discharge showed effect modification by venue of discharge, whereby patients with CI discharged to a facility had longer time to outcome as compared with those discharged home. Conclusions—Mini-Cog performance is a novel marker of posthospitalization risk. Discharge to facility rather than home may be protective for those patients with HF and CI. It is unknown whether structured in-home support would yield similar outcomes.Background— Heart failure (HF) guidelines recommend screening for cognitive impairment (CI) but do not identify how. The Mini-Cog is an ultrashort cognitive “vital signs” measure that has not been studied in patients hospitalized for HF. The purpose of this study was to evaluate whether CI as assessed by the Mini-Cog is associated with increased readmission or mortality risk after hospitalization for HF.nnMethods and Results— We analyzed 720 consecutive patients who completed the Mini-Cog as a part of routine clinical care during hospitalization for HF. Our primary outcome was time between hospital discharge and first occurrence of readmission or mortality. There was a high prevalence of CI as quantified by Mini-Cog performance (23% of cohort). During a mean follow-up time of 6 months, 342 (48%) patients were readmitted, and 24 (3%) died. Poor Mini-Cog performance was an independent predictor of composite outcome (adjusted hazard ratio, 1.90; 95% confidence interval, 1.47–2.44; P <0.0001) and was identified as the most important predictor among 55 variables by random survival forest analysis. Inclusion of Mini-Cog performance in risk models improved accuracy (bootstrapped c -index, 0.602 versus 0.624) and risk reclassification (category-free net reclassification improvement, 27%; 95% confidence interval, 14%–40%; P <0.001). Secondary analysis of initial 30 days post discharge showed effect modification by venue of discharge, whereby patients with CI discharged to a facility had longer time to outcome as compared with those discharged home.nnConclusions— Mini-Cog performance is a novel marker of posthospitalization risk. Discharge to facility rather than home may be protective for those patients with HF and CI. It is unknown whether structured in-home support would yield similar outcomes.

Impaired Systolic Function in Loeys-Dietz Syndrome A Novel Cardiomyopathy?

Loeys-Dietz syndrome (LDS) is a recently described autosomal dominant genetic syndrome caused by mutations in the gene encoding transforming growth factor-β receptor 1 or 21 with no known cardiac involvement. Common characteristics include aortic and arterial aneurysms or dissections, orbital hypertelorism, and cleft palate or bifid uvula. We report the first case of a cardiomyopathy associated with LDS in a patient with a novel transforming growth factor-β receptor mutation and pathological evidence of microvascular coronary artery dysplasia.nnA 44-year-old tall, thin, white man with “borderline” hypertension and sleep apnea developed a severe, painful stabbing sensation in his throat while walking. He presented to a local hospital and was found to have an acute thoracoabdominal aortic dissection (Stanford type A) without involvement of the coronary …

Medication self-management skills and cognitive impairment in older adults hospitalized for heart failure: A cross-sectional study:

Background: Cognitive impairment is highly prevalent among older adults (aged ≥65u2009years) hospitalized for heart failure and has been associated with poor outcomes. Poor medication self-management skills have been associated with poor outcomes in this population as well. The presence and extent of an association between cognitive impairment and poor medication self-management skills in this population has not been clearly defined. Objective: We assessed the cognition of consecutive older adults hospitalized for heart failure, in relation to their medication self-management skills. Methods: We conducted a cross-sectional study of older adults (aged ≥65u2009years) who were hospitalized for heart failure and were being discharged home. Prior to discharge, we assessed cognition using the Mini-Cog. We also tested patients’ ability to read a pill bottle label, open a pill bottle safety cap, and allocate mock pills to a pill box. Pill allocation performance was assessed quantitatively (counts of errors of omission and commission) and qualitatively (patterns suggestive of knowledge-based mistakes, rule-based mistakes, or skill-based slips). Results: Of 55 participants, 22% were found to have cognitive impairment. Patients with cognitive impairment tended to be older as compared to those without cognitive impairment (mean ageu2009=u200981 vs 76u2009years, pu2009=u2009NS). Patients with cognitive impairment had a higher prevalence of inability to read pill bottle label (prevalence ratiou2009=u20095.8, 95% confidence intervalu2009=u20093.2–10.5, pu2009=u20090.001) and inability to open pill bottle safety cap (prevalence ratiou2009=u20093.3, 95% confidence intervalu2009=u20091.3–8.4, pu2009=u20090.03). While most patients (65%) had pill-allocation errors regardless of cognition, those patients with cognitive impairment tended to have more errors of omission (mean number of errorsu2009=u200948 vs 23, pu2009=u20090.006), as well as more knowledge-based mistakes (75% vs 40%, pu2009=u20090.03). Conclusion: There is an association between cognitive impairment and poor medication self-management skills. Medication taking failures due to poor medication self-management skills may be part of the pathway linking cognitive impairment to poor post-discharge outcomes among patients with heart failure transitioning from hospital to home.

Verification of Heart Disease: Implications for a New Heart Transplantation Allocation System

OBJECTIVESnThis study sought to determine the accuracy of the pre-transplantation clinical diagnosis of heart disease in the United Network for Organ Sharing (UNOS) database.nnnBACKGROUNDnBecause survival on the heart transplantation waitlist depends on underlying heart disease, a new allocation system will include the type of heart disease. Accuracy of the pre-transplantation clinical diagnosis and the effect of misclassification are unknown.nnnMETHODSnWe included all adults who received transplants at our center between January 2009 to December 2015. We compared the pre-transplantation clinical diagnosis at listing with pathology of the explanted heart and determined the potential effect of misclassification with the proposed allocation system.nnnRESULTSnA total of 334 patients had the following clinical cardiac diagnoses at listing: 148 had dilated cardiomyopathy, 19 had restrictive cardiomyopathy, 103 had ischemic cardiomyopathy, 24 had hypertrophic cardiomyopathy, 11 had valvular disease, 16 had congenital heart disease (CHD), and 13 patients had a diagnosis of other. Pathology of the explanted hearts revealed 82% concordance and 18% discordance (10% coding errors and 8% incorrect diagnosis). The most common incorrect diagnoses were sarcoidosis (66%), arrhythmogenic right ventricular dysplasia (60%), and other causes of predominately right-sided heart failure (33%). Among the misclassified diagnoses, 40% were listed as UNOS status 2, 8% remained at status 2 at transplantation, and only sarcoidosis and CHD were potentially at a disadvantage with the new allocation.nnnCONCLUSIONSnThere is high concordance between clinical and pathologic diagnosis, except for sarcoidosis and geneticxa0diseases. Few misclassifications result in disadvantages to patients based on the new allocation system, but rarexa0diseases like sarcoidosis remain problematic. To improve the UNOS database and enhance outcome research, pathology of the explanted hearts should be required post-transplantation.