Association Between Care Fragmentation and Total Spending After Durable Left Ventricular Device Implant: A Mediation Analysis of Health Care-Associated Infections Within a National Medicare-Society of Thoracic Surgeons Intermacs Linked Dataset.

BACKGROUND: Care fragmentation is associated with higher rates of infection after durable left ventricular assist device (LVAD) implant. Less is known about the relationship between care fragmentation and total spending, and whether this relationship is mediated by infections. METHODS: Total payments were captured from admission to 180 days post-discharge. Drawing on network theory, a measure of care fragmentation was developed based on the number of shared patients among providers (ie, anesthesiologists, cardiac surgeons, cardiologists, critical care specialists, nurse practitioners, physician assistants) caring for 4,987 Medicare beneficiaries undergoing LVAD implantation between July 2009 - April 2017. Care fragmentation was measured using average path length, which describes how efficiently information flows among network members; longer path length indicates greater fragmentation. Terciles based on the level of care fragmentation and multivariable regression were used to analyze the relationship between care fragmentation and LVAD payments and mediation analysis was used to evaluate the role of post-implant infections. RESULTS: The patient cohort was 81% male, 73% white, 11% Intermacs Profile 1 with mean (SD) age of 63.1 years (11.1). The mean (SD) level of care fragmentation in provider networks was 1.7 (0.2) and mean (SD) payment from admission to 180 days post-discharge was $246,905 ($109,872). Mean (SD) total payments at the lower, middle, and upper terciles of care fragmentation were $250,135 ($111,924), $243,288 ($109,376), and $247,290 ($108,241), respectively. In mediation analysis, the indirect effect of care fragmentation on total payments, through infections, was positive and statistically significant (ß=16032.5, p=0.008). CONCLUSIONS: Greater care fragmentation in the delivery of care surrounding durable LVAD implantation is associated with a higher incidence of infections, and consequently, higher payments for Medicare beneficiaries. Interventions to reduce care fragmentation may reduce the incidence of infections and in turn enhance the value of care for patients undergoing durable LVAD implantation.

Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) trial.

AIMS: Hawthorn's efficacy when added to contemporary evidence-based heart failure therapy is unknown. We aimed to determine whether hawthorn increases submaximal exercise capacity when added to standard medical therapy. METHODS AND RESULTS: We performed a randomized, double-blind, placebo-controlled trial in 120 ambulatory patients aged > or = 18 years with New York Heart Association (NYHA) class II-III chronic heart failure. All patients received conventional medical therapy, as tolerated, and were randomized to either hawthorn 450 mg twice daily or placebo for 6 months. The primary outcome was change in 6 min walk distance at 6 months. Secondary outcomes included quality of life (QOL) measures, peak oxygen consumption, and anaerobic threshold during maximal treadmill exercise testing, NYHA classification, left ventricular ejection fraction (LVEF), neurohormones, and measures of oxidative stress and inflammation. There were no significant differences between groups in the change in 6 min walk distance (P = 0.61), or on measures of QOL, functional capacity, neurohormones, oxidative stress, or inflammation. A modest difference in LVEF favoured hawthorn (P = 0.04). There were significantly more adverse events reported in the hawthorn group (P = 0.02), although most were non-cardiac. CONCLUSION: Hawthorn provides no symptomatic or functional benefit when given with standard medical therapy to patients with heart failure. This trial is registered in ClinicalTrials.gov ID: NCT00343902.

Vitamin D and cardiovascular disease.

The hormonal derivative of vitamin D, 1,25-dihydroxyvitamin D (1,25[OH](2)D) or calcitriol, has been implicated in many physiologic processes beyond calcium and phosphorus homeostasis, and likely plays a role in several chronic disease states, in particular, cardiovascular disease. Experimental data suggest that 1,25(OH)(2)D affects cardiac muscle directly, controls parathyroid hormone secretion, regulates the renin-angiotensin-aldosterone system, and modulates the immune system. Because of these biologic effects, vitamin D deficiency has been associated with hypertension, several types of vascular diseases, and heart failure. We conducted a MEDLINE search of the English-language literature (1950-2008) to identify studies that examined these relationships; additional citations were obtained from the articles retrieved from the literature search. Treatment with vitamin D lowered blood pressure in patients with hypertension and modified the cytokine profile in patients with heart failure. Measurement of serum 25-hydroxyvitamin D concentration usually provides the best assessment of an individual's vitamin D status. Serum levels below 20 ng/ml represent vitamin D deficiency, and levels above 30 ng/ml are considered optimal. Although the observational data linking vitamin D status to cardiovascular disease appear robust, vitamin D supplementation is not recommended as routine treatment for heart disease until definitive prospective, randomized trials can be carried out to assess its effects. However, such supplementation is often appropriate for other reasons and may be beneficial to cardiovascular health in certain patients.

The effect of Crataegus oxycantha Special Extract WS 1442 on clinical progression in patients with mild to moderate symptoms of heart failure.

AIM: To examine whether hawthorn (Crataegus Special Extract WS 1442 {CSE}) inhibits progression in heart failure (HF) patients. METHODS: We performed a retrospective analysis of data from the HERB CHF study in which patients with mild to moderate HF were randomised to either CSE 900 mg or placebo for 6 months. The primary outcome was time to progression of HF (HF death, hospitalisation, or sustained increase in diuretics) as assessed by log-rank tests and by Cox modelling. RESULTS: Progression of HF occurred in 46.6% of the CSE and 43.3% of the placebo groups (OR 1.14, 95% CI=0.56, 2.35: p=0.86). Patients receiving CSE were 3.9 times (95% CI=1.1-13.7: p=0.035) more likely to experience HF progression at baseline. In adjusted analysis, the risk of having early HF progression in the CSE group increased to 6.4 (95% CI=1.5, 26.5: p=0.011). In patients with LVEF< or =35%, those taking CSE were at significantly greater risk (3.2, 95% CI=1.3, 8.3: p=0.02) than the placebo group. CONCLUSIONS: CSE does not reduce heart failure progression in patients who have HF. CSE appears to increase the early risk of HF progression.

The prevalence and pattern of complementary and alternative supplement use in individuals with chronic heart failure.

BACKGROUND: There are few data on the prevalence and pattern of complementary and alternative medicine (CAM) supplement use among people with chronic heart failure (CHF). The aim of this survey was to characterize the prevalence, pattern, and reasons for use of CAM supplements among those with CHF. METHODS AND RESULTS: We conducted a cross-sectional survey in 2 groups: CHF patients who had participated in the Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) Trial, and CHF patients who attended the University of Michigan's CHF Outpatient Clinic. We received 252 surveys. One third of respondents had used a CAM supplement in the last 6 months. There were 24 different supplements used. Reasons for use included heart problems, anxiety, weight loss, and arthritis. No demographic or behavioral characteristic identified CAM supplement users, although a 50% lower use among HERB CHF participants approached statistical significance (P = .08). CONCLUSION: One third of our CHF patients were taking CAM supplements, several of which may interact negatively with typical heart failure medications. CAM supplement use for weight loss may be underreported. Demographic and behavioral characteristics may not have identified people with CHF who were using CAM supplements.

Effect of oral vitamin E and C therapy on calcineurin inhibitor levels in heart transplant recipients.

BACKGROUND: A recent prospective trial demonstrated that oral vitamins C and E retard the early progression of transplant-associated coronary arteriosclerosis; as a result, a number of centers have added these agents to their maintenance regimens. This study reviewed the impact of vitamin E and C supplementation on calcineurin inhibitor trough concentrations. METHODS: A retrospective chart review of the first 29 heart transplant patients prescribed anti-oxidant agents was performed. Twenty-two patients taking cyclosporin A (CsA) and 7 patients taking tacrolimus were prescribed vitamin C (500 mg twice a day) and vitamin E (400 IU twice a day). Serum chemistries and drug levels were measured before and after vitamin therapy was initiated. RESULTS: The baseline CsA trough concentration (mean +/- SD) was 137 +/- 39 ng/ml and it declined to 99 +/- 54 ng/ml (p = 0.007) after anti-oxidant therapy was initiated. The average percentage decrease in the CsA trough concentration was 30%. No significant changes were seen in the patients taking tacrolimus. CONCLUSIONS: These data demonstrate that supplementation with the anti-oxidant agents vitamin C and vitamin E decreases CsA concentrations but does not appear to effect tacrolimus concentrations. Although more detailed pharmacokinetic analysis is necessary to clarify the exact mechanism of this interaction, physicians who take care of transplant recipients should be aware that more frequent CsA concentration monitoring is warranted after initiating these anti-oxidant agents.

Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.

BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.

Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha).

Hawthorn, an herbal supplement, is currently being evaluated for the treatment of heart failure. The flavonoid components of hawthorn may be responsible for hawthorn's beneficial effects in the treatment of heart failure. However, these components may also affect P-glycoprotein function and cause interactions with drugs that are P-glycoprotein substrates, such as digoxin, which is also used to treat heart failure. Therefore, the purpose of this study was to determine the effect of hawthorn on digoxin pharmacokinetic parameters. A randomized, crossover trial with 8 healthy volunteers was performed evaluating digoxin 0.25 mg alone (D) for 10 days and digoxin 0.25 mg with Crataegus special extract WS 1442 (hawthorn leaves with flowers; Dr. Willmar Schwabe Pharmaceuticals) 450 mg twice daily (D + H) for 21 days. Pharmacokinetic studies were performed for 72 hours. There were no statistically significant differences in any measured pharmacokinetic parameters. The AUC0-infinity, Cmax-Cmin, Cmin, and renal clearance for the D group were 79 +/- 26 mcg.h/L, 1.4 +/- 0.7 mcg/L, 0.84 +/- 0.2 mcg/L, and 74 +/- 10 mL/min versus 73 +/- 20 mcg.h/L, 1.1 +/- 0.1 mcg/L, 0.65 +/- 0.2 mcg/L, and 81 +/- 22 mL/min for the D + H group, respectively (p > 0.05). Following 3 weeks of concomitant therapy, hawthorn did not significantly alter the pharmacokinetic parameters for digoxin. This suggests that both hawthorn and digoxin, in the doses and dosage form studied, may be coadministered safely.