EDTA Chelation Therapy to Reduce Cardiovascular Events in Persons with Diabetes.

The Trial to Assess Chelation Therapy (TACT) was a randomized double-blind placebo-controlled trial enrolling patients age ≥50 years with prior myocardial infarction. TACT used a 2 × 2 factorial design to study ethylene diamine tetraacetic acid (EDTA) chelation and high-dose vitamin supplementation. Chelation provided a modest but significant reduction in cardiovascular endpoints. The benefit was stronger and significant among participants with diabetes but absent in those without diabetes. Mechanisms by which chelation might reduce cardiovascular risk in persons with diabetes include the effects of EDTA chelation on transition and toxic metals. Transition metals, particularly copper and iron, play important roles in oxidative stress pathways. Toxic metals, in particular cadmium and lead, are toxic for the cardiovascular system. This review discusses the epidemiologic evidence and animal and human studies supporting the role of these metals in the development of diabetes and ischemic heart disease and potential ways by which EDTA chelation could confer cardiovascular benefit.

Reduced dietary salt for the prevention of cardiovascular disease.

BACKGROUND: This is an update of a Cochrane review that was first published in 2011 of the effects of reducing dietary salt intake, through advice to reduce salt intake or low-sodium salt substitution, on mortality and cardiovascular events. OBJECTIVES: 1. To assess the long-term effects of advice and salt substitution, aimed at reducing dietary salt, on mortality and cardiovascular morbidity.2. To investigate whether a reduction in blood pressure is an explanatory factor in the effect of such dietary interventions on mortality and cardiovascular outcomes. SEARCH METHODS: We updated the searches of CENTRAL (2013, Issue 4), MEDLINE (OVID, 1946 to April week 3 2013), EMBASE (OVID, 1947 to 30 April 2013) and CINAHL (EBSCO, inception to 1 April 2013) and last ran these on 1 May 2013. We also checked the references of included studies and reviews. We applied no language restrictions. SELECTION CRITERIA: Trials fulfilled the following criteria: (1) randomised, with follow-up of at least six months, (2) the intervention was reduced dietary salt (through advice to reduce salt intake or low-sodium salt substitution), (3) participants were adults and (4) mortality or cardiovascular morbidity data were available. Two review authors independently assessed whether studies met these criteria. DATA COLLECTION AND ANALYSIS: A single author extracted data and assessed study validity, and a second author checked this. We contacted trial authors where possible to obtain missing information. We extracted events and calculated risk ratios (RRs) and 95% confidence intervals (CIs). MAIN RESULTS: Eight studies met the inclusion criteria: three in normotensives (n = 3518) and five in hypertensives or mixed populations of normo- and hypertensives (n = 3766). End of trial follow-up ranged from six to 36 months and the longest observational follow-up (after trial end) was 12.7 years.The risk ratios (RR) for all-cause mortality in normotensives were imprecise and showed no evidence of reduction (end of trial RR 0.67, 95% confidence interval (CI) 0.40 to 1.12, 60 deaths; longest follow-up RR 0.90, 95% CI 0.58 to 1.40, 79 deaths n=3518) or in hypertensives (end of trial RR 1.00, 95% CI 0.86 to 1.15, 565 deaths; longest follow-up RR 0.99, 95% CI 0.87 to 1.14, 674 deaths n=3085). There was weak evidence of benefit for cardiovascular mortality (hypertensives: end of trial RR 0.67, 95% CI 0.45 to 1.01, 106 events n=2656) and for cardiovascular events (hypertensives: end of trial RR 0.76, 95% CI 0.57 to 1.01, 194 events, four studies, n = 3397; normotensives: at longest follow-up RR 0.71, 95% CI 0.42 to 1.20, 200 events; hypertensives: RR 0.77, 95% CI 0.57 to 1.02, 192 events; pooled analysis of six trials RR 0.77, 95% CI 0.63 to 0.95, n = 5912). These findings were driven by one trial among retirement home residents that reduced salt intake in the kitchens of the homes, thereby not requiring individual behaviour change.Advice to reduce salt showed small reductions in systolic blood pressure (mean difference (MD) -1.15 mmHg, 95% CI -2.32 to 0.02 n=2079) and diastolic blood pressure (MD -0.80 mmHg, 95% CI -1.37 to -0.23 n=2079) in normotensives and greater reductions in systolic blood pressure in hypertensives (MD -4.14 mmHg, 95% CI -5.84 to -2.43 n=675), but no difference in diastolic blood pressure (MD -3.74 mmHg, 95% CI -8.41 to 0.93 n=675).Overall many of the trials failed to report sufficient detail to assess their potential risk of bias. Health-related quality of life was assessed in one trial in normotensives, which reported significant improvements in well-being but no data were presented. AUTHORS' CONCLUSIONS: Despite collating more event data than previous systematic reviews of randomised controlled trials, there is insufficient power to confirm clinically important effects of dietary advice and salt substitution on cardiovascular mortality in normotensive or hypertensive populations. Our estimates of the clinical benefits from advice to reduce dietary salt are imprecise, but are larger than would be predicted from the small blood pressure reductions achieved. Further well-powered studies would be needed to obtain more precise estimates. Our findings do not support individual dietary advice as a means of restricting salt intake. It is possible that alternative strategies that do not require individual behaviour change may be effective and merit further trials.

Symptom burden, depression, and spiritual well-being: a comparison of heart failure and advanced cancer patients.

BACKGROUND: A lower proportion of patients with chronic heart failure receive palliative care compared to patients with advanced cancer. OBJECTIVE: We examined the relative need for palliative care in the two conditions by comparing symptom burden, psychological well-being, and spiritual well-being in heart failure and cancer patients. DESIGN: This was a cross-sectional study. PARTICIPANTS: Sixty outpatients with symptomatic heart failure and 30 outpatients with advanced lung or pancreatic cancer. MEASUREMENTS: Symptom burden (Memorial Symptom Assessment Scale-Short Form), depression symptoms (Geriatric Depression Scale-Short Form), and spiritual well-being (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being scale). MAIN RESULTS: Overall, the heart failure patients and the cancer patients had similar numbers of physical symptoms (9.1 vs. 8.6, p = 0.79), depression scores (3.9 vs. 3.2, p = 0.53), and spiritual well-being (35.9 vs. 39.0, p = 0.31) after adjustment for age, gender, marital status, education, and income. Symptom burden, depression symptoms, and spiritual well-being were also similar among heart failure patients with ejection fraction < or =30, ejection fraction >30, and cancer patients. Heart failure patients with worse heart failure-related health status had a greater number of physical symptoms (13.2 vs. 8.6, p = 0.03), higher depression scores (6.7 vs. 3.2, p = 0.001), and lower spiritual well-being (29.0 vs. 38.9, p < 0.01) than patients with advanced cancer. CONCLUSIONS: Patients with symptomatic heart failure and advanced cancer have similar needs for palliative care as assessed by symptom burden, depression, and spiritual well-being. This implies that heart failure patients, particularly those with more severe heart failure, need the option of palliative care just as cancer patients do.

Symptoms, depression, and quality of life in patients with heart failure.

BACKGROUND: Little is known about symptoms and their burden in outpatients with chronic heart failure. Diverse symptoms may be associated with poor heart failure-related quality of life, and depression may be related to increased symptoms. METHODS AND RESULTS: The number of symptoms and symptom distress (physical symptoms on the Memorial Symptom Assessment Scale-Short Form), depression (Geriatric Depression Scale-Short Form), and heart failure-related quality of life (Kansas City Cardiomyopathy Questionnaire) were measured cross-sectionally in 60 patients with heart failure from two outpatient cardiology clinics. Patients experienced a mean of nine symptoms in the previous week. More than half reported shortness of breath, lack of energy, pain, feeling drowsy, or dry mouth. In unadjusted analyses, more severe depression was associated with a greater number of symptoms (r = 0.51, P < .0001) and greater overall symptom distress (r = 0.58, P < .0001). For each additional depression symptom, the number of symptoms reported increased by 0.6 after adjustment for age, race, and N-terminal pro-brain natriuretic peptide (P = .01). The number of symptoms accounted for 32% of the variance in quality of life (P < .0001). CONCLUSIONS: Patients with heart failure report a large number of distressing symptoms. Depression in patients with heart failure is associated with a greater number of symptoms, which in turn is associated with a decrease in heart failure-related quality of life. Treatment of depression and the diverse symptoms reported by patients with heart failure might significantly improve quality of life.

Spiritual well-being and depression in patients with heart failure.

BACKGROUND: In patients with chronic heart failure, depression is common and associated with poor quality of life, more frequent hospitalizations, and higher mortality. Spiritual well-being is an important, modifiable coping resource in patients with terminal cancer and is associated with less depression, but little is known about the role of spiritual well-being in patients with heart failure. OBJECTIVE: To identify the relationship between spiritual well-being and depression in patients with heart failure. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty patients aged 60 years or older with New York Heart Association class II-IV heart failure. MEASUREMENTS: Spiritual well-being was measured using the total scale and 2 subscales (meaning/peace, faith) of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being scale, depression using the Geriatric Depression Scale-Short Form (GDS-SF). RESULTS: The median age of participants was 75 years. Nineteen participants (32%) had clinically significant depression (GDS-SF > 4). Greater spiritual well-being was strongly inversely correlated with depression (Spearman's correlation -0.55, 95% confidence interval -0.70 to -0.35). In particular, greater meaning/peace was strongly associated with less depression (r = -.60, P < .0001), while faith was only modestly associated (r = -.38, P < .01). In a regression analysis accounting for gender, income, and other risk factors for depression (social support, physical symptoms, and health status), greater spiritual well-being continued to be significantly associated with less depression (P = .05). Between the 2 spiritual well-being subscales, only meaning/peace contributed significantly to this effect (P = .02) and accounted for 7% of the variance in depression. CONCLUSIONS: Among outpatients with heart failure, greater spiritual well-being, particularly meaning/peace, was strongly associated with less depression. Enhancement of patients' sense of spiritual well-being might reduce or prevent depression and thus improve quality of life and other outcomes in this population.

Rapid titration of carvedilol in patients with congestive heart failure: a randomized trial of automated telemedicine versus frequent outpatient clinic visits.

BACKGROUND: Because of potential side effects and logistical difficulty of titrating medications, outpatients with congestive heart failure rarely receive appropriate doses of carvedilol or other beta-blockers. To address these obstacles, we studied if an automated telemedicine system named TeleWatch (TW) could facilitate carvedilol titration in outpatients with left ventricular systolic dysfunction. METHODS: Forty-nine patients with New York Heart Association class II and III left ventricular systolic dysfunction, who were tolerating appropriate afterload-reducing therapy and not receiving beta-blockers, were enrolled into a 3-month study. Patients were randomized to have clinic-only (CO) (n = 24) carvedilol titration or titrations which combined clinic visits with TW monitoring (n = 25). All patients were seen in clinic biweekly, and those in the TW group were remotely monitored daily. Using a predefined algorithm, patients in the CO and TW groups were eligible for carvedilol titration on a biweekly or weekly basis, respectively, by physicians blinded to group assignment. RESULTS: There was no statistical difference in the mean final daily dose of carvedilol between the CO and TW groups (39.4 vs 36.2 mg/d, P = .52). Because remote telemedicine titrations were as successful as titrations in the clinic, the time to reach the final dose of carvedilol was significantly shorter in the TW group (33.6 vs 63.7 days, P < .0001). There were 5 serious adverse events in the study, 4 of which were in the TW group (P = .29); however, TW prospectively detected 2 adverse events. CONCLUSIONS: Remote monitoring with an automated telemedicine system can successfully facilitate titration of carvedilol in outpatients with New York Heart Association class II and III congestive heart failure.

Modifications of coronary risk factors.

In addition to the revascularization and glycemic management interventions assigned at random, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) design includes the uniform control of major coronary artery disease risk factors, including dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle. Target levels for risk factors were adjusted throughout the trial to comply with changes in recommended clinical practice guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active smokers. Algorithms were developed for the pharmacologic management of dyslipidemia and hypertension. Dietary prescriptions for the management of glycemia, plasma lipid profiles, and blood pressure levels were adapted from existing clinical practice guidelines. Patients with a body mass index >25 were prescribed moderate caloric restriction; after the trial was under way, a lifestyle weight-management program was instituted. All patients were formally prescribed both endurance and resistance/flexibility exercises, individually adapted to their level of disability and fitness. Pedometers were distributed as a biofeedback strategy. Strategies to achieve the goals for risk factors were designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and nonpharmacologic intervention) and the ongoing implementation of the strategies is monitored by lipid, hypertension, and lifestyle intervention management centers.

A randomized trial of the efficacy of multidisciplinary care in heart failure outpatients at high risk of hospital readmission.

OBJECTIVES: We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period. BACKGROUND: Hospital admission for CHF is an important problem amenable to improved outpatient management. METHODS: Two hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient's primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patient's primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis. RESULTS: The median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups. CONCLUSIONS: This study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF.

Care management interventions for older patients with congestive heart failure.

OBJECTIVES: To identify interventions and outcome measures that should be included when designing care management programs for older patients with congestive heart failure (CHF) and assessing the overall effectiveness of these programs. STUDY DESIGN: Structured literature review and assessment. METHODS: A systematic literature search was conducted to identify articles that described interventions and outcome measures designed to improve care for older patients with CHF. Resultant studies were classified according to design, and interventions and outcome measures were categorized. Finally, the data were analyzed to identify care management strategies and outcome measures associated with effective studies (defined as those that achieved improvement in more than half of the important outcome measures). RESULTS: Thirty-two studies were identified. Most of the effective programs employed both a physician and a nurse; 12 employed a case manager. Hospital utilization was typically reduced by 30% to 80% in studies that measured this factor, although utilization increased in 2 studies. Only 6 studies showed significant reductions in costs. Fifteen of the studies were categorized as effective; 15 showed trends toward improvement; and 2 studies in which intervention subjects worsened appeared to have design flaws and subject selection biases. CONCLUSION: Care management interventions can be clinically effective, although cost effectiveness remains to be established. Common elements in effective care management programs included the teaming of a physician with a nurse or care manager; frequent patient monitoring for CHF decompensation; and patient education to improve self-assessment skills. Most ineffective programs showed deficiencies in nurse training, study design, or patient selection.