Heart Failure Due to Reduced Ejection Fraction: Medical Management.

Heart failure is an increasingly common condition resulting in high rates of morbidity and mortality. For patients who have heart failure and reduced ejection fraction, randomized clinical trials demonstrate consistent mortality benefit from angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, direct-acting vasodilators, beta blockers, and aldosterone antagonists. Additionally, some data show benefits from two new classes of drugs: angiotensin receptor blocker/neprilysin inhibitor and sinus node modulator. Diuretics and digoxin can be used as needed for symptom control. Statins are not recommended solely for treatment of heart failure. Implantable cardioverter-defibrillators and biventricular pacemakers improve mortality and function in selected patients. For patients who have been hospitalized for heart failure, disease management programs and telemonitoring can reduce hospitalizations and mortality.

Hyponatremia, Cognitive Function, and Mobility in an Outpatient Heart Failure Population.

BACKGROUND The association of hyponatremia with cognitive impairment and mobility in heart failure (HF) patients is unknown. The purpose of this study was to determine if hyponatremia is associated with cognitive and mobility impairment as measured by simple, validated, and time-sensitive tests. MATERIAL AND METHODS This was a prospective study in patients with reduced and preserved ejection fraction (HFrEF, HFpEF) seen in outpatient HF clinics. Hyponatremia was defined as sodium level ≤136 mEq/L. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) tool, and mobility was measured with the Timed Up and Go test (TUG-t). RESULTS A total of 121 patients were evaluated; 30% were hyponatremic (134±1.9 mEq/l, range 128-136 mEq/l). Overall, 92% of hyponatremic patients had cognitive impairment (MoCA <26) compared to 76% of the non-hyponatremic patients [relative risk 1.2 (confidence interval: 1.02-1.4, p=0.02)]. In regard to mobility, 72% of hyponatremic patients and 62% of non-hyponatremic patients (p=0.4) had TUG-t times that were considered to be worse than average. A total of 84% (N=76) of HFrEF and 71% (N=22) of HFpEF patients had cognitive impairment (p=0.86). HFrEF patients had significantly lower overall MoCA scores (21.2±3.7 vs. 23.3±3.6, p=0.006) and similar TUG-t times compared to HFpEF patients. CONCLUSIONS Most heart failure patients (HFrEF and HFpEF) seen in an ambulatory setting had impairment of cognitive function and mobility, with a higher prevalence among those with hyponatremia. Screening can be done using tests that can be administered in a clinical setting.

Heart failure assessment at the community pharmacy level: a feasibility pilot study.

BACKGROUND: A key element missing in disease-management programs for heart failure (HF) is participation of the community pharmacist. The purpose of this study is to determine if a simple and efficient clinical tool will allow community pharmacists to identify patients at risk for worsening HF. DESIGN: The One Minute Clinic for Heart Failure (TOM-C HF) was developed as a simple six-item symptom screening tool to be used during routine patient/customer interactions. SETTING: Ten community pharmacies located in the upper Midwest. PATIENTS: Self-identified HF patients. RESULTS: 121 unique patients were evaluated over a 12-month period. The application of this clinical tool took between 1 and 5 minutes in over 80% of the interactions. Seventy-five patients (62%) had one or more signs or symptoms of worsening HF. The most common symptoms detected included edema (39%) and increased shortness of breath (17%). Self-reported weight gain of more than 5 pounds was seen in 19% of patients. CONCLUSION: The TOM-C HF tool was used to identify patients in a time-efficient manner in the community pharmacy setting who appear to be developing worsening HF. Inclusion of the community pharmacists as an early screen for HF decompensation may be an important link in disease-management programs to help reduce hospital readmission rates.

Immune cell-mediated venous thrombus resolution.

Herein, we review the current processes that govern experimental deep vein thrombus (DVT) resolution. How the human DVT resolves at the molecular and cellular level is not well known due to limited specimen availability. Experimentally, the thrombus resolution resembles wound healing, with early neutrophil-mediated actions followed by monocyte/macrophage-mediated events, including neovascularization, fibrinolysis, and eventually collagen replacement. Potential therapeutic targets are described, and coupling with site-directed approaches to mitigate off-target effects is the long-term goal. Similarly, timing of adjunctive agents to accelerate DVT resolution is an area that is only starting to be considered. There is much critical research that is needed in this area.

Case report of heart transplantation for giant cell myocarditis in a patient with common variable immunodeficiency.

BACKGROUND: Solid-organ transplantation in patients with common variable immunodeficiency (CVID) is controversial due to the risk for severe and recurrent infections. Determining transplantation candidacy in CVID patients is further complicated by the presence of CVID-related non-infectious complications that can reduce overall survival and also recur in the transplanted organ. Data regarding solid organ transplantation in patients with CVID are limited, particularly in heart transplantation. CASE SUMMARY: A 32-year-old female with CVID presented with new heart failure after 3 months of dyspnoea on exertion. Her echocardiogram showed severe global systolic dysfunction with an ejection fraction of approximately 10%, and her right heart catheterization revealed severe biventricular pressure overload and severely reduced cardiac output. Endomyocardial biopsy revealed giant cells and mononuclear infiltrate consistent with giant cell myocarditis (GCM). Despite medical management, she developed progressive cardiogenic shock and underwent uncomplicated orthotopic heart transplantation on hospital Day 38. After 2 years of follow-up, she has had no major infectious complications and continues to have normal graft function with no recurrence of GCM. CONCLUSION: We report a case of successful heart transplantation for GCM in a patient with CVID, with no major infectious complications after 2 years of follow-up. CVID should not be considered an absolute contraindication for heart transplantation.

Food: an unrecognized source of loop diuretic resistance.

Food significantly affects the pharmacokinetics of oral loop diuretics in healthy individuals, but studies have not been performed in patients with edema. Because of this omission, food's effect on pharmacokinetics has been overlooked and may decrease the pharmacodynamic response in patients who rely on diuretics. Despite this potential interaction, reference manuals do not provide warnings about the effects of food on loop diuretic absorption. We reviewed the published human studies investigating the effects of food on loop diuretics. Peak plasma concentrations and urinary recovery were significantly decreased when taken with food, but only one study showed a corresponding decrease in total urine output, which is likely related to the diuretic threshold effect. These healthy subjects probably were always above the diuretic threshold under both fed and fasting conditions and thus could not augment their urine output. Based on these data in healthy subjects, the special implications for patients who routinely take diuretics are discussed. Therefore, food is more likely to have a clinical effect on the diuretic threshold given its effect in healthy subjects and the special considerations for patients with edema. Additional studies are needed to help answer these questions. Until such data are available, the most conservative, effective clinical approach is to administer oral loop diuretics without food.

Controversies in the use of beta blockers in heart failure.

Recent evidence from randomized controlled trials has provided compelling evidence to support the use of beta blockers in most patients with heart failure due to systolic dysfunction. There is little disagreement about the mortality benefit provided by adding beta blockers to standard therapy, which may include angiotensin-converting enzyme inhibitors, diuretics, and sometimes digoxin. A few areas are still controversial. The authors review the available literature encompassing four of those controversial areas: 1) the comparability among beta blockers; 2) the utility of beta blockers among patients with New York Heart Association class I and class IV heart failure symptoms; 3) the impact of race on the effectiveness of beta blockers; and 4) the safety and efficacy of beta blockers among patients on concomitant therapy with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or spironolactone.

Beyond the "self" in self-efficacy: Spouse confidence predicts patient survival following heart failure.

Ratings of patient efficacy to manage illness, made by 191 congestive heart failure patients and their spouses, were examined as predictors of patients' survival over the next 4 years. When considered alone, both the patient's self-efficacy and the spouse's confidence ratings predicted survival, but only spouse confidence remained significant when both partners" efficacy ratings were included in the same Cox regression model. The overlapping prognostic significance of spouse confidence and a global, multicomponent measure of marital quality positioned the former as a proxy for the latter, reflecting a fundamentally social protective factor in patient survival. Successful adaptation to heart failure appears to involve more than the patient's personal agency, and psychosocial data from spouses can improve prediction of patient outcomes.

Couples coping with congestive heart failure: role and gender differences in psychological distress.

Psychological distress and marital quality were assessed with male (n = 128) and female (n = 49) congestive-heart-failure (CHF) patients and their spouses. Hopkins Symptom Check List--25 scores were in the distressed range for 57% of patients and 40% of spouses. This role difference was greater for men than for women, and a gender difference (more distress in women than men) was greater for spouses than for patients. The patient's distress, but not the spouse's, reflected the severity of the patient's illness, and distress for both partners correlated negatively with ratings of marital quality. Female-patient couples reported better relationship quality than male-patient couples, however, and a mediation analysis indicated that the gender difference in spouse distress could be explained by marital quality. Results highlight the contextual nature of CHF distress and suggest that role differences in distress vary by gender.

Systolic blood pressure influences the interpretation of cardiopulmonary exercise tests and helps identify a very high-risk cohort of heart failure patients.

BACKGROUND: Ventilatory inefficiency (high volume of expired air/volume of carbon dioxide eliminated [Ve/Vco2] slope), and impaired exercise tolerance (low peak volume of oxygen consumption) obtained from cardiopulmonary exercise testing (CPX) strongly predict mortality in heart failure (HF) patients; however, other CPX variables may also contain prognostic information. Therefore, the purpose of this study was to determine the prognostic power of the aggregate of CPX data. METHODS: The study prospectively monitored 390 patients referred for cardiac transplantation evaluation for 10 years for events (death, urgent transplant, left ventricular assist devices). Cox regression was used to analyze 18 CPX variables to identify the best survival model. RESULTS: Ve/Vco2 slope was the most powerful mortality predictor, and only resting systolic blood pressure (SBP) added additional independent prognostic power when expressed at its threshold effect value as SBP ≤ 100 mm Hg. Patients with low SBP had a greater risk than those who were within the next higher quartile of Ve/Vco2 slope with SBP > 100 mm Hg. A very high-risk cohort included 9% of the population that had a Ve/Vco2 slope > 41 and SBP ≤ 100 mm Hg and an associated 2-year event rate of 67%; conversely, a low-risk cohort had a Ve/Vco2 slope ≤ 30 and SBP >100 mm Hg and associated 2-, 5-, and 10-year event rates of 5%, 12%, and 30%, respectively. CONCLUSIONS: Ve/Vco2 slope was the best individual predictive CPX variable and its interpretation was significantly altered by the presence of hypotension. An algorithm combining these CPX variables identifies a HF population at very high risk of early death and warranting advanced therapies.

Acute necrotizing eosinophilic myocarditis in a patient taking Garcinia cambogia extract successfully treated with high-dose corticosteroids.

A previously healthy 48-year-old woman was evaluated for lightheadedness and chest heaviness 2 weeks after starting the herbal supplement Garcinia cambogia. She was found to be hypotensive and had an elevated serum troponin level. The patient had a progressive clinical decline, ultimately experiencing fulminant heart failure and sustained ventricular arrhythmias, which required extracorporeal membrane oxygenation support. Endomyocardial biopsy results were consistent with acute necrotizing eosinophilic myocarditis (ANEM). High-dose corticosteroids were initiated promptly and her condition rapidly improved, with almost complete cardiac recovery 1 week later. In conclusion, we have described a case of ANEM associated with the use of Garcinia cambogia extract.

Heart failure: clinical problem and management issues.

Heart failure (HF) often presents as dyspnea either with exertion and/or recumbency. Patients also experience dependent swelling and fatigue. Measurement of the left ventricular ejection fraction (LVEF) identifies HF patients who may respond to pharmacologic therapy and/or electrophysiologic device implantation. Angiotension converting enzyme inhibitors, beta blockers, and aldosterone inhibitors can significantly lower the mortality and morbidity of HF in patients with an LVEF less than 35%. Cardiac defibrillators and biventricular pacemakers can also improve outcomes in selected patients with a decreased LVEF. The authors provide a guide for therapeutic decisions based on the inclusion criteria of the major clinical trials.

Prognostic ability of resting periodic breathing and ventilatory variation in closely matched patients with heart failure.

PURPOSE: Periodic breathing (PB), characterized by waxing and waning oscillations of ventilation, has been reported in some patients with heart failure. Although PB is usually assessed in sleeping patients, PB has also been observed in awake patients. We tested the hypothesis that PB in awake, resting patients with heart failure predicts mortality. METHODS: Resting gas exchange data were collected in consecutive, awake patients with heart failure referred for possible cardiac transplantation. Periodic breathing was defined as oscillations of resting ventilation, that is, 30% or more during 2 consecutive cycles. Each PB patient was matched to a comparison patient by age, gender, heart failure etiology, peak oxygen consumption, peak respiratory exchange ratio, and ventilatory efficiency slope. RESULTS: Forty-four of 355 patients met the criteria for PB and were matched to 44 comparison patients. During an average follow-up of 4.9 +/- 0.1 years, 30 patients with PB (68%) versus 23 comparisons (52%) died or were transplanted urgently (P = NS). However, among the 88 PB patients and comparisons, ventilatory variation was an independent predictor of mortality by Cox regression analysis (P = .004). Resting ventilatory variation increased the explained variation in mortality by 44%, from 16% to 23%, in a mortality model that included ventilatory efficiency slope, peak oxygen consumption, left ventricular ejection fraction, systolic blood pressure, sex, age, heart rate, and etiology. CONCLUSION: Resting ventilatory variation independently and powerfully predicted mortality in this cohort of patients with heart failure.

Pharmacologic management of heart failure caused by systolic dysfunction.

Heart failure caused by systolic dysfunction affects more than 5 million adults in the United States and is a common source of outpatient visits to primary care physicians. Mortality rates are high, yet a number of pharmacologic interventions may improve outcomes. Other interventions, including patient education, counseling, and regular self-monitoring, are critical, but are beyond the scope of this article. Angiotensin-converting enzyme inhibitors and beta blockers reduce mortality and should be administered to all patients unless contraindicated. Diuretics are indicated for symptomatic patients as needed for volume overload. Aldosterone antagonists and direct-acting vasodilators, such as isosorbide dinitrate and hydralazine, may improve mortality in selected patients. Angiotensin receptor blockers can be used as an alternative therapy for patients intolerant of angiotensin-converting enzyme inhibitors and in some patients who are persistently symptomatic. Digoxin may improve symptoms and is helpful for persons with concomitant atrial fibrillation, but it does not reduce cardiovascular or all-cause mortality. Serum digoxin levels should not exceed 1.0 ng per mL (1.3 nmol per L), especially in women.

Combining peak oxygen consumption and ventilatory efficiency in the prognostic assessment of patients with heart failure.

Exercise ventilatory efficiency (VE/VCO2 slope) and peak oxygen consumption (VO2) are strong mortality predictors in patients with heart failure and we combined these 2 variables' beta coefficients from Cox regression to investigate a new prognostic index. Average follow-up was 3.8+/-1.8 years for 355 patients (72% male, 51+/-10 years). The beta coefficients from peak VO2 (17.3+/-5.0 ml x kg(-1) x min(-1)) and VE/VCO2 slope (37.0+/-9.0) constructed an exercise index defined as one half the peak VO2 subtracted from one fifth of the VE/VCO2 slope. The mean index was -1.14+/-3.79 and a more positive index was always associated with a higher probability of death. Patients with extremely poor prognoses were identified equally well by the index and by individual thresholds for peak VO2 (<14 ml x kg(-1) x min(-1)) and of VE/VCO2 slope (>40). In conclusion, the index did not add additional prognostic information in this cohort but it did display the prognostic superiority of VE/VCO2 slope.

Standardizing and predicting results from cardiopulmonary exercise testing in patients with heart failure.

PURPOSE: Cardiopulmonary exercise testing is a common prognostic tool in heart failure, yet it is not standardized. The purpose of this study was to evaluate a means of standardizing oxygen consumption (VO(2)) measurement and to evaluate the ability to predict peak VO(2) from submaximal exercise. METHODS: Fifty consecutive exercise tests with a respiratory exchange ratio > or =1.10 were evaluated. VO(2) was graphed against respiratory exchange ratio and the peak VO(2) was determined with logarithmic, linear, power, and exponential regression lines. To predict a peak VO(2), each patient's submaximal exercise data (respiratory exchange ratio < or =0.98) were fitted to each regression line. The mean of the last 30 seconds of un-averaged breath-by-breath data was used as the reference value. Peak VO(2) assessments are also provided from the metabolic cart, a rolling time average, and the graphical method. RESULTS: Logarithmic regression best standardized peak VO(2). Mean absolute bias (mL x kg x min) was 0.60 +/- 0.44 for logarithmic, 0.61 +/- 0.47 for linear, 0.85 +/- 0.67 for power, and 1.44 +/- 2.22 for exponential. The mean absolute bias between the peak logarithmic predicted VO(2) and the reference peak VO(2) was 1.62 +/- 1.20 mL x kg x min (9.5% of the peak VO(2)). CONCLUSION: Among the methods studied, logarithmic regression analysis was the best method to standardize and predict peak VO(2) in this cohort of patients with heart failure.

Determining the best ventilatory efficiency measure to predict mortality in patients with heart failure.

BACKGROUND: Ventilatory efficiency, the relationship between ventilation (VE) and carbon dioxide production (VCO2), predicts mortality in heart failure patients, but its determination has not been standardized. Additionally, it is unclear if the prognostic power of ventilatory efficiency is independent of exercise intensity. Therefore, we investigated the relative prognostic power of different measures of ventilatory efficiency calculated from maximal and sub-maximal exercise in patients with heart failure. METHODS AND RESULTS: Heart failure patients (n = 355, 72% males, age 51 +/- 10 years) had follow-up for at least 5 years from an exercise test. There were 145 events (133 deaths and 12 emergent cardiac transplants). Ventilatory efficiency calculations were not equivalent. Of the different measures of ventilatory efficiency, the VE/VCO2 slope to peak exercise was the most significant predictor of mortality in a multivariable Cox model, including ejection fraction, systolic blood pressure, peak oxygen consumption (VO2), gender, etiology, and heart rate. A 5 U increment of the VE/VCO2 slope to peak exercise corresponded to a 9% increase in mortality risk. When tests were grouped by peak exercise intensity, by quartiles of peak respiratory exchange ratio, the VE/VCO2 slope to peak exercise was always a better predictor than peak VO2. CONCLUSION: Peak and sub-maximal measures of ventilatory efficiency were not equivalent, and the VE/VCO2 slope to peak exercise was the best predictor of mortality in patients with heart failure. Thus, the prognostic power of ventilatory efficiency is enhanced when exercise extends beyond the ventilatory threshold and includes all of the available exercise data.

Neutral effect on markers of heart failure, inflammation, endothelial activation and function, and vagal tone after high-dose HMG-CoA reductase inhibition in non-diabetic patients with non-ischemic cardiomyopathy and average low-density lipoprotein level.

OBJECTIVES: This study sought to determine the effect of aggressive 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy on surrogate markers in non-ischemic cardiomyopathy (NICM) patients and average low-density lipoprotein (LDL) concentrations. BACKGROUND: The effects of statins may well go beyond lipid lowering, and these pleiotropic effects may be of benefit in the treatment of heart failure. METHODS: Fifteen patients with NICM on standard maximized heart failure medication were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial. Patients received 80 mg atorvastatin (ATV) or matching placebo for a 12-week treatment period with a minimum of an 8-week washout period. The following surrogate markers were evaluated: N-terminal-pro brain natriuretic peptide, high-sensitivity C-reactive protein, oxidized LDL antibody, soluble receptor tumor necrosis factor, tumor necrosis factor-alpha, circulating levels of vascular adhesion molecule-1, intercellular adhesion molecule-1, P-selectin, non-invasive endothelial function studies, and heart rate variability. RESULTS: After ATV therapy, there was a significant decrease in LDL concentration from 110 +/- 27 mg/dl to 55 +/- 18 mg/dl (p < 0.05). There were no differences between ATV and placebo with regard to the surrogate markers measured. CONCLUSIONS: Based on these findings, it seems that the administration of high-dose statins to a heart failure population with modest LDL levels and no other indication for statin therapy was neither beneficial nor detrimental as determined by surrogate marker measures. Further studies are needed to determine whether there is an appropriate patient population and optimal dose (LDL concentration) for the treatment of systolic heart failure with statin therapy.