Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients With Chronic Heart Failure

Abstract

OverviewNonpharmacologic management strategies represent an important contribution to heart failure (HF) therapy. They may significantly impact patient stability, functional capacity, mortality, and quality of life. Most of the recommendations that follow derive from consensus expert opinion or are based on theory extrapolated from limited trial data in the elderly or chronic disease populations.Diet and NutritionRecommendations6.1Dietary instruction regarding sodium intake is recommended in all patients with HF. Patients with HF and diabetes, dyslipidemia, or severe obesity should be given specific dietary instructions. (Strength of Evidence = B)6.2Dietary sodium restriction (2-3 g daily) is recommended for patients with the clinical syndrome of HF and preserved or depressed left ventricular ejection fraction (LVEF). Further restriction (<2 g daily) may be considered in moderate to severe HF. (Strength of Evidence = C)BackgroundExcessive dietary sodium intake is a common proximate cause of worsening symptoms and hospitalization for HF exacerbation.1Bennet S.J. Huster G.A. Baker S.L. Milgrom A.L.B. Kirchgassner Birt J. et al.Characterization of the precipiatants of hospitalization for heart failure decompensation.Am J Crit Care. 1998; 7: 168-174PubMed Google Scholar, 2Michalsen A. Konig G. Thimme W. Preventable causative factors leading to hospital admission with decompensated heart failure.Heart. 1998; 80: 437-441PubMed Google Scholar, 3Tsuyuki R.T. McKelvie R.S. Arnold J.M. Avezum Jr., A. Barretto A.C. Carvalho A.C. et al.Acute precipitants of congestive heart failure exacerbations.Arch Intern Med. 2001; 161: 2337-2342Crossref PubMed Google Scholar Furthermore, dietary sodium restriction typically results in a decrease in the diuretic dose required for maintenance of a euvolemic state and clinical stability. This is important because loop diuretics increase plasma renin activity and may adversely impact clinical outcomes through neurohormonal stimulation.4Francis G.S. Benedict C. Johnstone D.E. Kirlin P.C. Nicklas J. Liang C.S. et al.Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD).Circulation. 1990; 82: 1724-1729Crossref PubMed Google Scholar Studies of sodium restriction indicate an impact on such parameters as quality of life and even functional status,5Colin Ramirez E. Castillo Martinez L. Orea Tejeda A. Rebollar Gonzalez V. Narvaez David R. Asensio Lafuente E. Effects of a nutritional intervention on body composition, clinical status, and quality of life in patients with heart failure.Nutrition. 2004; 20: 890-895Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar but not mortality. Despite limited clinical trial data, sodium restriction remains an important and common component of HF disease management programs.6Meadows R. Johnson E.D. Clinical inquiries. Does a low salt diet reduce morbidity and mortality in congestive heart failure?.J Fam Pract. 2002; 51: 615PubMed Google ScholarThe “average” American diet contains between 8,000 and 10,000 mg sodium; certain ethnic diets are typically several-fold higher. (See Table 3.3 in Section 3 for salt-sodium equivalents.) A “low-sodium” or “no added salt diet” as defined by the American Heart Association is 4000 mg sodium. The current recommendation from the American Heart Association and the United States Department of Agriculture (USDA) for the general population is to limit sodium intake to 2300 mg per day, while the current USDA recommendation for those with hypertension, blacks and middle-aged and older people is 1500 mg per day for hypertension prevention.7American Heart Association website. http://www.americanheart.org/presenter.jhtml?identifier=4708. Accessed November 25, 2008.Google Scholar Thus, although there remains no evidence about the ideal level of sodium restriction in patients with HF because of lack of studies on this topic, it is reasonable to recommend that sodium intake be limited to 2000–3000 mg per day.Because following a low sodium diet is a specific activity, greater patient success can be expected when the clinician provides the patient with a daily sodium intake target and the knowledge and skills to reach that target. It is not enough to simply ask patients to follow a low salt diet. Nor is it sufficient to advise not salting food at the table or while cooking as most (∼70%) of our daily sodium intake comes from processed and pre-packaged foods. Appropriate education and counseling regarding the 2000–3000 mg sodium diet recommendation is covered in Section 8.Additional dietary instruction should be provided to all patients with HF who have comorbid conditions, including arteriosclerosis, diabetes, renal insufficiency, or obesity. Patients with hyperlipidemia or known underlying coronary or peripheral arteriosclerosis should be given specific instruction regarding dietary fat and cholesterol restriction according to national guidelines, such as the National Cholesterol Education Program. Diabetics exhibiting poor glycemic control or with significant albuminuria should receive individualized nutritional counseling regarding protein and carbohydrate consumption and caloric constraints as indicated to reduce risk for morbidity and mortality. Aggressive management of hyperglycemia diminishes osmotic forces leading to water retention and glomerular hyperfiltration, while reducing infection risk and the long-term risk of additional end-organ damage.8Estes Jr., E.H. Sieker H.O. Mclntosh H.D. Kelser G.A. Reversible cardio-pulmonary syndrome with extreme obesity.Circulation. 1957; 16: 179-187Crossref PubMed Google Scholar Patients with significant underlying renal insufficiency may require individualized instruction regarding protein, potassium, phosphorus, or other dietary constraints to preserve electrolyte and acid-base homeostasis.Obesity is independently associated with HF and contributes to the development of additional HF risk factors, including hypertension, LV hypertrophy and diastolic filling abnormalities. Obesity is linked to insulin resistance and glucose intolerance, hyperaldosteronism, salt sensitivity, and plasma volume expansion, creating both pressure and volume overload stressors with increased systemic vascular resistance. The metabolic demand of excessive adipose tissue increases cardiac output requirements, making cardiomyopathy with HF the leading cause of death in patients with severe obesity. Arrhythmia risk is increased in association with prolongation of the QT interval frequently seen in the setting of morbid obesity. Sleep-disordered breathing is linked to pulmonary hypertension, right ventricular failure, and hypoxemia. For both obesity-cardiomyopathy and obesity-hypoventilation syndromes, weight loss and sodium restriction are effective measures to improve symptoms and prognosis.9Alpert M.A. Terry B.E. Mulekar M. Cohen M.V. Massey C.V. Fan T.M. et al.Cardiac morphology and left ventricular function in normoten-sive morbidly obese patients with and without congestive heart failure, and effect of weight loss.Am J Cardiol. 1997; 80: 736-740Abstract Full Text Full Text PDF PubMed Scopus (146) Google ScholarA number of recent studies evaluating the relationship between body mass index (BMI) and mortality have suggested that overweight (BMI 25–29.9 kg/m2) and obese (BMI ≥30 kg/m2) people with HF have a better survival than healthy weight people (BMI 18.5–24.9 kg/m2) with HF.10Horwich T.B. Fonarow G.C. Hamilton M.A. MacLellan W.R. Woo M.A. Tillisch J.H. The relationship between obesity and mortality in patients with heart failure.J Am Coll Cardiol. 2001; 38: 789-795Abstract Full Text Full Text PDF PubMed Scopus (328) Google Scholar, 11Davos C.H. Doehner W. Rauchhaus M. Ciciora M. Francis D.P. Coats A.J. et al.Body mass and survival in patients with chronic heart failure without cachexia: the importance of obesity.J Card. Fail. 2003; 9: 29-35Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 12Curtis J.P. Selter J.G. Wang Y. Rathore S.S. Jovin I.S. Jadbabaie F. et al.The obesity paradox: body mass index and outcomes in patients with heart failure.Arch Intern Med. 2005; 165: 55-61Crossref PubMed Scopus (320) Google Scholar, 13Fonarow G.C. The relationship between body mass index and mortality in patients hospitalized with acute decompensated heart failure.Am Heart J. 2007; 154: e21Abstract Full Text Full Text PDF PubMed Google Scholar Reasons for this “obesity paradox” remain unexplained. Low BMI (<18.5 kg/m2) subjects with HF appear to have the highest mortality.11Davos C.H. Doehner W. Rauchhaus M. Ciciora M. Francis D.P. Coats A.J. et al.Body mass and survival in patients with chronic heart failure without cachexia: the importance of obesity.J Card. Fail. 2003; 9: 29-35Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 12Curtis J.P. Selter J.G. Wang Y. Rathore S.S. Jovin I.S. Jadbabaie F. et al.The obesity paradox: body mass index and outcomes in patients with heart failure.Arch Intern Med. 2005; 165: 55-61Crossref PubMed Scopus (320) Google Scholar, 13Fonarow G.C. The relationship between body mass index and mortality in patients hospitalized with acute decompensated heart failure.Am Heart J. 2007; 154: e21Abstract Full Text Full Text PDF PubMed Google Scholar, 14Kenchaiah S. Pocock S.J. Wang D. Finn P.V. Zornoff L.A. Skali H. et al.Booody mass index and prognosis in patients with heart failure: insights from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.Circulation. 2007; 116: 627-636Crossref PubMed Scopus (95) Google Scholar At least one study suggests that severely obese subjects (BMI ≥35 kg/m2) also have a higher mortality than normal weight or mild to moderately obese people with HF, resulting in a “J” shaped curve for the BMI-mortality relationship.14Kenchaiah S. Pocock S.J. Wang D. Finn P.V. Zornoff L.A. Skali H. et al.Booody mass index and prognosis in patients with heart failure: insights from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.Circulation. 2007; 116: 627-636Crossref PubMed Scopus (95) Google ScholarWhen risk of death was assessed in 359,387 people from the general population using BMI, waist circumference and waist-hip ratio, general and abdominal obesity were associated with risk of death.15Pischon T. Boeing H. Hoffman et al.General and abdominal adiposity and risk of death in Europe.N Engl J Med. 2008; 359: 2105-2120Crossref PubMed Scopus (643) Google Scholar In patients with HF, central adiposity, assessed by waist-hip ratio, but not BMI, was predictive of all-cause mortality independent of age and gender.16Ammar K.A. Redfield M.M. Mahoney D.W. Johnson M. Jacobsen S.J. Rodeheffer R.J. Central obesity: association with left ventricular dysfunction and mortality in the community.Am Heart J. 2008; 156: 975-981Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Of note, waist-hip ratio was more strongly associated with LV diastolic function as well. After adjustment for LVEF and diastolic function, waist-hip ratio was no longer a risk factor for mortality. Thus, ventricular dysfunction may be an important mediating factor between waist-hip ratio and mortality.16Ammar K.A. Redfield M.M. Mahoney D.W. Johnson M. Jacobsen S.J. Rodeheffer R.J. Central obesity: association with left ventricular dysfunction and mortality in the community.Am Heart J. 2008; 156: 975-981Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Another explanation for the “obesity paradox” may be that it is the change in weight over time, not the specific weight at any given time, that predicts mortality. Normal weight people with HF may have been overweight or obese and are actively losing weight.11Davos C.H. Doehner W. Rauchhaus M. Ciciora M. Francis D.P. Coats A.J. et al.Body mass and survival in patients with chronic heart failure without cachexia: the importance of obesity.J Card. Fail. 2003; 9: 29-35Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar It is also possible that HF is detected earlier in overweight and obese people due to symptom exacerbation caused by excess weight.12Curtis J.P. Selter J.G. Wang Y. Rathore S.S. Jovin I.S. Jadbabaie F. et al.The obesity paradox: body mass index and outcomes in patients with heart failure.Arch Intern Med. 2005; 165: 55-61Crossref PubMed Scopus (320) Google Scholar Other explanations include the use of higher doses of beneficial medications or the benefits of elevated TNF-α receptor levels in the obese.17Sagar U.N. Ahmed M.M. Adams S. Whellan D.J. Does body mass index really matter in the management of heart failure: a review of the literature.Cardiol Rev. 2008; 16: 124-128Crossref PubMed Scopus (7) Google Scholar, 18Mohamed-Ali v Goodrick S. Bulmer K. Holly J.M. Yudkin J.S. Coppack S.W. Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo.Am J Physiol. 1999; 277: E971-E975PubMed Google Scholar Although it seems unlikely that there is a beneficial effect of obesity in people with HF, the explanation for the “obesity paradox” remains uncertain. Until further data are available, caloric restriction as part of the treatment of the severely obese patient with HF and weight stabilization or reduction in overweight and mildly obese patients seems reasonable.There are defined risks of extreme calorie and carbohydrate restriction that may be increased in patients with HF. Electrolyte abnormalities and ketosis may occur with these diets and require frequent monitoring and physician oversight.For HF patients with a BMI >35, gastrointestinal surgery is an option, with operative risk dependent on clinical symptoms, hemodynamic stability, and stability of coronary artery disease.19Hernandez A.F. Whellan D.J. Stroud S. Sun J.L. O'Connor C.M. Jollis J.G. Outcomes in heart failure patients after major noncardiac surgery.J Am Coll Cardiol. 2004; 44: 1446-1453Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar Surgical intervention is the only weight loss therapy with reasonable long-term result maintenance, although operative morbidity and mortality are substantial.20Flum D.R. Dellinger E.P. Impact of gastric bypass operation on survival: a population-based analysis.J Am Coll Surg. 2004; 199: 543-551Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar One recent study found that weight reduction after bariatric surgery in subjects with morbid obesity may reverse LV hypertrophy.19Hernandez A.F. Whellan D.J. Stroud S. Sun J.L. O'Connor C.M. Jollis J.G. Outcomes in heart failure patients after major noncardiac surgery.J Am Coll Cardiol. 2004; 44: 1446-1453Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar Preliminary data also suggest that in subjects with morbid obesity and reduced systolic function, bariatric surgery may lead to improvements in cardiac function.21Ikonomidis I. Mazarakis A. Papadopoulis C. Patsouras N. Kalfarentzos F. Lekakis J. et al.Weight loss after bariatric surgery improves aortic elastic properties and left ventricular function in individuals with morbid obesity: a 3-year follow-up study.J Hypertens. 2007; 25: 439-447Crossref PubMed Scopus (45) Google Scholar, 22Ristow B. Rabkin J. Haeusslein E. Improvement in dilated cardiomyopathy after bariatric surgery.J Card Fail. 2008; 14: 198-202Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 23McClosky C.A. Ramani G.V. Mathier M.A. Schauer P.R. Eid G.M. Mattar S.G. et al.Bariatric surgery improves cardiac function in morbidly obese patients with severe cardiomyopathy.Surg Obes Relat Dis. 2007; 3: 503-507Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar It is therefore a consideration in morbidly obese patients for whom all other weight loss measures have failed.Recommendation6.3Restriction of daily fluid intake to <2 L is recommended in patients with severe hyponatremia (serum sodium <130 mEq/L) and should be considered for all patients demonstrating fluid retention that is difficult to control despite high doses of diuretic and sodium restriction. (Strength of Evidence = C)BackgroundFluid restriction is indicated in the setting of symptomatic hyponatremia (serum sodium <130 mEq/L), whether or not it is precipitated by pharmacologic therapy. Concomitant dietary sodium restriction facilitates maximal diuresis and may reduce hospital length of stay. In the outpatient setting, fluid restriction generally is reserved for advanced HF refractory to high doses of oral diuretic agents. Fluid restriction in the outpatient setting has many inherent logistical difficulties, often leading to increased stress, anxiety, and poor adherence with therapy. Most disease management programs monitor patient volume status reliably and effectively through the attainment of daily morning weight, rather than through patient measurement of daily intake and output.24Whellan D.J. Gaulden L. Gattis W.A. Granger B. Russell S.D. Blazing M.A. et al.The benefit of implementing a heart failure disease management program.Arch Intern Med. 2001; 161: 2223-2228Crossref PubMed Google ScholarApparent diuretic refractoriness is most often a reflection of nonadherence with dietary sodium restriction or prescribed pharmacologic therapy, unrecognized drug interactions (eg, nonsteroidal anti-inflammatory agents [NSAIDs] and glitazones) or the uncommon patient with excessively high fluid intake (>6 L/day). Physiologic diuretic refractoriness can be observed with chronic loop diuretic administration, primarily from distal renal tubular hypertrophy that facilitates enhanced sodium reabsorption. On the other hand, “true” diuretic refractoriness may reflect underlying disease progression with reduced cardiac output and effective renal plasma flow, development of significant intrinsic renal insufficiency, or nephrosis.Recommendation6.4It is recommended that specific attention be paid to nutritional management of patients with advanced HF and unintentional weight loss or muscle wasting (cardiac cachexia). Measurement of nitrogen balance, caloric intake, and prealbumin may be useful in determining appropriate nutritional supplementation. Caloric supplementation is recommended. Anabolic steroids are not recommended for cachexic patients. (Strength of Evidence = C)BackgroundCardiac cachexia is a well-described phenomenon that is associated with intense activation of the cytokine, tumor necrosis factor-α, or chronically low cardiac output states. Similar features are observed in patients with terminal cancer, acquired immunodeficiency syndrome (AIDS), and chronic inflammatory diseases. Such patients are at extremely high risk for serious morbidity, such as infection, hospitalization and impaired wound healing.In HF patients with reduced LVEF, tumor necrosis factor-α, levels are highest in advanced disease and correlate with the highest risk of mortality. Formal metabolic evaluation and determination of minimal nutritional requirements should be strongly considered for patients demonstrating this muscle-wasting syndrome. Specific recommendations have been made for these patients, including altering the size and frequency of meals and ensuring a high-energy diet.25Gibbs C.R. Jackson G. Lip G.Y. ABC of heart failure. Non-drug management.BMJ. 2000; 320: 366-369Crossref PubMed Google ScholarThere are no data to support the use of anabolic steroids or human growth hormone supplementation in patients with cardiac cachexia and skeletal muscle wasting. Initial enthusiasm for this approach was based on data suggesting that small doses of testosterone have a beneficial effect on dysfunctional myocardium.26English K.M. Steeds R.P. Jones T.H. Diver M.J. Channer K.S. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study.Circulation. 2000; 102: 1906-1911Crossref PubMed Google Scholar However, long-term exposure to these compounds has been reported to increase ischemia risk and to promote adverse ventricular remodeling risk. Fluid retention and electrolyte abnormalities are frequently observed with the use of this therapy. Additional serious risks include increased thrombogenicity and erythrocytosis, as well as benign prostatic hypertrophy and prostate cancer.Recommendation6.5Patients with HF, especially those on diuretic therapy and restricted diets, should be considered for daily multivitamin-mineral supplementation to ensure adequate intake of the recommended daily value of essential nutrients. Evaluation for specific vitamin or nutrient deficiencies is rarely necessary. (Strength of Evidence = C)BackgroundBased on research, dietary guidelines for individuals at risk for developing HF are more established than for those who already have the condition.27Ershow A.G. Costello R.B. Dietary guidance in heart failure: a perspective on needs for prevention and management.Heart Fail Rev. 2006; 11: 7-12Crossref PubMed Scopus (18) Google Scholar Balanced nutrition with multivitamin/mineral supplementation to fulfill the recommended daily value of essential nutrients is prudent for persons with any chronic disease, including HF. Multivitamin/mineral supplementation may offset nutritional imbalances from early satiety and altered digestive efficiency related to decreased absorption, enhanced water-soluble vitamin and mineral loss from diuretic administration, and increased utilization due to oxidative stress.28Witte K.K. Clark A.L. Micronutrients and their supplementation in chronic cardiac failure. An update beyond theoretical perspectives.Heart Fail Rev. 2006; 11: 65-74Crossref PubMed Scopus (18) Google Scholar It should also be recognized that population-related issues, such as old age or other chronic conditions, rather than HF itself, can be responsible for nutritional deficiencies in patients with HF.29Gorelik O. Almoznino-Sarafian D. Feder I. Wachsman O. Alon I. Litvinjuk V. et al.Dietary intake of various nutrients in older patients with congestive heart failure.Cardiology. 2003; 99: 177-181Crossref PubMed Scopus (26) Google ScholarIn general, for most patients with HF, a prudent diet providing adequate protein, carbohydrate, and calories according to age, gender, and activity level is advisable. Dietary supplementation consisting of a daily multiple-vitamin should be considered, given that most American diets are inadequate in providing the recommended basic nutrient requirements.Studies estimate that approximately 50% of patients with HF consume herbal, megavitamin, or other dietary supplements.30Ackman M.L. Campbell J.B. Buzak K.A. Tsuyuki R.T. Montague T.J. Teo K.K. Use of nonprescription medications by patients with congestive heart failure.Ann Pharmacother. 1999; 33: 674-679Crossref PubMed Scopus (27) Google Scholar The likelihood of an adverse reaction or vitamin toxicity increases with consumption of multiple supplements, the safety and efficacy of which are not well documented. It is therefore important to ask patients with HF about supplements they are already taking before recommending a daily multiple vitamin.Recommendation6.6Documentation of the type and dose of naturoceutical products used by patients with HF is recommended. (Strength of Evidence = C)Naturoceutical use is not recommended for relief of symptomatic HF or for the secondary prevention of cardiovascular events. Patients should be instructed to avoid using natural or synthetic products containing ephedra (ma huang), ephedrine, or its metabolites because of an increased risk of mortality and morbidity. Products should be avoided that may have significant drug interactions with digoxin, vasodilators, beta blockers, antiarrhythmic drugs, and anticoagulants. (Strength of Evidence = B)BackgroundNaturoceutical use cannot be recommended for the relief of HF symptoms or for the secondary prevention of cardiovascular events. Given the paucity of efficacy data about naturoceutical products, reporting suspected adverse effects or drug interactions to the Food and Drug Administration is strongly encouraged.There are several agents with documented potential to do harm. Natural or synthetic catecholamine-like products containing ephedra (ma huang), ephedrine metabolites, or imported Chinese herbs are specifically contraindicated in HF. Hawthorne (Cratageus) products appear to have inodilator activity, increasing the risk of orthostatic hypotension and possibly arrhythmia. Hawthorne potentiates the action of vasodilator medications and increases serum digoxin levels. One recent long-term placebo-controlled trial failed to show any incremental benefit when hawthorn extract was given with standard drug therapy to patients with chronic HF. It did show, however, that the drug appeared safe to use with angiotensin converting enzyme (ACE) inhibitors, beta blockers, and other standard HF medications.31Holubarsch C.J. Colucci W.S. Meinertz T. Gaus W. Tendera M. on behalf of the Survival and PrognosisInvestigation of Crataegus Extract WS® 1442 in CHF (SPICE) trial study groupThe efficacy and safety of Crataegus extract WS® 1442 in patients with heart failure: The SPICE trial.Eur J Heart Fail. 2008 Nov 17; PubMed Google Scholar Many other naturoceutical products, including garlic, gingko biloba, and ginseng, have antiplatelet effects or potential anticoagulant interactions.32D'Arcy P.F. Adverse reactions and interactions with herbal medicines. Part 2-Drug interactions.Adverse Drug React Toxicol Rev. 1993; 12: 147-162PubMed Google ScholarOther TherapiesRecommendation6.7Continuous positive airway pressure to improve daily functional capacity and quality of life is recommended in patients with HF and obstructive sleep apnea documented by approved methods of polysomnography. (Strength of Evidence = B)BackgroundSleep-disordered breathing is highly prevalent in HF patients.33Javaheri S. Parker T.J. Liming J.D. Corbett W.S. Nishiyama H. Wexler L. et al.Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalence, consequences, and presentations.Circulation. 1998; 97: 2154-2159Crossref PubMed Google Scholar, 34Sin D.D. Fitzgerald F. Parker J.D. Newton G. Floras J.S. Bradley T.D. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure.Am J Respir Crit Care Med. 1999; 160: 1101-1106Crossref PubMed Google Scholar, 35Tremel F. Pepin J.L. Veale D. Wuyam B. Siche J.P. Mallion J.M. et al.High prevalence and persistence of sleep apnoea in patients referred for acute left ventricular failure and medically treated over 2 months.Eur Heart J. 1999; 20: 1201-1209Crossref PubMed Scopus (88) Google Scholar Formal sleep evaluation is therefore recommended for patients who remain symptomatic despite optimal HF therapy. Testing should be considered for patients with a positive screening questionnaire or whose sleep partner reports signs suggesting apnea or periodic breathing. Whether clinical outcome is favorably affected by treatment of sleep-disordered breathing is unclear, but patient quality of life and functional capacity is increased by treatment when the respiratory disturbance index is at least moderately elevated, and individual studies have shown that use of continuous positive airway pressure (CPAP) reduces edema, daytime muscle sympathetic nerve activity, systolic blood pressure, frequency of ventricular premature beats during sleep, and improves LV function.36Pepperell J.C. Maskell N.A. Jones D.R. Langford-Wiley B.A. Crosthwaite N. Stradling J.R. et al.A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure.Am J Respir Crit Care Med. 2003; 168: 1109-1114Crossref PubMed Scopus (199) Google Scholar, 37Kaneko Y. Floras J.S. Usui K. Plante J. Tkacova R. Kubo T. Ando S. Bradley T.D. Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea.N Engl J Med. 2003; 348: 1233-1241Crossref PubMed Google Scholar, 38Blankfield R.P. Ahmed M. Zyzanski S.J. Effect of nasal continuous positive airway pressure on edema in patients with obstructive sleep apnea.Sleep Med. 2004; 5: 589-592Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 39Usui K. Bradley T.D. Spaak J. Ryan C.M. Kubo T. Kaneko Y. Floras J.S. Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure.J Am Coll Cardiol. 2005; 45: 2008-2011Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar, 40Ryan C.M. Usui K. Floras J.S. Bradley T.D. Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea.Thorax. 2005; 60: 781-785Crossref PubMed Scopus (113) Google Scholar Concomitant treatment for restless leg syndrome may be reduced when the patient is treated for associated sleep-disordered breathing.The other component of sleep-disordered breathing, central sleep apnea, was studied in a large-scale trial that tested the hypothesis that CPAP would improve the survival rate without transplantation for patients with central sleep apnea and HF. The Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure trial (CANPAP) of 258 patients found that those patients randomized to CPAP had attenuated central sleep apnea, improved nocturnal oxygenation, increased LVEF, and improved 6-minute walk distances, but did not survive longer.41Bradley T.D. Logan A.G. Kimoff R.J. Series F. Morrison D. Ferguson K. et al.CANPAP Investigators. Continuous positive airway pressure for central sleep apnea and heart failure.N Engl J Med. 2005; 353: 2025-2033Crossref