Congestive heart failure treatment of patients at high risk for developing heart failure (Stage A)

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Medical Therapy:

Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Nitrates
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Hormonal Therapies
Drugs to Avoid
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Treatment of underlying causes
Associated conditions

Exercise Training

Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Ultrafiltration
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Left Ventricular Assist Devices (LVADs)
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ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Saleh El Dassouki, M.D. [2]; Lakshmi Gopalakrishnan, M.B.B.S. [3]Mahmoud Sakr, M.D. [4],Seyedmahdi Pahlavani, M.D. [5]

Overview

Early detection and mitigation of risk factors associated with the subsequent development of heart failure may have a tremendous impact on public and individual health.

Treatment of Hypertension

Controlling both systolic and diastolic hypertension has been associated with a significant reduction in the risk of subsequent HF.[1] Control of systolic blood pressure is consistently associated with a 50% reduction in new heart failure. Other complications of hypertension include left ventricular hypertrophy (LVH), MI, stroke and sudden death.[2]In the Framingham heart study, hypertension was present in 39% of men and in 59% of women with heart failure. These numbers emphasize the importance of managing hypertension at an early stage to avoid complications such as heart failure.

Lowering both systolic and diastolic blood pressure in accordance with the recommendations provided in published guidelines has proven its effectiveness in lowering systemic vascular resistance, improving ventricular remodeling and decreasing hemodynamic load on the failing ventricle in patients with established heart failure. The treatment of hypertension in patients with HF should take into consideration the type of heart failure that is present: In systolic dysfunction the biggest problem is the impaired contractility whereas in diastolic dysfunction, the main issue is the limitation of diastolic filling and therefore abnormal forward cardiac output due to increased ventricular stiffness.

When any anti-hypertensive regimen is prescribed, an important aspect to keep in mind is the presence of concomitant medical problems as CAD, diabetes, renal disease, pulmonary disease in many patients suffering from HF, which requires the health care providers to keep in mind the priority of lowering blood pressure while trying not to affect the treatment of those diseases.

Diuretic-based antihypertensive therapy has repeatedly been shown to prevent HF in a wide range of target populations.[3]Patients may also benefit from the usage of ACE inhibitors(ACEIs) and beta blockers, which are proven to be effective in preventing HF in hypertensive individuals. However, ACEIs and beta blockers, as single therapies, are not superior to other antihypertensive drug classes in the reduction of all cardiovascular outcomes.

Nevertheless, among patients with diabetes and other cardiovascular complications, ACEIs have shown to reduce the onset of HF and progression of nephropathy.[4]Another significant reduction of HF incidence in comparison to placebo in patients with type 2 diabetes mellitus and nephropathy has been achieved by the usage of ARB’s losartan and irbesartan.[5] As previously mentioned an ultimate and appropriate hypertensive treatment would take into consideration all the concomitant diseases in an HF patient, and would involve multiple drugs used in combination.

Treatment of Diabetes Mellitus

Diabetes increases the risk of HF in all patients groups whether coronary heart disease or hypertension is present and it may cause cardiomyopathy.[6] A gender difference in terms of HF risk in diabetic patients is present, since the increase of HF for diabetic men is 3 times less than that for a diabetic woman.[7] In a study of patients with type 2 diabetes mellitus over 50 years old, with urinary albumin greater than 20 mg/l, 4% of patients developed HF over the study period, of whom 36 % died.[8] Health care providers should closely monitor hyperglycemia and target a certain blood glucose level to avoid end-organ complications in such patients since each 1% increase in (Hb)A1c is associated with an 8% increase risk of heart failure, and an (Hb)A1c > 10 increases the risk of CHF by 1.56 compared to an (Hb)A1c less than 7 [9][10]ACEIs and ARBs have been proven to reduce the development of end-organ disease and the occurrence of clinical events in diabetic patients even when hypertension is not present. Long term treatment with ACEIs and ARBs has been shown to lower various dangerous complications in diabetic patients such as renal disease and prolonged treatment with ACEI ramipril has been shown to decrease the event of cardiovascular death, MI, and CHF. Long term therapy with ARBs has also been proven to lower cardiovascular complication, decreasing the incidence of first HF hospitalization and improving renal function in diabetic patients.[11]

Management of Metabolic Syndrome

The metabolic syndrome or syndrome X is mainly linked to obesity (mainly abdominal obesity), insulin resistance, hypertriglyceridemia, low HDL, hypertension and fasting hyperglycemia. Those combined metabolic risks promotes vascular endothelial dysfunction, vascular inflammation and thus, the development of atherosclerotic cardiovascular disease.[12] The major complication of metabolic syndrome is coronary artery disease which in turn increases the incidence of congestive heart failure in the general population;[13] For this reason, the appropriate management of hypertension, diabetes mellitus, and dyslipedemia can significantly reduce the risk of developing CHF.

Management of Anemia

Routine baseline assessment of all patients with HF includes an evaluation for anemia in addition to other baseline laboratory measurements. Anemia is independently associated with HF disease severity, and iron deficiency appears to be uniquely associated with reduced exercise capacity. When iron deficiency is diagnosed and after full evaluation for cause, intravenous repletion of iron, especially in the setting of concomitant hepcidin deficiency in HF, may improve exercise capacity and quality of life.

Management of Atherosclerotic Disease

Atherosclerotic diseases (eg., of the coronary, cerebral, peripheral blood vessels) are an important risk factor in the development of CHF.[14] A series of different large scale studies involving the long term usage of ACEIs, produced mixed data and recommendations.[15] In one study, the treatment with ACEIs proved to decrease the risk of the primary endpoint of cardiovascular death, MI and stroke in patients with previous vascular disease who were without evidence of HF or reduced LVEF at the time of randomization, but the incidence of HF was not a primary or secondary endpoint, although it was improved.[4] A more recent trial of ACEIs versus placebo didn’t prove to be effective in reducing the primary composite endpoint, although a post hoc analysis did show a decrease in HF hospitalization.

Those various findings led the AHA to change the level of recommendation for the use of ACEIs for stage A patients from Class 1 to Class 2a[16]. Treatment of hyperlipidemia has also been shown to reduce the risk of death and of HF in patients with a history of MI.

Sleep Disordered Breathing

Sleep disorders are common in patients with HF. A study of adults with chronic HF treated with evidence-based therapies found that 61% had either central or obstructive sleep apnea. It is clinically important to distinguish obstructive sleep apnea from central sleep apnea, given the different responses to treatment. Adaptive servo-ventilation for central sleep apnea is associated with harm. Continuous positive airway pressure (CPAP) for obstructive sleep apnea improves sleep quality, reduces the apnea-hypopnea index, and improves nocturnal oxygenation.[17][18]

Control of Conditions That May Cause Heart Failure

Cardiotoxic effect of various agents and substances should be closely controlled, especially in patients at higher risk of developing HF. Smoking, alcohol, amphetamines, cocaine and other illicit drugs are some of the most common substances that patients should be advised about. Several HF programs limit alcoholic beverage consumption to no more than one alcoholic beverage a day for all the patients with LV dysfunction, regardless of cause[19]. Cardiac injuries could be sustained from other causes and interventions, such as ionizing radiation involving the mediastinum, chemotherapeutic agents such as anthracyclines, immunotherapy such as trastuzumab, or high dose-cyclophosphamide.[20] Trastuzumab in particular when combined with anthracyclines increase the risk of HF and may occur years after the initial exposure.

2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure/2013 ACC/AHA Guideline, 2009 ACC/AHA Focused Update and 2005 Guidelines for the Diagnosis and Management of Heart Failure in the Adult (DO NOT EDIT) [21][22]

Hypertension in Patients at High Risk for Developing Heart Failure (Stage A) (DO NOT EDIT) [23]

Class I
"1. In patients at high risk for developing heart failure, systolic and diastolic hypertension should be controlled in accordance with contemporary guidelines. [1][24][25][26](Level of Evidence: A) "
"2. In patients at increased risk, stage A HF, the optimal blood pressure in those with hypertension should be less than 130/80 mm Hg.[27][28] (Level of Evidence: B-R) "
Class IIa
"1. Angiotensin converting enzyme inhibitors can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: A) "
"2. Angiotensin II receptor blockers can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: C) "

Diabetes Mellitus in Patients at High Risk for Developing Heart Failure (Stage A) (DO NOT EDIT) [23]

Class I
"1. For patients with diabetes mellitus (who are all at high risk for developing heart failure), blood sugar should be controlled in accordance with contemporary guidelines. (Level of Evidence: C) "
Class IIa
"1. Angiotensin converting enzyme inhibitors can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: A) "
"2. Angiotensin II receptor blockers can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: C) "

Sleep disordered breathing in Patients at High Risk for Developing Heart Failure (Stage A) (DO NOT EDIT)

Class IIa
" In patients with NYHA class II–IV HF and suspicion of sleep disordered breathing or excessive daytime sleepiness, a formal sleep assessment is reasonable.[17][18] (Level of Evidence: C-LD) "
Class IIb
" In patients with cardiovascular disease and obstructive sleep apnea, CPAP may be reasonable to improve sleep quality and daytime sleepiness.[29] (Level of Evidence: B-R) "
Class III (Harm)
" In patients with NYHA class II–IV HFrEF and central sleep apnea, adaptive servo-ventilation causes harm.[30] (Level of Evidence: B-R) "

Metabolic Syndrome in Patients at High Risk for Developing Heart Failure (Stage A) (DO NOT EDIT) [23]

Class I
"1. In patients at high risk for developing heart failure, systolic and diastolic hypertension should be controlled in accordance with contemporary guidelines. (Level of Evidence: A) "
"2. In patients at high risk for developing heart failure, lipid disorders should be treated in accordance with contemporary guidelines. (Level of Evidence: A) "
"3. For patients with diabetes mellitus (who are all at high risk for developing heart failure), blood sugar should be controlled in accordance with contemporary guidelines. (Level of Evidence: C) "
"4. In patients at high risk for developing heart failure who have known atherosclerotic vascular disease, healthcare providers should follow current guidelines for secondary prevention. (Level of Evidence: C) "
Class IIa
"1. Angiotensin converting enzyme inhibitors can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: A) "
"2. Angiotensin II receptor blockers can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: C) "

Anemia in Patients at High Risk for Developing Heart Failure (Stage A) (DO NOT EDIT)[31][32]

Class IIb
"1.In patients with NYHA class II and III HF and irondeficiency (ferritin <100 ng/mL or 100 to 300 ng/mL if transferrin saturation is <20%), intravenous iron

replacement might be reasonable to improve functional status and quality of life. (Level of Evidence: B-R) "

Class III (No Benefit)
"1. In patients with HF and anemia, erythropoietin stimulating agents should not be used to improve morbidity and mortality. (Level of Evidence: B-R) "

Atherosclerotic Disease in Patients at High Risk for Developing Heart Failure (Stage A) (DO NOT EDIT) [23]

Class I
"1. In patients at high risk for developing heart failure who have known atherosclerotic vascular disease, healthcare providers should follow current guidelines for secondary prevention. (Level of Evidence: C) "
Class IIa
"1. Angiotensin converting enzyme inhibitors can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: A) "
"2. Angiotensin II receptor blockers can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: C) "

High Risk Patients (Stage A) (DO NOT EDIT) [23]

Class I
"1. Patients at high risk for developing heart failure should be counseled to avoid behaviors that may increase the risk of heart failure (e.g., smoking, excessive alcohol consumption, and illicit drug use). (Level of Evidence: C) "
"2. Ventricular rate should be controlled or sinus rhythm restored in patients with supraventricular tachyarrhythmias who are at high risk for developing heart failure. (Level of Evidence: B) "
"3. Thyroid disorders should be treated in accordance with contemporary guidelines in patients at high risk for developing heart failure. (Level of Evidence: C) "
"4. Healthcare providers should perform periodic evaluation for signs and symptoms of heart failure in patients at high risk for developing heart failure. (Level of Evidence: C) "
"5. Healthcare providers should perform a noninvasive evaluation of left ventricular function (i.e., left ventricular ejection fraction) in patients with a strong family history of cardiomyopathy or in those receiving cardiotoxic interventions. (Level of Evidence: C) "
Class III (No Benefit)
"1. Routine use of nutritional supplements solely to prevent the development of structural heart disease should not be recommended for patients at high risk for developing heart failure. (Level of Evidence: C) "

Patients at High Risk for Developing Heart Failure (Stage A) (DO NOT EDIT) [23]

Class I
"1. In patients at high risk for developing heart failure, systolic and diastolic hypertension should be controlled in accordance with contemporary guidelines. (Level of Evidence: A) "
"2. In patients at high risk for developing heart failure, lipid disorders should be treated in accordance with contemporary guidelines. (Level of Evidence: A) "
"3. For patients with diabetes mellitus (who are all at high risk for developing heart failure), blood sugar should be controlled in accordance with contemporary guidelines. (Level of Evidence: C) "
"4. Patients at high risk for developing heart failure should be counseled to avoid behaviors that may increase the risk of heart failure (e.g., smoking, excessive alcohol consumption, and illicit drug use). (Level of Evidence: C) "
"5. Ventricular rate should be controlled or sinus rhythm restored in patients with supraventricular tachyarrhythmias who are at high risk for developing heart failure. (Level of Evidence: B) "
"6. Thyroid disorders should be treated in accordance with contemporary guidelines in patients at high risk for developing heart failure. (Level of Evidence: C) "
"7. Healthcare providers should perform periodic evaluation for[signs and symptoms of heart failure in patients at high risk for developing heart failure. (Level of Evidence: C) "
"8. In patients at high risk for developing heart failure who have known atherosclerotic vascular disease, healthcare providers should follow current guidelines for secondary prevention. (Level of Evidence: C) "
"9. Healthcare providers should perform a noninvasive evaluation of left ventricular function (i.e., left ventricular ejection fraction) in patients with a strong family history of cardiomyopathy or in those receiving cardiotoxic interventions. (Level of Evidence: C) "
Class III (No Benefit)
"1. Routine use of nutritional supplements solely to prevent the development of structural heart disease should not be recommended for patients at high risk for developing heart failure. (Level of Evidence: C) "
Class IIa
"1. Angiotensin converting enzyme inhibitors can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: A) "
"2. Angiotensin II receptor blockers can be useful to prevent heart failure in patients at high risk for developing heart failure who have a history of atherosclerotic vascular disease, diabetes mellitus, or hypertension with associated cardiovascular risk factors. (Level of Evidence: C)"

Vote on and Suggest Revisions to the Current Guidelines

External Links

References

  1. ↑ 1.0 1.1 Kostis JB, Davis BR, Cutler J, Grimm RH, Berge KG, Cohen JD, Lacy CR, Perry HM, Blaufox MD, Wassertheil-Smoller S, Black HR, Schron E, Berkson DM, Curb JD, Smith WM, McDonald R, Applegate WB (1997). "Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group". JAMA : the Journal of the American Medical Association. 278 (3): 212–6. PMID 9218667. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  2. ↑ Swamy RS, Lang RM (2010). "Echocardiographic quantification of left ventricular mass: prognostic implications". Current Cardiology Reports. 12 (3): 277–82. doi:10.1007/s11886-010-0104-y. PMID 20424973. Retrieved 2011-03-28. Unknown parameter |month= ignored (help)
  3. ↑ Staessen JA, Wang JG, Thijs L (2003). "Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003". Journal of Hypertension. 21 (6): 1055–76. doi:10.1097/01.hjh.0000059044.65882.db. PMID 12777939. Retrieved 2011-03-28. Unknown parameter |month= ignored (help)
  4. ↑ 4.0 4.1 Fox KM (2003). "Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)". Lancet. 362 (9386): 782–8. PMID 13678872. Retrieved 2011-03-28. Unknown parameter |month= ignored (help)
  5. ↑ Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau JL, Drury PL, Esmatjes E, Hricik D, Parikh CR, Raz I, Vanhille P, Wiegmann TB, Wolfe BM, Locatelli F, Goldhaber SZ, Lewis EJ (2003). "Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy". Annals of Internal Medicine. 138 (7): 542–9. PMID 12667024. Retrieved 2011-03-28. Unknown parameter |month= ignored (help)
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  9. ↑ Kasiske BL, Kalil RS, Ma JZ, Liao M, Keane WF (1993). "Effect of antihypertensive therapy on the kidney in patients with [[diabetes]]: a meta-regression analysis". Annals of Internal Medicine. 118 (2): 129–38. PMID 8416309. Retrieved 2011-03-29. Unknown parameter |month= ignored (help); URL–wikilink conflict (help)
  10. ↑ Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993). "The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group". The New England Journal of Medicine. 329 (20): 1456–62. doi:10.1056/NEJM199311113292004. PMID 8413456. Retrieved 2011-03-29. Unknown parameter |month= ignored (help)
  11. ↑ Fox KM (2003). "Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)". Lancet. 362 (9386): 782–8. Retrieved 2011-03-29. Unknown parameter |month= ignored (help)
  12. ↑ Wilson PW, Grundy SM (2003). "The metabolic syndrome: practical guide to origins and treatment: Part I". Circulation. 108 (12): 1422–4. doi:10.1161/01.CIR.0000089505.34741.E5. PMID 14504251. Retrieved 2011-03-30. Unknown parameter |month= ignored (help)
  13. ↑ Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ (2004). "Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines". Journal of the American College of Cardiology. 44 (3): 720–32. doi:10.1016/j.jacc.2004.07.001. PMID 15358046. Retrieved 2011-03-30. Unknown parameter |month= ignored (help)
  14. ↑ Smith SC, Blair SN, Bonow RO, Brass LM, Cerqueira MD, Dracup K, Fuster V, Gotto A, Grundy SM, Miller NH, Jacobs A, Jones D, Krauss RM, Mosca L, Ockene I, Pasternak RC, Pearson T, Pfeffer MA, Starke RD, Taubert KA (2001). "AHA/ACC Scientific Statement: AHA/ACC guidelines for preventing heart attack and death in patients with atherosclerotic cardiovascular disease: 2001 update: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology". Circulation. 104 (13): 1577–9. PMID 11571256. Retrieved 2011-03-30. Unknown parameter |month= ignored (help)
  15. ↑ Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000). "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators". The New England Journal of Medicine. 342 (3): 145–53. doi:10.1056/NEJM200001203420301. PMID 10639539. Retrieved 2011-03-30. Unknown parameter |month= ignored (help)
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  17. ↑ 17.0 17.1 Arzt M, Floras JS, Logan AG, Kimoff RJ, Series F, Morrison D, Ferguson K, Belenkie I, Pfeifer M, Fleetham J, Hanly P, Smilovitch M, Ryan C, Tomlinson G, Bradley TD (2007). "Suppression of central sleep apnea by continuous positive airway pressure and transplant-free survival in heart failure: a post hoc analysis of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure Trial (CANPAP)". Circulation. 115 (25): 3173–80. doi:10.1161/CIRCULATIONAHA.106.683482. PMID 17562959.
  18. ↑ 18.0 18.1 Somers VK (2005). "Sleep--a new cardiovascular frontier". N. Engl. J. Med. 353 (19): 2070–3. doi:10.1056/NEJMe058229. PMID 16282183.
  19. ↑ Abramson JL, Williams SA, Krumholz HM, Vaccarino V (2001). "Moderate alcohol consumption and risk of heart failure among older persons". JAMA : the Journal of the American Medical Association. 285 (15): 1971–7. PMID 11308433. Retrieved 2011-04-01. Unknown parameter |month= ignored (help)
  20. ↑ Sparano JA (2001). "Cardiac toxicity of trastuzumab (Herceptin): implications for the design of adjuvant trials". Seminars in Oncology. 28 (1 Suppl 3): 20–7. PMID 11301371. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  21. ↑ 21.0 21.1 Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, McBride PE; et al. (2013). "2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. doi:10.1016/j.jacc.2013.05.019. PMID 23747642.
  22. ↑ 22.0 22.1 Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG et al. (2009) 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119 (14):1977-2016.DOI:10.1161/CIRCULATIONAHA.109.192064 PMID: 19324967
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  24. ↑ Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel (2012). "Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): 7S–47S. doi:10.1378/chest.1412S3. PMC 3278060. PMID 22315257.
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  26. ↑ Verdecchia P, Sleight P, Mancia G, Fagard R, Trimarco B, Schmieder RE; et al. (2009). "Effects of telmisartan, ramipril, and their combination on left ventricular hypertrophy in individuals at high vascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease". Circulation. 120 (14): 1380–9. doi:10.1161/CIRCULATIONAHA.109.865774. PMID 19770395.
  27. ↑ Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, Woodward M, MacMahon S, Turnbull F, Hillis GS, Chalmers J, Mant J, Salam A, Rahimi K, Perkovic V, Rodgers A (2016). "Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis". Lancet. 387 (10017): 435–43. doi:10.1016/S0140-6736(15)00805-3. PMID 26559744.
  28. ↑ Thomopoulos C, Parati G, Zanchetti A (2016). "Effects of blood pressure lowering on outcome incidence in hypertension: 7. Effects of more vs. less intensive blood pressure lowering and different achieved blood pressure levels - updated overview and meta-analyses of randomized trials". J. Hypertens. 34 (4): 613–22. doi:10.1097/HJH.0000000000000881. PMID 26848994.
  29. ↑ McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS (2016). "CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea". N. Engl. J. Med. 375 (10): 919–31. doi:10.1056/NEJMoa1606599. PMID 27571048.
  30. ↑ Cowie MR, Woehrle H, Wegscheider K, Angermann C, d'Ortho MP, Erdmann E, Levy P, Simonds AK, Somers VK, Zannad F, Teschler H (2015). "Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure". N. Engl. J. Med. 373 (12): 1095–105. doi:10.1056/NEJMoa1506459. PMC 4779593. PMID 26323938.
  31. ↑ Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P (2009). "Ferric carboxymaltose in patients with heart failure and iron deficiency". N. Engl. J. Med. 361 (25): 2436–48. doi:10.1056/NEJMoa0908355. PMID 19920054.
  32. ↑ Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, McDonagh T, Parkhomenko A, Tavazzi L, Levesque V, Mori C, Roubert B, Filippatos G, Ruschitzka F, Anker SD (2015). "Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency†". Eur. Heart J. 36 (11): 657–68. doi:10.1093/eurheartj/ehu385. PMC 4359359. PMID 25176939.

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