Top Clinical Issues

1. Top Clinical Issues Eltanya A. Patterson, MD

2. Heart Failure Guidelines Eltanya A. Patterson, MD

3. Definition • Complex clinical syndrome • Any structural or functional impairment of ventricular filling or ejection of blood • Cardinal s/sx • Dyspnea and fatigue • Fluid retention • Pts may c/o exercise intolerance with little fluid retention. • Others may c/o the peripheral edema, SOB, or fatigue

4. Etiology • The clinical syndrome of HF may result from • disorders of the pericardium, myocardium, endocardium, heart valves, or great vessels, • or from certain metabolic abnormalities, • but most patients with HF have symptoms due to impaired left ventricular (LV) myocardial function.

5. Definition • Some patients present without s/sx of fluid overload, therefore, the term “HEART FAILURE” is preferred over “CONGESTIVE HEART FAILURE.” • No single diagnostic test for HF. • HF is largely a clinical diagnosis based on a careful history and physical examination. • **HF is not synonymous with either cardiomyopathy or LV dysfunction; these latter terms describe possible structural or functional reasons for the development of HF. • is preferable to use the terms preserved or reduced EF over preserved or reduced systolic function.

6. New Terminology • HFrEF = Heart Failure with reduced Ejection Fraction • HFpEF = Heart Failure with preserved Ejection Fraction • Most pts with HF with have systolic and diastolic. • Reasons why EF is important • Demographics • Comorbidities • Prognosis • Response to therapies • **Most clinical trials selected pts based on EF

7. Definition: Redefining HF

8. ACCF/AHA Stages of HF

9. NYHA Functional Classification

10. Epidemiology • 20% lifetime risk for Americans ≥ 40 yo. • Incidence stable over last several decades. • >650,000 new diagnoses yearly • Prevalence: ~5.1 million. • 1 in 5 will be >65 yo by 2050. • Highest HF prevalence.

11. Disparities Identified • Blacks - highest risk for HF. • White women – lowest incidence. • Black men – highest incidence. • 5-year mortality rate – blacks > whites. • Prevalence: • Non-Hispanic black males - 4.5% • Non-Hispanic females – 3.8% • Non-Hispanic white males - 2.7% • Non-Hispanic white females - 1.8%

12. Diagnostic Tests: Class I • Initial laboratory evaluation • CBC, CMP, Magnesium, FLP, TSH, urinalysis. (C) • Serial monitoring • Serum electrolytes and renal function. (C) • Initial 12-lead electrocardiogram. (C)

13. Diagnostic Tests: Class IIa • Screening: • Hemochromatosis or HIV - reasonable in selected patients. (C) • Other tests: • Rheumatologic diseases. • Amyloidosis. • Pheochromocytoma. • Reasonable if clinical suspicion. (C)

14. Outpatient Biomarkers: Class I • Ambulatory patients with dyspnea, it is useful to measure B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP). It supports clinical decision. Especially if uncertain.(A) • Measure BNP or NT-proBNPto establish prognosis or disease severity in chronic HF.(A)

15. Outpatient Biomarkers: Class IIa • Well-structured HF disease management program: BNP- or NT-proBNP−guided HF therapy can be useful to achieve optimal dosing of GDMT in select clinically euvolemicpatients. (B)

16. Outpatient Biomarkers: Class IIb • Serial BNP: • Usefulness in reducing hospitalization or mortality is not well established. (B) • Other clinically available tests • Biomarkers of myocardial injury or fibrosis - additive for risk stratification in chronic HF. (B)

17. Hospitalized/Acute: Class I • Measurement of BNP or NT-proBNP • Useful to support clinical judgment for the diagnosis of acutely decompensated HF. (A) • Measurement of BNP or NT-proBNP and/or cardiac troponin • Useful for establishing prognosis or disease severity in acutely decompensated HF.(A)

18. Hospitalized/Acute: Class IIb • Usefulness of BNP- or NT-proBNP−guided therapy for acutely decompensated HF is not well established. (C)

19. Noninvasive Cardiac Imaging: Class I • Patients with suspected or new-onset HF, or those presenting with acute decompensated HF, should undergo • CXR - to assess heart size and pulmonary congestion and to detect alternative cardiac, pulmonary, and other diseases that may cause or contribute to the patient’s symptoms. (C) • 2D echocardiogram with Doppler • Initial evaluation to assess ventricular function, size, wall thickness, wall motion, and valve function. (C)

20. Noninvasive Cardiac Imaging: Class I • Repeat measurement of EF and severity of structural remodeling is useful when: • There’s significant change in clinical status; • In those who have experienced or recovered from a clinical event; • In those who have received treatment that might have had a significant effect on cardiac function • Those who may be candidates for device therapy • (Level of Evidence: C)

21. Noninvasive Cardiac Imaging: Class IIINo Benefit • Routine repeat measurement of LV function in pt w/o a change in clinical status or treatment interventions should not be performed. (B)

22. Treatment of Stage A to D: Recommendations: Stage A Class I • Treat Hypertension and Hyperlipidemia, according to guidelines, to lower the risk of HF.(A) • Control or avoid other conditions that may lead to or contribute to HF • Obesity • Diabetes mellitus • Tobacco use • Known cardiotoxicagents • (Level of Evidence: C)

23. Treatment of Stage A to D: Recommendations: Stage B Class I • Recent or remote h/o MI or ACS and reduced EF= ACEI. (A) • ACEI prevent symptomatic HF and reduce mortality. • If intolerant to ACEIs  ARBs. (A) • Beta blockers to reduce mortality.(B) • In recent or remote history of MI or ACS  statins to prevent symptomatic HF and cardiovascular events.(A) • ACE inhibitors  in all patients with a reduced EF  to prevent symptomatic HF, regardless of history of MI. (A)

24. Treatment of Stage A to D: Recommendations: Stage B Class I • Beta blockers  in all patients with a reduced EF  to prevent symptomatic HF, even if no history of MI. (C)

25. Treatment of Stage A to D: Recommendations: Stage B Class IIa • Placement of an implantable cardioverter-defibrillator (ICD) • To prevent sudden death • Is reasonable in patients with • asymptomatic ischemic cardiomyopathy • who are at least 40 days post-MI, • have an LVEF of 30% or less, • are on appropriate medical therapy, • and have reasonable expectation of survival • with a good functional status for more than 1 year. • (Level of Evidence: B)

26. Treatment of Stage A to D: Recommendations: Stage B Class III Harm • Nondihydropyridinecalcium channel blockers with negative inotropic effects may be harmful in asymptomatic patients with low LVEF and no symptoms of HF after MI. (Level of Evidence: C)

27. Oral Anticoagulants

28. Anticoagulants • Heparins • Vitamin K Antagonists • Fondaparinux • Direct Thrombin Inhibitors (DTI) • Direct Factor Xa Inhibitors (DFXaI)

29. Thrombin • Final enzyme in clotting cascade that produces fibrin. • Activates other procoagulant factors. • Active in both circulating and clot-bound forms. • DTI block action of both forms of thrombin. • Heparins only inactivate thrombin in fluid phase via antithrombin

30. Factor Xa • Acts at convergence point of intrinsic and extrinsic coagulation pathway. • One molecule of factor 10a can cleave over 1000 molecules of prothrombin to thrombin. • Active in circulating and clot-bound forms. • DXa inhibitors block the action in both forms. • Indirect Factor Xa inhibitors (heparin and fondaparinux) only able to inactivate Xa in the fluid phase.

31. Anticoagulant Terminology • Anithrombotic Agent • Antiplatelet • anticoagulant • Antiplatelet • ASA • Clopidogrel • Anticoagulant • DTI • DFXaI

32. Anticoagulant Terminology • Other Acronyms • TSOACs • DOACs • ODI • NOACs • Newer • Nonvitamin K antagonists

33. Comparison • Anticoagulants differ in efficacy depending on clinical setting. • There are differences in dosing, monitoring, cost, and risk. • Advantages and disadvantages of each agent must be individualized.

34. Comparison

35. Contraindications • Pregnancy • Prosthetic Heart Valve • Renal Impairment • Compliance • GI Disease

36. Indications • DVT prophylaxis and treatment • Afib • Unstable angina • MI • Coronary Stenting • Heparin –Induced Thrombocytopenia

37. Bleeding • Warfarin - Vitamin K • Dabigatran – Clotting factor products, i.e. FFP • Rivaroxaban - Clotting factor products, i.e. FFP • Apixaban- Clotting factor products, i.e. FFP

38. Surgery/Invasive Procedure • Warfarin - Stopped 5 days before surgery • Dabigatran – Stopped 2-3 days before surgery • Rivaroxaban - Stopped 2-3 days before surgery • Apixaban - Stopped 2-3 days before surgery

39. Dabigatran – Overview • Orally administered prodrug. Converted in the liver. • Active DTI • Inhibits clot-bound and circulating thrombin • T1/2 ~12 to 17 hours • Max anticoag effect @ 2-3 hrs of ingestion • Renal excretion. Not used if CrCl <15 • **Capsules in original bottle only!!! • Used within 4 months.

40. Dabigatran- Indicator • DVT prophylaxis and treatment. • Stroke prevention in Afib • PE

41. Dabigatranvs Coumadin • Meta-analyses an dlarge observational studies • Overall bleeding rates are similar • Dabigatranmay be assoc’d with a slightly lower rate of ICH and death • Dabigatran may be assoc’d with a slightly higher rate of GIB • Lacks a specific antidote • Dyspepsia – common SE

42. Rivaroxaban - Overview • DFXaI • T1/2 ~7to 17 hours • Indicator: DVT prophylaxis and treatment and stroke prevention in Afib. • Contraindicated in pregnancy, prosthetic heart valve • Taken with food • Not recommended for use in CrCl <30. Not used if CrCl <15 or significant hepatic impairment (Child-Pugh Class B and C with coagulopathy) • Rivaroxabaninteracts with CYP-3A4 and P-glycoprotein inh • Drug levels are relatively predictable

43. Apixaban - Overview • DFXaI • T1/2 ~5 to 9 hours • Indicator: DVT prophylaxis and treatment and stroke prevention in Afib. • Contraindicated in pregnancy or those with prosthetic heart valve • Drug levels are relatively predictable

44. CYP-3A4 and P-glycoprotein inh • Ketoconazole • Itraconazole • Voriconazole • Posaconazole • Ritonavir

45. 2013 ACC/AHA Blood Cholesterol Guideline

46. Purpose • The American College of Cardiology (ACC) and the American Heart Association (AHA) have collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations to: • to provide a strong evidence-based foundation for the treatment of cholesterol • for the primary and secondary prevention of ASCVD in women and men.

47. ASCVD • Atherosclerotic cardiovascular disease • ASCVD includes • coronary heart disease (CHD) • stroke • peripheral arterial disease

48. The Research • Based on the highest quality evidence available. • Expert panel did not consider evidence beyond 2011. • Recommendations were derived from randomized trials, meta-analyses, and observational studies evaluated for quality. • A limited number of expert opinion recommendations were made only when RCT evidence was not present and after a thorough consideration of what the Expert Panel had learned from the RCTs. • Plan to begin updating these guidelines starting in 2014.

49. Lipid Lowering Strategies • Strategies for using drug therapy • Treat-to-cholesterol target • Lower cholesterol is better • Risk-based treatment approaches. • Only 1 approach evaluated in multiple RCTs • Using fixed doses of cholesterol-lowering drugs to reduce the ASCVD risk. • Bulk of evidence from statin trials • Expert Panel focused on statin RCTs to develop the evidence-based guidelines

50. RCTs • Either compared fixed doses of statins with placebo or untreated controls, • Or compared fixed doses of higher-intensity statins with moderate-intensity statins. • The trials were not designed to evaluate the effect of titrated (dose-adjusted) statin treatment to achieve a specific LDL–C or non-HDL–C.