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Systolic Heart Failure 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Some terminologies ► Systolic dysfunction: contractility. presence of impaired LV There maybe substantial discordance between symptoms and the degree of LV dysfunction. ► NYHA class: Most commonly used classification system to describe symptoms, though the definition is vague and physicians can disagree about what class they will assign to a particular patient. Class I: no limitations Class II: no limitations with ordinary activity Class III: limitations with ordinary activity. Class IV: symptoms at rest 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Etiologies ► Important to identify reversible causes. ► Most common etiology in the United States are due to hypertension and coronary artery disease. ► Important reversible causes which can be treated includes valvular disease, toxins (alcohol, adriamycin…etc), metabolic derangements (thyroid disease, high-output failure due to anemia…etc). ► Other causes include viral, peripartum, idiopathic…etc. 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Initial Assessment ► ► clinical assessment is addressed in detail later on in the talk. Common laboratory assessment includes: CBC (assess anemia), BMP (lytes and renal function), LFTs (assess hepatic congestion), TFTs (assess reversible cause), BNP (confirm diagnosis and assess severity). ► ► Echoardiogram is very useful- gives detailed information about structure/function Pursue work-up for cardiac ischemia in patients with risk factors via ETT (with imaging) or cardiac catheterization. Cardiac ischemia is very common reversible cause of cardiomyopathy ► 2008 Biopsy of the heart muscle rarely needed as it rarely influences treatment. Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Assessment and Treatment of Acute Decompensated Heart failure (what we deal with on the inpatient service) 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Assessment ► Needs to assess whether the patient have signs and symptoms of low output, congestion, or both to formulate a plan for treatment 2008 Warm/dry Warm/wet (most common presentation, needs diuresis) Cold/dry Cold/wet (over-diuresed) (end-staged, may need inotrope and/or other therapies) Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Signs, symptoms, and labs ► Low output ► Congestion Fatigue Dizziness Low blood pressure Low pulse pressure Lower than baseline weight Cool extremities on exam Oliguria/ azotemia Higher than baseline weight Left sided congestion: ► Dypsnea, orthopnea ► Rales, s3 (in patients with advanced heart failure, often don’t hear rales). Right sided congestion: ► Anorexia (from bowel edema) ► JVD, ascites, edema ► Increase LFTs 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Diuretics ► Given for symptom control and not expected to improve survival Aldosterone antagonists are an exception ► Patients in heart failure are less responsive to diuretics compared to a normal person because: Low cardiac output means less delivery of the drugs to the kidneys Activation of the renal-angiotensin-aldosternone system results in higher sodium absorption Flow dependent hypertrophy of the distal tubules Often have concomitant renal insufficiency 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Diuretics ► Loop diuretics are the mainstay: For furosemide (the most common drug used), the starting dose is 20-40mg PO, the max dose is around 200mg. If the initial dose is ineffective, double the dose and try again. Much less effective to try the same dose several hours later. Adding thiazide diuretics greatly potentiates diuresis (but low K). Oral furosemide has about 50% bioavailability and is sometimes erratically absorbed Worse when patients have substantial right sided failure and bowel edema ► IV lasix often preferred in acute exacerbation ► lasix 20mg IV equals 40mg PO…etc Lasix gtt can results in greater fluid removal and less ototoxicity. ► Bumetanide and torsemide are alternative oral regiments that have more reliable oral absorption. Bumetanide to lasix ratio is 40:1 in those with normal kidney, 20:1 in those with abnormal kiney. 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Diuretics ► In patients with edema, interstitial fluid is quickly mobilized to the vasculature and there is no “ceiling” per se for rate of diuresis Needs to be careful about electrolyte abnormalities…etc. ► Generally expect diuresis to decrease pre-load and hence cardiac output, however, sometimes the opposite occur (Cr improves after diuresis), some explanations are: In patients with markedly dilated ventricle and substantial MR as a consequence, diuresis may shrink the ventricle and improve MR. Decrease wall stress by decreasing the diameter of the ventricle On the “plateau” portion of the Starling curve ► Effect of diuretics is maximal on the 1st dose and gradually wears off over 2 weeks. Afterwards, the medicine will maintain but no longer reduce weight. Likewise, electrolyte abnormalities also reach their steady- state at this time. No need to re-check electrolytes unless the clinical situation changes. ► 2008 Diuretics are generally continued indefinitely. Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. How a dilated ventricle begets more MR 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Intravenous Inotropes used in people who are stage III-IV and refractory to other therapies (the patient is cold and wet) as palliative measures or bridge to other treatment (like tranpslant or LVAD). ► Acute hemodynamic improvement but chronic administration (at least oral forms) leads to increased mortality. ► Dobutamine (dose of 5mcg/kg/min and up)- beta 1 agonist, can cause tachycardia ► Milrinone (dose of 0.325mcg/kg/min and up)phosphodiesterase inhibitor. Can cause hypotension and arrhythmias. Can be used with a beta-blocker ► 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. How to prevent future exacerbations? ► Why did most patients get in the trouble in the 1st place? Dietary indiscretion Medication non-compliance Worsening underlying heart function ► ► ► Very important to elicit these information and modify behavior/treat underlying cause. Important to record baseline “dry weight” (in d/c summary, clinic notes…etc) so we know (roughly) what to aim for if the patient gets into trouble again In general, in treatment of CHF patients Do not be afraid to diurese until they patient is dry even if it causes a little bit of azotemia Do not be afraid of low blood pressure (SBP around 90 perfectly acceptable) unless the patient is symptomatic. 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Chronic Therapy for CHF with proven efficacy 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. ACE- I ► ► Improves survival in all severities of systolic heart failure, ranging from asymptomatic left ventricular dysfunction to moderate to severe CHF (about 20%-30%). If tolerated, the target dose should be: In the SOLVD prevention trial of 4228 patients (83 percent post-MI) with asymptomatic left ventricular dysfunction, prophylactic administration of enalapril reduced the probability of death or congestive heart failure (p<0.001). Data from The SOLVD Investigators, N Engl J Med 1992; 327:685. Enalapril 20mg BID Captopril 50mg TID Lisinopril 40mg qd These relatively high doses were used in successful trial. Decreased mortality in patients with advanced NYHA class III or IV heart failure after treatment with enalapril compared to placebo (p = 0.003). Data from The CONSENSUS Trial Study Group, N Engl J Med 1987; 316:1429. 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Beta-blockers ► Additional benefit on top of ACE-I Meta-analysis suggests another 20-30% reduction in mortality, Less information is available in patients with class IV CHF. However, the COPERNICUS trials and subgroup analysis from MERIT-HF showed equivalent benefit in those with class IV failure. ► Carvedilol vs Metoprolol? Carvedilol ► Alpha, beta1, beta2 blocker, results in greater reduction in BP Metoprolol ► Beta1 blocker. Better tolerated in hypotension. Use long-acting form in CHF COMET trial ► ► Compares coreg and metoprolol- use of coreg results in lower mortality but the dose of coreg used maybe higher. When/how to start? Start with care in patients with severe/decompensated CHF Usually start ACE-I 1st Start low, but target dose of coreg 25-50mg BID, Toprol 200mg qd 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Hydralazine and Nitrates Hydralazine 25mg PO TID and titrate up as tolerated, imdur (40-120mg daily) or isosorbide dinitrate (40mg TID or QID) modest benefit in patients with CHF and is less effective than ACE-I. JN, Johnson, G, Ziesche, S, et al, N Engl J Med 1991; 325:303 Generally poor compliance due to the TID/QID dosing Arguably effective in African Americans who are already on optimal therapy and can tolerate the regiment (A-HeFT). This population maybe arguably less responsive to ACE-I ► In general, reasonable to use in: Patients who can’t tolerate ACE-I/ARBs Patients on other optimal CHF therapy with more blood pressure to burn who remains symptomatic. 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Aldosternone antagonists Aldactone and eplerenone (less gynecomastia, a lot more expensive) ► RALES trial- 30% reduction in mortality at 2 years in patients with class IV CHF or class III CHF with class IV symptoms in the previous 6 months. ► EPHESUS trial- 15% reduction in mortality in post-MI patients with EF<40 and evidence of CHF or DM ► Benefits probably related to K sparing effects as well as minerocorticoid blockade. ► Use in patients with moderate to severe CHF and reduced LVEF with relatively normal Cr and low or normal K ► 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Digoxin ► Control symptoms, does not prolong survival The DIG trial (dig vs placebo in patient otherwise receiving optimal CHF therapy) shows reduced hospitalization but no reduction in survival. (N Engl J Med 1997 Feb 20;336(8):525-33 ) Some intriguing subgroup analysis (but take with grain of salt, as they are just that): ► worse in women compare to men ► When serum concentraion is between 0.5 and 0.8ng/ml in men, survival is improved compared to placebo. It is significantly worsen when serum conc >1.2ng/ml. Generally, use in addition to optimal CHF therapy to treat symptoms. 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Devices ► ICD for primary prevention: (pts with CHF are at increased risk of malignant arrhythmias): MADIT-II-ischemic cardiomyopathy and EF of <=30% has survival benefit SCD-HeFT: class II-III CHF with EF <35% has survival benefit (HR 0.77) ► Biventricular PPM (for resynchronization therapy): Presence of interventricular conduction delay or bundle branch block results in dysynchronous contraction and worsens cardiac output. For patients with wide QRS (>120ms), LVEF of <=35%, and class III- IV CHF despite optimal medical therapy, there is symptomatic improvement/survival benefit (CARE-HF and COMPANION) Some in the group above responds while others do not, no great predictors of who would respond. 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C. Stepwise treatment of CHF 2008 Zoll Firm Lecture Series Joyce Meng, M.D. Eli V. Gelfand, M.D, F.A.C.C.