Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
David W Kabel MD FACC NH activation is an acute adaptation that initially allows BP and cardiac output to be maintained NH activation rapidly becomes detrimental Vasoconstriction is a hallmark of untreated LV dysfunction Starts a self perpetuating cycle of cell death and remodelling with further NH activation Pump failure is sensed as hypovolemia RAS activation leads to increases levels of angiotensin II ANS activation leads to increased circulating catecholamines Hyperaldosteronism Myocyte dysfunction and cell death Remodeling occurs LV dilatation Increased wall stress Ischemia Energy depletion Interstitial fibrosis More NH activation Mitral regurgitation Change from ellipsoid to spherical shape Relieve Symptoms Improve LV function-both systolic & diastolic Reduce hospitalizations Improve prognosis Increased ejection fraction is associated with improved prognosis Diastolic function can also improve Manage expectations Pharmacologic Diuretics Neurohormonal inhibitors Antiarrhythmic drugs Device therapies AICD Resynchronization therapy LV assist devices Adjunctive measures Diet Fluid restriction Home monitoring Treat co-morbidities according to guidelines Hypertension!-Systolic BP<120 Diabetes-some hypoglycemic drugs may worsen HF Lipid abnormalities Sleep apnea! Atrial fibrillation Avoid drugs which may exacerbate HF Anti-arrhythmic drugs other than amiodarone and dofetilide Calcium blockers-verapamil, diltiazem NSAIDS Sodium retention Inhibit effects of diuretics, ACEIs and ARBs Renal toxicity Monitor Weight Blood pressure Renal function Home health monitoring can reduce hospital admissions Regular low to moderate physical activity Medicare now pays for Cardiac Rehab for CHF Avoid dietary indiscretion Stop smoking First goal is to achieve euvolemia Initiate therapy to block neurohormonal activation Treat comorbidities Most patients can be treated effectively with inexpensive generics Relieve symptoms faster than any other drugs Relieve dyspnea Reduce edema Improve exercise tolerance Only drugs that control fluid retention Should not be used alone in symptomatic patients Increase sodium excretion by 20-25% Enhance free water clearance Maintain efficacy in reduced GFR Increase sodium excretion 5-10% Reduce free water clearance Lose effectiveness with decreased GFR Better antihypertensive drugs than loop diuretics Longer duration of action Too little Too much Fluid retention Reduced effectiveness of other therapies Volume contraction Hypotension Hyponatremia Renal insufficiency Right dose may be difficult to determine Dosage requirements change with change in clinical status Initiate with loop diuretics Furosemide most common Torsemide or butenamide may work better in a few patients, especially with deteriorating renal function Start low dose once a day Titrate up and go to BID dosage as needed I like AM and noon schedule Reduces nocturia Restrict dietary sodium Maintenance therapy may require lower doses than at initiation Monitor electrolytes frequently Some class I and II patients may not need any diuretics for a time Consider lower dose while up-titrating other drugs, especially if BP is low Fluid retention may result in poor absorption from GI tract Reduced GFR requires increased dose of loop diuretics Intermittent IV loop diuretics Combination therapy Add metolazone Electrolyte imbalance-sodium, potassium, and magnesium Volume contraction Hypotension Azotemia Hearing loss Hypotension, fluid retention, and azotemia together have a poor prognosis Block effects of circulating catecholamines Sympathetic activation initially beneficial to increase cardiac output Long term ANS activation is deleterious Increased LV volume and pressure overload Vasoconstriction Impaired renal sodium excretion LV hypertrophy and dilatation Myocardial fibrosis Arrhythmias Benefits outweigh negative inotropic effects Three drugs are approved for use in HF Carvedilol Metoprolol succinate Bucindolol All patients with reduced EF should receive beta blockers unless contraindicated Reduced mortality Increased EF Symptomatic relief Do not start until vascular congestion is relieved Start at same time as ACEI or ARB Effects are additive Small doses of both are more effective than higher dose of a single drug Even a small dose is better than none Use with caution with COPD or bradycardia Initiate at small doses Titrate up every 2-4 weeks as tolerated Monitor fluid balance Unless replacing another beta blocker Daily weights Continue even if clinical improvement is not evident Avoid abrupt withdrawal Worsening CHF and fluid retention Increase diuretics Can usually continue beta blockers Fatigue Often resolves in a few days or weeks Reduce dose or change to a different drug Hypotension Often occurs for 1st 24-48 hours Decrease diuretic dose Give beta blocker and ACEI at different times of day Bradycardia and heart block May require pacemaker Best studied of RAS inhibitors First class of drugs shown to improve EF and prognosis Prevent conversion of Angiotensin I to Angiotensin II Modifies LV remodelling possibly more than ARBs All ACEIs equivalent Tissue ACEI? Improve symptoms and clinical class Reduce SCD Reduce combined risk of hospitalization and death Improve outcomes in presence or absence of CAD Improvement occurs in all NYHA classes Prevent Angiotensin II from attaching to vascular receptors-Prevents vasoconstriction Modify LV remodelling perhaps less than ACEIs Less data than ACEIs but clinical effects are similar Fewer hospitalizations and deaths Seen in all NYHA classes May be better than ACEIs in preventing atrial fibrillation Most commonly used for patients who develop cough while taking ACEIs Use in all patients with reduced EF unless contraindicated Even Class I Use with beta blockers Use with diuretics if fluid retention Start at low doses and titrate up unless hypertensive Check BMP at 1-2 weeks and q3-6 months after that Tolerated by 85-90% of patients Try to achieve maximum dose Symptomatic relief may come in a few days or several months Continue treatment even in absence of symptomatic improvement Don’t delay beta blockers while titrating up Avoid NSAIDs No data supporting ACEIs and ARBs in same patient-some data against it Avoid in: Hx of angioneurotic edema-high incidence of crossreactivity between ACEIs and ARBs Oliguric renal failure Pregnancy Use with caution in: Hypotension Creatinine>2.0 Bilateral renal artery stenosis Serum potassium >5.0 Spironolactone and Elperenone (Inspra) Main advantage of Inspra is decrease in side effectsbreast pain, GI, but much more costly Block effects of aldosterone in renal tubule Enhance effects of loop diuretics Increased sodium excretion Potassium retention Most difficult drugs to use in HF Under-utilized even by experts who advocate increased usage Added after beta blockers and ACEIs, ARBs Should be used with caution in absence of loop diuretic or thiazide Monitoring aldosterone antagonists-AHA recommendations for K+ and renal monitoring 3 days 7days Monthly for 3 months 3-6 months after that Both venous (nitrate) and arterial (hydralazine) vasodilatation Both preload and afterload reduction Reduce mortality but not hospitalizations Inferior to ACEIs, ARBs Frequent side effects Headache GI symptoms Lupus like syndrome Most effective in African-American patients when added to standard therapy Suitable alternative for patients intolerant to ACEIs and ARBs Angioneurotic edema Azotemia May be added to standard therapy if patient remains hypertensive Compliance may be an issue Large number of pills TID dosage Nitrate tolerance Only indication is for rate control in atrial fibrillation If beta blockers are ineffective Should consider pacemaker & AV node ablation instead Has mild positive inotropic effects Dosage-Never exceed 0.125 mg daily-less if decreased GFR Followup to AFFIRM trial showed 40% increased all cause mortality for AF patients on digoxin Look for reasons to DC the drug Avoid in patients with recent MI or ischemia Toxicity enhanced by hypokalemia, hypoxia, thyroid disease Side effects Bradycardia and heart block Re-entrant tachycardias Anorexia, weight loss, nausea Visual disturbances-yellow vision, hoarfrost Mental status change Achieve euvolemia Start beta blockers and ACEIs, ARBs at low doses Push beta blockers faster-more effect on prognosis May increase both at once depending on BP Titrate up q2-4 weeks BMP on each visit May have to go slowly in elderly Maximum dose determined by BP, renal function Inform patient of possible side effects Fatigue May disappear after several days Ask patient to stick with therapy Lightheadedness Hypotension may require dose reduction Drug specific side effects Increase meds to maximum tolerated dosage Check LV function after 3-4 months of maintenance therapy Add spironolactone Add hydralazine-nitrates If little or no improvement in EF If loop diuretics and metolazone ineffective In African-American patients If response to standard Rx inadequate Add additional antihypertensives to achieve systolic BP of <120 If BP not controlled with standard Rx Hydralazine Amlodipine-Only calcium blocker to use in LV dysfunction Clonidine 30% of patients with low EF and Class III-IV symptoms have QRS>120 msec Mechanical consequences of dysynchrony Suboptimal LV filling Reduced rate of rise of LV contractility Prolonged duration of mitral regurgitation Paradoxical septal motion Dysynchrony increases mortality Pacemaker therapy-Biventricular Three leads Right atrium if in sinus rhythm Right ventricular apex Coronary sinus for left ventricular pacing LV and RV are paced in synchronous fashion Septum contracts with rest of LV May require echo guided adjustments Novel agent designed to slow HR in systolic HF and EF<40% already on beta blockers. Sinus rhythm Target HR 50-60 bpm Demostrated that lower resting HR correlated with improved prognosis Does not lower BP Systolic Heart failure treatment with the If inhibitor ivabradine Trial Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study Effect of ivabradine on outcomes in patients with chronic heart failure and HR 75 bpm Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com To assess the effect of ivabradine on outcomes in heart failure patients on recommended background therapies with heart rates ≥75 bpm in the SHIFT trial Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Ivabradine Placebo n=2052 n=2098 Mean age, years 60 60 Male, % 77 77 BMI, kg/m2 28 28 Mean HF duration, years 3.4 3.4 HF ischemic cause, % 66 65 NYHA class III, % 50 51 NYHA class IV, % 2 2 Mean LVEF, % 28.7 28.5 Mean HR, bpm 84.3 84.6 Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Ivabradine Placebo n=2052 n=2098 87 88 At least half target dose 55 56 At target dose 26 26 ACE inhibitors/ARBs, % 90 90 Diuretics (excludes AAs), % 85 83 Aldosterone antagonists, % 63 61 β-Blockers, % Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Effect of ivabradine on primary outcome CV death or hospitalization for HF Patients with primary composite end point (%) Hazard ratio=0.76 P<0.0001 40 Placebo 30 Ivabradine 20 10 0 0 6 12 18 24 30 Time (months) Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Effect of ivabradine on cardiovascular death Hazard ratio=0.83 Patients with cardiovascular death (%) 30 P=0.0166 Placebo 20 Ivabradine 10 0 0 6 12 18 24 30 Time (months) Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Effect of ivabradine on hospital admission for worsening heart failure Hazard ratio=0.70 Patients with cardiovascular death (%) 30 Placebo P<0.0001 20 Ivabradine 10 0 0 6 12 18 24 30 Time (months) Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Effect of ivabradine on major outcomes Hazard ratio P 95% CI Primary composite end point 0.76 0.68-0.85 Cardiovascular mortality 0.83 0.71-0.97 0.70 0.61-0.80 0.61 0.46-0.81 <0.000 1 0.83 0.72-0.96 0.0006 0.82 0.75-0.90 0.0109 0.79 0.71-0.88 <0.000 1 Hospitalization for worsening HF Death from HF All-cause mortality All-cause hospitalization Any cardiovascular hospitalization 0.20 Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 0.40 0.60 Favors ivabradine <0.000 1 0.0166 0.80 1.00 1.20 Favors placebo <0.000 1 www.shift-study.com Effect of ivabradine on outcomes according to HR achieved at 28 days Patients with primary composite end point (%) 40 75 bpm 30 70 to <75 bpm 65 to <70 bpm 60 to <65 bpm 20 <60 bpm 10 0 0 Day 28 6 12 18 24 Time (months) Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Effect of ivabradine on outcomes according to magnitude of HR reduction Patients with primary composite end point (%) 40 0 bpm -10 to <0 bpm 30 < -10 bpm 20 10 0 0 Day 28 6 12 18 24 Time (months) Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Conclusions In HF in sinus rhythm with HR ≥75 bpm heart rate reduction with ivabradine improves outcomes, including all-cause death and cardiovascular death reduces § Ivabradine-associated risk reductions are related to both HR achieved and magnitude of HR reduction § Patients achieving <60 bpm or with >10 bpm reduction have the best prognosis Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com Younger than normal patient population Less that optimal doses of beta blockers Ivabradine can cause atrial fibrillation Useful in limited number of patients Cost Neprilysin degrades several vasoactive peptides BNP,bradykinin, adrenomedullin Neprilysin inhibition increases levels of natiuretic peptides, thus counteracting RAS activation LCZ696 compared to enalapril Combination of valsartan with neprilysin inhibitor sacubitril Would LCZ696 improve outcomes over enalapril? Kaplan–Meier Curves for Key Study Outcomes, According to Study Group. McMurray JJV et al. N Engl J Med 2014;371:993-1004 Kaplan–Meier Curves for Key Study Outcomes, According to Study Group. McMurray JJV et al. N Engl J Med 2014;371:993-1004 Kaplan–Meier Curves for Key Study Outcomes, According to Study Group. McMurray JJV et al. N Engl J Med 2014;371:993-1004 Kaplan–Meier Curves for Key Study Outcomes, According to Study Group. McMurray JJV et al. N Engl J Med 2014;371:993-1004 Adverse Events during Randomized Treatment. McMurray JJV et al. N Engl J Med 2014;371:993-1004 Primary and Secondary Outcomes. McMurray JJV et al. N Engl J Med 2014;371:993-1004 Conclusions Neprilysin inhibition is similar to other effective therapies Beta blockers ACEI, ARB Blocks neurohormonal activation Appropriate for most patients with HF Elderly Atrial fibrillation Will probably become part of standard CHF regimen Cost will be a factor EF less than 35% LBBB with QRS >150 msec HFSA recommends for QRS >120 RV pacing with EF <35% should be upgraded to CRT MADIT II trial showed benefit for Class I-II patients Usually combined with AICD Depends on patient preferences and prognosis Improves LV contraction Increases EF by 5-10% (or more) Reduces mitral regurgitation Improves hemodynamics Clinical improvement Symptoms may improve by 1-2 classes QOL improvement Improved exercise tolerance and O2 comsumption Reduced hospitalizations Improved survival New generation of ICDs can monitor volume status by measuring thoracic impedance Can be measured in office with a programmer Optivol by Medtronic Detects fluid retention before clinical signs and symptoms Can help to determine if symptoms are due to fluid retention Allows early intervention Prevents hospitalizations Outpatient IV diuretics Enhances standard therapy Devices have alarms but FDA requires them to be turned off Strict criteria for implantation-Eligibility limited Indications EF< 35% with Class IV symptoms refractory to standard therapy Refractory VT and VF LVAD used to be considered bridge to transplant LVAD now may be destination therapy for some patients Often the most difficult aspect of therapy Disease is progressive Therapy tends to become less effective over time Most patients with HF will die of it Need to be honest with patient and family Get 2nd opinion if necessary May benefit from Hospice or Palliative Care Timing is difficult Prognosis less certain than with cancers and neurologic diseases World Health Organization reports worldwide mortality rate holding steady at 100%The Onion We physicians don’t prevent anything, we merely postpone-Anonymous