What s new in heart failure management? Yonsei Cardiovascular Center Yonsei University College of Medicine

What s new in heart failure management? Yonsei Cardiovascular Center Yonsei University College of Medicine

Current Guideline of Treatment Asymptomatic Mild/Mod Severe Refractory Correct Cause: Arrhythmias Ischemia Pressure Load Inotropes,, mitral repair, VAD, Tx Tailored Rx Digoxin Diuretics (Spironolactone( Spironolactone) Carvedilol/ -Blockers Angiotensin Converting Enzyme Inhibitors No Added Salt Activity as Tolerated 2 gm Na Customized Ex Training

What s new in HF? Pharmacologic therapy Nonpharmacologic therapy Cardiac resynchronization therapy Mechanical support Palliative therapy in HF

Pharmacologic therapy

Beta blocker Issues in beta blocker Eur J Heart Fail 2007;9:901 9

Beta blocker COMET 752/3029 patients (361:carvedilol, 391:metoprolol) who had a non-fatal HF hospitalization Eur J Heart Fail 2007;9:901 9

J Am Coll Cardiol 2008; 52:190 9

Beta blocker OPTIMIZE-HF 1,350:receiving BB before admission & continued on therapy 632: newly started 79: withdrawn 303 (12.8%): eligible but not treated. J Am Coll Cardiol 2008; 52:190 9

Beta blocker Issues in BB Unless withdrawal is deemed clearly necessary, BB should be maintained during an episode of decompensated heart failure.

Statins Statins in HF CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) : 5,011 older patients with ischemic CMP rosuvastatin vs. placebo a median of 2.7 years follow-up N Engl J Med 2007;357:2248 61

Statins CORONA trial N Engl J Med 2007;357:2248 61

Statins CORONA trial N Engl J Med 2007;357:2248 61

Lancet 2008; 372: 1231 39

Statins GISSI-HF trial Lancet 2008; 372: 1231 39

Statins Statins in HF The current level of evidence has yet to support routine statin use in patients with heart failure.

Vasoactive therapy Nesiritide Recombinant human BNP Vasodilatory, natriuretic, and lusitropic activity Neurohormonal antagonism,reverse remodeling Currently indicated for patients with ADHF to reduce PCWP and improve short-term dyspnea Circ Heart Fail. 2008;1:9-16

Outpatient serial nesiritide infusions for ACC/AHA stage C/D heart failure Safe but not effective in achieving its end points Circ Heart Fail. 2008;1:9-16

High-dose NTG in the emergency department was associated with fewer inhospital cardiac or respiratory complications, even though length of stay and readmissions were similar.

Vasoactive therapy Sidenafil Stable CHF, placebo (23 patients) or sildenafil (23 patients) FMD, cardiopulmonary exercise testing, ergoreflex response. In CHF, patients treated with 6 months of sildenafil demonstrated greater improvements in FMD, cardiopulmonary exercise testing indexes, and ergoreflex testing data J Am Coll Cardiol 2007;50:2136 44

Vasoactive therapy Conclusion: vasoactive therapy Potential benefits of careful patient selection and titration of vasodilators when used in the AHFS setting very large multinational clinical trial of nesiritde

Novel drugs Ghrelin (GH releasing peptide) Current opinion in pharmacology

Ghrelin Ghrelin and heart failure Synthetic ghrelin (2 g/kg twice a day) was intravenously administered to 10 patients with CHF for 3 weeks. Ghrelin administration improves LV function, exercise capacity, and muscle wasting in patients with CHF. Circulation. 2004;110:3674-3679

Testosterone Testosterone Chronic HF: maladaptive and prolonged neurohormonal & proinflammatory cytokine activation metabolic shift favouring catabolism, vasodilator incapacity, loss of skeletal muscle bulk and function. Testosterone replacement therapy at physiological doses in 76 men Improves functional capacity and symptoms in men with moderately severe heart failure. Eur Heart J 2006;27:57-64

Novel drugs Istaroxime A novel inotropic agent with lusitropic properties Na+/K+-ATPase inhibitor/sarcoplasmic reticulum calcium pump (SERCA2a) activator In patients hospitalized with HF, istaroxime improved PCWP and possibly diastolic function. In contrast to available inotropes, istaroxime increased SBP and decreased HR. HORIZON-HF Am Heart J 2009;157:1035-41 J Am Coll Cardiol 2008;51:2276 85 Drugs Fut 2007; 32: 595

Nonpharmacologic therapy; Cardiac resynchronization therapy

Dyssynchrony in HF Sinus node AV node Delayed lateral wall contraction Disorganized ventricular contraction Decreased pumping efficiency Conduction block

Increased mortality with LBBB All patients N= 5517 HR * 1.70 (1.41-2.05) LBBB N=1391 Increased 1-year mortality with presence of complete LBBB (QRS > 140 ms) Risk remains significant even after adjusting for age underlying cardiac disease indicators of HF severity HF medications 1-Year Mortality (%) 11.9 16.1 All Cause HR * 1.58 (1.21-2.06) 5.5 Cause of Death 7.3 Sudden Cardiac

Biventricular pacing (CRT)

Ventricular resynchronization Sinus node AV node Conduction block Stimulation therapy Intraventricular activation Organized ventricular activation sequence Coordinated septal and free-wall contraction Improved pumping efficiency

Indication for CRT NYHA III or ambulatory IV HF symptoms with optimal medical therapy LVEF 35% QRS 120 ms ACC/AHA/HRS 2008 Guidelines Class IA recommendation

REVERSE trial 610 pts in NYHA II (82%) or I (18%) CRT plus optimal medical therapy (CRT ON) can attenuate heart failure (HF) progression compared to optimal medical therapy alone (CRT OFF) J Cardiac Fail 2008;14:798

CRT responder? NYHA III or ambulatory IV HF symptoms with optimal medical therapy LVEF 35% QRS 120 ms 20~30% non-responder! ACC/AHA/HRS 2008 Guidelines Class IA recommendation

PROSPECT PROSPECT Circulation 2008;117:2608-2616

Conclusion No single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines Circulation 2008;117:2608-2616

Nonpharmacologic therapy; Mechanical support

Left ventricular assist device HeartMate II 1 st nonpulsatile LVAD, as a bridging to heart transplantation Circulation 2007;116:I8 15

HeartMate II Small pump size, greater long-term mechanical reliability improvement equivalent to traditional pulsatile LVADs in exercise capacity and symptom relief, even though the traditional LVADs achieved greater unloading Circulation 2007;116:I8 15

Cardiac support device A fabric mesh device surgically implanted around the heart Provide circumferential diastolic support and reduce LV wall stress Ann Thorac Surg 2007;84:1236 42 Ann Thorac Surg 2007;84:1226-35

Cardiac support device Ventricular restoration surgery with the CorCap (Acorn Cardiovascular, St. Paul, Minnesota) device led to favorable long-term results in preventing cardiac remodeling, justifying additional studies Ann Thorac Surg 2007;84:1236 42 Ann Thorac Surg 2007;84:1226-35

Palliative Care in HF

Issues in Palliative Care in HF Hospitalization only improves symptoms in 35-40% (Ward, Heart, 2002) Only 4% of patients dying of CHF get palliative care (40% in cancer pts) (Gibbs, Heart, 2002) Average performance status score of hospice admissions is 32 (range 50-10) (Zambroski, Am Heart J 2005)

Issues in Palliative Care in HF Severe symptoms in last 48-72 hrs prior to death (SUPPORT study, JAMA, 1995) Breathlessness 66% Pain 41% Severe confusion 15% Regional study of Care of the Dying (RSCD) study (Palliative Med. 1995) Dyspnea 50% Pain 50% Low mood 59% Anxiety 45% In several studies pyschcogenic symptoms most distressing

Who should provide palliative care? Primary care clinicians Expert HF Palliative care clinicians Specific Interdisciplinary Team in large center.

Cardinal symptoms in HF Fatigue Lack of energy Dyspnea Pain Cognitive impairment And Depression!!

Etiology of symptoms in HF Not directly related to PCWP or C.O. Rather, broader systemic effect of CHF including myopathy ( sarcopenia ) via neurohormonal effect Wilson et al, Circulation, 1995

Sarah et al, JACC, 2009

Interventions to address the neurohormonal alterations in HF and symptoms ACEi ARB Aldosterone antagonist Beta-Blocker CPAP

Other treatments to palliate symptoms Loop diuretics Dietary intervention (restricts fluids and sodium intake) Oral Opioids Antidepressants (not SSRI but TCA) Exercise

Summary (I) BB should be maintained during an episode of ADHF. Statins are not yet recommended routine use. Vasoactive drugs have potential benefits in managing HF. We can consider use of new drugs: istaroxime, ghrelin, testosteron

Summary (II) The current challenge of CRT is to justify the risks and validate the benefits, but beforeimplantation predictors of response to CRT is still controversial. Treatment for end-stage HF remains challenging. Additional evidence is needed to direct care at the end of life in end-stage HF.