Heart Failure 2012 Dr Eric Klug Sunninghill, Sunward Park, CM Johannesburg Academic Hospital
PRELOAD COWS Reduction in milk production INOTROPY & HEART RATE AFTERLOAD DISTRIBUTION NETWORK
THE CLASSIC APPROACH CARDIO-RENAL SYNDROME IN CHF Decreased cardiac performance Decreased cardiac output Increased water & Na + retention Impaired renal function Structural renal changes NATRIURETIC PEPTIDE SYSTEM RAA SYSTEM SYMPATHETIC NERVOUS SYSTEM Neurohormonal activation Diminished blood flow Decreased renal perfusion
LV Geometry Renlund D and Kfoury A. N Engl J Med 2006;355:1922-1925
CHF SUCCESS Improvement in LVEF has been reported to be a major predictor of improved survival Am Heart J 2012;163:49-56.e2
Drugs Used in Heart Failure Patients Diuretic ACE inhibitor Beta-blocker Aldosterone antagonist Nitrates plus arteriodilator Digitalis Sinus Rate slowing agents Even if these drugs lower blood pressure, they can paradoxically improve cardiac output Angiotensin-receptor blockers Antiarrhythmics Calcium channel blockers Cardiotonic/inotropic agents
Maximal treadmill exercise time before and after a diuretic Exercise duration (mins) B A
AT REST: PRE AND POST DIURETIC Plasma ALDOSTERONE AFTER EXERCISE: PRE AND POST DIURETIC Plasma ALDOSTERONE
Courtesy of the Mary Evans Picture Library DIGITALIS Eichhorn, E. J. et al. N Engl J Med 2002;347:1394-1395
Percent of Patients ACE Inhibitors vs Placebo in Symptomatic CHF: Overview 35 30 25 35% Risk Reduction P>0.01 35% Risk Reduction P>0.001 Placebo ACEI 20 15 10 5 31% Risk Reduction P>0.001 30% Risk Reduction P=0.04 0 Total Mortality Garg R, Yusef S. JAMA. 1995;273:1450-1456. Death or CHF Hospitalization CHF Death Fatal MI
Mortality According to Adherence Score Drug Adherence Overall >80 <80 Candesartan 23.3% 21.7% 34.1% Placebo 24.9% 23.2% 37.9%
The balance in care Cardiologists adhere more closely to evidencebased guidelines Generalists provide more comprehensive care overall, especially to elderly patients with complex co-morbidities Am Heart J 2012;163:252-9
HF is such a common problem, it is not possible to have cardiologists involved in the care of all patients; as such improving outcomes in patients with HF treated by generalist physicians is an important objective Am Heart J 2012;163:252-9
Non Pharmacologic Management Employment Dietary sodium restriction Restriction of daily fluid intake Obstructive sleep apnoea
OSA/CSA 40 50% of CHF patients > 50% are asymptomatic CPAP improves LVEF by 8 10%, with clinical symptom improvement CPAP decreases MR, HR, and afterload Nocturnal oxygen therapy is effective in patients who have CSR/CSA and CHF Respir Care 2006;51(4):403 412
NSAIDS: Composite End Point: Death from CVS Causes, MI, CVA, or HF among Patients Who Received Celecoxib (200 mg BD or 400 mg BD) or Placebo.
Pulmonary hypertension prognosis in CHF PHT NO PHT Mortality at 28 months (%) 57 17
Pulmonary Hypertension Sildenafil can be considered in carefully selected patients with pulmonary hypertension and LVSD CHF CHF and suspected pulmonary vascular remodeling with sustained significant elevations of mpap (mpap >25 mmhg), and/or uncontrolled RV failure after all other conventional strategies have been aggressively exhausted.
Nitrate/Hydralazine: Overall Survival 180 days 43% improved survival p=0.01 Taylor, A. et al. N Engl J Med 2004;351:2049-2057
Nitrosative stress Oxidative stress NEJM 351;20
Nitrate/Hydralazine in CHF 225 mg Hydralazine 120 mg Isosorbide dinitrate 3 divided doses Starting dose 37.5/20 mg tds, uptitrated rapidly within a week by telephone! Target dose achieved in 68% of I/H group Only 1 patient with lupus-like syndrome Indicated in symptomatic black patients on background chronic anti-failure therapy
EMPHASIS-HF NYHA class II 2737 patients Eplerenone or placebo N Engl J Med 2011; 364:11 21.
EMPHASIS-HF The number needed to treat to postpone one death per year was 51 and to prevent one primary outcome from occurring was 19 Death from any cause Hospitalization for heart failure or death from cardiovascular causes (%) N Engl J Med 2011; 364:11 21.
Side effects of eplerenone compared with placebo N Engl J Med 2011; 364:11 21. Which MRA?
Diuretic Resistance Present in approximately 25% - 30% of patients with CHF Defined as reduced diuresis and natriuresis in response to a constant high dose of loop diuretics. Circ Heart Fail 2009;2;370-376
Kaplan Meier Curves for the Clinical Composite End Point of Death,Rehospitalization, or Emergency Department Visit. Bolus vs Infusion? Low vs High dose?
Diuretic synergy
Renal dysfunction frequent co-morbidity in CHF 60% % pts CrCL< 60ml/min, independently associated with All cause death Pump failure death HF hospitalisation In real life RD may be more common Patients with severe RD excluded from the trials 62% 40% 20% GFR < 60 21% GFR < 60 36% GFR 58 50% GFR: 60-75 34% GFR: 45-60 GFR < 45 SOLVD-P NYHA I-II (n=3673) SOLVD-T NYHA II-III (n=2161) PRIME-II NYHA III-IV (n=1702) VALIANT (post AMI, CHF / LVD) (n=14527) Dries et al.; JACC 2000;35:681 Hillege et al., Circulation 2000;102:203 Anavekar et al., N Engl J Med 2004;351:1285
Ivabradine SHIFT Inhibit the If current in the sinoatrial node, reducing heart rate NYHA class II or III Mean baseline HR was 80, dropped to 64 at 1 month, 67 after 32 months in the ivabradine group, compared with 75 (P) Lancet 2010;376:875 885
Effects of ivabradine versus placebo on primary and major secondary end points Lancet 2010;376:875 885 On maximal tolerated beta-blocker, heart rate above 75 beats/min
Impact of Mechanical Dyssynchrony MRI-Tagged 3-D Cine-Imaging A Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13. Adapted from Leclercq C, et al. Circulation. 2001;106:1760-1763.
RV LV
CRT -Cardiac Resynchronisation Therapy Over last decade, > 8200 patients have been studied Reduces morbidity and mortality (NYHA) class III and prolonged QRS duration >130 ms, (LBBB) + (LVEF) < 35% Reduces death and hospitalisation (NYHA) class II and wide complex QRS, (LVEF) < 35%
ICD: Implantable Cardioverter Defibrillators Lancet 2011; 378: 722 30
Prevalence of Atrial Fibrillation Increases with Severity of HF Prevalence of atrial fibrillation in clinical studies of CHF CONSENSUS OPTIME CHF GESICA PRIME DIAMOND CHF MERIT HF MERIT HF CIBIS II COMET CHF STAT Val-HeFT I and II DIG OPTIMAAL SOLVD Rx SOLVD Px NYHA I II NYHA II III NYHA III IV NYHA IV 0 10 20 30 40 50 60 Patients with atrial fibrillation (%) Savelieva. Europace 2004;5(Suppl. 1):S5 19
Warfarin Patients with heart failure have an increased risk of stroke and of systemic thromboembolic events, which are believed to arise from within the heart May 2, 2012 (10.1056/NEJMe1202504)
WARCEF trial Homma S et al. N Engl J Med 2012;366:1859-1869 Cumulative Incidence of the Primary Outcome.
WARCEF trial Anticoagulant therapy prevents stroke, probably embolic stroke, in patients with SR and severe systolic dysfunction Rates of stroke are too low to justify the routine clinical use of warfarin in most patients with heart failure, in light of the increase in the risk of bleeding. N Engl J Med 2012; 366:1859-1869
Dabigatran Compared with Warfarin in Patients with Atrial Fibrillation and Symptomatic Heart Failure: A Subgroup Analysis of the RE-LY Trial The overall benefits of dabigatran for stroke/see prevention, major bleeding and ICH events relative to warfarin in the RE-LY trial were essentially unchanged in patients with previous CHF. Volume 124(AHA MeetingAbstracts) Supplement 1, 22 November 2011
-Blocker Continuation or Withdrawal J. Am. Coll. Cardiol. 2008;52;190-199
The Beta-Blocker and DHF In patients admitted to hospital due to worsening HF, a reduction in the -blocker dose may be necessary. In severe situations, temporary discontinuation can be considered. Low-dose therapy should be re-instituted and up-titrated as soon as the patient s clinical condition permits, preferably prior to discharge. Eur J Heart Failure 2008:10;933
Treatment Algorithm Systolic Heart Failure. NEJM 362;3