Presentation on theme: "Advanced Heart Failure: My Approach"— Presentation transcript:
1Advanced Heart Failure: My Approach Feb 4, 2011Advanced Heart Failure: My ApproachJ.L. Mehta, MD, PhDStebbins Chair in CardiologyProfessor of Internal Medicine, Physiology and BiophysicsUniversity of Arkansas for Medical SciencesLittle Rock, AR
2Topics to be Discussed Burden of heart failure Causes of heart failure, morbidity and mortalityPathophsiologyRole of RAAS and SNS blockers, and diureticsWhen to use defibrillators/biventricular pacing
3Burden of Heart Failure CHF affects more than 4.5 million people in the USA and 0.5 million new cases are diagnosed each year1.2-2% of the population has CHF, with 75-80% of the group are above the age of 65 yearsNearly 20 million people have unsuspected disease and likely to develop CHF in the next 1- 5 yearsCHF is responsible for >11 million visits to a physician's office and result in 3.5 million hospitalizations per yearMedian survival following onset is 1.7 years for men and 3.2 years for women- worse than lung cancer
4Causes of Heart Failure, Morbidity and Mortality - Ischemic heart disease- Hypertension- Cardiomyopathies (viral, alcohol)Causes of Hospitalization- Non-compliance with drugs- Excessive salt and alcohol intake- Infections- Anemia- Co-morbidity (e.g. renal dz, Liver dz, depression)
5Myocardial ischemia and Low Cardiac Output State Angiotensin - Angiotensin - AngiotensinInflammationRelease of Catecholamines, ANP, BNP and ET-1TGFb1, PAI-1, ROS expressionRelease of MMPs and collagen degradationMyocyte apoptosis, Fibroblast growthMyocyte hypertrophyMyocyte slippageCollagen formationCardiac enlargement and fibrosisWall thinning and regional dilatation Wall stressLocal Ang II releaseEarly Stage Intermediate Stage Late StageMehta JL, 2010
6Neurohormonal Activation in Heart Failure Myocardial injury to the heartInitial fall in LV performance, wall stressActivation of SNSFibrosis, apoptosis, hypertrophy, cellular, alterations, myotoxicityRemodeling and progressiveworsening of LV functionPeripheral vasoconstrictionHemodynamic alterationsCHF symptomsMorbidity and mortalityArrhythmiasPump failureRenal dysfnFatigue Chest congestion Edema SOBRAS, renin-angiotensin system; SNS, sympathetic nervous system.
7Mortality by Baseline Plasma Norepinephrine Level 100> 900 pg/mL8060> 600 and < 900 pg/mLCumulative Mortality (%)40< 600 pg/mLHeart failure patients demonstrate long-term activation of the sympathetic nervous system. The level of adrenergic nervous system activation correlates with the concentration of plasma norepinephrine, as well as with levels of left ventricular filling pressures and mean right atrial pressure.1 The extent of elevation of plasma norepinephrine concentration occurring in patients with heart failure correlates directly with the severity of left ventricular dysfunction,2 and with cardiac mortality.3Measurements of plasma norepinephrine and plasma renin activity were performed in the Vasodilator-Heart Failure Trial II (V-HeFT II) to assess the effect of therapy on neuroendocrine activation and examine the response to therapy among patients with different degrees of activation. Baseline plasma norepinephrine data were grouped into three relatively homogeneous strata for analysis. Cumulative mortality between the three strata was significantly different (P < .0001). The patients with plasma norepinephrine > 900 pg/mL had a higher mortality than those with corresponding values < 600 pg/mL or from 601 to 900 pg/mL. In these three groups mortality was directly related to increased plasma norepinephrine levels. This study thus confirms the relationship between baseline PNE values and cumulative mortality in heart failure patients.4Slide and Notes References1. Leimbach WN Jr, Wallin G, Victor RG, et al. Direct evidence from intrarenal recordings for increased central sympathetic outflow in patients with heart failure. Circulation. 1986;73:2. Thomas JA, Marks BH. Plasma norepinephrine in congestive heart failure. Am J Cardiol. 1978;41:3. Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:4. Francis GS, Cohn JN, Johnson G, et al. Plasma norepinephrine, plasma renin activity, and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation. 1993;87(suppl VI):VI-40–VI-48.20OverallP < .00016121824303642485460MonthsFrancis G et al. Circulation. 1993;87(suppl VI):VI VI-48.10
8When to Use ß-blockers and RAS Inhibitors It dose not matter which agent is started first, but early ß-blockade reduces the risk of sudden death in the first yearThe usual practice of starting the ACE inhibitor first may lead to under-treatment with ß-blockersThe CIBIS III trialWillenheimer, Eur Heart J Suppl 2009;11:A15-A20
9Treatment of Advanced of Heart Failure Part 1 Hospitalize earlyTreat first with usual drugs- if patient not responsive, then change RxLimit salt intakeTreat hypertensionTreat infections- usually UTI or pulmonaryTreat anemia to hemoglobin to ~10 g/100 mlTreat co-morbidity (e.g. renal dz- may need fluids)Treat abnormal thyroid functionIf patient has angina, use anti-ischemic therapyIf patient has valvular dz, may consider surgery when patient is stable
10Treatment of Advanced Heart Failure Part 2 ACE inhibitors, ARBs, Hydralazine and NitratesUse maximal dose of ACE inhibitors, if not tolerated then use ARBsMay combine the two groups of drugsIf patient is already taking ACE inhibitors/ARBs, switch to hydralazine + nitrates- use adequate dose, response is quickDose of hydrazine mg TID and ISD- 40 mg TID
11Treatment of Advanced Heart Failure Part 3 DiureticsExcessive diuresis can cause metabolic alkalosis and poor renal perfusion- if present hold diureticsIf no alkalosis, use IV lasix or metalazoneIf alkalosis present, use K+ and Mg+ supplementationPatient may have acute renal failure from excessive diuresis, consider gentle fluid administrationIf patient has hyponatremia, consider half or normal saline (250 ml per hr until urine output improves or patient develops rales when diuresis may be begun)
12RALES: Probability of Survival Patients with Class II-IV CHF30% reduction in risk of death31% reduction in cardiac death,P<0.001Kaplan-Meier Analysis of the Probability of Survival among Patients in the Placebo Group and Patients in the Spironolactone GroupPitt, B. et al. N Engl J Med 1999;341:
13Eplerenone in Mild CHF- EMPHASIS-HF Patients with class I-II CHFNNT-19Zannad F et al. N Engl J Med 2011;364:11-21.
14Treatment of Advanced Heart Failure Part 4 Other therapiesDigitalis- increases CO and makes patient feel betterDobutamine / milrinone- use short course only- no long tem benefitNasiritide - no role in the therapy of CHFCCBs – no role in the therapy of CHFUltra-filtration - no better than diuresis
15Cardiac Resynchronization Therapy: Treatment of Advanced Heart Failure Part 5CRT improves functional capacity, quality of life, and reduces hospitalization in patients with advanced symptomatic CHF, and evidence of a ventricular conduction abnormality.Appropriate method patient selection for CRT is not clear.Issues about the placement of LV lead remain.
16Treatment of Advanced Heart Failure Part 6 ICD Therapy:Treatment of Advanced Heart Failure Part 6Implantable defibrillators reduce the risk of sudden death in patients with CHF, with and without prolonged QRS durationPatients with Class II-III benefit more than Class IV patientsIssues:- Who are the best candidates for defibrillators?- Is the cost of implanting and maintaining these devices worth the benefit?- How can side effects and risks be minimized?
17CRT / ICD and Death or Hospitalization for CHF In class II or III CHF patients, with wide QRS complex, and EF <30%, the addition of CRT to ICD reduced rates of death and hospitalization for CHF. This improvement was accompanied by more adverse events in 1 month (pneumothorax, hematoma and infections).Tang AS et al. N Engl J Med 2010;363: