Acute heart Failure. Critical cardiac care: update Markku S. Nieminen Helsinki, Finland. M S Nieminen, AHF ,ESC Stockholm

Transcription

1 Acute heart Failure Critical cardiac care: update 2010 Markku S. Nieminen Helsinki, Finland M S Nieminen, AHF ,ESC Stockholm

2 Acute heart Failure Critical cardiac care: update 2010 Markku S. Nieminen Helsinki, Finland No conflict of interest, MSN: Advisory board membership: Biogen, Otsuka, Orionpharma, J&J, Servier M S Nieminen, AHF ,ESC Stockholm

3 Acute heart Failure Topics: Patient population New agents Generalcomments M S Nieminen, AHF ,ESC Stockholm

4 AHF - the patient population is complex The mean age of patients, 74 y and increasing Complex population: Anemia 16 % Pulmonary disease 21 Renal dysfunction 20 Thyroid dysfunction 12 Diabetes 34 Compex cardiovascular etiology CAD % Hypertension 63 Valvular dysfunction 38 (severe. MR) Diastolic dysfunction 50 Atrial fibrillation 46 Ventricular dysrhythmia Bradycardia Gender, Females 40-50%, often diastolic heart failure M S Nieminen, AHF ,ESC Stockholm

5 y / % Key characteristics in different surveys EHFI EHHFII Adhere Effica Italian registry m Age, y Women denovo na EF< Finn akva In-hosp. mortality 6,9 6, ,3 7,0 LOS M S Nieminen, AHF ,ESC Stockholm

6 % % Prevalence of valvular dysfunction in AHF patients - EHHFII echo results (A) Moderate to severe Mild AS AR MS MR TR (B) Moderate to severe Mild AS AR MS MR TR (C) Moderate to severe Mild AS AR MS MR TR overall de novo AHF ADCHF patients M S Nieminen, AHF ,ESC Stockholm

7 MITRAL REGURGITATION IN ACUTE HEART FAILURE MR has been in focus as a complicating or even a cause for decompensation in ACS Frequent Complicates especially ACS Is dynamic, volume overload dependent Requires unloading Several studies on advanced ECHO methodology M S Nieminen, AHF ,ESC Stockholm

8 M S Nieminen, AHF ,ESC Stockholm ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008

9 Classification of AHF ESC guidelines, EHJ 2008 Hypertensive AHF Right Heart Failure PULMONARY EDEMA ACS and Cardiogenic shock Acutely Decompensated Chronic HF Heart Failure a. 50% of denovo Classifications: Killip since 1967 Forrester, 1977 M S Nieminen, AHF ,ESC Stockholm

10 COROGENE-study: 5200 cosequent Angio pts, ACS and HF Preliminary analysis!, unpublished ACS n= % NO CAD n= % n= % n=994 75% n=340 25% Average Age 66.0 ± 11.8v Women 30.7 % DM 23.1 % BMI 27.4 ± 4.7 Corrent smoker 31 % THX x-ray was taken on 64% of all ACS patients n= 1337 of them: ACS With Congestion in THX x-ray ACS No Congestion STABLE CAD ACS Ass. prof Juha Sinisalo M S Nieminen, AHF ,ESC Stockholm

11 COROGENE-study: ACS patients and congestion II Preliminary analysis! 1.5 year follow up n=340 Ass. prof Juha Sinisalo, personal communication ASC with congestion 92 deaths = 27% mortality/ n=994 ACS and HF mortality 3-fold ACS No Congestion 86 deaths = 9% M S Nieminen, AHF ,ESC Stockholm

12 M S Nieminen, AHF ,ESC Stockholm

13 Survival EHFS II Decompensated chronic HF: Survival after discharge Hyponatremic (Na < 135 mmol/l) vs. Normonatremic patients (Na 135 mmol/l) 1,0 0,8 0,6 0,4 0,2 0,0 log-rank test p < Patients at risk n= Months after discharge Normonatremia Hyponatremia M S Nieminen, AHF ,ESC Stockholm

14 Chronic HF N=2121 EHFS II, Demographics of pts with hyponatremia (S-Na < 135) in Chronic HF Hyponatremia N=487 Normonatremia N=1634 M S Nieminen, AHF ,ESC Stockholm P<0,05 Age 68,3 70,1 <0,03 Male 65,1 62,8 NS Hepatic failure 4,5 2,1 < 0,005 Depression 67,6 59,5 < 0,000 SBP <0,01 EF <0,001 TR gr ,5 34,0 <0,001 Ald. antag 50,3 33,1 <0,000

15 New agents: ADHF therapeutic prospects THERAPY AHF CDHF IV /PO Minipums Shock +, CS - - Bedside dialysis Severe CHF +, volume overl + - Adenosine 2 antag Vasopressiini 2 antag. Levosimendan Renal protection, +, Diuretic eff. + + / + Na and water diuresis Ca-sensitizer, vasodilator +, only in hyponatremia GNP activ, mitoc K- ch M activator., S Nieminen, AHF ,ESC Stockholm vasodil, + +/+ + +? + /+? Serca sensitizers Ca- uptake + +? +/+? Istaroksime Na+,K+-ATPase inh / + BNP analogues Vasodilatators, ie. nesiritide, relaxin + + /- Myosin activators + +? + / + sgc-activator, Cinaciguat +? +

16 kg mm Effects of Oral Tolvaptan in Patients Hospitalized for Worsening Heart Failure The EVEREST Outcome Trial Konstam M etal JAMA Change in Body Weight Change in Global Clinical Status P< Tolvaptan Additional weight loss 0.6 kg 0.9 kg P< n=997 n=1007 n=1031 n= Placebo P=0.51 Trial A P=0.52 n=903 n=910 n=931 n=900 Trial B Trial A M S Nieminen, AHF ,ESC Stockholm Trial B Composite Component(Day 7 or Discharge) No difference in GCS improvement

17 Proportion Without Event Everest; CV Mortality or HF Hospitalization Konstam M et al JACC Peto-Peto Wilcoxon Test: P=0.55 HR 1.04; 95%CI ( ) TLV 30 mg PLACEBO TLV PLC Months In Study M S Nieminen, AHF ,ESC Stockholm

18 Rolofylline and tonapofylline Adenosine 1 receptor antagonists Similar studies and main endpoints: Protect, Trident Change in body weight at 24 hours* Improvements in Dyspnea Symptom Score % of subjects with worsening renal function (increase in serum creatinine of > 0.3 mg/dl) up to Day 5/discharge Length-of-stay during the initial hospitalization Days of hospital-free survival (DHFS) All-cause mortality or cardiovascular re-hospitalization M S Nieminen, AHF ,ESC Stockholm

19 TRIDENT - 1 M S Nieminen, AHF ,ESC Stockholm

20 TRIDENT - 1 M S Nieminen, AHF ,ESC Stockholm

21 BNP analogs nesiritide et al M S Nieminen, AHF ,ESC Stockholm

22 BNP analogs nesiritide et al ASCEND HF recruitment has ended at 7100 patients overall in the world, results to be reported this year, pt population similar to EHFS II M S Nieminen, AHF ,ESC Stockholm

23 mmhg L/min Cinaciguat is a NO- and hemeindependent activator of soluble Guanylate Cyclase (sgc). PCWP Cardiac Output ,7 20,68 18,18 16,86 19, ,35 5,04 5,59 6,04 5, BL BAY after 2h 4h 6h FU 2h 3 BL BAY after 2h 4h 6h FU 2h M S Nieminen, AHF ,ESC Stockholm

24 DIURETIC use in AHF, new evidence, DOSE study, Felker, ACC 2010 Secondary outcomes at 72-hour assessment in DOSE, low-dose vs highdose groups Outcome Low-dose, n=151 High dose, n=157 p Dyspnea self-assessment, AUC Congestion-free (%) Change in weight (lbs) Net volume loss (ml) Change in NT-proBNP (pg/ml) Cr increase >3 mg/dl (%) The hazard ratio for death, rehospitalization, or an emergency-department visit at 60 days was 1.19 (95% CI , p=0.30) for continuous vs every-12-hour dosing and 0.83 (95% CI , p=0.28) for high-dose vs low-dose. M S Nieminen, AHF ,ESC Stockholm

25 Treatment of congestive heart failure: present and future Marked improvement over the past 25 years. 1. Neurohumoral antagonists 2. Cardiac surgical interventions CABG interventions that remodel the heart and repair the mitral valve (RCTs?) 3. Cardiac devices CRT, ICD LVADs, pumps: rapid technological progress either temporary or end-of life therapies M S Nieminen, AHF ,ESC Stockholm

26 Treatment of congestive heart failure: present and future. 4. Treatment of congestion with CPAP: yes in ADHF, no mortality benefit 5. Immune modulation therapy: in AHF& myocarditis 6. Cell therapy: promise? 7. Gene therapy - remarkable preclinical results - need for better vectors and more effective techniques to deliver these vectors 8. Way to provide care greater involvement of health care professionals other than physicians, emphasis on outpatient care, early detection and prevention, and evidence-based practice. M S Nieminen, AHF ,ESC Stockholm

27 PROBLEMS FOR AHF DRUG - therapy development Why many studies have turned neutral, or negative?, ie.survive, Revive,Everest,even Protect, trident, Nesiritide Major complication is hypotension The new drugs are effective, either rapid filling pressure decrease by vasodilatation or by diuresis Current therapy by diuretics and dobutamine is easy as BP is sustained during first 24 h Secondly - acute treatment in HF population does not impact long term results favourably as that is driven by arrythmias and other causes, elderly population etc. M S Nieminen, AHF ,ESC Stockholm

28 AHF treatment today Treat according to background illness / chronic decompensated HF or acute de novo HF Chronic pts are usually characterised by volume retention and overload, with adaptation of both peripheral and central circulation associated with high neuroendocrine control Acute de novo patients, are mainly ACS pts, with or without MR, without adaptation, and usually with vasoconstriction, thus ready for adverse hypotension if therapies are not implemented with carefull hemodynamic monitoring and readiness for fluid filling M S Nieminen, AHF ,ESC Stockholm

29 Treatment of AHF Oxygen/CPAP Loop diuretic +/- vasodilator Clinical evaluation ESC HF guidelines 2008 SBP >100 mmhg SBP mmhg SBP <90 mmhg Vasodilator (NTG, nitroprusside, nesiritide, levosimendan) Vasodilator and/or Inotrope (dobutamine, PDEI, levosimendan) Fluid challenge? Inotrope and/or Dopamine Good response Stabilise and initiate diuretic, ACE-I/ARB, beta-blocker M S Nieminen, AHF ,ESC Stockholm Poor response inotropic agents vasopressor mechanical support PAC

30 AHF treatment today New therapeutic agents have opportunities, though long term survival is probably affected by other cardiac causes in this elderly population Vasodilatation, levosimendan, BNP analogs, GC-agonists and agents that effect contractility without incr. in intracellular calcium are promising Study design and concept of trials has to be accommodated with patient population and focus on acute effects, ie 30 day outcome. M S Nieminen, AHF ,ESC Stockholm