Heart Failure treatment during pregnancy

Transcription

1 Heart Failure treatment during pregnancy Angeles Alonso García Hospital Universitario Puerta de Hierro. Majadahonda. Madrid. Spain European Society of Cardiology. Stockholm. 29 August 2010

2 Starting Point Evidence-based of HF drugs in pregnancy HF drugs during Pregnancy (efficacy/safety)

3 Starting Point Physiological changes during pregnancy Maternal risk. Fetal/Neonatal risk HF management: General approach Evidence-based of HF drugs in pregnancy HF drugs during Pregnancy (efficacy/safety)

4 Physiological changes in pregnancy

5 Peripheral Hypoperfusion CO SYMPTOMS OF HEART FAILURE Pulmonary Congestion PCWP Ejection of Blood Retrograde accumulation of blood FAILING LV

6 High maternal risk: Pre-existing conditions 1. Pulmonary artery hypertension of any cause 2. LV inflow or outflow obstruction: ME,AE, HM 3. The fragile aorta (Marfan or coarctation) 4. Valvular protheses requiring anticoagulation 5. ANY PATIENT REACHING HF wt NYHA III-IV 6. Severe cyanotic congenital disease European Heart Journal (2003) 24,

7 High fetal/neonatal risk: Maternal conditions 1. ANY PATIENT REACHING HF wt NYHA III-IV 2. Pre-eclamsia and eclampsia 3. Severe cyanotic congenital disease European Heart Journal (2003) 24,

8 Peripartum cardiomyopathy Time of diagnosis Uri. Elkayam. Women at Heart ESC: Nov 2005

9 Severe HF Management: General approach 1. Pregnancy is not recommended 2. Termination should be advised: Mortality 8-35%. Morbidity: 50% 3. If termination is refused the patient must be seen frequently. European Heart Journal (2003) 24,

10 Severe HF Management: General approach 4. The presence of HYHA III/IV during pregnancy requires immediate hospitalization and prompt Tx 5. Unless hemodynamic improvement is obtained termination of the pregnancy or delivery should be considered European Heart Journal (2003) 24,

11 MANAGEMENT OF CV DISEASES DURING PREGNANCY European Heart Journal (2003) 24,

12 Starting Point Evidence-based of HF drugs in pregnancy Women population in RCT HF drugs: Clinical guidelines HF drugs: Risk to the fetus categories HF drugs during Pregnancy (efficacy/safety)

13 Reasons why women are not enrolled in RCT Trials more complex Enrollment more difficult Pregnancy Higher cost

14 Gender differences in pharmaceutical effects J. of Cardiovasc. Trans. Res. (2009) 2:

15 HF Risk Factors No Heart disease No symptoms A Stages in Heart Failure Progression Heart disease No symptoms B Asymptomatic LV dysfunction C Prior or current HF Symptoms D Refractory HF symptoms

16 HF drugs: evidence-based in pregnancy 1. Clinicians responsible for managing pregnant women with HF must frequently make treatment decisions without adequate evidence or consensus expert opinion. 2. Pregnant women have not been adequately represented in RCT. There is a need for further evaluation of treatments

17 HF drugs: evidence-based in pregnancy 3. Management is guided by observational studies. 4. During pregnancy, many of these therapies are associated with an increased risk to the fetus, but if the benefits to the mother are thought to outweigh the risks, then they are used.

18 Medical therapy for HF CHF Guidelines Reduced LVEF ACE-I or ARBs Beta-blockers Diuretics Fluid retention Aldosterone antagonists Hydralacine and Isosorbide Digoxin Anticoagulants (if AF) Eur Heart J 2008: 29; Class I I I I IIa IIa I Level A A B B B B A pregnancy FDA drug risks A (safest) X (known danger: do not use!)

19 Starting Point Evidence-based of HF drugs in pregnancy HF drugs during Pregnancy (efficacy/safety)

20 ACE-I & ARBs in Pregnancy FETAL EFFECTS UROGENITAL DEFECTS NEONATAL ANURIC RENAL FAILURE INTRAUTERIN GROWN RETARDATION DEATH INDICATION IN PREGANCY HF NOT INDICATED SHOULD BE DISCONTINUED

21 bblockers in HF from a gender perspective RR and 95%CI: / b-blockers in HF Jochmann: European Heart Journal (2005) 26,

22 bblockers in Pregnancy FETAL EFFECTS MAY DECREASE UTEROPLANCETAL BLOOD FLOW MAY IMPAIR FETAL RESPONSE TO HYPOXIC STRESS MAY BE ASSOCIATED WITH NEONATAL HYPOGLYCEMIA AT HIGH DOSES POSSIBLE LOWER BIRTH WEIGHT INDICATION IN PREGANCY HF CAN BE CONTINUED THROUGHOUT THE PREGNANCY, INCLUDING THE FIRST TRIMESTER AE MOST OFTEN WITH ATENOLOL

23 Cortex DIURETICS Thiazides Inhibit active exchange of Cl-Na in the cortical diluting segment of the ascending loop of Henle K-sparing Inhibit reabsorption of Na in the distal convoluted and collecting tubule Medulla Loop of Henle Loop diuretics Inhibit exchange of Cl-Na-K in the thick segment of the ascending loop of Henle Collecting tubule

24 Diuretics in Pregancy FETAL EFFECTS CAN CAUSE VOLUMEN CONTRACTION AND ELECTROLYTE DISORDERS INDICATION IN PREGANCY HF TO DECREASE CONGESTION

25 Aldosterone antagonist in Pregancy No data Espironolactone: Fetal antiadrogenic effects Eplerenone: Seems safe

26 Hydralacine & Nitrates in Pregnancy FETAL EFFECTS NO MAJOR ADVERSE EFFECTS POSSIBLE BRADICHARDIA INDICATION IN PREGANCY HF INDICATED FOR: VASODILATATION DECREASE VENOUS CONGESTION

27 Digoxin in HF from a gender perspective DIG study: /. Survival according dig/plac Rathore. N Engl J Med 2002;347:

28 DIGOXIN FETAL EFFECTS NO MAJOR ADVERSE EFFECTS INDICATION IN PREGANCY HF INDICATED FOR: SUPRAVENTRICULAR ARRTHYMIA

29 1. No data on HF (extrapolation from anticoagulation data on pregnant women with cardiac valve substitutes or DVT) 2. Incidence of thromboembolism in pregnant women with mechanical prostheses: 7-25% varying with prostheses s type and anticoagulation regimen Mortality: 40% 3. Warfarin Embriopathy ANTICOAGULANTS Born D Am Heart J 1992,124:413 Sbarouini E Br heart J 1993,71:196

30 UFH Metanalysis: Maternal complications Chan WS. Arch Intern Med 2000; 160:191

31 UFH Metanalysis: Fetal complications Chan WS. Arch Intern Med 2000; 160:191

32 Introduction of the concept of modulating anticoagulation intensity (AHA/ACCP Guidelines 2001) Taken from Cotrufo M. Women at Heart ESC: Nov 2005

33 Anticoagulation: Which regimen? Taken from Cotrufo M. Women at Heart ESC: Nov 2005

34 Peripartum cardiomyopathy Treatment Experimental Drugs INMUNE GLOBULINE Uri. Elkayam. Women at Heart ESC: Nov 2005 PENTOXYFILINE

35 Peripartum cardiomyopathy Treatment of severe HF Uri. Elkayam. Women at Heart ESC: Nov 2005

36 CONCLUSIONS 1. Pregnancy may lead to deterioration of HF due to the rise in blood volume and increase in cardiac output, as well as the substantial increase in extravascular fluid. 2. Importantly, many medications used in HF treatment are contraindicated during pregnancy

37 CONCLUSIONS 3. The risk of pregnancy is considered greater than the risks linked to contraceptive use 4. It is recommended that women with HF discuss contraceptives and planned pregnancy with a physician in order to take an informed decision based on assessment of potential risks.

38 CONCLUSIONS 5. Early admission to hospital is wise especially as both ACE-I & ARBs are contraindicated and treatment options are much more limited than outside pregnancy.

39 CONCLUSIONS 6. A multidisciplinary approach (cardiologists, gynecologists, GPs, anaesthesists, neonatologist) is needed 7. Continuous Information to women: before, during and after pregnancy is required