Βασιλική Κατσή. Καρδιολόγος ΓNA Ιπποκράτειο

Transcription

1 Βασιλική Κατσή Καρδιολόγος ΓNA Ιπποκράτειο

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3 40 διαφάνειες ίσως

4 Και πρέπει και δικαιούνται ΣΥΧΝΟΤΕΡΑ

5 76-96%

6 3343 men and 4199 women followed for 25 years, no HF at baseline BP (mm Hg) <140/ /90-99 >160/100 Lifetime risk % Age 0 Male Female Male Female Male Female 40 years 60 years 80 years Lloyd-Jones et al Circulation 2002

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9 Aggressive blood pressure control Aggressive blood pressure control in patients with prior MI Decreases risk of new HF by ~50% 1 56% in T2DM 2 Decreases risk of new HF by ~80% 3 1. Dahlöf B et al. Lancet. 1991;338: ; 2. UKPDS Group. BMJ. 1998;317:703-13; 3. Kostis JB et al. JAMA. 1997;278:212-6.

10 J Hypertens Mar;34(3): : Effects of blood pressure-lowering treatment. 6. Prevention of heart failure and new-onset heart failure - meta-analyses of randomized trials. Thomopoulos C 1, Parati G, Zanchetti A.

11 Πιο συχνή, το ίδιο σοβαρή European Heart Journal (2008) 29,

12 LV between HF pts with Low vs Normal EF LOW EF Myocyte hypertrophy Interstitial fibrosis Abnormal Ca handling Reduced contractility Slowed relaxation Depleted preload reserve Large volumes NORMAL EF Myocyte hypertrophy Interstitial fibrosis Abnormal Ca handling Reduced contractility Slowed relaxation Depleted preload reserve Small volumes J Card Failure, 2003:9:1-3

13 Pathophysiology In HFpEF is complex, incompletely understood and related to 1) Cardiac structural and functional alterations 2) Systemic and pulmonary vascular abnormalities 3) Extra-cardiac causes of volume overload(e.g Kidney disease) Signs and symptoms of HF Major challenges: 1) Truly representative experimental models of HFpEF DO NOT exist 2) Human data(myocardial analysis) remain limited

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15 HFpEF συννοσηρότητες AGE

16 Definition Huffing and Puffing (dyspnea and exercise intolerance)

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18 The seminal studies on HFpEF explained HF in the presence of: Normal systolic LV performance Diastolic LV dysfunction (prolonged isovolumic LV relaxation, slow LV filling and increased diastolic LV stiffness)

19 Pathophysiology of HFpEF Alterations in active relaxation AF> dias[ca] + ischemia Depress the SERCA2a Ventr.Stiffness.

20 Extracellular Matrix PICP PINP In HFpEF patients: Stiffness of the EM is largely determined by collagen through regulation of its total amount, relative abundance of collagen type 1 and degree of collagen crosslinking

21 Pathophysiology of HFpEF Changes in cytoskeleton isoforms Titin is responsible for anchoring the thick filament to the Z disc in a sarcomere, sustaining the majority of diastolic tension in myofibril bundles.

22 Pathophysiology of HFpEF Pulmonary Hypertension

23 Pathophysiology of HFpEF Systolic dysfunction Borlaug BA,et al. J Am Coll Cardiol 2009;54:

24 Pathophysiology of HFpEF Ventricular-arterial coupling and vascular dysfunction

25 Acute Heart Failure Syndrome(s) Acute heart failure (AHF) is defined as a rapid onset or change in the signs and symptoms of HF, resulting in the need for urgent therapy. Symptoms are primarily the result of severe pulmonary congestion due to elevated left ventricular (LV) filling pressures (with or without low cardiac output). AHFS can occur in patients with preserved or reduced ejection fraction (EF). Concurrent cardiovascular conditions such as coronary heart disease (CHD), hypertension, valvular heart disease, atrial arrhythmias, and/or noncardiac conditions (including renal dysfunction, diabetes, anemia) are often present and may precipitate or contribute to the pathophysiology of this syndrome Filippatos et al. Eur Heart J 2008

26 AHF with preserved EF: prevalence in various registries Yancy et al. J Am Coll Cardiol 2006;47: Parissis et al. EJHF 2015

27 AHF with preserved vs reduced EF: ALARM-HF clinical phenotypes AHF with preserved EF:

28 AHF Syndromes with Preserved EF: a pathophysiologic basis Kumar et al. Crit Care Med 2008

29 AHF Syndromes: Preserved EF Additional non-diastolic pathophysiologic mechanisms - Regional systolic disturbances/ reduced contractile reserve - Venoconstriction/volume re-distribution - Volume overload - Left atrium dysfunction/ atrial arrhythmias - Ventricular/ vascular coupling abnormalities - Pulmonary hypertension / RV dysfunction - Endothelial dysfunction - Chronotropic incompetence - Co-morbidities (more inflammatory activation) - Renal artery stenosis (8%, flash PE) Bench et al. Current Heart Failure Reports 2009, 6:57 64

30 Acute HF with preserve vs reduced EF: Two Different Clinical Scenarios Cardiovascular Failure (volume re-distribution) High blood pressure Rapid worsening Cardiac Failure (real volume overload) relatively rapid Gheorghiade M. Am J Cardiol 2005;96[suppl]:11G-17G.

31 AHF with preserved EF: therapeutic considerations AHF with preserved EF needs: More vasodilators More CPAP Less diuretics Less inotropes/vasoconstrictors Less IABP Less renal replacement therapy Curr Heart Fail Rep ;10(3):1189 Am J Cardiol 2011;107:79

32 Kumar et al. Crit Care Med 2008

33 Vasodilators or Diuretics Driven Treatment in Acute Hypetensive HF Cotter et al, Lancet 1998

34 Serelaxin in AHF patients with preserved LVEF: RELAX-AHF sub-analysis More beneficial effect of serelaxin on dyspnea scores in patients with preserved EF Filippatos et al Eur Heart J 2013

35 Acute Heart Failure Syndromes: Response to vasodilatory therapy

36 AHF with preserved vs reduced EF: discharge medications Fonarow et al. J Am Coll Cardiol. 2007; 50

37 AHF with pef has unique clinical characteristics and underlying pathophysiology in comparison to AHF with ref. In contrast to CHF, these conditions are treated in the same way according to SBP and existence of pulmonary and/or peripheral congestion. There is a lack of evidence-based guidelines for the specific management of AHF in patients with pef. Future AHF trials of agents should include adequate numbers of HFpEF patients to allow determination of potential differential effects in HFpEF vs HFrEF.

38 Other influential factors beyond blood pressure:

39 The challenges of treating DHF Nitrate s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction NEAT-HFpEF Patients with HFpEF were randomized to a long-acting nitrate (n = 51) versus placebo (n = 59). Study medication (isosorbide mononitrate or placebo) was up-titrated to 120 mg over a 6-week period. After a 2-week washout period, subjects crossed over to the opposite treatment assignment with up-titration for 6 weeks. Among individuals with HF due to pef, long-acting nitrates failed to improve exercise tolerance compared with placebo. More patients in the long-acting nitrate group discontinued study medication due to side effects.

40 The challenges of treating DHF The role of exercise training Large-scale trials have not evaluated the effect of exercise on outcomes in patients with HFpEF Grewal et al :in patients with preserved systolic function and no evidence of exercise-induced ischemia, DD was strongly and inversely associated with exercise capacity. Conversely, exercise training may improve diastolic dysfunction JAMA 2009 Takemoto et al: LV diastolic dysfunction associated with aging is less pronounced in exercise trained individuals. Am Heart J 1992 Aerobic exercise could be beneficial in this population in terms of improved functional capacity,weight loss and benefits through risk reduction such as improvement in HTN and diabetes control.

41 Current research interest is the reduction of fibrosis and changes in ECM that contributes to the diastolic stiffness ALT-711 (Alagebrium chloride) is a novel compound that breaks glucose cross-links and improves ventricular and arterial compliance in animals, reduces blood pressure and vascular stiffness in hypertension TGF-b (Transforming growth factor beta) is a profibrotic cytokine,infusion of TGF-b neutralizing antibody in a rat model of pressure overload was found to reduce fibrosis and development of diastolic dysfunction

42 novel therapeutic targets focusing on disease mechanism SERCA2a gene transfer using adeno-associated vectors: to improve Ca homeostasis and active relaxation NO donors or FH4: to recouple NO synthase Modification of titin (principal determinant of passive cardiomyocyte tension) PKG phosphorylation sites may dynamically modulate titin stiffness.

43 SPRINT

44 SPRINT major protective cardiovascular effect was evident primarily for heart failure (P=0.002),

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46 ΠΡΩΤΟΙ ΣΤΑ ΑΡΜΑΤΑ ΣΤΑ ΓΡΟΣΣΙΑ ΚΑΙ ΣΤΑ ΓΡΑΜΜΑΤΑ Eυχαριστώ πολύ