Αντιμετώπιση καρδιακής ανεπάρκειας προχωρημένου και τελικού σταδίου Β. Μπιστόλα Καρδιολόγος Μονάδα Καρδιακής Ανεπάρκειας Β’ Παν/κη Καρδιολογική Κλινική ΠΓΝ ΑΤΤΙΚΟΝ

Conflict of interest Honoraria/travel grants: Novartis, Servier, Pfizer

Which treatment(s) improve survival and QoL in advanced HF? Heart transplantation Left ventricular assist devices Chronic inotropic infusions 1+ 2 All of the above

Which treatment(s) improve survival and QoL in advanced HF? Heart transplantation Left ventricular assist devices Chronic inotropic infusions 1+ 2 All of the above

Natural history of heart failure Allen LA, et al. Circulation. 2012

Dismal prognosis of advanced HF 1-year survival of inotrope dependent patients: 11% Rogers J, JACC 2007

ESC HF treatment algorithm

Stepwise therapy for heart failure Stepwise therapy for heart failure. Medication and device therapy for heart failure due to systolic dysfunction is based on the patient's New York Heart Association class. Clinical trials with various therapies show mortality benefit when added to existing therapy; hence, the stepwise approach. ACE indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CRT, cardiac resynchronization therapy; VAD, ventricular assist device; and NYHA, New York Heart Association. Owens, Brozena, Jessup. Circ Res. 2016

Who should be evaluated for advanced HF therapies? ESC ACC/AHA Metra M, et al. Eur J Heart Fail. 2007 Yancy CW, et al. Circulation 2013

Therapeutic decision making algorithm in advanced HF Ammirati et al. Eur J Int Med 2014

LVAD indications ESC HF GD 2016

LVADs improve survival awaiting transplantation Frazier OH, et al. JTCS 2001;122:1186-1195

LVAD as destination therapy-REMATCH trial 122 pts NYHA IV LVEF≤25% 70% on inotropes Rose EA, et al. N Engl J Med 2001; 345:1435-1443

Continuous vs pulsatile VADs Slaughter MS et al. NEJM 2009;361:2241-2251

DT CAP Trial Quality Of Life Improvements 74 225 m 30 Park SJ. AHA Scientific Sessions, November 2010.

LVADs: unresolved issues Complications Bleeding (perioperative-3mo/gastrointestinal>3mo) Infections (most common >3mo) Stroke Right heart failure Hemolysis/thrombosis Very high cost Incremental cost-effectiveness ratio of destination therapy CF VAD vs OMT $198.184 per QALY Kirklin et al. 8th annual INTERMACS report JHLT 2017 Rogers JG, et al. Circ Heart Fail 2012

VAD technology

Axial vs centrifugal pump HEARTWARE noninferior to HMII Lower rates of device removal with HEARTWARE (8.8% vs 16.2%) Higher rates of stroke with HEARTWARE (29.7% vs. 12.1%)

Mehra MR et al. N Engl J Med 2017;376:440-450 Reduced pump thrombosis with fully magnetically levitated centrifugal HMIII pump HMIII vs HMII 294 patients with advanced HF 97.4% INTERMACS 2-4 Primary EP: Survival free of disabling stroke or free of reoperation for replacement or removal of pump within 6 months Mehra MR et al. N Engl J Med 2017;376:440-450

Is the time ready to expand use of LVADs in ambulatory advanced HF? 200 pts, ambulatory advanced HF Nonrandomized, HMII vs OMT

LVAD is superior to OMM in ambulatory advanced HF with poorer baseline QoL Stehlik, J et al. Circ Heart Fail. 2017

OMT vs LVAD in INTERMACS 4-7 ISHLT 2017- featured abstract MEDAMACS Registry: Ambulatory patients (NYHA III–IV, EF ≤ 35%, INTERMACS 4-7) 1 HF hosp +1 high-risk feature: Additional HF Hosp/Low Peak VO2 or 6MWT<300m/NT-BNP >4000/SHFM 1-y survival ≤ 83%

Heart transplantation: the gold standard therapy for advanced HF Drakos S. JACC 2014

Heart transplantation: indications and contraindications CPET Off β-blocker: pVO2 ≤14 ml/kg/min On β-blocker: pVO2 ≤12 ml/kg/min Age <50y or women: additional criteria, ≤50% pVO2 Prognostic scores (additionally to CPET): Seattle HFM: 1-y <80% HFSS: medium/high risk ESC HF Guidelines 2016

The heart transplant evaluation The heart transplant evaluation. The advanced heart failure specialist must determine whether the patient's functional status is limited enough, with optimal medical therapy to require transplantation and ensure that there are no medical, social, or psychological contraindications to transplantation. See text for details. Kittleson M M , Circulation. 2011;123:1569-1574

Heart transplants in Europe (n=2235 in 2015) Source: European Council newsletter

Medical therapy of advanced HF Heart 2007;93;626

Recommendations for inotropes in end-stage HF

Inotropes in end-stage HF Ginwalla M, Heart Fail Clin 2016

Pulsed levosimendan infusions in outpatients with advanced HF-LEVOREP study Four 2-weekly infusions 120 advanced heart failure (EF≤35%, NYHA class III/IV) Primary EP: % of patients showing a ≥20% improvement in the 6MWT and a ≥15% score increase in KCCQ at 24 weeks Pre-specified secondary EP: short-term (8weeks) and long-term (24weeks) event-free survival

Levosimendan plus dobutamine vs single dobutamine in refractory HF Nanas et al. Am J Cardiol 2004;95:94;1329 Nanas et al. Am J Cardiol 2005;95:768

Chronic home inotropes in end-stage HF Survival in non-HTx/LVAD candidates: 1-y 48%, 2-y 38% 197 advanced HF Hashim T, et al. Circ Heart Fail 2015

Take home messages Advanced HF is associated with high mortality rate. Treatment should be individualized and includes heart transplantation, LVAD implantation and medical therapies. Timely referral to an advanced HF center for LVAD/HTx evaluation should be done before irreversible end-organ damage. Heart transplantation remains the gold standard therapy. However, donor organ shortage limits its availability. LVAD use is expanding, due to technological advances that have improved device durability, patient outcomes and device-related complications. There is a continuing need to reduce device-related complications and cost.