Latest therapies for patients with HF. Dr AIGUL BALTABAEVA PhD, FESC, FRCP RBHT & ASPH

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Latest therapies for patients with HF Dr AIGUL BALTABAEVA PhD, FESC, FRCP RBHT & ASPH

ESC HF Guidelines 2016

ESC HF Guidelines 2016: Pharmacological Treatments

Pathways blocked by ACE-I, ARB and NI

Effect of ARNI

PARADIGM-HF: ARNI vs Enalapril in HF

NICE: ARNI Appraisal

Recent trials of newer glucose-lowering agents have 8 been neutral on the primary CV outcome HR: 1.0 (95% CI: 0.89, 1.12) SAVOR-TIMI 53 HR: 0.98 (95% CI: 0.88, 1.09) TECOS HR: 0.96 (95% CI: UL 1.16) EXAMINE 2013 2014 2015 DPP-4 inhibitors* Lixisenatide Empagliflozin HR: 1.02 (95% CI: 0.89, 1.17) ELIXA EMPA-REG OUTCOME

Empagliflozin 9 Empagliflozin is a highly selective inhibitor of the sodium glucose cotransporter 2 (SGLT2) in the kidney Glucose reduction occurs by reducing renal glucose reabsorption and thus increasing urinary glucose excretion In patients with type 2 diabetes, empagliflozin leads to 1 : Significant reductions in HbA1c Weight loss Reductions in blood pressure without increases in heart rate

Adjusted mean (SE) HbA1c (%) Empagliflozin: HbA1c 9.0 8.5 8.0 7.5 Placebo Empagliflozin 10 mg Empagliflozin 25 mg 7.0 6.5 6.0 0 12 28 40 52 66 80 94 108 122 136 150 164 178 192 206 Week Placebo Empagliflozin 10 mg Empagliflozin 25 mg 2294 2296 2296 2272 2272 2280 2188 2218 2212 2133 2150 2152 2113 2155 2150 2063 2108 2115 2008 2072 2080 1967 2058 2044 1741 1805 1842 1456 1520 1540 1241 1297 1327 1109 1164 1190 962 1006 1043 705 749 795 420 488 498 151 170 195 10

Adjusted mean (SE) systolic blood pressure (mmhg) Empagliflozin: Systolic BP 11 145 143 141 139 137 135 133 131 Placebo Empagliflozin 25 mg Empagliflozin 10 mg 129 127 125 0 16 28 40 52 66 80 94 108 122 136 150 164 178 192 206 Week Placebo 2322 Empagliflozin 10 mg 2322 Empagliflozin 25 mg 2323 2235 2250 2247 2203 2161 2235 2193 2221 2197 2133 2174 2169 2073 2125 2129 2024 2095 2102 1974 2072 2066 1771 1853 1878 1492 1556 1571 1274 1327 1351 1126 1189 1212 981 1034 1070 735 790 842 450 518 528 171 199 216

CV death 12

CV death 13 Empagliflozin 10 mg HR 0.65 (95% CI 0.50, 0.85) p=0.0016

Hospitalisation for heart failure 14

ESC HF Guidelines 2016

Effective LV Pacing

CRT Correction of LV Dyssynchrony the Abolition of the Septal Flash Before CRT After CRT Septal Flash No Septal Flash Septal Flash No Septal Flash

HF: CRT Therapy J Gamble et al, Cardiostim, 20009 J B Van Rees et al, JACC, 2011

Failed LV lead 53 y old female Broad LBBB Normal coronaries CRT (PPM switched off) NYHA III

WiSE - European CE Mark 2015

ESC HF Guidelines 2016

HF: Effect of LV Remodelling Volume Overload Acute/ Chronic LV remodelling Development of MR

HF: Moderate-to-Severe MR Large Centre US Cohorts: 29% of HF, I/P with HF 74% Italian registry: 42% of HF, increases with age (>70 y.o.) Bursi et al, European Journal of Heart Failure, 2010

Surgical Correction of Severe MR Tribouilloy C et al, Circulation. 1999

Mitral Devices

Key design features of the MitraClip system Cobalt-chromium implant Polyester clip cover designed to promote tissue healing Independent capture of each leaflet for secure attachment MRI safe to 3 Tesla Preserved surgical options if needed

Advantages of the MitraClip procedure Catheter based delivery system: minimally invasive, Less trauma, Short hospital stay and recovery time No cardiopulmonary bypass No chest incision Controlled systematic procedure, with stable hemodynamics Precise positioning and accurate placement of the device MitraClip Real-time efficacy assessment

Edge-to-Edge & MitraClip Concepts Facilitates proper leaflet coaptation Mechanical solution to a mechanical problem Degenerative - Anchor flail and prolapsed leaflets (similar to chordal transfer/replacement) Functional - Coapts tethered leaflets to reduce time and force required to close valve Reduces LV volume overload by reducing MR Creates tissue bridge Limits dilatation of annulus Septal-lateral (anterior-posterior) dimension Supports durability of repair Restrains LV wall Limits LV dilatation Porcine model, 6M

EVEREST II: 5 Year Results

EVEREST II: HRR

Survival Post-procedure J Am Coll Cardiol. 2014 Bhatia RS et al, NEJM, 2006

HF NYHA Class at Baseline, 1 & 12/12 F/U In high-risk patients with severe mitral regurgitation, percutaneous MitraClip therapy significantly improved NYHA functional class at 30 days and at 12 months relative to baseline (p < 0.001).

EII HRR: Clinical Results J Am Coll Cardiol. 2014;64(2):172-181

87 y old male Hx of late presentation MI in cardiogenic shock and pulm. oedema, req. intubation and ventilation Long stay in CTITU complicated by LRTI Echo: Severe ischaemic MR PCI to LCx, mild reduction in MR NYHA III

MitraClip Procedure

MitraClip

Acute Effect of Mitral Clip

RBHT: MitraClip Programme Courtesy of Dr R. Smith, 2016

Conclusions Time Life New drugs have made convincing entrance to HF guidelines New drugs are being trialled and tested New approach is taken in device therapy New approach is taken in re-shaping the failing heart