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在“2018深圳心力衰竭国际发展论坛暨心力衰竭治疗研讨会·深圳站”会议上，来自乔治华盛顿大学医学院的Gurusher Panjrath教授为我们带来了'Guideline to Clinical Practice: Treatment Strategies in Heart Failure(临床实践指南：心力衰竭的治疗策略)'的精彩报告。
54yoAsian American man, non ischemic CM, EF 28%, diagnosed 2 yrback. BIV/ICD 2hospitalizations, has dyspnea walking in park, nipple tenderness with Aldoantagonist Meds:Metoprololsuccinate100 QD, Furosemide 80, Enalapril 10 mg BID, Exam:BP 102/80 mmHg, HR 52 bpm, JVP~7, no S3/S4. no edema Pt wants to know how he is going to do?
A) I don’t know! B) You will do really well C) You will likely not be around
Epidemiology of Heart Failure——insights from past decadeWide variation inmortality based on geographical area Risk for CV death higherfor HFrEF Hospitalizations are on the rise Mortality slightly improved (likely from GDMT and ICD) but still high
Residual Risk for HFrEF Despite Conventional GDMT26.5% of patients randomized to enalapril in PARADIGM trial had CV death or HF hospitalization as 1st event Of all patients randomized to enalapril, the absolute risk of CV death as a first event was 10.9%
A) Increase beta blocker B) Add aldosterone antagonist C) Switch to Sacubitril/valsartan or neprilysin inhibitor D) Do nothing
Neprilysin Inhibition and ARNI: Evolution 
Balance of NEP Inhibition
The antihypertensive effects may beoffset by an increased activity of the RAAS and sympathetic nervous systemand/or by downregulation of ANP receptors.
Dual NEP / ACE inhibitors
synergistic effect
Vasopeptidase Inhibitor Omapatrilat Dual NEP / ACE inhibitor
↑ ↑ ↑ increased angioedema
PARADIGM-HF: Entry CriteriaNYHAclass II-IV (less than 1 % NYHA IV) heart failure LVEF≤ 40% then ≤35%: 2/3 pts EF≤ 35 %, 1/3EF 35-40 %) BNP≥ 150 (or NT-proBNP ≥ 600) Guideline-recommendeduse of β-blockers , MRA, Background therapy to include ACEi of ARB equivalent to enalapril 10 mg/day at least for 4 weeks Systolic BP ≥ 95 mm Hg, eGFR ≥30 ml/min/1.73 m2 and serum K ≤ 5.4 mEq/Lat randomization
PARADIGM-HF:Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint)
PARADIGM-HF:Cardiovascular Death
Both SCD(HR 0.80, 95% CI 0.68-0.94, P = 0.008) and death due to worsening HF(HR 0.79, 95% CI 0.64-0.98, P = 0.034) were reduced by treatment with LCZ696comp with enalapril. Death due to MI orstroke not different (infrequent)
PARADIGM-HF:All-Cause Mortality
PARADIGM-HF:Effect of LCZ696 vs Enalapril on HF Hospitalization or nonfatalclinical deterioration
PARADIGM-HF: Adverse Events
2017.ACC/AHA/HFSA.Update:
Recommendations for Stage C HFrEF
Whento switch to ARNI? – symptomatic HF, on ACE/ARB ARNIor Beta blocker First? – not tested Tolerabilityand dosing of ARNI in Asians? Data missing ARNIin Class IV HF- ongoing studies ARNIin HFpEF- ongoing studies Longterm- beta amyloid deposition?- appears to be safe
If ion channel (the funny current) is highly expressed in spontaneously activecardiac regions, such as the sinoatrial node, the AV node and the Purkinje fibers. The funny current isa mixed Na/ K current that activates upon hyperpolarization at voltages in thediastolic range
HeartRate Modulation with Ivabradine—The Systolic HFtreatment with the If inhibitor Ivabradine Trial SHIFT Trial
NYHA II–IV, SR rateof ≥70 bpm randomized to ivabradine added to background therapy including abeta-blocker (90%), and an MRA (60%). Only26% of patients were on full-dose β-blocker
Heart Rate Modulation with Ivabradine——The Systolic HF treatment with the If inhibitor ivabradine Trial SHIFT Trial
Effect.of.ivabradine.in.prespecified.subgroups
2017.ACC/AHA/HFSA.Update: Recommendations.for.Stage.C HFrEF
2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapyfor Heart Failure ACC/AHA/HFSA, A Report of the American College ofCardiology/American Heart Association/Heart Failure Society of America, YancyCW, et al. JAm CollCardiol.
Benefits of Evidence-Based Therapies for PatientsWith HFrEF
2016.ACC/AHA/HFSA.Update: Recommendations.for.HFpEF
2017ACC/AHA/HFSA.Update: Recommendations.for.Comorbidities.in.HF
Iron Deficiency inHeart Failure- Prevalent around the world Irondeficiency (ID) is most common nutritional disorder in the world Commonin HF Irondeficiency, both with and without anemia, isassociated with adverse clinical outcomes Variableprevalence due to lack of standard criteria for ID
Iron Deficiency Impacts Clinical Outcomes in HF
Intravenous (IV) iron repletion favorably affects patients’global assessment and NYHA functional class
2016 ESC Guidelines for the Diagnosis and Treatment of Acuteand Chronic HF
Convenient,readily available and inexpensive, butoral iron is not absorbed well, particularly in patients Elevatedhepcidin prevents iron absorption by reducing transmembrane ferroportin on enterocytes Tolerabilityand compliance with of oral iron is low due to GI side effects
largest phase 2 ,double blind RCT 225 patients withNYHA class II-IV HF with HFrEF Hb 9-15 g/dL (men) or9-13.5 g/dL women) and ID (ferritin 15-100 ug/Lor 100-299 ug/L with TSAT <> oral ironpolysaccharide 150 mg twice daily or placebo
At 16 weeks, there was no significant difference in primary end point: change in peak VO2 from baseline, Or secondaryendpoints : 6MWD, NT-proBNP levels or KCCQ score oral iron increasedTSAT, ferritin and hepcidin, and reduced solubletransferrin receptor levels
PossibleExplanations for Failure of Oral Iron in HF
Higher baseline hepcidin levels associated with lessimprovement in TSAT and ferritin
Higher hepcidin levels may limit responsiveness to oral iron,inhibit duodenal iron absorption
- In HFrEFNYHA class II or III pts who tolerate anACE inhor an ARB, replacement with an ARNI is recommended to further reducemorbidity and mortality - Ivabradine can be beneficial in stable chronicsymptomatic HFrEFwith elevated heart rate to further reducemorbidity
Future studies to answer: nonpharmacological therapy (exercise,stem cells, rehab, mind body medicine) , treatment of HFpEF and hospitalized HF
Gurusher Panjrath教授 乔治华盛顿大学医学院
医学博士，FACC, FAHA，主任，心力衰竭和机械支持项目，华盛顿特区乔治华盛顿大学医学院医学副教授，美国心脏病学院，心力衰竭和移植科
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