Workshop on Heart Failure in Geriatric Population

Dr Irfan Muneeb Consultant Geriatrician

FRCP, MRCP(GIM), SCE(Geriatrics)

Disclosures

I have no conflict of interest or disclosure in relation to this presentation

Contents• Heart Failure: Scope of the problem

• Pathophysiology of Heart Failure

• Diagnosis of HF

• Heart Failure with Preserved Ejection Fraction. Diagnosis and management.

• Case Discussion and trials

Ageing population• We have an ageing

population• In US, the population of

above 65 and older is projected to more than double from 46 million today to over 98 million by 2060.

• Qatar is experiencing trends in ageing similar to that of other developed countries and the proportion of older people is expected to grow.

Heart Failure and Ageing

• Heart failure is the most common Medicare DRG.

• 10% of patients older than 65 years have heart failure

• 80% of hospitalized patients with heart failure are older than 65 years.

Definition of Heart Failure

• Heart failure can be defined as an abnormality of cardiac structure or function leading to failure of the heart to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissues, despite normal filling pressures (or only at the expense of increased filling pressures).

Terminologies used to describe of HF

• Related to EF: – HFrEF (reduced ejection fraction: EF<40%)– HFmrEF (mid range EF: EF 40-49%)– HFpEF (preserved ejection fraction: EF ≥50%)*

• Related to time-course: – Acute– Chronic

• Related to progression – Stable – Decompensated

• Related to location: – Left heart– Right heart– Combined

Aetiologies of HF

Valvular Heart Diseases

Myocardial Disease e.g. CHD

Arrythmias

Pericardial Disease Heart Failure Endocardial

Disease

High Output States Congenital Heart Disease

Pulmonary Hypertension

(COPD)

Unique Aspects of Ageing and Heart Failure

• Increased myocardial stiffness and diastolic dysfunction

• More exposure to standard comorbidities that lead to CAD and systolic dysfunction

• Less data based decision making (older population is under represented)

• More dangerous drug-drug-interactions• More complex psycho-social issues• Greater procedural/surgical risk

Heart Failure Pathophysiology

Myocardial Injury Fall in LV Performance

Activation of RAAS, SNS, ET, and Others

Myocardial ToxicityANP Peripheral Vasoconstriction BNP Hemodynamic Alterations

Remodeling andProgressive

Worsening of LV Function Heart Failure SymptomsMorbidity and Mortality

Shah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2–S6.

Symptoms and Signs of HFSymptomsBreathlessnessOrthopneaParoxysmal Nocturnal DyspneaReduced Exercise ToleranceFatigue, Tiredness, increased time to recover after exerciseAnkle Swelling

SignsElevated JVPHepatojugular ReflexAnkle or Sacral OedemaThird Heart Sound (Gallop Rhythm)Laterally displaced apical impulseCardiac murmur

Classification of Heart FailureStage ACC/AHA stages of HF

(based on structure and damage to heart)

Stage A At high risk for HF, but without structural or functional abnormalityNo signs or symptoms

Stage B Developed structural heart disease strongly associated with development of HF, but without signs or symptoms

Stage C Symptomatic HF associated with underlying structural heart disease

Stage D Advanced structural heart disease and marked symptoms of HF at rest, despite maximal medical therapy

Class NYHA functional classification(based on symptoms or physical activity)

Class I No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or dyspnoea

Class II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in HF symptoms

Class III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in HF symptoms

Class IV Symptoms of HF present at rest. If any physical activity is undertaken, discomfort is increased

Principles of diagnosis of HFØ Consider: Medical history, Symptoms, SignsØ Confirm: Natriuretic peptides, EchocardiographyØ Assess clinical phenotype: HFrEF vs. HFpEFØ Assess etiology: Angiography, cMRI, BiopsyØ Risk stratificationØ Workup for targeted therapies

Clinical uses of NP as a Marker• The plasma concentration of natriuretic peptides (NPs) can be

used as an initial diagnostic test, especially in the non-acute setting.

• Diagnostic values apply similarly to HFrEF and HFpEF; on average, values are lower for HFpEF than for HFrEF

• The negative predictive value of NPs is high, therefore, the use of NPs is recommended for ruling-out HF, but not to establish the diagnosis.

• Patients discharged with BNP > 400-500 pg/ml at discharge are at a higher risk for HF readmissions and mortality

Natriuretic Peptide Cut Point for Diagnosis of Heart Failure

(Acute Onset)

ESC Guidelines 2016

Clinical Heart Failure

HFrEF (EF<40%) HFpEF (EF 50% and above)

Ischemic66%

Non Ischemic24%

Other 10%

Wide Differentials

Heart Failure with Preserved Ejection Fraction

• The diagnosis of HFpEF remains challenging.

• LVEF is normal and signs and symptoms for HF are often non-specific

• The diagnosis of HFpEF requires the following conditions to be fulfilled Ø The presence of symptoms and/or signs of HFØ A ‘preserved’ EF (defined as LVEF ≥50% or 40–49% for HFmrEF)Ø Elevated levels of NPs (BNP 35 pg/mL and/or NT-proBNP 125 pg/mL)Ø Objective evidence of other cardiac functional and structural

alterations underlying HF

Characteristics of Patients with Reduced and Preserved LVEF

Baseline Variables Reduced EF(<40%, n=1570)

Preserved EF(>50%, n = 880)

P-value

Mean LVEF % 25.9 62.4 <0.001

Age-years 71.8 ± 12 75.4 ± 11.51 <0.001

Female (%) 37.4 65.7 <0.001

Coronary artery disease (%) 48.7 35.5 <0.001

Angina (%) 28.0 22.8 <0.005

Prior myocardial infarction (%) 39 16.6 <0.001

Prior CABG (%) 12.9 5.8 <0.001

Hypertension (%) 84 91 <0.001

Diabetes (%) 38.9 31.7 <0.001

Atrial Fibrillation (%) 23.6 31.8 <0.001

COPD (%) 13.2 17.7 <0.002

Hemoglobin <10 g/dl (%) 9.9 21.1 <0.001

Systolic blood pressure-mm Hg 146 156 <0.001

Bhatia et al, NEJM 2006;355:251-9

ADHERE RegistryPreserved ejection fraction (n=26,322

Age 74Women % 62Hypertension % 77CAD % 50MI hx % 24SBP>140 % 61SBP (mmHg) 152A Fib % 21

COPD/Asthma % 31

Reduced ejection fraction (n=25,865)

Age 70Women % 40Hypertension% 69CAD% 59MI hx % 36SBP>140 % 44SBP (mmHg) 139A Fib% 17COPD/Asthma 27

JACC 2006;47:76-84

Pathophysiology of HFpEF

• It is a heterogeneous disease with multifactorial pathology.

• There is abnormal LV active relaxationØ related to ischemia of cardiomyocytesØabnormality in myocardial energy metabolism

• There is increased diastolic LV stiffnessØ excessive collagen type I deposition àstiff and

noncompliant extracellular matrixØ Inc LVEDP, dec stroke volume à limit cardiac output

Paradigm for HFpEF

• Comorbidities such as obesity, diabetes, chronic obstructive pulmonary disease, hypertension

• Inc Proinflammatory state• Inc Coronary microvascular endothelial inflammation• Dec NO bioavailability, cGMP contents, protein

kinase G activity• Inc resting tension• High diastolic left ventricular stiffness• HF sequence

Case MB

• Mrs MB, 79 year old, presented to ED department with the following symptoms– Increasing symptoms of dyspnea and lower extremity

swelling over the last 4 weeks– Decline in functional capacity and increasingly tired.

• She had a past medical history of – Hypertension à She takes amlodipine 5mg PO OD. – CKD àNon proteinuric (Baseline GFR 45)– No previous history of MI, CAD, PVD or HF

Case MB---Examination

• BP 180/90 with HR 102 bpm and regular• RR of 28 with O2sats 88% on RA• JVP 6cm ASA with +HJR, +3 Pedal Edema• +S3 with soft systolic murmur• Mild wheeze with bilateral diffuse inspiratory

crackles• Abdominal examination---Slight tenderness on

deep palpation in RHC• Other examination was unremarkable

Case MB--- Investigations

• Labs– Na+ 130– K+ 4.2– eGFR 44ml/min– Troponin –ve

• CXR• ECG

Case MB---CXR

• Alveolar pulmonary edema

• Cephalization of blood vessels

• Peri bronchial cuffing• Bilateral small pleural

effusions

Case MB---ECG

Impression So far

Heart Failure

Treatment and Progress

• ED Treatment– Oxygen through nasal cannula– Furosemide 80mg IV stat– IV GTN

• Progress– Clinically improving, BP 140/80– O2 sats 98% with 4L Oxygen through NC– Had good diuresis with 1.5Litres in ED

• Referred to Cardiology and Internal Medicine

What Test would you do Next

• A---BNP• B---TTE• C---BNP and TTE• C---MPS (Myocardial Perfusion Scan) • Coronary Angiogram

Results

• NT-pro BNP– 2800 pg/ml

• TTE– Normal LV size– Concentric LVH– No regional wall motion abnormalities– LVEF 55% by Simpson method– Mild MR and TR– Elevated filling pressures– ASE diastolic indices: moderate diastolic dysfunction

Management on Ward

• Admitted on the internal medicine ward• IV GTN stopped• Started on regular frusemide 40mg IV BD for next

48 hrs• Oxygen weaned down to 2L through NC• Orthopnea and dyspnea improved significantly• Cardiology team reviewed and agreed with plan

Discharge

• Oxygen weaned down and stopped.• Frusemide changed to Oral• Labs at discharge

– Na+ 138– K+ 4.2– e GFR 45ml/min– NT-pro BNP 400

• HF education and cardiology follow up

What is the optimal management to prevent re-admission

• Up titration of existing anti-hypertensive therapies– Target BP <140/90

• Addition of ARB• Addition of MRA• All of the above

Charm Preserved

• Double Blind Multi Centre RCT– 3023 patients randomized into candesartan and

placebo group– 618 centers in 26 countries

• Inclusion Criteria– LVEF >40%– NYHA class II-IV symptoms for at least 4 weeks– History of at least one cardiac hospitalization

• Exclusion Criteria– LVEF less than or equal to 40%

Charm Preserved Results

• In patients with HFpEFand NYHA class II-IV symptoms, the addition of candesartan modestly reduced the rate of HF-related hospitalizations, but had no effect on CV mortality.

Mrs MB Case

• Candesartan was started • Discharge medication included

– Amlodipine 5mg OD– Candesartan 4mg with a plan to titrate it up to

maximum dose of 32mg– Furosemide 40mg BD

TOPCAT TrialTreatment Of Preserved Cardiac Function

Heart Failure with an Aldosterone anTagonist• Multicenter, randomized, placebo-

controlled, trial– N=3,445 patients randomized into

Spironolactone and placebo group– 233 sites in 6 countries

• Mean follow-up: 3.3 years

• Primary outcome: CV mortality, aborted cardiac arrest, or HF hospitalization

Inclusion Criteria• Age ≥50 years• ≥1 sign and symptom of HF:• CXR with HF changes• LVEF ≥45% in prior 6 months • One of the following:

– HF hospitalization in prior 12 months with a component of the inpatient care involving HF management

– Elevated BNP in prior 60 daysExclusion Criteria• MI, CABG, PCI, or stroke in prior 90

days• Severe illness limiting life expectancy

to <3 year• GFR <30 mL/min/1.73 m2 or

creatinine ≥2.5 mg/dL

TOPCAT Analysis

• 35% RRR in primary endpoint among patients enrolled with elevated NP levels, P=0.003

• 15% RRR in primary endpoint among patients enrolled in Americas, P=0.043

Case MB, Follow Up• MB seen in clinic 4 weeks after discharge• Still has NYHA class 2 symptoms• Examination

– HR 80– BP 150/80– JVP, not raised, no edema, clinically euvolemic– Home weight stable at 82 Kg

• Medications– Candesartan now on 32 mg– Furosemide 40mg BD– Amlodipine 5mg

• Labs– Na+ 135– K+ 4.4– eGFR 42 ml/min

Case MB, Follow up

• What would you do next– A Add an MRA– B Increase dose of amlodipine to 10mg– C Add an ACE-I

• Started on MRA

• Doctor, I have read on Google about a new medication. I have spoken to a lot of patients on the heart failure forum. They are on this new drug. Can I also have it?

The Prospective comparison of ARNI with ARB on Management Of heart failUre with preserved ejectioN

fraction (PARAMOUNT) Trial• The PARAMOUNT trial was designed to test the safety

and efficacy of LCZ696 in patients with HFpEF• LCZ696 is combination of two antihypertensives

valsartan and sacubitril.• NT-proBNP is released from the ventricular

myocardium in response to increase in wall stress and levels have a prognostic implication.

• It was hypothesized that LCZ696 would reduce NT-proBNP to a greater extent than the ARB valsartan at 12 weeks, and would be associated with favorable changes in cardiac structure and function at 36 weeks

LCZ696 is a A First-in-Class Angiotensin Receptor Neprilysin Inhibitor

Why it Should Work in HFpEF?

Solomon SD, Zile M, Pieske B, et al Lancet 2012;380:1387-95

key inclusion Criteria Paramount Trial• Double blind randomized

controlled trial• 308 patients randomized

– LCZ696 200mg (n=149)– Valsartan 160mg (n=152)

• Patients were followed up to 12 weeks and then period extended by another 24 weeks.

PARAMOUNT Results• It was found that patients

with HFpEF LCZ696 reduced NT-BNP, a marker associated with worse outcomes in comparison with valsartan.

• There was reduction in left atrial size indicative of reverse left atrial remodeling and improvement in NYHA scores after 36 weeks in comparison with valsartan.

• LCZ696 was well tolerated.

Mrs MB Case

• Mrs MB remained stable up to 6 months • She has a readmission with worsening SOB• Exam in ED

– HR 120/min irregular– BP 130/85– BNP 1500

• What is your impression?

Mrs MB ---ECG

AF with Fast Ventricular Rate

What will be your next steps?

• A---Increase Diuretics• B---Start Beta blockers to lower HR• C---Start Digoxin to lower HR• D---Arrange for Cardioversion• E---Start on oral anticoagulation

AF with HFpEF

• AF and HF frequently co-exist.• Prevalence increases with HF severity (Both

Systolic and Diastolic)– 5 %in NYHA1 and 50% in class 4

• Incidence is higher in HFpEF in comparison to HFrEF– 17% in <70 years of age and 36 % in >70 years of

age

Beta Blockers in HFpEF• Beta blockers are established drugs in HFrEF but

have they got a role in HFpEF?• It should work as

– Control of HTN– Arrythmia prophylaxis– Prolongation of diastolic filling time and reduction of

myocardial ischemia• However role is limited

– Seniors trial– Results of other observational studies and meta

analysis

Beta Blockers in HFpEF

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Rhythm versus Rate ControlAF-CHF Trial

• 1376 with HFrEF with NYHA1 to 4

• Clinically significant AF• Rhythm

– Class 3 antiarrythmics and cardioversion

• Rate– Beta Blockers, Digoxin and AVN

ablation• Follow up of 37 months• The AFFIRM trial also showed

that among patients with non-valvular AF, there was no significant mortality difference between rate-control and rhythm-control strategies

Optimal Heart Rate in AFRACE 2 Trial

• Among patients with permanent atrial fibrillation, what is the effect of lenient <110 bpm compared to strict rate control <80bpm strategies on cardiovascular events?

• Small group of patients had HFrEF

Anticoagulant Choice

Choice of OACMajor Bleeding Events

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Back To Mrs MB Case• Diuretics increased and patient became euvolemic on

day2• Bisoprolol started at a dose of 2.5mg and dose titrated

later to 5mg. • Started on NOAC

– GFR 48• Patient improved and discharged with the following

observations– HR—80bpm– BP125/70

• Geriatric and Cardiology follow up arranged.

ConclusionsHFpEF

• A pleomorphic condition.• The diagnosis appears to be best made by

clinical signs and symptoms supported by echo/doppler (LA volume is best if TD is not available) and Natriuretic peptides.

• Guidelines suggest: Control blood pressure to target levels and carefully manage volume.

• There is no proven evidence-based therapy to reduce mortality.

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References

• Global Public Health Burden Of Heart Failure, CFR, Volume 3, 2017

• Moph.gov.qa/healthyageing• AHA Journal/CircHeartfailure.113• ESC Guidelines for Heart Failure 2016• Shah M et al. Rev Cardiovasc Med. 2001;2(suppl

2):S2–S6• Bhatia et al, NEJM 2006;355:251-9• Adhere Registry, JACC 2006;47:76-84

Any Questions?

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