Rollington Ferguson, M.D., F.A.C.C.

Systolic Heart Failure

Pathophysiology Etiologies

Clinical Evaluation
Treatment

Acute Physiologic Responses to Systolic Dysfunction

Initiator
Insult to LV Function (e.g. MI, Myocarditis)

Acute Adaptation
Neurohormonal Activation (SNS, RAAS, AVP)

CO BP

Increased Preload volume (Frank- Starling) Tachycardia, vasoconstriction, contractility, Na+ & volume retention

Preserve Co and systemic pressures

Cellular Responses
Hypertrophy ( protein synthesis, shift toward fetal gene expression )

Insult leads to: 1. Change in neurohormonal milieu 2. Change in local environment (wall stress)

Activation of signaling pathways

Myocyte dysfunction, apoptosis, matrix changes , fibrosis

Progressions of Ventricular Dysfunction and HF

Ventricular Remodeling

Key Neurohormonal mediators in HF

Neurohormone

__________________________________________________________________________________________ Bad Mediators Good Mediators __________________________________________________________________________________________ Norepinephrine (NE) Natriuretic peptides (NP) Angiotensin ll (Ang ll) Nitric Oxide (NO) Aldosterone (aldo) Prostacyclin (PGI2) Endothelin (ET) Tumor Necrosis Factor (TNFa) Vasopressin (AVP) _________________________________________________________________________________________ Cellular/ Organ Level effects Stimulate hypertrophy, remodeling, fibrosis, apoptosis, fetal gene expression, Anti-hypertrophic Anti-proliferative

contractile abnormalities Vasodialtory __________________________________________________________________________________________ Integrated Lead to vasoconstriction, Relax ventricular loading Pathophysiology sodium and fluid retention, Conditions, promote Diuresis, anti-Effects endothelial dysfunction remodeling, Enhance endothelium

Extracardiac Sequelae
Renal Dysfunction Skeletal muscle changes/atrophy

Cytokine Activation (cardiac cachexia)

Hepatic Congestion/dysfunction/ascites Anemia

Endothelial Dysfunction

Coronary Artery Disease

Most common cause of SHF (65%) USUALLY clinically obvious

Most have hx of MI 7% of primary DCM

CAD is a reversible causepotential to

significantly improve LV function with revascularization if viable

Idiopathic Dilated Cardiomyopathy

Most common single cause after coronary

disease
50% of cases of initially unexplained DCM

Diagnosed when all other causes have been

excluded

Toxin-Induced Cardiomyopathy
Alcohol has direct acute and chronic toxic effects on the

myocardium

Alcoholic cardiomyopathy typically diagnosed in a heavy drinker (7 drinks/day for 5 yrs) with DCM in the absence of other causes
Cocaine and other catecholaminergic drugs cause DCM Chemotherapeutic agents commonly cause DCM

(anthracyclines, cyclophosphamide, trastuzumab) Radiation-induced (often restrictive CM constriction)

Infectious and Inflammatory Causes

Coxsackie B, influenza, adenovirus Mycoplasma pneumoniae Lyme disease HIV, HCV Chagas diseaseendemic in South and Central America; caused by Trypanosoma cruzi, predilection to form aneurysms Lupus, scleroderma, RA, Kawasaki, Churg-Strauss, others Hypereosinophilic syndrome (Loefflers) Inflammatory causes may respond to corticosteroids/immunosuppressive Rx

Familial Dilated Cardiomyopathy

20-30% of all idiopathic DCM Can be autosomal dominant, X-linked,

autosomal recessive, or mitochondrial Muscular dystrophiesX-linked, elevated CK, confirm with diagnosis with muscle biopsy Hereditary Hemochromatosis ECG and echo for all 1 relatives

Peripartum Cardiomyopathy
Development of HF + EF in the last month or first 5 months

post partum in the absence of other causes or pre-existent heart disease Risk factors include HTN, multiparity, age, preeclampsia, genetics, prior PPCM Etiology: immune vs. pre-existent occult LV dysfunction Half of women normalize LVEF at 6 months (good prognosis) No ACEI/ARBs for baby! (substitute iso/hydral if still pregnant), BB, diuretics, digoxin all OK Women who fail to normalize LVEF should be strongly discouraged about becoming pregnant, those who normalize more controversial

Stress-Induced Cardiomyopathy
Synonyms include Tako-Tsubo, apical ballooning, or

broken heart syndrome Reversible cause of acute systolic dysfunction, resembles large anterior MI Associated with emotional, surgical or other dramatic stresses and catecholamine surge Improves over days to weeks, usually with complete resolution of LV function

Endocrine/Nutritional Causes
Hypothyroidism>thyrotoxicosis (latter more likely high

output HF) Diabetes Mellitus Obesity Acromegaly and GH deficiency Pheochromocytoma Thiamine (wet beriberihigh output form) Carnitine, Selenium Treatment is to correct underlying abnormality (replace deficiencies, render euthyroid, etc.)

Iron Overload Cardiomyopathy

Can be 1 (hereditary hemochromatosis, HH) or 2

(polytransfusions for sideroblastic anemia or thalassemia) HH is autosomal recessive, common in Northern Europeans (1/200), Fe2+ deposition in heart, joints, liver, exocrine/endocrine glands, skin (bronze diabetes) ferritin, iron/TIBC>50% Gold standard diagnosis is with liver biopsy, also can use cardiac MRI or endomyocardial biopsy Treat with phlebotomy or chelation therapy Screen 1 family members

Tachycardia-Mediated Cardiomyopathy
Often cannot discern whether tachycardia is

primary force driving the cardiomyopathy or secondary phenomenon Treatment of heart rate improves and can normalize LV function

Pharmacologic, cardioversion, or ablation

Hypertensive Cardiomyopathy
Hypertension is the single largest modifiable risk factor for heart failure

Typically seen in patients with severe

chronic HTN who with no other identifiable cause

Infiltrative Cardiomyopathies
Typically produce a restrictive cardiomyopathy, but

occasionally dilated with systolic dysfunction (especially late)WORST outcomes of all DCM Amyloidserum/urine electrophoresis; low ECG volts + LVH on echo; confirm with endomyocardial biopsy Sarcoidpatchy inflammatory granulomas, dx on biopsy and/or with scintigraphy/MRI, can Rx with immunosuppressive

ACC/AHA Staging System of Heart Failure

Stage ARisk factors for HF (CAD, HTN, DM,

MS, obesity, family hx, cardiotoxic drugs) Stage BStructural heart disease but no symptoms (e.g. LVH, MR, low EF) Stage CSymptomatic HF that can be managed predominantly as an outpatient Stage DAdvanced, severe HF with frequent hospitalizations, requiring advanced therapies

NYHA Functional Classification

Class Ipatients with disease but no symptoms that

limit activity. Class IIpatients with slight limitation of physical activity related to symptoms of HF (dyspnea, fatigue) Class IIIpatients with marked limitations of physical activity, but no symptoms at rest Class IVpatients cannot carry out any physical activity without limitation and may have symptoms even at rest

Goals of Evaluation
Determine Etiology

Treat reversible causes (e.g. ischemia) directly Prognostic significance Determine Functional class History Cardiopulmonary Exercise test or 6 minute walk Certain therapies only recommended for higher NYHA class Determine Ventricular size and function Guides treatment decisions, prognostic value Establish Volume status Determine need for diuretics

Diagnostic Evaluation (Class I)

History Symptoms Establish NYHA class Look for history of angina, syncope, arrhythmia Clues to etiology Alcohol or illicit drug use Family history of CAD, heart failure, sudden death Prior history of chemotherapy or radiation Antecedent viral prodrome

Physical Exam Pearls for chronic SHF

Appearance State of mentation (low output), cachexia Jugular distention prominent V wave Lungs Usually clear with chronic HF, pleural effusions common Cardiac Cardiomegaly on palpation, dyskinesis from aneurysm Soft S1 (low contractility 1 AV block) +S3 (congestion), +S4 (stiff LV congestion) Loud P2 (pulmonary hypertensionusually secondary) Mitral and tricuspid regurgitation murmurs common Abdomen Pulsatile hepatomegaly, ascites Extremities Cool (vasoconstriction from low output), pitting edema Pulses Diminished, Pulsus Alternans in severe LV dysfunction

Diagnostic Evaluation (Class I)

Laboratory

Chemistries, renal function, CBC, LFTs, TSH, HbA1c, lipids, BNP or NTproBNP (IIahigh negative pred. value) Chest Radiography Electrocardiogram Echocardiogram

UA,

Rule out CAD

Coronary Angiography:

Class I if angina or known ischemia Class IIa if atypical CP, known, or suspected CAD Noninvasive stress imaging: Class IIa if known CAD but no angina Class IIb to define likelihood of CAD Wall motion/perfusion defects common in nonischemic HF Bottom Line: Usually go straight to Angiogram

Endomyocardial Biopsy
Usually not indicated in systolic HF(class III for routine evaluation of systolic HF) Only useful if results are likely to influence therapy: Sarcoidosis, amyloidosis Hypereosinophilic Syndrome or hypersensitivity myocarditis Hemochromatosis Fulminant Myocarditis Giant Cell Myocarditis Drug toxicities (hydroxychloroquine, doxorubicin) Somewhat controversial when to biopsy Will either show clues for infiltration or else acute presentation of new HF with rapidly progressive, unstable hemodynamics, severe symptoms

Other Evaluations
Other labs (class IIa), especially for those at risk:

Iron studies, HIV, protein electrophoresis, autoimmune serologies and inflammatory markers, endocrine/metabolic Cardiopulmonary Exercise testing Determine cardiac versus noncardiac cause of symptoms Quantify severity in consideration of advanced therapies (<14 ml O2/kg*min) Evaluation for sleep disordered breathing Stress imaginglack of specificity (nuclear/echo) Cardiac MRImay be useful in iron overload, sarcoid, myocarditis, viability, pericardium, othersevolving modality

 Synonyms Systolic heart failure Heart failure with reduced ejection fraction Typically ejection fraction 40%

NON-PHARMACOLOGIC TREATMENT OF HEART FAILURE

Acute or chronic, reduced or normal EF

Nutritional counseling

Sodium restriction Fluid restriction Alcohol Daily weights, symptom assessment, action plan Regular physical activity Compliance

Patients and family/ caregivers receive individualized education and counseling that emphasizes self-care. Adequate f/u.

DRUGS TO AVOID IN PATIENTS WITH HEART FAILURE WITH REDUCED EF

Nonsteroidal anti-inflammatory Most antiarrhythmics

Most calcium channel blockers

Felodipine, amlodipine likely safe

Thiazolidinediones

Pioglitazone (Actos), rosiglitazone (Avandia)*

GOALS OF TREATMENT
FEEL BETTER
Minimize congestion
Reverse remodel the ventricle (or stall remodeling process )

LIVE LONGER

ICD

DIURETICS
Fluid overload, dyspnea; never use as

monotherapy in heart failure with reduced EF even if symptoms are controlled Further aggravates neurohormonal and sympathetic nervous system derangements Potentiates effects ( BP) and side-effects ( creatinine) of ACE-I Loop > thiazide (espec if renal insuffic) Role for metolazone (potentiate loop), spironolactone (reduce hypokalemia)

At Risk for Heart Failure

Stage A At high risk for HF but without structural heart disease or symptoms of HF e.g.: Patients with: Hypertension Atherosclerotic disease Diabetes Metabolic syndrome or Patients Using cardiotoxins With HFx CM
Therapy Goals Treat hypertension Encourage smoking cessation Treat lipid disorders Encourage regular exercise Discourage alcohol intake, illicit drug use Control metabolic syndrome Drugs ACEI or ARB in appropriate patients

Heart Failure
Stage C Structural heart disease with prior or current symptoms of HF Stage D Refractory HF requiring specialized interventions e.g.: patients Who have marked symptoms at rest despite maximal medical therapy (e.g. those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions) e.g.: Patients with: Hypertension Atherosclerotic disease Diabetes Metabolic syndrome or Patients Using cardiotoxins With HFx CM

Stage B Structural heart disease but without symptoms of HF

e.g.: Patients with: previous MI LV remodeling Including LVH and low EF asymptomatic Valvular disease

e.g.: Patients with: Known structural heart disease And Shortness of breath and fatigue, reduced exercise tolerance
Therapy Goals all measures under stages A and B Dietary for Routine Use Diurectic for fluid retention ACEI Beta-Blockers Drugs in selected patients Aldosterone antagonist ARBs Digitalis Hydralazine/nitrates Devices in selected Patients Biventricular pacing Implantable

Therapy Goals All measures under stage A Drugs ACEI or ARB in appropriate patients Devices in selected patients Implantable defibrillators

ACE INHIBITORS Key Points

Start low dose, up titrate to target Contraindications:

doses from trials Check K+, creatinine within 1-2 weeks of each dose increase Minimize coincident ASA dose

Hx life-threatening adverse effects Hypotension Creatinine >3 g/dL Bilateral renal artery stenosis K+5.5 mmol/L

Bradykinin System Kininogen

Angiotensin System Angiotensinogen Renin

Endothelium +

Bradykinin +

Angiotensin I

ACE

+ Angiotensin II

Prostaglandins Nitric oxide

Inactive peptide
Vasoconstriction

Vasodilation

aldosterone Cell growth

ARBs Key Points

ACE-I remain drug of first choice to inhibit

renin-angiotensin-aldosterone system Use ARB instead of ACE-I if history of cough or angioedema with ACE-I Evidence of benefit from addition to ACE-I is soft All comments about ACE-I starting dose, titration, lab monitoring, and non-allergic contraindications also apply to ARBs

BETA BLOCKERS Key Points

Favor use of carvedilol, metoprolol

succinate, bisoprolol Start at low dose, slowly up-titrate Delay starting if significant volume overload or hypovolemia Relative contraindications: Reactive airways disease, asymptomatic bradycardia, DM with recurrent hypoglycemia, resting limb ischemia

ALDOSTERONE ANTAGONISTS Key Points

Limited study populations

NYHA III-IV HF; post-MI reduced EF with either Killip 2 or DM Caution re:use and dose if creat >1.5 mg/dL (creat cl <50 ml/min) or K+ >5 mmol/L Close surveillance of K+ and creat Avoid K+ and salt substitutes

ALDOSTERONE ANTAGONISTS Key Points

Limited study populations

NYHA III-IV HF; post-MI reduced EF with either Killip 2 or DM Caution re:use and dose if creat >1.5 mg/dL (creat cl <50 ml/min) or K+ >5 mmol/L Close surveillance of K+ and creat Avoid K+ and salt substitutes Urgently address diarrhea or other causes of dehydration

DIGOXIN Key Points

Symptomatic improvement, reduce

hospitalizations in patients with mild to moderate heart failure Minimally studied in pts on ACE-I and -blockers DIG Study subanalysis Less effective in women than men Optimal target level 0.6-0.9 ng/dL Drug interactions: Amiodarone, verapamil, quinidine

NITRATE - HYDRALAZINE Key Points

For patients who develop hyperkalemia

or renal dysfunction with ACE-I or ARBs In addition to ACE-I and -blocker therapy in African-American patients who have persistent NYHA class II-IV symptoms

 VT, ICD, CRT Dr. Charles Athill

Congestion?
Orthopnea, rales, JVD, ascites, edema

No
Dry And Warm Dry And Cold

Yes
Wet And Warm Wet And Cold

Yes Adequate Perfusion?

Pulse pressure, cool extremities, altered mentation

No

Congestion?
Not presenting as ADHF Orthopnea, rales, JVD, ascites, edema

No
Dry And Warm Dry And Cold

Yes
Wet And Warm Wet And Cold

Yes Adequate Perfusion?

Pulse pressure, cool extremities, altered mentation

No

Congestion?
Orthopnea, rales, JVD, ascites, edema

No
Dry And Warm Dry And Cold

Yes
Wet And Warm Wet And Cold

Yes Adequate Perfusion?

Pulse pressure, cool extremities, altered mentation

Gently hydrate, then vasodilate

No

Congestion?
Orthopnea, rales, JVD, ascites, edema

No
Dry And Warm Dry And Cold

Yes
Wet And Warm Wet And Cold Diurese, inotropes, vasodialte

Yes Adequate Perfusion?

Pulse pressure, cool extremities, altered mentation

No

TREATMENT OF HEART FAILURE

WITH REDUCED EJECTION FRACTION Key Points
Guidelines Importance of pathophysiology

All: Non-pharmacologic treatment, diuretics are a deal with the devil Chronic: Neurohormonal blockade to reverse remodel ADHF: Classify wet/dry and perfusion status; after load affects output; get on right meds pre-discharge

TREATMENT OF HEART FAILURE WITH REDUCED EJECTION FRACTION Key Points

Guidelines Importance of pathophysiology

All: Non-pharmacologic treatment, diuretics are a deal with the devil Chronic: Neurohormonal blockade to reverse remodel ADHF: Classify wet/dry and perfusion status; afterload affects output; get on right meds pre-discharge End-stage: Pt may need unblocked RAAS and sympathetic NS to survive