Heart Failure

Question 1

heart failure

Answer 1

•Heart failure is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood.

A CLINICAL DIAGNOSIS All HF patients, regardless of ejection fraction status (EF value), have the clinical syndrome of heart failure (HF).

Question 2

heart failure epidemiology

Answer 2

• In the US 6.5x 10⁶ have it
• Over age 65 years incidence: 10 per 1000
• > 68,000 die per year with HF as 1⁰ Dx
• 2.4-3.6 X 10⁶ hospitalized per year
• 40—50% annual mortality rate
• Women: More have it and more die of it than men
• blacks have the highest risk for HF

Question 3

two most common underlying causes of HF

Answer 3

• coronary artery disease
• hypertension
• CORONARY ARTERY DISEASE 60-75%
• HYPERTENSION IN 75% INCLUDING THOSE WITH CAD
• CAD, HTN AND DIABETES INTERACT TO AUGMENT RISK
• 20-30% of cases of HFrEF cause is unknown = nonischemic or dilated or idiopathic cardiomyopathy

Question 4

the two presentations of HF in terms of LVEF

Answer 4

LV EJECTION FRACTION = SV/EDV

HFrEF EF ≤ 50%

HFpEF EF ≥ 50% I

t is only in HFrEF that evidence - based pharmacotherapy has been demonstrated to confer morbidity and mortality benefits (M&M).

Question 5

HFrEF

Answer 5

• EF≤ 40%
• Also referred to as systolic HF.
• Trials of pharmacotherapy have mainly enrolled subjects with HFrEF, and it is only in these patients that therapies with morbidity/ mortality benefits have been shown
• coronary artery disease
• HTN –> LVH –> increased O2 demand

Question 6

HFpEF

Answer 6

• EF ≥ 50% Most common EF normal, SV low - not filling up enough, reduced preload
• Also referred to as diastolic HF.
• Various criteria have been used to further define HFpEF.
• The diagnosis is one of exclusion of other potential noncardiac causes of symptoms suggestive of HF.
• To date efficacious therapies have not been identified
• hypertension –> LVH –> less room
• aortic stenosis
• hypertrophic cardiomyopathy
• restrictive cardiomyopathy
• ABOUT 50% OF PERSONS WITH HF
• RELATIVELY NORMAL LV FUNCTION
• DIASTOLIC HF
• CARDIAC OUTPUT LIMITED BY:
• ABNORMAL LV FILLING
• DISORDERED VENTRICULAR RELAXATION DURING EXERCISE
• VENTRICULAR PRESSURES ELEVATED FOR A GIVEN VOLUME WITH: PULMONARY CONGESTION DYSPNEA PERIPHERAL EDEMA
• OLDER WOMEN WITH

a-FIBRILLATION

• HTN

–DM

-OBESITY CKD

• HYPERTENSION THE CAUSE IN ~ 60% TO 89%

Question 7

other causes of HF

Answer 7

*Genetic defects Most are autosomal dominant

-Genes that encode cytoskeletal proteins

• Alcohol
• Cancer chemotherapeutic agents

-Trastuzumab (Herceptin®)

–Anthracyclines - Adriamycin 

•Cocaine

Question 8

associated disorders

Answer 8

DISEASES OF:

 PERICARDIUM

 MYOCARDIUM

 HEART VALVES

 GREAT VESSELS

 PERIPHERAL VESSELS

 METABOLIC ABNORMALITIES

Question 9

clinical syndrome

Answer 9

 DYSPNEA

 FATIGUE EXERCISE INTOLERANCE

FLUID RETENTION

Sx 2 0 to impaired LV function

ECHO evidence of systolic and / or diastolic dysfunction

Pulmonary/splanchnic congestion & Peripheral edema

Exercise intolerance little fluid retention

Others c/o edema, dyspnea or fatigue

 No single diagnostic test

 A clinical Dx based on Hx & PE

Question 10

All HF Patients, Regardless of EF value, Have the Clinical Syndrome HF

Answer 10

• Abnormal left ventricular (LV) filling dynamics
• Elevated LV diastolic pressure
• LV systolic and diastolic dysfunction
• Neurohormonal activation
• Impaired exercise tolerance, frequent hospitalization, and reduced survival.

Question 11

The Clinical Manifestations of HF are Similar Regardless of the EF

Answer 11

• Reduced exercise tolerance
• Dyspnea on exertion
• Orthopnea
• Paroxysmal nocturnal dyspnea
• Peripheral edema
• Pulmonary congestion apparent on chest radiographs or computed tomography (CT) scans

Question 12

Answer 12

Question 13

Answer 13

Question 14

Answer 14

Question 15

HF Classification

Answer 15

• NYHA A functional classification-Sx Classes I-IV
• ACC/AHA Stages using risk factors and structural abnormalities Stages A-D

Question 16

precipitating causes of HF

Answer 16

PRECIPITATING CAUSES

• Arrhythmias
• Thyrotoxicosis
• Pregnancy
• Myocarditis
• Myocardial infarction
• PE
• Infective endocarditis
• Infection
• Hypertension
• Anemia
• Physical, dietary, fluid, environmental or emotional excesses

Question 17

HF Neurohumoral activation

Answer 17

• RENIN ANGIOTENSIN ALDOSTERONE ANGIOTENSIN II (Ang II) ALDOSTERONE
• SYMAPATHETIC NERVOUS SYSTEM NOREPINEPHRINE (NE)
• VASOPRESSIN(ADH)
• ENDOTHELIN
• CYTOKINES
• NATRIURETIC PEPTIDES (BNP, NT-pro- BNP)

Question 18

Indicators of Cardiac Stress, Malfunction & Injury

Answer 18

 Inflammation – TNF, Interleukins & CRP

 Oxidative stress – Oxidized low density lipoproteins

 Neurohormonal pathway activation – NE, Ang II, Aldosterone, ADH & Endothelin

 Extracellular matrix remodeling – Matrix metalloproteinases

 Myocyte injury – cardiac specific troponins ***diagnosis

 Myocyte stress – Brain natriuretic peptide (BNP) & N-terminal pro-BNP (NT pro-BNP)

***diagnosis and monitoring

Question 19

LV REMODELING IN HFrEF

Answer 19

• LV remodeling develops in response to a series of complex events that occur at the cellular and molecular levels. These changes include:
• (1) Myocyte hypertrophy
• (2) Alterations in the contractile properties of the myocyte
• (3) Progressive loss of myocytes through necrosis, apoptosis, and autophagic cell death
• (4) β-adrenergic desensitization
• (5) Abnormal myocardial energetics and metabolism
• (6) Reorganization of the extracellular matrix

Question 20

Determinants of Myocardial Function

Answer 20

Preload - determines volume and therefore sarcomere length

Contractility – determined by Ca²⁺ availability

Afterload - determines how much work the heart must do to successfully eject blood

Heart rate - contributes to Ca²⁺-loading of SR and therefore contractility

Question 21

source of natriuretic peptides

Answer 21

SOURCE

• BRAIN
• HEART
• VASCULATURE
• KIDNEY

Question 22

action of natriurectic peptides

Answer 22

• VASODILATION
• NATRIURESIS
• RAAS INHIBITION
• SNS INHIBITION
• ANTIPROLIFERATIVE
• ANTIHYPERTROPHIC

Question 23

BNP

Answer 23

 Dx of HF

 Association between concentration and severity

 Correlates with neurohormonal activation: SNS, RAAS & Endothelin

 Assessment of response to therapy

Question 24

BIOMARKERS OF RESPONSE TO CARDIAC INJURY/ STRESS

Answer 24

NEUROHORMONAL ACTIVATION – NE – ANG II – ADH – ALDOSTERONE – ENDOTHELIN

Question 25

Activation of the SNS

Answer 25

Question 26

HF PATHOPHYSIOLOGY NOREPINEPHRINE

Answer 26

* ↑CONTRACTILITY & HEART RATE * ↑VENTRICULAR PRELOAD & AFTERLOAD * CONSTRICTION AFFERENT GLOMERULAR ARTERIOLE * ↑RENIN * ↑PROXIMAL TUBULAR Na⁺ REABSORPTION * ↓REGULATION OF β-1 RECEPTORS

Question 27

activation of the RAS

Answer 27

Question 28

HF PATHOPHYSIOLOGY ANGIOTENSIN II

Answer 28

Angiotensin II actions are similar to those of norepinephrine and also include: * Increase in CNS sympathetic outflow * Enhancement of peripheral noradrenergic (norepinephrine) neurotransmission * Release of aldosterone * Actions on myocytes and other cells to alter cardiovascular structure and function = remodeling

Question 29

HF PATHOPHYSIOLOGY ALDOSTERONE

Answer 29

Aldosterone, released from the adrenal cortex and produced locally, has actions that include: * Increase in renal reabsorption of Na+ and H2O and increased renal excretion of K+ /H⁺ * Stimulation of collagen synthesis causing fibrosis (remodeling)

Question 30

HF PATHOPHYSIOLOGY ANTIDIURETIC HORMONE (VASOPRESSIN)

Answer 30

Antidiuretic hormone: release occurs as a consequence of baroreceptor activation by low cardiac output. The actions which serve to increase blood pressure and cardiac preload include: * Vasoconstriction with increase in systemic vascular resistance * Stimulation of thirst * Increase in water reabsorption in the renal collecting ducts

Question 31

functional modifications of neurohormonal activation in HF

Answer 31

* increased inotropy - maintaining CO * increased heart rate - maintaining CO * vasoconstriction - maintains BP * salt and water retention -preload increase, maintaining CO this leads to ... * increased energy demand * altering loading conditions * altered vascular/diastolic properties * proarrhythmogenic effect

Question 32

structural modifications of neurohormonal activation in HF

Answer 32

* hypertrophy * increased nonmuscular tisue * increased expression of adult cardiac genes this leads to ... * increased energy demand * altering loading conditions * altered vascular/diastolic properties * proarrhythmogenic effect

Question 33

Homeostatic Responses to Impaired Cardiac Performance (Due in part to activation of the renin-angiotensin-aldosterone system (RAAS) and of the sympathetic nervous system).

Answer 33