Heart failure - pathogenesis and current management

HEART FAILURE - PATHOGENESIS AND CURRENT MANAGEMENT

Dr Subhasish DebDept. of General MedicineBurdwan Medical College

Definition “Heart (or cardiac) failure is the patho-

physiological state in which the heart is unable to pump blood at a rate to commensurate with the requirements of the metabolizing tissues or can do so only from an elevated filling pressure”

- Eugine Braunwald

Disease Burden Reliable estimates of heart failure

are lacking in India because of the absence of a surveillance program to track incidence and prevalence

Prevalence in developed countries = 2%

Among people over 65yr = 6-10%

Etiology

1.

2.

3.

CO = HR * stroke volume Intrinsic health of

myocardium Preload Afterload

AFTERLOAD

EDVEDV

PRELOAD

INTRINSIC ACTIVITY

Pathogenesis Described in the context of 3

phases:1. The Index event2. Compensatory mechanism

activationa) Advantagesb) Disadvantages

3. LV Remodeling

INDEX EVENT Anything that causes a loss of

functioning cardiac myocytes My be abrupt in onset (MI) or

insidious (chronic volume or pressure overload states)

It ultimately causes a decline in pumping capacity of the heart

Compensatory mechanism These are activated in the

presence of cardiac injury, allowing patients to sustain and modulate LV function for a period of months to years

I. Activation of sympathetic system:CCF decreased BP in carotid sinus stimulation of CNS inc. sympatheic

outflowAdvantages:1. Stimulates SA node – inc HR2. Symp outflow acts as inotrope – inc CO3. Adrenals stimulated – release of adrenaline –

inc HR & CO4. Venoconstriction – inc EDV – inc stroke volume

II. Activation of RAASStimulus : decreased renal perfusion

due to 1. dec CO 2. inc vasoconstriction due to sympathetic activity

Advantages:1. Angio II is a venoconsrtictor – inc EDV2. Simulates symp nerve endings3. Acts on ZG of adrenals – aldosterone –

retension of salt and water (intinaly good)

3. ADH/vasopressin release: Retention of water Veno and arteriolo constriction

4. ANP & BNP release: Beneficial as they counter the dangerous

effects of other compensation mechanisms. When more salt retained – natriuresis When more water retained – diuresis If vasoconsriction is too much – vasodilatation

Disadvantages of neurohumoral activities

If we allow the compensatory mechanisms to go chronic, don’t correct the underlying cause and do not correct these comp. mechanisms pharmacologically, they bring about disadvantages.

1. Chronic salt and water retension = chronic preload

2. Chronic arterioloconstriction = chronic afterload

These chronic preload and afterload cause rmodeling of the heart

Remodeling Chronic stress causes altered genomic

expression of myocardium which starts producing altered proteins which are not good functionally

Ex of altered protein : CaATPaseCalcium handling is abnormal

Pathophysiology in relation to ventricular function curve

CO

EDV

5

140

In L/min

In ml

23

200 250LVEF =50%HR=72/min

A

B

C

D

A= normalB= uncompensatedC= compensatedD= decompensated

Effect of drugs on ventricular function curve

CO

EDV

5

140

In L/min

In ml

23

200 250LVEF =50%HR=72/min

A

B

C

D

diureticinotrope

Does not ascend in the same pathwhen drugs given

Laplace’s Law Pressure = Tension/Radius Diuretic/ACEi/ARB : radius decreases so

pressure generated inc. Inotrope: increases the tension so

pressure in creases.

Pathophysiology in a nutshell

Index event/ increased work load on heart

Activation of compensatory mechanisms

Compensated HF

Self-defeating effects of compensatory mechanisms

Decompensated HF

Stages of heart Failure NYHA classification:I. AsymptomaticII. Symptoms at moderate physical

activityIII. Symptoms on mild activityIV. Symptoms at rest

ACC/AHA stages of Heart Failure

ARisk Factors

Risk Factors +Structural/Functionalchanges

Risk Factors +Structural/FunctionalChanges +Has clinicalFeatures / ontrearment

Very frequentlyHospitalizedAnd cannot beDischarged Safely orCannot wean offFrom IV ionotropes orOn mechanical assist device orWaiting for heart transplant

B

C

D

SYMPTOMATIC

•HTN•DM•h/o Cardiotoxic drug•Rhumatic fever•f/o cardiomyopathy

•Wall Hypertrophy•Fibrosis•Dilatation•RWMA•Valve lesion•Post MI(scarred heart)

Refractory

AHA stages vs NYHA1. No criteria to treat pts early (stage A)2. NYHA is subjective so cannot be

uniform (pts tell you the symptom)3. Cannot develop a proper prognosis (pt on NYHA III can go to II after

treatment. But once in Stage C can never go back to Stage B. No jumping of stages)

This classification system is intended to complement but not to replace the New York Heart Association (NYHA) functional classification, which primarily gauges the severity of symptoms in patients who are in stage C or D.

Management of Heart failure

1. Initial and serial evaluation of the HF pt

2. Treatment through stages A to D3. Acute Heart Failure

Initial and serial evaluation of the HF patient

1. History and Physical Examination2. Diagnostic tests3. Biomarkers in ambulatory/outpatients4. Biomarkers in hospitalized pts5. Non invasive cardiac imaging6. Invasive cardiac imaging

History and physical examination Thorough history and physical exam

should be obtained/performed to identify cardiac and non cardiac disorders

A 3 generation family hist. in pts with idiopathic DCM

Assessment of volume status and vital signs Weight Peripheral edema JVP estimate Orthopnea

Diagnostic tests Initial labs:

I. CBCII. Urine r/eIII. Electrolytes (including Ca & Mg)IV. BUN, CrV. FBS, PPBSVI. LFTVII. Fasting lipidVIII. TSH

Serial monitoring with electrolytes and RFT

Biomarkers in ambulatory/outpatients

BNP and NT-proBNP for supporting clinical decision making regarding diagnosis

BNP and NT-proBNP for prognosis

Biomarkers in Acute/Hospitalized BNP and NT-proBNP for supporting

clinical decision making regarding diagnosis

BNP and NT-proBNP for prognosis

Non invasive cardiac imaging CXR to assess cardiac size, pulmonary

congestion and to detect other cardiac or non cardiac disease

2D echo with doppler to asses:1. EF2. Wall thickness3. Wall motion 4. Valve function

Repeat measurement of EF in:1. HF pts with significant change in clinical

status2. Who have recovered from a clinical event3. Who may be candidates for device

therapy

Invasive cardiac imaging Invasive hemodynamic monitoring with

pulmonary artery catheter should be performed to guide therapy in patients who have reparatory distress or clinical evidence of impaired perfusion in whom adequacy or excess of intracardiac filling pressure cannot be determined from clinical assessment

Management of Heart failure

1. Initial and serial evaluation of the HF pt2. Treatment through stages A to D

3. Acute Heart Failure

STAGE A Htn and lipids should be managed as per

contemporary guidelines

Other risk factors such as DM, tobacco smoking, obesity, cardiotoxic agents should be controlled or avoided

STAGE B Pts with recent or remote h/o of MI or

ACS and reduced Ef, ACEi should be used to prevent symptomatic HF and reduced mortality

For all pts. with a recent or old h/o of MI or ACS and reduced EF, evidence based beta blockers should be used to reduce mortality

For all pts. with a recent or old h/o of MI or ACS statins should be used to reduce symptomatic HF and cardiovascular events

In patients with structural cardiac abnormalities, including LV hypertrophy, in the absence of a history of MI or ACS, blood pressure should be controlled in accordance with clinical practice guidelines for hypertension to prevent symptomatic HF

ACE inhibitors should be used in all patients with a reduced EF to prevent symptomatic HF, even if they do not have a history of MI

Beta blockers should be used in all patients with a reduced EF to prevent symptomatic HF, even if they do not have a history of MI

STAGE C – Non pharmacological t/t

Device therapy in HFrEF ICD for primary prevention of SCD in

1. HFrEF, 40 days post MI2. NYHA class II or III3. LVEF <= 35%4. On chronic GDMT and expected to live >1

yr ICD for primary prevention of SCD in

1. HFrEF, 40 days post MI2. NYHA class I3. LVEF <=30%4. On chronic GDMT and expected to live >1

yr

Sudden Cardiac Death Sudden cardiac death (SCD) is an

unexpected death due to cardiac causes that occurs in a short time period (generally within 1 hour of symptom onset) in a person with known or unknown cardiac disease.

Implantable Cardiac Defibrillator ICD keeps track of each beat If heart goes into a fast rhythmwhich is potentially life threatening -- SHOCK

Cardiac Resynchronization therapyBACKGROUND: Approx 25% pts with CHF have

intraventricular conduction delay; commonly LBBB

Electrical activation of lateral aspect of LV can be delayed in relation to that of RV and/or IV septum

This results in:1. Dyssynchronous electrical activation and

contraction2. Unequal distribution of myocardial work load3. Altered myocardial blood flow and

metabolism

Lateral view X-ray of 1st successful cardiac resynchronization therapy

University hospital of Rennes, 1994

Simultaneous pacing ofRV & LV = BIVENTRICULARPACING Leads in RA, RV & LV LV paced via coronary sinus

Stage D A subset of patients with chronic HF will

continue to progress and develop persistently severe symptoms despite maximum GDMT.

Various terminologies have been used to describe this group of patients who are classified with ACCF/AHA stage D HF, including “advanced HF,” “end-stage HF,” and “refractory HF.”

In the 2009 ACCF/AHA HF guideline, stage D was defined as “patients with truly refractory HF who might be eligible for specialized, advanced treatment strategies, such as MCS, procedures to facilitate fluid removal, continuous inotropic infusions, or cardiac transplantation or other innovative or experimental surgical procedures

Fluid restriction (1.5 to 2 L/d) is reasonable in stage D, especially in patients with hyponatremia, to reduce congestive symptoms.

Ionotropes: Until definitive therapy (eg, coronary

revascularization, MCS, heart transplantation) or resolution of the acute precipitating problem, patients with cardiogenic shock should receive temporary intravenous inotropic support to maintain systemic perfusion and preserve end-organ performance.

Cardiac transplant: Evaluation for cardiac transplantation is

indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management

Management of Heart failure

1. Initial and serial evaluation of the HF pt2. Treatment through stages A to D3. Acute Heart Failure

ACUTE HEART FAILURE

ESC guidelines for diagnosis and treatment of acute HF

AHF Definition: Rapid onset or change in signs and

symptoms of heart failure, resulting in the need of urgent therapy.

It may present as new HF or worsening HF in presence of chronic HF

Diuretic tit-bits Bumetanide – most potent Torsemide – longest T ½ (24 hr action) Drug interactions:

1. Thiazide/loop diuretic with Digitalis – hypokalemia casing digitalis toxicity

2. ACEi with spironolactone – hyperkalemia can cause cardiac arrest in diastole. (*hypercalcemia causes cardiac arrest in systole)

3. loop diuretic with aminogylcoside – ototoxicity Spironolactone in HF heart failure (provided

CrCl >30 mL/min and serum K <5 mEq/dL)

Some new drugs in HF management Nesiritide:

Synthetic form of BNP Causes natriuresis and diuresis Rapidly metabolized by vasopeptidase (a

neutral endopeptidase) thus given in infusion

Carperitide: ANP analogue

Uralitide: Analogue of Urodilatin which is a peptide

like ANP and BNP

Ompatrilat & Sampatrilat: Inhibits neutral endopeptidase Also inhibits ACE

Levosimendan & Pimobendan: Ca sensitisers Has phosphodiesterase III blocking property

(levosimendan) Isteroxine:

Na K atpase pump (like digitalis)

Cinacigaut: Nitrates act by stimulating guanyl cyclase

to produce NO for vasodilatation In guanyl cyclase resistant people direct

stimulaton by this compound Aka Bay compounds

studied in 12 patients with severe congestive heart failure and compared with those of dopamine in 10 clinically similar patients. Dobutamine produced a distinct increase in cardiac index, while lowering left ventricular end-diastolic pressure and leaving mean aortic pressure unchanged. Dopamine also significantly improved cardiac index, but at the expense of a greater increase in heart rate than occurred with dobutamine.

Because it has comparatively little effect on heart rate and aortic pressure, both major determinants of myocardial oxygen consumption, it may be of special value in patients with the low output syndrome associated with coronary heart disease

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