cardiovascular remodeling and it's prevention

Good Afternoon

ROLE OF DRUGS IN PREVENTING THE

REMODELING OF CARDIOVASCULAR

SYSTEM IN FOLLOW UP OF HF PATIENT

ROLE OF DRUGS IN PREVENTING THE

REMODELING OF CARDIOVASCULAR SYSTEM IN FOLLOW UP OF HF PATIENT

PRESENTED BY- SUBRATA DAS

ASISH BARUI

Definition- This is a clinico-pathological condition in whichheart cannot maintain adequate cardiac output to meet theMetabolic demand of the tissue in response to normal venous reterurn

HEART FAILURE

• Cardiac injury –> depressed cardiac function poor tissue perfusion

• Cardiac output must increase– Activation of neurohormonal axis– Norepi, AVP, angiotensin II, endothelin

• Chronic NH release is dysfunctional– Alterations in HR, contractility– Myocardial hypertrophy and ischemia

PATHOPHYSIOLOGY

Neurohormonal changes

CHF Vicious Cycle

LOW CARDIAC OUT PUT

Increased Preload Increased Aft erload Norepinephrine

Increased Salt Vasoconstricti on Renal Blood Flow

ReninAngiotension IAngiotension IIAldosterone

Circulating and local (tissue) RAS influence on the cardiovascular system

Circulating RASShort-term effects

Sodium/water reabsorption via aldosterone secretion

Local RASLong-term effects

Intraglomerular hypertension

Vascular hypertrophyby Increase production of

growth factors &extracellular matrix

HeartHeart

VasoconstrictionPositive chronotropic effects/ arrhythmogenic effects

Myocardial hypertrophy

ANGIOTENSIN II

BradykininAngiotensin I

Angiotensin IIACE inhibitor

AT1-blocker

VasodilatationNatriuresisExtracellular matrix degradationAngioedema

HypertensionAldosteroneTransforming growth factor Plasminogen activator

AT1Receptor AT2Receptor

Sympathetic stimulation

•Myocyte apoptosis•Hypertrophy•Focal myocardial necrosis

-blocker

Angiotesinogen

Renal hypoxia

Central Sympathetic stimulation

-blocker

Reduced cardiac output

Myocardial inadequacy

Cardiovascular remodeling

Digitalis

ACE INHIBITORs• ACE inhibitors interfere with the renin-

angiotensin system by inhibiting the enzyme that is responsible for the conversion of angiotensin I to angiotensin II.

• However, because ACE inhibitors also inhibit kininase II, they may lead to the upregulation of bradykinin, which may further enhance the beneficial effects of angiotensin suppression.

• ACE inhibitors stabilize LV remodeling, improve symptoms, reduce hospitalization, and prolong life

DRUGS & DOSE

Angiotensin-converting enzyme inhibitor

Initiating Dose Maximal Dose

Captopril 6.25 mg tid 50 mg tid

Enalapril 2.5 mg bid 10 mg bid

Lisinopril 2.5–5.0 mg qd 20–35 mg qd

Ramipril 1.25–2.5 mg bid 2.5–5 mg bid

Trandolapril 0.5 mg qd 4 mg qd

Angiotensin-converting enzyme inhibitor

Initiating Dose

Maximal Dose

Captopril 6.25 mg tid 50 mg tid

Enalapril 2.5 mg bid 10 mg bid

Lisinopril 2.5–5.0 mg qd 20–35 mg qd

Ramipril 1.25–2.5 mg bid 2.5–5 mg bid

Trandolapril 0.5 mg qd 4 mg qd

β BLOCKERS•Beta blocker block central sympathetic stimulation which activate the RAS & sympathetic stimulation by angiotensin II

•The beneficial affect due to antagonism of ventricular wall stress enhancing, apoptosis promoting and pathological remodeling effects of excess sympathetic activity

•It improve patient symptoms, prevent hospitalization, and prolong life

•The only contraindication is severe decompensate CHFCarvedilol 3.125 mg bid

Bisoprolol 1.25 mg qd

Metoprolol succinate CR 12.5–25 mg qd

DigitalisMechanism of Action

• +ve inotropic effect by ↑ intracellular Ca & enhancing actin-myosin cross bride formation (binds to the Na-K ATPase → inhibits Na pump → ↑ intracellular Na → ↑ Na-Ca exchange

• Vagotonic effect• Arrhythmogenic effect

Drug Initial dose Maintenance dose

Digoxin Tab 0.25 mg -4 tab stat. Tab 0.25 mg -1/2 to 1 tab daily

CONCLUSION

A. Myocardial & vascular remodeling is sing of progressive heart failure

B. Prevention of remodeling is proven benefit using ACE inhibitor, beta blocker & digitalis.

Thank You….

QUESTIONS?