MODULE 3 CHAPTER 1C
HYPERTENSION AND HEART FAILURE
Introduction- Good and Bad news
Good news : Decrease in mortality Advances in therapy Evidence based practice
Bad news : Increase in incidence Advances in therapy Increase in elderly population
Hypertension and Heart Failure
• Hypertension is the commonest cause of heart failure (HF)
• Hypertension predisposes to asymptomatic LV dysfunction,HF with preserved ejection fraction (HFPEF) as well as HF with reduced ejection fraction (HFREF)
• One of the most preventable complications from hypertension management is Heart Failure (HF)
CV Complications of Untreated Hypertension (N=500)
20
5
10
15
20
25
30
35
40
45
50
18
128
16
50
RenalFailure
Stroke Enceph MI Angina CHF
MI, myocardial infarction; CHF, chronic heart failure.Perera GA J. Chron Dis. 1955;1:33-42.
Eventrate(%)
CumulativeIncidence
(%)
Cumulative Incidence of Heart Failure by Baseline Hypertension Status
Stage 1
25
20
15
10
5
02 4 6 8 10 12 14 16
Stage 2+Men aged 60-69 y
Normotensive
25
20
15
10
5
02 4 6 8 10 12 14 16
Stage 2+
Stage 1
Women aged 60-69 y
Normotensive
40
CumulativeIncidence
(%)
Time (y)
Levy D et al. JAMA. 1996;275:1557-1562.
Stage 1
Normotensive
Stage 2+30
20
10
02 4 6 8 10 12 14
Women aged 70-79 y
2 4 6 8 10 12 14
Men aged 70-79 yStage 2+
Stage 1
Normotensive
40
30
20
10
0
Population-Attributable Risks for Development of CHF
AP5%DM
6%LVH4%
VHD7%
MI34%
HTN 39%
Men Women
HTN 59%
DM12%
LVH5%
VHD
8%
AP5%
MI12%
Population-attributable risk defined as: (100 x prevalence x [hazard ratio – 1])/(prevalence x [hazard ratio – 1] + 1)
CHF, chronic heart failure; AP, angina pectoris; DM, diabetes mellitus; LVH, left ventricular hypertrophy;VHD, valvular heart disease; HTN, hypertension; MI, myocardial infarction.Levy D et al. JAMA. 1996;275:1557-1562.
Left Ventricular HypertrophyIndependent Predictor of:
– Myocardial infarction– Stroke– Heart Failure– Total Mortality– Sudden Death
0 6 12 18 24 30 36 42 48 54 60
Month
0
1
2
3
4
5
6
7
End
poin
t Rat
e (%
)
CV Death Stratified by Time-Varying Presence of Echo-LVH
LVH AbsentLVH Present
HR=0.34, 95% CI 0.17-0.71P-0.004
Hazard ratios represent risk reduction associated with absence versus presence of LVH
Hypertension: A Major Risk Factor for CHF
Time, decades
Vasan RS, Levy D. Arch Intern Med. 1996;156:1789-1796.
Death
ObesityDiabetes
SmokingDyslipidemia
Systolic Dysfunction
Diastolic Dysfunction
SubclinicalLeft Ventricular
Dysfunction
CHF
Overt HeartFailure
Time, months
Hypertension
LVH
MI
Left VentricularRemodeling
Prevalence of Systolic and Diastolic Dysfunction by Age
Redfield MM et al. JAMA. 2003;289:194-202.
% of Population
0
10
20
30
40
50
EF<50% EF<40%
Diastolic Dysfunction Systolic DysfunctionMild Moderate Severe
45-54
55-64
65-74
>75
ALL
60
Heart Failure with Preserved Ejection Fraction (HF-PEF)
Current Concerts and Treatment
Introduction • Traditionally HF was thought to be due to systolic function
abnormality shown by EF• It is now known that about half of cases of HF have
preserved ejection fraction• Heart failure with a preserved ejection fraction (HFPEF) is
proving to be intriguing with only a few established facts but many myths.
• Over the past 20 years, significant advances in drug and device therapy have improved survival in patients with HFREF, yet evidence-based treatment for reducing cardiovascular mortality an morbidity in HFPEF is lacking.
Heart Failure with Preserved Ejection Fraction (HF-PEF)
• HFPEF is defined by heart failure symptoms with a normal or near-normal EF (>0.50 or 0.45).
• This cut of point does not exclude occult mild systolic dysfunction. (not normal ejection fraction)
• The term “preserved ejection fraction” is preferred because ejection fraction is what is commonly measured for systolic function.
• HF-PEF is often equated with diastolic heart failure but it is not so simple
Diagnostic Criteria
• Symptoms and signs compatible with heart failure
• Left ventricular ejection fraction >50%• LV EDV < 97ml/m2• Exclusion of severe valvular disease and
pericardial disease
Hunt SA et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. Circulation 112: e154–e235
Ejection Fraction in Subjects with CHF in the Cardiovascular Health Study
67%
10%
23%
Women
Normal (55%)
Mildly Reduced(45% - 54%)
Moderately (30-44%) or severely reduced (< 30%)
Kitzman, et. al.Am. J. Cardiol. 87:413-419 (2001)
27%
31%42%
Men
4,842 community-dwelling elderly (>66 yr.) subjects; CHF prevalence 8.8%
80% had normal EF(>45%)
3 Mechanisms1.An increase in intrinsic myocardial stiffness and
impaired relaxation in diastole result in higher left atrial pressures to fill adequately
2.Increased systolic ventricular and arterial stiffening—that is, deranged ventriculoarterial coupling, may contribute to the pathophysiology of HFPEF
3.Enhanced sensitivity to volume overload from increased LV remodelling and dilatation with volume-dependent elevation of filling pressures
↑ Vascular Stiffness ↓Vasodilitation Systemic Pulmonary
↑ LV Stiffness ↓Relaxation
LVH, Fibrosis, AGE, Titin, Myocyte Δs
↑ RV Load Rest Exercise
↑ Exertional BP Load → Diastolic Dysf
↓ Systolic Reserve
Atrial Dysfunction Atrial Failure (AF)
Renal Dysfunction Anemia Infection
Obesity
HFPEF
Ejection fraction• The misunderstanding of the pathophysiology began
when we defined systolic function solely on the basis of ejection fraction
• EF DOES NOT REPRESENT WHOLE SYSTOLIC FUNCTION • Ejection fraction does not take into account systolic
function in the longitudinal axis. A number of studies have now shown that LV longitudinal function is reduced not only in diastole but also in systole even though LV ejection fraction is within normal limits
The exact understanding of mechanisms that contribute to development of HFPEF is still evolving
• However, the main physiological difference between SHF and HFPEF is the increase in ventricular volume and change in shape due to ventricular remodeling.
• Remodeling leads to increased ventricular volumes and reduced ejection fraction. The rate of occurrence of remodeling is a major differentiating factor.
• For example; A myocardial infarction (or viral myocarditis) appears to be a potent stimulant for the remodeling process resulting in rapid progression to SHF compared to Hypertensive heart disease where remodeling is a slower process. In HHD compensatory increased radial contraction tends to normalize the ejection fraction however at later stages further remodeling will occur and the patient will slip from HFPEF to SHF hence DCM in “burnt out” hypertension.
Echocardiography
Bursi F, et al. JAMA 2006;296:2209-2216.
HF-PEF Current treatment targets and options
• LV volume & edema: Diuretics, salt restriction, nitrates
• Rx HTN: Diuretics, CCB, BB, ACEI, ARB
• Reverse LVH: ACEI,ARBS
• Prevent ischemia: BB, CA, nitrates
• Reduce HR, prevent AF: BB, rate lowering CA, ARB
• Bradycardia: Atrial Pacing
• Enhance relaxation: No current treatment
• Prevent vascular events: ACEI, ARB, BB
ANEMIA,KIDNEY DISEASE,PHT,FLUID OVERLOAD
Control of HypertensionRegression of LVH is an important therapeutic goal, since it has been shown to play a significant role in the pathophysiology of HFPEF
Effect of therapy with each of five antihypertensive drug classes on reduction in left ventricular mass in patients with hypertension. These data represent a meta-analysis of 80 trials of over 4100 patients. The decrease in left ventricular mass index, adjusted for the duration of therapy and diastolic pressure, was significantly higher with angiotensin II receptor blockers (13 percent), calcium channel blockers (11 percent), and angiotensin converting enzyme inhibitors (10 percent) compared to beta blockers (6 percent). Data from Klingbeil, AU, Schneider, M, Martus, P, et al, Am J Med 2003; 115:41.
HFREF
NYHA
• Cl. I – 1 year – 5% ; 4 year mortality – 19%• Cl.II / III - 1 year – 15% ; 4 year mortality – 40%• CL.IV – 6 months – 44%; 12 months 64% (without ACEI)
FRAMINGHAM CRITERIA : HEART FAILURE
MAJOR CRITERIA
• P.N.D. OR ORTHOPNOEA
• NECK VEIN DISTENTION
• RALES
• CARDIOMEGALY
• ACUTE PULMONARY EDEMA
• S3 GALLOP
• VENOUS PRESSURE > 16 Cm H2O
• HEPATO JUGULAR REFLEX
MINOR CRITERIA
• ANKLE EDEMA
• NIGHT COUGH
• EXERTIONAL DYSPNOEA
• HEPATOMEGALY
• PLEURAL EFFUSION
• TACHYCARDIA ( > 120 / Min )
SIMULTANEOUS PRESENCE OF2 MAJORS OR I MAJOR AND3 MINORS
(Porth, 2009). Picture retrieved from http://www.starsandseas.com/SAS
%20Physiology/Cardiovascular/Cardiovascular.htm
Goals of therapy
To relieve symptomsTo give good quality of life
To halt the progress of diseaseTo reduce mortality
Patient is happy
Doctor is happy
The ultimate goal is to make both doctor and patient happy
Types of therapy 1I – Mortality reducing drugs
Angiotensin converting enzyme inhibitorBeta blockersAldosterone antagonistsAngiotensin receptor blockersNitrates + Hydralazine
II - Morbidity reducing drugs Diuretics (Loop and Thiazide) Digoxin
III - Metabolically Active Drugs Trimetazidine L-Carnitine Co enzyme Q
IV – Newer, emerging drugsIvabradineOmega 3 fatty acids
Types of therapy 2- Supportive Drugs• Anemia – Iron,Erhythropoitin• Oral anticoagulants• Electrolytes- Na, K correcting drugs• Drugs for Co-MorbidsTypes of therapy 3- harmful drugs• Routine inotropes• Anti arrhythmics (except B Blockers and Amiodarone)• Calcium blockers ( non DHP)• High dose Digoxin
MANAGEMENT: GENERAL MEASURES• Correctable causes• Daily weighing – Report if >2kgs in 1-3 days• Self management of diuretics• Compliance with medication• Regular exercise• Stop smoking, Alcohol• Salt , fluid management- careful in summer,powercuts• Vaccination• Warning about other drugs (NSAIDS,VIT E, ALTERNATIVE
MEDICINES)• Treating precipitating factors of HF
Precipitating causes of Heart Failure
• Anemia,arrhythmia, alcohol• Beri beri• Cardiac toxins• Drugs – NSAIDS,Glitazones,Steroids• Exercise – severe, emotion, embolism• Fever • Goitre• Hypertension, hypoxia• Infections , iatrogenic, iv fluids
SUMMARY
Disease Modifying mortality
reducing drugs increase survival
+_ symptomsACEIB.Blockers
Aldosterone antagonists
ARBNitrates +
Hydralazine
MUSTIn all
patients
Doctor feels good
Symptom relieving quality of life providing
drugsDecrease
symptoms- survival
DiureticsDigoxin
More often
symptomatic
patients
Patient
feels good
Metabolically acting drugs? Symptoms
? survival
Trimetazidine
L-CarnitineCo enzyme
Q
Sometimes in
selected patients
Industry
feels good
Newer drugsYet to be proven
IvabradineOmega 3
fatty acids
Individualize
Who will feel
good?
1-4A-D
2-4C,D
Treatment of Hypertension and CVD Outcomes Placebo Controlled Trials
-16-21
-38
-50
-40
-30
-20
-10
0
Heartfailure
Fatal/nonfatalstrokes CVD deaths
Fatal/nonfatalCHD events
Riskreduction
(%)
17 randomized, placebo-controlled trials (48,000 subjects)—14 diuretic and 3 beta blocker based trials.All differences are statistically significant.CVD, cardiovascular disease; CHD, coronary heart disease.Herbert PR et al. Arch Intern Med. 1993;153:578-581.Moser M, Herbert PR. J Am Coll Cardiol. 1996;27:1214-1218.
-52-60
THE VERY ESSENCE OF CARDIOVASCULAR PRACTICE IS THE PREVENTION OF HEART FAILURE
PRACTICE IMPLICATION2013
THE VERY ESSENCE OF CARDIOVASCULAR PRACTICE IS THE EARLY DETECTION OF HEART FAILURE SIR THOMAS LEWIS 1933
CONCLUSION
• THE GREATEST BENEFIT OF TREATING HYPERTENSION IS THE PREVENTION OF HEART FAILURE AND STROKE
END OF MODULE 3 CHAPTER 1C