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Congestive Heart Failure- Etiologies, Prognosis and Treatment
C. Bradley Rash MD FACC
Medical Director, Cardiology
Sentara RMH Medical Center
ACVP Conference
March 10, 2018
Types of Heart Failure
▪ Systolic (or squeezing) heart failure – EF <50% ▪ Decreased pumping function of the heart, which results in fluid
back up in the lungs and heart failure
▪ Diastolic (or relaxation) heart failure – EF >50% ▪ Involves a thickened and stiff heart muscle
▪ As a result, the heart does not fill with blood properly
▪ This results in fluid backup in the lungs and heart failure
▪ BP = CO x SVR
▪ CO = SV x HR
Stage A: Those at risk for heart failure, but who have not yet developed
structural heart changes (diabetics, those with coronary disease without
prior infarct).
Stage B: Individuals with structural heart disease (i.e. reduced ejection
fraction, left ventricular hypertrophy, chamber enlargement), however
no symptoms of heart failure have ever developed.
Stage C: Patients who have developed clinical heart failure.
Stage D: Patients with refractory heart failure requiring advanced
intervention (biventricular pacemakers, left ventricular assist device, or
transplantation).
Class I: No symptoms of heart failure
Class II: Symptoms of heart failure with
moderate exertion
Class III: Symptoms of heart failure with
minimal exertion
Class IV: Symptoms of heart failure at rest
Underlying causes of SYSTOLIC heart failure include
the following:
•Coronary artery disease
•Diabetes mellitus
•Hypertension
•Valvular heart disease (stenosis or regurgitant lesions)
•Arrhythmia (supraventricular or ventricular)
•Infections and inflammation (myocarditis)
•Peripartum cardiomyopathy
•Congenital heart disease
•Drugs (either recreational, such as alcohol and cocaine,
or therapeutic drugs with cardiac side effects, such as
doxorubicin)
•Idiopathic cardiomyopathy
•Rare conditions (endocrine abnormalities, rheumatologic
disease, neuromuscular conditions)
Underlying causes of DIASTOLIC heart failure
include the following:
•Coronary artery disease
•Diabetes mellitus
•Hypertension
•Valvular heart disease (aortic stenosis)
•Hypertrophic cardiomyopathy
•Restrictive cardiomyopathy (amyloidosis, sarcoidosis)
•Constrictive pericarditis
•Aging
•Obesity
Underlying causes of ACUTE heart failure include the
following:
•Acute valvular (mitral or aortic) regurgitation
•Myocardial infarction
•Myocarditis
•Arrhythmia
•Drugs (eg, cocaine, calcium channel blockers, or beta-
blocker overdose)
•Sepsis
•Medical or dietary non-compliance
Underlying causes of HIGH-OUTPUT heart failure
include the following:
•Obesity
•Anemia
•Systemic arteriovenous fistulas
•Hyperthyroidism
•Beriberi heart disease
•Paget disease of bone
•Albright syndrome (fibrous dysplasia)
•Multiple myeloma
•Pregnancy
•Glomerulonephritis
•Polycythemia vera
•Carcinoid syndrome
Underlying causes of RIGHT heart failure include the following:
•Left ventricular failure (Most common)
•Coronary artery disease (ischemia)
•Pulmonary hypertension
•Pulmonary valve stenosis
•Pulmonary embolism
•Chronic pulmonary disease
•Neuromuscular disease
LEFT AND RIGHT HEART FAILURE
▪Left Heart Failure ▪Dyspnea
▪Orthopnea (+/- cough)
▪ PND
▪ Tachycardia
▪Right Heart Failure ▪ Lower extremity edema
▪ Ascites
▪ Hepatomegaly (+/- elevated LFTs)
▪ JVD / elevated JVP
▪ Cyanosis
▪ Abdominal swelling (gut edema / poor appetite)
TREATMENT OF SYSTOLIC CHF
▪DRUGS
▪DEVICES ▪CRT
▪Defibrillators
-- Lowers heart rate at the sinus
node
SHIFT TRIAL
-- Lancet (2010)
(all comparisons are versus
enalapril 20 mg daily, not versus placebo)
2 weeks 1-2 weeks 2-4 weeks
Single-blind run-in period Double-blind period
(1:1 randomization)
Enalapril
10 mg BID
100 mg BID
200 mg BID
Enalapril 10 mg BID
LCZ696 200 mg BID
PARADIGM-HF: Study Design
Randomization
LCZ696
10,521 patients screened at 1043 centers in 47 countries
Did not fulfill criteria for randomization
(n=2079)
Randomized erroneously or at sites closed due to GCP violations (n=43)
8399 patients randomized for ITT analysis
LCZ696 (n=4187)
At last visit
375 mg daily 11 lost to follow-up
Enalapril (n=4212)
At last visit
18.9 mg daily 9 lost to follow-up
median 27 months of follow-up
PARADIGM-HF: Patient Disposition
0
16
32
40
24
8
Enalapril (n=4212)
360 720 1080 0 180 540 900 1260
Days After Randomization
4187
4212
3922
3883
3663
3579
3018
2922
2257
2123
1544
1488
896
853
249
236
LCZ696
Enalapril
Patients at Risk
1117 K
ap
lan
-Me
ier
Es
tim
ate
of
Cu
mu
lati
ve
Rate
s (
%)
914
LCZ696 (n=4187)
PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint)
0
16
32
40
24
8
Enalapril (n=4212)
360 720 1080 0 180 540 900 1260
Days After Randomization
4187
4212
3922
3883
3663
3579
3018
2922
2257
2123
1544
1488
896
853
249
236
LCZ696
Enalapril
Patients at Risk
1117 K
ap
lan
-Me
ier
Es
tim
ate
of
Cu
mu
lati
ve
Rate
s (
%)
914
LCZ696 (n=4187)
HR = 0.80 (0.73-0.87)
P = 0.0000002
Number needed to treat = 21
PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint)
Enalapril (n=4212)
LCZ696 (n=4187)
HR = 0.80 (0.71-0.89)
P = 0.00004
Number need to treat = 32
Ka
pla
n-M
eie
r E
sti
ma
te o
f C
um
ula
tive
Rate
s (
%)
Days After Randomization
4187
4212
4056
4051
3891
3860
3282
3231
2478
2410
1716
1726
1005
994
280
279
LCZ696
Enalapril
Patients at Risk
360 720 1080 0 180 540 900 1260 0
16
32
24
8
693
558
PARADIGM-HF: Cardiovascular Death
PARADIGM-HF: All-Cause Mortality
4187
4212
4056
4051
3891
3860
3282
3231
2478
2410
1716
1726
1005
994
280
279
LCZ696
Enalapril
Enalapril (n=4212)
LCZ696 (n=4187)
HR = 0.84 (0.76-0.93)
P<0.0001 K
ap
lan
-Me
ier
Es
tim
ate
of
Cu
mu
lati
ve
Rate
s (
%)
Days After Randomization Patients at Risk
360 720 1080 0 180 540 900 1260 0
16
32
24
8
835
711
Clyde W. Yancy et al. JACC 2018;71:201-230 ©2018 by American College of Cardiology
DOSE TRIAL
-
NEJM 2011
Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial – Lancet Jan 2013
More definitive RELAX AHF 2 Trial is ongoing …
How about Cor Pulmonale?
▪Defined as an alteration in the structure and function of the right ventricle (RV) of the heart caused by a primary disorder of the respiratory system.
▪ Pulmonary hypertension is often the common link between lung dysfunction and the heart in cor pulmonale.
Pulmonary hypertension- WHO Classifciation
▪ Group 1: Pulmonary artery hypertension, including heritable causes; connective-tissue disorders, including scleroderma; and other idiopathic causes
▪ Group 2: pulmonary artery hypertension due to left ventricular [LV] dysfunction
▪ Group 3: Pulmonary hypertension due to lung disease and/or hypoxia; these disorders include chronic obstructive pulmonary disease (COPD), which is the most common cause of cor pulmonale. There have been studies correlating the degree of hypoxia with the severity of cor pulmonale. Other disorders that can result in cor pulmonale in this group include interstitial lung sisease (ILD) and obstructive sleep apnea (OSA)
▪ Group 4: Chronic thromboembolic pulmonary hypertension; blood clots that form in the lungs can lead to increased resistance, pulmonary hypertension and, subsequently, cor pulmonale
▪ Group 5: Pulmonary hypertension caused by other diseases or conditions, including sarcoidosis, polycythemia vera (which can lead to increased blood viscosity and, subsequently, pulmonary hypertension), vasculitis, and other disorders.
Cor Pulmonale
▪ The end result of the above mechanisms is increased pulmonary arterial pressure and resistance.
▪ The RV is a thin-walled chamber that is a better volume pump than a pressure pump. It is better suited to adapt to changing preload than afterload. With an increase in afterload, the RV systolic pressure is increased to maintain the circulatory gradient. At a critical point, a further increase in pulmonary arterial pressure and resistance produces significant RV dilatation, an increase in RV end-diastolic pressure, and RV circulatory failure.
Clyde W. Yancy et al. JACC 2018;71:201-230 ©2018 by American College of Cardiology
(Important in thinking
about strategies to
reduce readmission…)
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