Mercy Family Practice SC

Congestive Heart Failure

Table of Contents

Introduction

Congestive Heart Failure (CHF) is defined by the reduction in strength of the heart. The heart is too weak to pump enough blood through the body. There are several causes of CHF such as a heart attack, chronic alcoholism, or long-standing high blood pressure. In the latter, over many years, the high pressure in the aorta and peripheral vasculature causes stress of the heart muscle. At first, the heart responds by thickening the heart muscle itself. This is adaptive over the short term, but over many years the heart muscle begins to be replaced by scar tissue. The heart muscle thins out and the chambers of the heart dilate. In the early stages, we call this systolic dysfunction while the heart is still strong enough to pump. Toward the end when the heart muscle stiffens and dilates, we call this diastolic dysfunction. The end result is the same.

Once the heart muscle becomes weak, thin, and dilated, there is nothing that can be done to reverse the process. The goal of medical care is to optimize the physiology of the body to improve the conditions under which the heart functions. The goal of medical therapy lies in the following therapies: positive inotrope, reduce preload, reduce afterload, and negative chronotrope.

Positive Inotrope

Several decades ago it was discovered that lanoxin (Digoxin) had the effect of increasing the strength of the remaining heart muscle. It also had the effect of slowing conduction of electrical impulses through the atrioventricular (AV) node thereby slowing the heart rate and helping to make the heart beat more efficiently. This was the mainstay of therapy for many years. It is still used, but studies show that it reduces hospitalizations but does not affect overall mortality. Furthermore, it has a narrow therapeutic range, which means that if not monitored by blood levels, it can be toxic. The therapeutic range for Digoxin is 0.5 to 1.5 ng/ml.

Preload Reduction

As the heart weakens, fluid builds upstream from the heart. This exacerbates the problem because the extra fluid is delivered to a heart that cannot handle the extra load. This is called preload. For example, imagine that you are a single person standing in line during a Chinese fire drill. Each time someone hands you a bucket half filled with water. You have to pass it on to the next person, and so on. Now, imagine the next time, you are handed a full bucket of water. Your work load goes up by a factor of two. You will tire more easily. This is what happens to the heart in CHF. Now imagine we can reduce the volume to ¼ bucket, or reduce the volume by half. This would reduce your workload.

We used loop diuretics to reduce the amount of fluid in the body and reduce preload. This in turn reduces congestion. The term “loop” comes from the Loop of Henle which is a component of the nephron in the kidney upon which sodium reabsorption is inhibited, causing free water to be eliminated from the kidney Examples of loop diuretics are furosemide (Lasix), bumetanide (Bumex), and torsemide (Demadex).

Afterload Reduction

Often a weak heart has to push against high pressures and high vascular resistance. If we can lessen this pressure and resistance to flow, then we can help out the heart. For example, if you take the same Chinese fire drill mentioned above, if you can imagine you are on an incline, and are required to pass each bucket uphill, this would equate to what the heart has to do to push against high pressure and high resistance. If you can then level off the incline, your work load would lessen.

We reduce afterload through the use of medications that will dilate the vasculature and bring down blood pressure. The best example of this is with an angiotensin converting enzyme inhibitor (ACEI) such as Lisinopril, or an Angiotensin Receptor Blocker (ARB) such as Valsartan.

Negative Chronotrope

One way the heart compensates for weakness is to increase the heart rate. This allows it to deliver more blood through unit time by sending more blood downstream at a higher rate. Again, this is adaptive in the short term, say if you exert yourself; however, in the long term, the heart cannot maintain this activity. Over time it becomes mal adaptive.

We use beta blockers to slow down the heart rate and lengthen the time it takes for each contraction, which makes the heart work more efficient. The term beta comes from the beta 1 receptor found in the lining of the blood vessels found in the periphery. The term blocker comes from the inhibitory action that the drug has on the receptor. If you block a beta 1 receptor on the heart, it causes the heart to slow down and beat more efficiently. The main beta blockers in use are carvedilol (Coreg), metoprolol succinate (Toprol XL) and atenolol (Tenormin).

Heart Chambers

The anatomy of the heart is super imposed with the four therapeutic interventions (labeled in red).

Classification

The New York Heart Association (NYHA) Classification scheme is defined in the following table:

Table 1, NYHA Classification

ClassDefinition
class INo physical limitations
class IISlight limitation of physical activity
class III Marked limitation of physical activity
class IV Symptoms at rest

Literature

Okwuosa describes the ABCDE of CHF. He uses the alphabet as a method to organize the various therapeutic options offered in CHF. They include medical therapy as well as surgical interventions. To help organize the options, I have listed them in table 1. A represents ACEIs, ARBs, Alldosterone Antagonists and Angiotensin Receptor Neprolysin Inhibitors (ARNIs); B represents Beta Blockers and BNP monitoring; C represents Chronotropy reduction; D represents Digoxin, Diuretics and Devices; and E represents Exercise. None of these are a panacea but taken in combination they can assist the hart and improve mortality or exercise tolerance, which translates into improved quality of life.

Table 2, CHF Studies
StudyPopulationNMortNNTp
ACEI
CONSENSUSNYHA IV25326% vs 44%140.002
SOLVDEF <35%1,28436% vs 39.7%270.0036
ARBs
Val-HeftNYHA II III IV5,010Hosp 13.8% vs 18.2%460.009
CHARM-AddedEF <40%2,548Hosp 22.5% vs 28.1%
Mort 22.8% vs 26.2%
40
64
<0.001
<0.005
Aldosterone Antagonist
RALESEF <35%
NYHA IV
1,66330% vs 35%16<0.001
EMPHASIS-HFEF <50%2,737Hosp 18.3% vs 25.9%
Mort 12.5% vs 15.5%
13
33
<0.001
0.008
ARNI
PARADIGM-HFEF <30%10,521Hosp 12.8% vs 15.6%
Mort 13.3% vs 16.5%
36
31
<0.001
<0.001
Beta Blockers
US CarvedilolEF <35%1,094Hosp 14.1% vs 19.6%
Mort 3.2% vs 7.8%
18
22
0.036
<0.001
CIBIS-IIEF <35%2,64711.8% vs 17.3%18<0.0001
MERIT-HFEF <40%3,9917.2% vs 11%260.00009
COMETEF <35%1,51134% vs 40%170.0017
BNP Monitoring
TIME-CHFEF <40%499Hosp 62% vs 72%100.01
BATTLESCARREDBNP >503649.1 vs 18.9%100.03
PROTECTEF <40%
BNP >1000
151CV 38.4% vs 62.2%40.009
GUIDE IT-HFEF <40%
BNP >1000
1,100
Chronotropy Reduction
SHIFTEF <35%
HR >70
6,558Mort 14.5% vs 17.7%31<0.0001
Digoxin
DIGEF <45%6,800Hosp 26.8% vs 34.7%13<0.001
Diuretics
No RCT
Devices
Implantable Cardiac Defibrillators (ICD)
MADITEF <35%19616% vs 39%40.009
MADIT IIEF <30%1,23214.2% vs 19.8%180.016
SCD-HeFTEF <35%252118.2% vs 24.4%160.007
Left Ventricular Assist Devices
REMATCHNYHA IV129Mort 77% vs 92%70.09
HeartMate IINYHA IV281Continuous flow 24% vs pulsatile 58%30.008
ADVANCENYHA IV140Non inferior study<0.001
Cardiac Re- synchronization
MUSTICEF<35%
LVED >60mm
QRS >150ms
676-minute walk 399m vs 326m<0.001
MIRACLENYHA III
EF <35%
QRS >130ms
453Hosp 8% vs 15%
EF increase 4.6% vs -0.2%
140.02
<0.001
Exercise
HF-ACTIONNYHA III2,331Exercise improved
Mort NS
Hosp NS
<0.001

Abbreviations

AcronymTitle
ACEIAngiotensin Converting Enzyme Inhibitor
ADVANCEEvaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure
ARBAngiotensin Receptor Blockers
ARNIAngiotensin Receptor Neprolysin Inhibitors
BATTLESCARREDB-type Natriuretic Peptide Assisted Treatment to Lessen Serial Cardiac Readmissions and Death
BNPBrain-Type Naturetic Peptide (BNP)
CHARM-AddedCandesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity
CIBIS-IICardiac Insufficiency Bisoprolol Study II
COMETCarvedilol or Metoprolol European Trial
CONSENSUSCooperative North Scandinavian Enalapril Survival Study
DIGDigitalis Investigative Group
EFEjection Fraction, a measure of heart strength. Normal is 55-65%
EMPHASIS-HFEplerenone in Mild Patients Hospitalized and Survival Study in Heart Failure
GUIDEIT-HF Guiding Evidence based therapy using biomarker Intensified Treatment in Heart Failure
HeartMateII Thoratec Trial
HF-ACTIONA Controlled Trial Investigating Outcomes of Exercise Training
HospHospitalization
MADITMulticenter Automatic Defibrillator Implantation Trial with History of Myocardial Infarction and Ventricular Tachycardia
MERIT-HFMetoprolol Extended Release Randomized Intervention Trial in Heart Failure
MIRACLEMulticenter Insync Randomized Clinical Evaluation
MortMortality
MUSTICMultisite Stimulation in Cardiomyopathies
NNumber of subjects treated in a given trial
NNTNumber Needed to Treat
NYHANew York Heart Association Classification System
pProbability statistic where significant is defined as p $lt; 0.05 with a given type I error of 5%
PARADIGM-HFProspective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure
PROTECTProBNP Outpatient Tailored Congestive Heart Failure Therapy
RALESRandomized Aldactone Evaluation Study
REMATCHRandomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart failure
SCD-HeFTSudden Cardiac Death in Heart Failure Trial
SHIFTSystolic Heart failure treatment with the If inhibitor Ivabradine Trial
SOLVDStudy of Left Ventricular Dysfunction
TIME-CHFTrial of Intensified vs Standard Medical Therapy in Elderly Patients with Congestive Heart Failure
USCarvedilol US Carvedilol Heart Failure Study Group
Val-HeftValsartan Heart Failure Trial

Kaplin-Meier Curves on Select Studies

Figure 1, Beta-Blocker. Metoprolol succinate reduces mortality by 55%

MERIT Mortality

Based on the MERIT-HF study

Figure 2, ACEI. Enalapril reduces mortality by 40%

CONSENSUS Mortality

Based on the CONSENSUS study

Figure 3, ARB. Valsartan reduces mortality by 13.2%

Val-Heft Mortality

Based on the Val-Heft study

Figure 4, Aldosteron Antagonist. Spironolactone reduces mortality by 30%

RALES Mortality

Based on the RALES study

Figure 5, BNP Modification. Reducing BNP < 150 reduces mortality by 15.5-31.3%

BATTLESCARRED Mortality

Based on the BATTLESCARRED study; BNP monitored group (red); Clinical Group using CHF Scoring (green); Standard care (blue)

Therapeutic Algorithm

Okwuosa offers a therapeutic algorithm. Angiotensin converting enzyme inhibitor (ACEI), Angiotensin Receptor Blockers (ARBs), Beta Blockers and Loop Diuretics are considered the first line of therapy. Digoxin which was once considered the first line of therapy is now reserved for those with recurrent hospializations. This algorithm is developed after decades of mostly randomized controlled trials. This algorithm is consistent with CHF guidelines and most physicians now follow these guidelines.

CHF Flow

Modified from Okwuosa; Abbreviations: ACEI= angiotensin converting enzyme inhibitor; Adm= Admission; Aldo= Aldosterone; Antag= Antagonist; ARB= Angiotensin Receptor Blocker; ARNI= Angiotensin Receptor Neprolysin Inhibitor; EF= Ejection Fraction; HR= Heart Rate; ICD= Inplantable Cardiac Defibrillator; NYHA= New York Heart Association classification of heart failure; QRS= QRS segment of an electrocardiogram

Medications

Table 3, List of Medications for CHF

Angiotensin-converting enzyme inhibitors (ACEIs)

Generic nameDosing range $/Mo
Benazepril5-40 mg daily 89
Captopril6.5-50 mg thrice daily 110
Enalapril2.5-20 mg twice daily 45
Fosinopril5-40 mg daily 47
Lisinopril2.5-40 mg daily 41
Quinapril5-20 mg daily 46
Ramipril1.25-10 mg daily86
Trandoiapril1-45 mg daily42

Angiotensin II receptor blockers (ARBs)

Generic nameDosing range $/Mo
Candesartan4-32 mg daily 165
Losartan25-150 mg daily 84
Valsartan20-160 mg twice daily104

Aldosterone receptor antagonists

Generic nameDosing range$/Mo
Eplerenone25-50 mg daily115
Spironolactone12.5-25 mg once or twice daily29

Angiotensin-neprilysin inhibition (ARNI)

Generic nameDosing range $/Mo
Sacubitril-valsartan (Entresto)24-26 mg, 49-51 mg, or
97-103 mg twice daily
419

Beta-Blockers

Generic nameDosing range $/Mo
Bisoprolol1.25-10 mg daily 39
Carvedilol3.125-50 mg twice daily 78
Metoprolol succinate12.5-200 mg daily50

If Inhibition (Chronotrope Reduction)

Generic nameDosing range$/Mo
lvabradine(Corlanor)5.0-7.5 mg twice daily420

Digitalis Glycosides

Generic nameDosing range$/Mo
Lanoxin125-250 mcg daily88

Diuretics

Generic nameDosing range $/Mo
Bumetanide0.5-2.0 mg daily 39
Furosemide20-600 mg daily 34
Torsemide10-200 mg once daily15

Table 4, Typical Cost of Treatment

DrugDoseFreqMo ($)Yr ($)
Furosemide80 mgtwice daily34411
Lisinopril40 mgdaily22269
Lanoxin125 mcgdaily881,051
Metoprolol ER25 mgdaily33393
Total1772,124
Alternative
Furosemide80 mgtwice daily34411
Lanoxin0.125 mgdaily881,051
Metoprolol ER25 mgdaily33393
Entresto97/103 mg23754,500
Total5306,356

References

  1. Aaronson, Keith D, et al, Use of an Intrapericardial, Continuous-Flow, Centrifugal Pump in Patients Awaiting Heart Transplantation (ADVANCE), Circulation, 2012;125:3191-3200. click here
  2. Bavry, Anthony A, et al, Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure – PARADIGM-HF , American College of Cardiology, Oct 05, 2016. click here
  3. Bavry, Anthony A. Systolic Heart failure treatment with the IF inhibitor ivabradine Trial – SHIFT , American College of Cardiology, Aug 29, 2010. click here
  4. Bertram Pitt, et al, Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure – EMPHASIS-HF , American College of Cardiology, Aug 10, 2015. click here
  5. Cohn, Jay N, et al, A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure, New England Journal of Medicine, December 6, 2001, Vol 345, No 23, pp 1667-75. click here
  6. Felker, G Michael, et al, Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT), JACC: Heart Failure , 2014, Vol 2, No. 5, pp 457-465. click here
  7. Goldstein, Sidney, et al, Metoprolol Controlled Release/Extended Release in Patients With Severe Heart Failure Analysis of the Experience in the MERIT-HF Study, Journal of the American College of Cardiology, Vol. 38, No. 4, 2001 , pp 932-938. click here
  8. Gruberg, Luis, SCD-HeFT: Sudden Cardiac Death in Heart Failure Trial , Presenter: Gust H. Bardy, MD, Seattle Institute for Cardiac Research (Seattle, Washington), April 16, 2004 . click here
  9. Haigney, Mark C, et al, QT Interval Variability and Spontaneous Ventricular Tachycardia or Fibrillation in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II Patients, Journal of the American College of Cardiology, 2004, Vol 44, No 7, pp 1481-1487. click here
  10. Januzzi, James L, et al, Use of Amino-Terminal Pro–B-Type Natriuretic Peptide to Guide Outpatient Therapy of Patients with Chronic Left Ventricular Systolic Dysfunction, Journal of the American College of Cardiology, 2011, Vol 58, No 18, 2011, pp 1881-1889. click here
  11. Lainchbury, John G, et al, N-Terminal Pro–B-Type Natriuretic Peptide-Guided Treatment for Chronic Heart Failure Results From the BATTLESCARRED (NT-proBNP–Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) Trial, Journal of the American College of Cardiology , 2010, Vol. 55, No. 1, click here
  12. Multicenter Automatic Defibrillator Trial I (MADIT I), 1996. click here
  13. Multicenter InSync Randomized Clinical Evaluation - MIRACLE (Pacing Study) , American College of Cardiology, Jun 20, 2003. click here
  14. Multisite Stimulation in Cardiomyopathies Study - MUSTIC , American College of Cardiology, Nov 04, 2003. click here
  15. O'Connor, Christopher M, et al, Efficacy and Safety of Exercise Training in Patients With Chronic Heart Failure HF-ACTION Randomized Controlled Trial, Journal of the American Medical Association, April 8, 2009, Vol 301, No 14 , pp 1439-1450. click here
  16. Okwuosa, Ike S, et al, The ABCS of Managing Systolic Heart Failure: Past, Present, and Future, Cleveland Clinic Journal of Medicine , October 2016, Vol 83 , No 10 , pp 753-765. click here
  17. Pfisterer, Matthias, et al, BNP-Guided vs Symptom-Guided Heart Failure Therapy: The Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) Randomized Trial, Journal of the American Medical Association, May 3, 2009, Vol 301, No 4, pp 383-392. click here
  18. Pitt, Bertram, et al, The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure, New England Journal of Medicine, September 2, 1999, Vol 341 No 10, pp 709-717. click here
  19. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure – REMATCH , American College of Cardiology, Mar 05, 2002. click here
  20. The CONSENSUS Trial Study Group, Effects of Enalapril on Mortality in Severe Congestive Heart Failure, Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), New England Journal of Medicine, June 4, 1987, Vol 316 No 23, pp1429-1435. click here
  21. The Digitalis Investigation Group, The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure, New England Journal of Medicine, February 20, 1977, Vol 336 No 8, pp 525-533. click here
  22. The Studies of Left Ventricular Dysfunction (SOLVD) , Limited Access Database , August 2004, Version 2.0, pp 1-5. click here
  23. Young, James B, et al, Mortality and Morbidity Reduction with Candesartan in Patients with Chronic Heart Failure and Left Ventricular Systolic Dysfunction Results of the CHARM Low–Left Ventricular Ejection Fraction Trials, Circulation, 2004;110:2618-2626. click here

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