EKG

Normal Sinus Rhythm; Rate=66

Non-Specific T-wave abnormality in V2-V3
QT/QTc=424/444
CXR:
New pulmonary vascular congestion with bilateral pleural effusions, right greater than left.
Superimposed pneumonia or atelectasis cannot be excluded.
SECOND EKG:
Atrial Fibrillation with Rapid Ventricular Rate; Rate=116
Non-Specific T-wave abnormality in V2-V3
HR in irregular rhythm= (# QRS) *10

ACE = angiotensin-converting enzyme.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patientoriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case
series. For information about the SORT evidence rating system, see page 896
or http://www.aafp.org/afpsort.xml.
Diuretics= decreased end-diastolic volume and modestly increase SV and CO
- Diuretics improve exercise capacity and diminish symptoms caused by pulmonary and peripheral
edema
ACE-Inhibitors= Decreases in systemic vascular resistance, pulmonary capillary wedge pressure, right
atrial pressure, and end-diastole & end-systolic dimensions and improvement s in cardiac performances
as evidence due to increased in CO and SV and by improvement of fractional shortening determined by
echo
ACE-Inhibitors are the FIRST line treatment in ALL NYHA classes of chronic systolic HF
- CONSENSUS Enalapril Survival Study (1987) measured ACE-I in advanced HF
significant decrease in mortality throughout 1 year period
- Studies of Left Verntricular Dysfunction (SOLVD) measured in mild-mod chronic HF 16%
reduction in mortality
ARB
- ELITE II showed Valsartan non-inferior to Captopril
- Valsartan HF Trial (Val-HeFT) ACE-I + ARB favored addition of ARB, post-ad hoc data
analysis suggested increase mortality when valsartan added to ACE-I +Bblocker
- Candesartan in HR Assessment of reduction in Mortality and Morbidity (CHARM) trial
significant reduction in the combined end point of CV morbidity and mortality with ACE-I or
with ACE-I and Bblocker
Aldosterone Antagonist
- Randomized Aldactone Evaluation Study (RALES) significant reduction in pump failure
deaths as well as sudden cardiac deaths
- Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study
(EPHESUS) improved survival and reduced CV hospitalization compared to control
Beta Blockers :First general=propranolol and timolol; 2nd=metoprolol, atenolol, and bisoprolol; 3rd=
Carvedilol and Nebivolol
- Metoprolol-Dilated Cardiomyopathy (MDC) no significant decrease in mortality
- Cardiac Insufficiency Bisoprolol Survival (CIBIS) non-significant trend toward lower
mortality (20%) and 30% fewer hospitalizations
- Multicenter Oral Carvedilol HF Assessment (MOCHA) mortality reduction observed with
carvedilol was dose-related
- COPERMICUS: Safety and efficacy of beta-blockade in advanced HHF
- CAPPRICORN
- COMET
Vasodilators Hydralazine and Nitrites
- s
d
- d

19Recommendations for Pharmacological Therapy for Management of Stage C HFrEF

Table In the absence of contraindications to anticoagulation.
ACE indicates angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin-receptor
blocker; COR, Class of Recommendation; DM, diabetes mellitus; GDMT, guideline-directed medical
therapy; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure
with reduced ejection fraction; LOE, Level of Evidence; LVEF, left ventricular ejection fraction; MI,
myocardial infarction; N/A, not available; NYHA, New York Heart Association; and PUFA,
polyunsaturated fatty acids.
note: Intensity of shading reflects strength of recommendation.
ACC = American College of Cardiology; AHA = American Heart Association; NYHA = New York Heart
Association; ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker.
* ACE inhibitors, beta blockers, and spironolactone (Aldactone) should not be removed if symptoms
improve because these medications slow disease progression and decrease mortality.
Although ACE inhibitors are listed first, evidence shows that an ACE inhibitor or a beta blocker
may be started first and then the other added. It is reasonable to titrate the dosage of each agent in an
alternating step-wise fashion to reach the target dosage. For patients intolerant of ACE inhibitors, an
ARB can be substituted.
No explicit evidence of benefit exists for beta blockers in asymptomatic patients; however, many of
these patients will have other indications (e.g., coronary artery disease) for beta blockers.
Beta blockers may be safely added or continued in patients with rest dyspnea, except in those who
have signs of congestion or hemodynamic instability.
An aldosterone antagonist may be appropriately initiated for symptomatic patients within 14 days
of a myocardial infarction.
The benefit of the combination of isosorbide dinitrate and hydralazine occurred among patients
self-reported as black. This combination may be added (if tolerated by the patient's blood pressure)
without reducing the ACE inhibitor or beta blocker to subtarget dosages.
** These interventions may provide symptomatic benefit. If no benefit is perceived, the medications
may be withdrawn. With digoxin, however, withdrawal may lead to clinical deterioration and should be
done with caution.
When added to ACE inhibitors, ARBs may improve symptoms. Little evidence supports the safety
of using ACE inhibitors, aldosterone antagonists, and ARBs in the same patient. Because all agents can
increase potassium levels, it is prudent to avoid this combination or to use it with great caution.
Table 16: Recommendations for Treatment of HFpEF
ACE indicates angiotensin-converting enzyme; AF, atrial fibrillation; ARB, -blocker; CAD, coronary
artery disease; COR, Class of Recommendation; GDMT, guideline-directed medical therapy; HF, heart
failure; HFpEF, heart failure with preserved ejection fraction; and LOE, Level of Evidence.

Diuretics Diuretic therapy is used in patients with HFpEF to treat volume overload. Diuretic therapy
should be administered with caution to avoid excessive preload reduction and hypotension. The
beneficial effect of diuretics was suggested by an ancillary study from the CHAMPION trial (mentioned
above), in which medical treatment decisions driven by knowledge of pulmonary artery pressure data
were associated with a significant reduction in hospitalizations for HF. The majority of medication
changes were in diuretic usage, and mean diuretic dose increased significantly more in the pulmonary
artery pressure-guided treatment group. These data provide indirect evidence supporting the efficacy of
diuretics to reduce morbidity in HFpEF. (See 'Serial assessment' above.)
Beta blockers The role of beta blockade in treatment of HFpEF is uncertain. Direct evidence of
clinical benefit is lacking, although beta blockers have a variety of potential beneficial effects in patients
with HFpEF: by preventing tachycardia (thereby increasing the time available for both LV filling and
coronary flow, particularly during exercise), reducing myocardial oxygen demand, and by lowering the
blood pressure, reducing LVH. In addition, beta blocker therapy is indicated in patients with angina
(including dyspnea thought to be an anginal equivalent). (See "Beta blockers in the management of
stable angina pectoris".)
In the small SWEDIC trial, 113 patients with symptoms of HF, normal LVEF, and abnormal diastolic
function were randomly assigned to treatment with carvedilol or placebo, with echocardiographic
assessment at baseline and six months [26]. Carvedilol resulted in a significant improvement in the E/A
ratio, but no significant improvement in deceleration time, isovolumic relaxation time, or pulmonary
vein flow velocity.
However, direct evidence of the clinical efficacy of beta blocker therapy in patients with HFpEF is
lacking. While the SENIORS trial suggested that nebivolol (a beta blocker with vasodilating properties)
may be beneficial in patients regardless of EF, very few patients with HFpEF were included. The
OPTIMIZE-HF registry study found no clinical benefit of beta blocker therapy in this population.
In the SENIORS trial, 2128 patients 70 years of age with history of HF or known LVEF 35 percent
were randomly assigned to nebivolol or placebo [27]. Nebivolol therapy resulted in reduction in the
primary outcome of all-cause mortality or cardiovascular hospital admission (31 versus 35 percent) at
mean 21-month follow-up. While the majority of study patients had LVEF 35 percent, there was no
significant influence of EF <35 versus EF >35 percent on the effect of nebivolol on the outcome but the
trial included too few patients with HFpEF (ie, EF >50 percent) to determine if there is a benefit in
HFpEF [28].
A difference in the clinical efficacy of beta blocker therapy in patients with HFrEF versus patients with
HFpEF was suggested by an analysis of the OPTIMIZE-HF registry of 7154 elderly adults hospitalized
with HF [29]. Among patients with HFrEF, beta blocker therapy at hospital discharge was associated
with a reduced mortality and rehospitalization rates. In contrast, among patients with HFpEF, beta
blocker therapy was associated with no improvement in mortality or rehospitalization.