B.J. has responded poorly to IV furosemide, his renal function has deteriorated,
and his systolic BP is low. Patients with advanced HF and systemic hypoperfusion
often will not tolerate vasodilator therapy. Inotropic agents may be necessary to
maintain circulatory function in these patients. According to guidelines, IV inotropic
drugs may be considered for patients who have symptomatic hypotension despite
adequate filling pressure, who are unresponsive to diuretics and intolerant to
vasodilators, or who have worsening renal function. Phosphodiesterase inhibitors are
Patients should be on telemetry because milrinone has the potential to cause
arrhythmias. Vital signs, SCr, symptom relief, and urine output should be monitored.
Once the patient’s hemodynamic profile improves, milrinone should be discontinued,
and oral furosemide therapy can be resumed. At discharge, the outpatient HF
medications should be optimized.
Outpatient Inotropic Infusions
agents as part of a home-care regimen?
The long-term safety and efficacy of inotropic therapy is regarded with skepticism.
There are few studies assessing intermittent (e.g., weekly) infusions of dobutamine or
milrinone. Nearly all the data on this therapeutic approach are from open-label and
uncontrolled trials that compare two inotropic agents without a placebo.
thought that long-term therapy may be cardiotoxic. The only placebo-controlled trial
of intermittent infusion of dobutamine was terminated because of excess mortality
278 Death occurred in 32% of patients treated with dobutamine
versus 14% with placebo. Whether this was caused by progression of underlying
heart disease, continued drug therapy, or was a cardiotoxic effect remains unknown.
No corresponding data exist for milrinone, although a placebo-controlled trial with
milrinone failed to support the routine use of IV milrinone as an adjunct to standard
therapy in the treatment of patients hospitalized for an acute exacerbation of chronic
274,275 For this reason, the ACA/AHA guidelines indicate that intermittent
infusions of dobutamine and milrinone in the long-term treatment of HF, even in
advanced stages, should be avoided.
4 Chronic continuous infusions of dobutamine
and milrinone are sometimes administered in patients with refractory HF as
palliative therapy or in those awaiting transplant. The lowest dose possible should
be administered. The HFSA identifies the limited treatment options in advanced HF
and proposes patient-centered outcomes (survival vs. quality of life, palliative and
hospice care) to be incorporated into care plans.
Ventricular Arrhythmias Complicating Heart Failure
CASE 14-5, QUESTION 3: B.J. was stabilized during the next several days and discharged home with
ECG monitoring during B.J.’s hospital stay showed normal sinus rhythm, with 15 to 20 asymptomatic
asymptomatic. For the next several months, he continued to have frequent PVCs during follow-up
agent of choice, and what dose should be given?
PVCs and other arrhythmias are a common complication of LV dysfunction and
may be present regardless of whether the patient has had an MI. Approximately 50%
to 70% of patients with HF have episodes of nonsustained ventricular tachycardia on
4 This myocardial irritability may be a result of autonomic
hyperactivity or ventricular remodeling. It is not clear whether these rhythm
disturbances contribute to sudden death or simply reflect the underlying disease
process. Recent studies suggest that bradyarrhythmia or electromechanical
dissociation may be associated with sudden death in HF patients with nonischemic
283,284 More importantly, suppression of ventricular ectopy in patients
with HF has not been shown to lead to a reduction of sudden death in clinical trials.
Neither prophylactic antiarrhythmic therapy nor treatment of asymptomatic PVC after
an MI has been proven to improve outcome or survival. Because of concerns about
the proarrhythmic effects of most class IA and class IC drugs, treatment with these
Amiodarone has value in patients with HF with arrhythmias because it has
antiarrhythmic and coronary vasodilating effects as well as α- and β-blocking
properties. It may offer a dual benefit to reduce myocardial irritability and improve
In the Grupo de Estudio de la Sobrevida en la Insuficiecia Cardiaca en Argentina
285 516 patients with class II to IV HF symptoms (average EF 20%),
and frequent PVCs were randomly assigned to receive either standard treatment
(diuretics, vasodilators, digoxin) or a fixed dose of amiodarone plus standard
treatment. The dose of amiodarone was 600 mg daily for 2 weeks, then 300 mg/day
for at least 1 year. Fewer patients on amiodarone (33.5%) died compared with those
receiving standard treatment (41.4%), a statistically significant difference. Similarly,
the number of HF-related hospitalizations was reduced with amiodarone.
Somewhat different outcomes were noted in the Veterans Administration (VA)
Cooperative Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure
286,287 Entry criteria to this trial were similar to those in the
GESICA study, with a primary indicator being more than 10 asymptomatic PVCs per
hour on 24-hour monitoring, but without sustained ventricular tachycardia. A higher
dose of amiodarone was used, 800 mg for 2 weeks, then 400 mg/day for 1 year. The
dose was reduced to 300 mg/day after the first year, with the average
follow-up being 45 months. No difference was found between groups for either
all-cause mortality or SCD. EF improved more in the patients treated with
amiodarone, rising from a baseline average of 24.9% to 33.7%. The corresponding
change in the standard treatment group was from a baseline of 25.8% to 29.2% at
follow-up. Despite the increase in EF, symptom scores did not differ between the
Amiodarone does not have a negative effect on mortality as seen with some of the
other antiarrhythmic agents. Other factors to consider are the potential for significant
side effects with amiodarone (see Chapter 15, Cardiac Arrhythmias) and the drug
interaction with digoxin leading to the potential for digoxin toxicity.
The ACC/AHA guidelines do not recommend routine ambulatory ECG monitoring
to detect asymptomatic ventricular arrhythmias, and recommend against treatment if
such arrhythmias are inadvertently detected.
arrhythmias should arise or there is determined to be a high risk for sudden death,
one of the following should be considered: a β-blocking drug, amiodarone, or an
ICD. Nearly all patients with HF should have a β-blocker as part of their regimen
because these drugs reduce all-cause mortality, not just sudden death. B.J. continued
to have ectopy despite continued use of a β-blocker. Nonetheless, it is decided not to
use amiodarone because he is asymptomatic.
IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR
CASE 14-5, QUESTION 4: Is B.J. a candidate for an ICD implantation?
Although amiodarone is the preferred antiarrhythmic agent in patients with HF
with reduced EF to prevent recurrent AF and symptomatic ventricular arrhythmias, it
has not improved survival. Ventricular arrhythmias are associated with a high
frequency of SCD in patients with HF. Numerous trials have established the role of
ICDs in primary and secondary prevention of SCD. The earliest of the primary
prevention trials was the Multicenter Automatic Defibrillator Implantation Trial
288 This study was terminated early because of the survival benefit seen in
the ICD group compared with conventional therapy. There was no evidence that
amiodarone, β-blockers, or any other antiarrhythmic therapy had a significant
influence on the results. Unlike MADIT, the MADIT II
290 study enrolled patients with
no documented arrhythmias but with previous MI and LVEF less than 30%. Patients
received either an ICD or conventional medical therapy. The primary end point was
death from any cause. There was a 31% relative reduction in the risk of death and an
absolute reduction of 6% in the ICD group. This was the first trial to show mortality
benefits of ICDs in patients with no documented history of abnormal heart rhythms.
The Sudden Cardiac Death in Heart Failure trial (SCD-HeFT) evaluated the
efficacy of amiodarone in patients with LV dysfunction (EF ≤ 35%).
(NYHA class II–III) were receiving conventional therapy and randomly assigned to
placebo, amiodarone, or an ICD. Amiodarone was no better than placebo, whereas
ICD decreased mortality by 23% (p = 0.007). A subgroup analysis showed that
patients with class II HF had a greater drop in mortality with ICD use than class III
patients, whereas amiodarone decreased survival in class III. The role of amiodarone
in patients with NYHA class III needs to be further evaluated before it is routinely
used in patients with LV dysfunction.
recommend the use of ICDs in patients after MI with
reduced LVEF and who have a history of ventricular arrhythmias. ICDs are also
recommended for primary prevention in patients with nonischemic cardiomyopathy
and ischemic heart disease who have an LVEF of 30% or less, those with NYHA
functional class II or III symptoms while on optimal standard oral therapy, and
patients who have reasonable expected survival with a good functional status of one
or more years. Patients with ischemic heart disease should receive an ICD at least 40
days after MI. B.J. is currently on optimal HF drug regimen, and his EF is 20%.
According to guidelines, B.J. would benefit from ICD implantation.
CARDIAC RESYNCHRONIZATION THERAPY
QUESTION 1: C.M., a 49-year-old woman with a history of cardiomyopathy (EF 25%), presents to the HF
bpm and a QRS duration of 144 ms. Is she a candidate for CRT?
Approximately one-third of the patients with advanced systolic HF exhibit
intraventricular or interventricular conduction delays that cause the ventricles to beat
291 Ventricular dyssynchrony is seen on ECG as a wide QRS complex
with a left bundle branch block, and can lead to deleterious effects on cardiac
function. Patients may present with reduced EF, decreased CO, and presence of
NYHA class III or IV HF symptoms. These are all associated with increased
CRT is the use of cardiac pacing to coordinate the contraction of the left and right
Initial randomized trials of CRT show reduced HF symptoms and
improved exercise tolerance and quality of life. The Comparison of Medical
Therapy, Pacing, and Defibrillator in Heart Failure (COMPANION) trial
1,520 patients with NYHA class II or IV (QRS interval of at least 120 ms, and LVEF
≤35%) who were treated with optimal drug therapy (ACEIs, diuretics, β-blockers,
and spironolactone). Patients were randomly assigned to receive optimal drug
therapy alone, optimal drug therapy and CRT with a pacemaker, or optimal drug
with a decreased risk of primary end point compared with optimal drug therapy
alone. All-cause mortality at 1 year was decreased by 24% in the CRT group (which
did not reach statistical significance) and 43% in the CRT-D group.
The results of the Cardiac Resynchronization in Heart Failure study (CARE-HF)
extended the findings of the COMPANION trial. CARE-HF demonstrated a
significant all-cause mortality reduction for CRT pacing without defibrillator backup
(CRT) in patients with HF who received similar medical treatment. The inclusion
criteria were NYHA class III or IV, EF of 35% or less, and QRS duration of 120 ms
or longer. The primary end point of all-cause deaths and hospitalizations for a CV
reason occurred in fewer patients with CRT compared with the optimal drug therapy
(39% vs. 55%; p < 0.001). Death or hospitalization for worsening HF was also
significantly reduced with CRT.
The combined results of CARE-HF and COMPANION confirm the importance of
CRT and CRT-D in improving ventricular function, HF symptoms, and exercise
tolerance, while also reducing frequency of HF hospitalizations and death.
role of CRT in patients with mild HF symptoms, narrow QRS, chronic AF, and right
bundle branch block needs to be explored.
According to the ACC/AHA guidelines,
1 patients with NYHA class III and
ambulatory patients with class IV HF should receive CRT (unless contraindicated) if
they meet the following criteria: LVEF of 35% or less, presence of a wide QRS
(>120 ms), and receiving optimal HF standard medical therapy. Despite optimal
doses of HF medications, C.M. continues to have HF symptoms. CRT therapy
could provide incremental benefits beyond what is provided with drug therapy.
CASE 14-6, QUESTION 2: If C.M. presented with NYHA class I or II symptoms, would she be a candidate
for CRT therapy? What is the evidence to support CRT in NYHA class I and II patients?
As mentioned in Case 14-6, Question 1, the CARE-HF and COMPANION trials
provide strong evidence that CRT induces reverse modeling in patients with
symptomatic NYHA class III and ambulatory class IV HF. The next logical step was
to evaluate the benefits of CRT therapy in HF patients with milder symptoms. The
Multicenter InSynch ICD Randomized Clinical Evaluation (MIRACLE-ICDII)
randomized class II through IV HF patients but with separate specified end points for
class II patients. In this trial, 186 patients with NYHA class II HF, an LVEF of less
than 35%, and a QRS of more than 130 ms received a CRT-ICD device. Subjects
were randomly assigned to active CRT group (ICD activated and CRT on) or control
group (ICD activated and CRT off). The primary end point was progression of HF,
defined as all-cause mortality, hospitalizations for HF, and ventricular tachycardia or
ventricular fibrillation requiring device intervention. A 15% reduction in HF
progression was observed with active CRT, but did not reach statistical significance.
At 6 months, patients with active CRT had improved exercise tolerance, but this was
not significantly different from the control group. However, there was a significant
decrease in ventricular end-systolic volume and increased LVEF after 6 months of
therapy. Even though the study results did not translate into improved exercise
tolerance, it helped to set the stage for future trials in patients with less symptomatic
74 enrolled 610 participants with NYHA class I or II HF,
LVEF less than 40%, and with a QRS duration of more than 120 ms who received a
CRT device (with or without ICD) in combination with optimal drug therapy. The
patients in the active CRT group had significant improvement in LV end-systolic
volume index, LV end-diastolic volume index, and LVEF compared to control. The
primary clinical end point (the percentage of patients with worsened clinical
composite score) did not reach statistical significance at 12 months in patients
enrolled in the United States, but in the European cohort
was seen at 24 months, primarily driven by the time to first hospitalization The
aggregate data from these two clinical trials provided overwhelming evidence that
linked CRT with substantial reverse remodeling in mild HF patients.
75 was the largest randomized trial designed to determine
whether CRT-D therapy would reduce the primary end point (all-cause mortality or
HF events) when compared with patients receiving ICD-only therapy. The study
population involved cardiac patients in NYHA functional class I or II with LVEF of
30% or less and QRS duration of more than 130 ms. There was a 34% (p < 0.001)
reduction in the primary end point, and a 44% (p < 0.001) reduction in HF events
when compared with ICD therapy. Patients with CRT-D therapy showed an 11%
improvement in LVEF after 1 year, compared with 3% improvement for ICD-alone
patients. Both MADIT-CRT and REVERSE excluded patients with AF. Both studies
failed to show a benefit for CRT in patients with QRS duration less than 150 ms.
The Resynchronization/Defibrillation for Ambulatory Heart Failure Trial
295 confirmed that CRT benefited patients with a QRS duration of 150 ms or
more and in those with left bundle branch block. The RAFT investigators randomly
assigned 1,798 patients with NYHA class II or III HF, LVEF of 30% or less, and a
QRS duration of at least 120 ms (or a paced QRS of at least 200 ms) to either ICD
therapy alone or an ICD with CRT (CRT-D). The primary outcome was a
combination of total mortality and HF hospitalization, which was significantly higher
in the ICD group compared with the ICD-CRT group (40% vs. 33%, respectively).
These findings demonstrate that earlier intervention with CRT-D, in addition to
guideline recommended medical and ICD therapy, benefits this patient population.
HEART FAILURE WITH PRESERVED EJECTION
Cardiac examination reveals a prominent S4
heart sound. Echocardiography reveals an EF of 50%. Prior
CCB to control the BP and HR. Why might this consideration be appropriate?
This case exemplifies a patient with HF with preserved LVEF (HFpEF),
previously referred to as diastolic HF. Risk factors for HFpEF include advanced
age, female sex, HTN, and CAD. This diagnosis can be made on the basis of LVH,
clinical evidence of HF, a normal EF, and echocardiography findings. The ideal
treatment for HFpEF has not been extensively validated. A review of trials
evaluating specific drug therapy in HFpEF is listed in Table 14-13. No drug
selectively enhances myocardial relaxation without having associated effects on LV
contractility or on the peripheral vasculature.
Factors affecting HF control, such as adherence to medication and diet, including
NSAID and herbal remedy use, should be appropriately managed along with drug
therapy. Symptomatic HFpEF is initially treated similar to other forms of HF, by
slow diuresis. Diuresis decreases preload and lessens passive congestion of the
ventricles. Excessive lowering of ventricular filling pressures, however, can
decrease CO and cause hypotension.
The most common cause of HFpEF is HTN that leads to LVH and decreased
297 The ACC/AHA/HFSA guidelines recommend a SPB goal of
<130 mmHg in patients with HFpEF and persistent hypertension after management of
fluid overload. Drugs that cause regression of LVH (e.g., ACEIs, ARBs, β-blockers)
may also slow or reverse structural abnormalities associated with HFpEF.
In the Perindopril in Elderly patients with Chronic HF (PEP-CHF) trial,
Comments
Post a Comment
اكتب تعليق حول الموضوع