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11.13 ADHF Clinical Pearls
C. E. Kulig
11.13.1
Due to liver congestion, there may be altered liver metabolism when a patient is in
ADHF, which may affect drug dosing. A common co-administered medication is
warfarin. Patients in ADHF may present with supratherapeutic INRs, which may
not be a true indicator of their warfarin dosing. For example, a patient on warfarin
in ADHF that presents with a supratherapeutic INR may not necessarily require a
warfarin dose adjustment on discharge as their liver congestion decreases and blood
ow returns to normal.
er Metabolism
Liv
11.13.2 Volume ofDistribution
Also keep in mind that as peripheral edema and water retention increase, so does the
volume of distribution in patients. This may affect drug dosing and considerations.
11.13.3 Avoid Phenylephrine
In the circumstance that vasopressors are needed, a general rule of thumb is that
phenylephrine should be avoided. Phenylephrine is a pure alpha-1 agonist and
increases vasoconstriction in the peripheries and therefore increases afterload, without any increase in heart contraction (inotropy). This may exacerbate an ADHF
episode as the heart needs to compensate as it ghts against the increased afterload.
Phenylephrine can also increase pulmonary pressures making it more difcult for
the heart to pump blood effectively.
11.13.4 Use Mean Arterial Pressure (MAP)
As we do in most of our critically ill patients, consider using MAP in evaluating
these patients, as systolic/diastolic pressures may be misleading. Patients with
severe HFrEF often are unable to generate high systolic pressures due to weakened
ventricular squeeze. Because of this, they may at rst glance incorrectly appear to
be hypotensive if MAP is not utilized.
11 Acute Decompensated Heart Failure
313
11.14 Guideline-Directed Medical Therapy
Guideline-directed medical therapy is extremely important in chronic heart failure
and should be continued during ADHF whenever possible, with a class 1 recommendation in those with HFrEF to continue and optimize all preexisting GDMT
unless contraindicated [2]. True contraindications are fairly rare, but include
advanced-degree heart block without pacemaker for beta-blockers, angioedema for
ACE-I or ARNI, and cardiogenic shock [2].
Acute kidney injury and hypotension can be common during ADHF, and in those
who have a mild decrease in renal function or asymptomatic hypotension, GDMT
should be continued [2].
If GDMT is discontinued or decreased, it should be restarted or optimized,
respectively, as soon as possible once stable [2].
Why is there such an emphasis on GDMT in these patients? Apart from GDMT
being extremely important in reducing mortality and morbidity in chronic heart
failure, data supports that continuation of oral GDMT during hospitalization lowers
postdischarge death and readmission vs. patients in which GDMT was discontinued
[2]. Despite the importance of GDMT, the rate of GDMT prescribing after hospitalization is staggeringly low, with 42% of patients not on any GDMT or GDMT
monotherapy within 1year post-hospitalization [2]. As the 2022 AHA/ACC/HFSA
guidelines put perfectly: “it cannot be assumed that oral GDMT will be initiated or
optimized after hospitalization with HFrEF” [2].
Keep in mind that all GDMT in heart failure should be increased until target dose
is reached or at the highest tolerated dose. Importantly, asymptomatic hypotension
is not an indication to stop uptitrating these medications. See Table 11.7 for target doses.
Implementing and optimizing GDMT are one of the most important goals of
ADHF hospitalization and one that should not be overlooked.
11.15 Venous Thromboembolism (VTE) Prophylaxis
In patients hospitalized with heart failure, VTE prophylaxis is recommended and is
guideline supported with a class 1 recommendation.
11.16 Conclusion
ADHF is a complex but interesting disease state that every critical care practitioner
will likely encounter at one time or another. Treatment of these patients is extremely
nuanced, and an understanding of the underlying cardiac issues of each patient is of
utmost importance.
314
C. E. Kulig
Table 11.7
Commonly used medications in heart f
ailure
Drug Initial daily dose(s) Target dose(s)
Angiotensin-converting enzyme inhibitors (ACEis)
a
Captopril 6.25mg TID 50mg TID
Enalapril 2.5mg BID 10–20mg BID
Fosinopril 5–10mg QD 40mg QD
Lisinopril 2.5–5mg QD 20–40mg QD
Perindopril 2mg QD 8–16mg QD
Quinapril 5mg BID 20mg BID
Ramipril 1.25–2.5mg QD 10mg QD
Trandolapril 1mg QD 4mg QD
a
ARB
Candesartan 4–8mg QD 32mg QD
Losartan 25–50mg QD 50–150mg QD
Valsartan 20–40mg QD 160mg BID
a
ARNi
Sacubitril/valsartan 24/26mg BID 97/103mg BID
Beta-blockers
a
Bisoprolol 1.25mg QD 10mg QD
Carvedilol 3.125mg BID 25–50mg BID
Carvedilol CR 10mg QD 80mg QD
Metoprolol succinate 12.5–25mg QD 200mg QD
Mineralocorticoid receptor antagonists
a
Spironolactone 12.5–25mg QD 25–50mg QD
Eplerenone 25mg QD 50mg QD
a
SGLT2i
Dapagliozin 10mg QD 10mg QD
Empagliozin 10mg QD 10mg QD
Sotagliozin 200mg QD 200mg QD
Isosorbide dinitrate and hydralazine
Fixed dose combination 20mg and 37.5mg TID 40mg and 75mg TID
Isosorbide dinitrate and
hydralazine
20–30mg and 25–50mg
TID-QID
120mg and 300mg in divided
doses
Other
Ivabradine 5mg BID 7.5mg BID
Vericiguat 2.5mg QD 10mg QD
a
Indicates GDMT
References
1. Heart Failure Society of America. HFSA. 2024. https://hfsa.org/patient- hub/heart- failure- facts-
information. Accessed 20 Dec 2023.
2. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the
management of heart failure: a report of the American College of Cardiology/American
Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol.
2022;79(17):e263–421.
11 Acute Decompensated Heart Failure
3. Nair R, Lak H, Hasan S, Gunasekaran D, Babar A, Gopalakrishna KV. Reducing all-cause
30-day hospital readmissions for patients presenting with acute heart failure exacerbations: a
quality improvement initiative. Cureus. 2020;12(3):e7420. Published 2020 Mar 25. https://doi.
org/10.7759/cureus.7420.
ang SY, Valero-Elizondo J, Ali HJ, etal. Out-of-pocket annual health expenditures and nan-
4.
W
cial toxicity from healthcare costs in patients with heart failure in the United States. J Am Heart
Assoc. 2021;10(14):e022164. https://doi.org/10.1161/JAHA.121.022164.
er GM, Lee KL, Bull DA, etal. Diuretic strategies in patients with acute decompensated
5.
Felk
heart failure. N Engl J Med. 2011;364(9):797–805. https://doi.org/10.1056/NEJMoa1005419.
6.
Cox ZL, Hung R, Lenihan DJ,
acute heart failure: the 3T trial. JACC Heart Fail. 2020;8(3):157–68. https://doi.org/10.1016/j.
jchf.2019.09.012.
7.
Schulze PC, Bogo
sis and kidney function in patients with acute decompensated heart failure (EMPAG-HF).
Circulation. 2022;146(4):289–98. https://doi.org/10.1161/CIRCULATIONAHA.122.059038.
8.
ers E, Dauw J, Martens P, et al. Renal function and decongestion with acetazolamide
Meek
in acute decompensated heart failure: the ADVOR trial. Eur Heart J. 2023;44(37):3672–82.
https://doi.org/10.1093/eurheartj/ehad557.
viku J, Westphal J, etal. Effects of early empagliozin initiation on diure-
Testani JM.Diuretic strategies for loop diuretic resistance in
315
Chapter 12
Right Ventricular Failure andPulmonary
Hypertension intheICU
AdaSelinaJutba
12.1 Introduction
Right ventricular (RV) failure is a heterogeneous syndrome with various etiologies.
The syndrome involves dysfunction of the heart, lungs, or a combination of both.
While the left ventricle is often the center of attention with respect to cardiac function and systemic circulation, the RV is also essential for maintaining hemodynamics. RV failure was noted to be the primary cause of hospitalizations for 2.2% of
heart failure admissions within the CHARITEM registry by Mockel and colleagues,
so it is relatively uncommon compared to LV failure. However, RV failure was present secondary to acute LV failure in over 20% of the cases highlighting the interdependence of the ventricles [1].
Many situations in the critical care setting, whether it is the underlying disease
state or through an iatrogenic cause, may progress to RV failure. Unlike other shock
states that generally have a protocolized approach to treatment, understanding the
etiology is imperative to guide management of critically ill patients with RV failure.
Treatment involves a nuanced balance between preload optimization, afterload
reduction, and contractility augmentation. Pharmacists play a vital role in ensuring
safe and appropriate use of high-risk and specialty medications used in RV failure
and pulmonary hypertension specically; therefore, it is essential for them to be
knowledgeable on the complexities of this disease state.
A. S. Jutba (*)
Department of Pharmacy, Memorial Hermann Memorial City Medical Center,
Houston, TX, USA
e-mail: AdaSelina.Jutba@memorialhermann.org
Switzerland AG 2025
Y. Alzaidi, M. A. Gebily (eds.), The Pharmacist’s Expanded Role in Critical
Care Medicine, https://doi.org/10.1007/978-3-031-77335-8_12
317© The Author(s), under exclusive license to Springer Nature
318
A. S. Jutba
12.2 Pathophysiology ofRight Ventricular Failure
The right ventricle of the heart is connected to systemic venous return and pulmonary circulation. Compared to the left ventricle, the right ventricle is thinner and has
less muscle bers because the pressure in pulmonary circulation is signicantly
lower than the pressure in systemic circulation. Furthermore, the right ventricle is
slightly larger and more compliant. This makes the right ventricle very sensitive to
changes in afterload, and it will hypertrophy and dilate to preserve stroke volume.
While an increase in afterload in the left ventricle will undoubtedly decrease stroke
volume, the same increase will reduce the stroke volume in the right ventricle even
further [2]. Sagawa and colleagues dened RV failure as a state in which the RV is
unable to meet the demands for blood ow without excessive use of the FrankStarling mechanism [
be described as altered preload, increased RV afterload, decreased RV contractility,
altered ventricular interdependence, and arrhythmias. None of the aforementioned
mechanisms are mutually exclusive but rather concomitant.
Group 2 PH (discussed below) is caused by left ventricular dysfunction, valvular
insufciency, and congenital abnormalities. Collectively, their hemodynamics are
represented by elevated mean pulmonary artery pressure (mPAP) and elevated pulmonary capillary wedge pressure (PCWP), or RV preload. This can lead to chronic
excessive RV preload. The passive backward ow of lling pressures, either through
loss of atrial compliance, diastolic dysfunction, or regurgitation, results in excessive
RV preload. The worsening of pulmonary vascular remodeling over time precipitates RV failure.
Pulmonary diseases play a role in the development of RV failure due to the outow of the RV to the lungs via the pulmonary artery. A high-risk pulmonary embolism (PE) occurs when over 50% of the pulmonary vasculature is occluded by
thrombosis [4]. The degree of occlusion, coupled with hemodynamic instability,
increases RV afterload. Chronic respiratory disorders can also cause acute RV failure. In chronic thromboembolic pulmonary hypertension (CTEPH), secondary
remodeling of the arterioles and myocardium over time causes a gradual increase in
RV afterload [5]. In chronic obstructive pulmonary disease (COPD), pulmonary
hyperination, airway resistance, chronic CO
function, and rarefaction of the vascular bed are all mechanisms that increase RV
afterload [2].
Cardiac diseases involving the right side of the heart, such as RV ischemia or
infarction, lead to decreased perfusion in the right side of the heart, which decreases
RV contractility and progresses to RV failure. Cardiomyopathies can alter the structure of the RV.Dilated cardiomyopathy involves the enlargement of the left ventricle. Hypertrophic obstructive cardiomyopathy is the muscle thickening of the
interventricular septum. Both structural abnormalities affect the RV’s contractility
and may lead to RV failure. Pericardial diseases (e.g., tamponade) may alter ventricular interdependence. Tachyarrhythmias can also precipitate RV failure. For
3]. The underlying mechanisms of right ventricular failure can
retention, hypoxia, endothelial dys-
2
12
Right Ventricular Failure andPulmonary Hypertension intheICU
319
instance, atrial brillation increases LV lling pressures, subsequently causing PH
and eventually RV failure [2, 6].
An iatrogenic cause of right ventricular failure common in critically ill patients
is the use of mechanical ventilation. Humans normally breathe through negativepressure respiration. During inhalation, the chest cavity and rib cage expand while
the diaphragm contracts causing a decrease in intrathoracic pressure. Air enters the
lungs through negative pressure. During exhalation, the diaphragm relaxes and creates positive pressure to ow air out of the lungs. Conversely, mechanical ventilation administers positive pressure to the upper airways, thereby increasing
intrathoracic pressure. Increased intrathoracic pressure can subsequently increase
right atrial pressure and consequently decrease venous return (i.e., right ventricular
preload) and cardiac output. Furthermore, prolonged mechanical ventilation may
lead to atelectatic and overdistended alveoli, both of which compress alveolar vessels and increase RV afterload [2, 7–9].
12.3 Diagnostic Findings
Signs of RV failure are the downstream effects of systemic congestion and hypoperfusion. Systemic congestion can present as jugular venous distension and peripheral
edema. Hypoperfusion can lead to organ dysfunction like acute kidney injury,
hepatic congestion, and impairment of the intestinal barrier in the gastrointestinal
tract. If collected, elevated brain natriuretic peptides may be sensitive but not specic for diagnosing right ventricular failure. Patients may endorse symptoms of
dyspnea, fatigue, lower extremity edema, exercise intolerance, and right upper
quadrant tenderness [7–10].
Echocardiography can provide comprehensive information regarding the right
heart’s morphology, right ventricular function, valvular abnormalities, and estimated hemodynamics. The American Society of Echocardiography and the
European Association of Cardiovascular Imaging recommend quantitative assessment of RV function using at least one of the following parameters: fractional area
change, tricuspid annular plane systolic excursion, systolic S′ velocity of the tricuspid annulus by Doppler tissue imaging (DTI), and right ventricular index of myocardial performance (Table 12.1) [10–12]. A more invasive diagnostic tool is a
pulmonary artery (PA) catheter, or Swan-Ganz catheter. The PA catheter measures
continuous hemodynamic parameters about right and left atrial pressures,
Table 12.1 Echocardiographic ndings in RV failure
Parameter Abnormality threshold
Fractional area change <35%
Tricuspid annular plane systolic excursion <17mm
DTI-derived systolic S’ velocity of the tricuspid annulus <9.5cm/s
RV index of myocardial performance >0.54
320
Table 12.2 Pulmonary artery catheter measurements
Parameter Normal values
Right atrial pressure (RAP) 2–6mmHg
Right ventricular systolic pressure (RVSP) 15–25mmHg
Right ventricular diastolic pressure (RVDP) 0–8mmHg
Mean pulmonary artery pressure (mPAP) 8–20mmHg
Pulmonary capillary wedge pressure (PCWP) ≤15mmHg
Cardiac output (CO) 4–8L/min
Cardiac index (CI) 2.5–4.0L/min.m
2
A. S. Jutba
pulmonary vascular resistance, and cardiac output (Table 12.2). The pressures on
the right side of the heart, the mPAP, or the PCWP can be elevated in RV failure
depending on the etiology. The cardiac output and index will likely be reduced in
decompensated RV failure.
12.4 Management ofAcute Decompensated Right
Ventricular Failure
12.4.1 Oxygen Therapy
Oxygen therapy should be used to maintain arterial oxygen saturation greater than
90%. Hypoxia, hypercapnia, and acidosis promote vasoconstriction in the pulmonary vasculature, which further increases RV afterload. Patients with respiratory
failure and hypercapnia may benet from noninvasive ventilation. Positive-pressure
ventilation with intubation should be avoided if possible because it can also increase
RV afterload. Furthermore, intravenous sedation that may be required during
mechanical ventilation may lead to systemic hypotension, thereby decreasing LV
preload [10].
12.4.2 Pharmacological Management
Treatment of acute right ventricular failure is determined by the underlying insult
and can be either optimizing preload, reducing afterload, or increasing right ventricular contractility [2, 8, 12]. Patients with RV failure may be preload dependent,
but volume loading should be done cautiously and only in the setting of low arterial
pressure without elevated lling pressures. Volume loading can potentially overdistend the right ventricle, decrease contractility, and ultimately reduce systemic cardiac output. Rather, patients may benet from volume removal to normalize preload
to decrease stress on the right ventricle [2, 9, 10]. Volume reduction can be done
through the use of loop diuretics. Loop diuretics inhibit the
12 Right Ventricular Failure andPulmonary Hypertension intheICU
321
sodium-potassium- chloride cotransporter in the thick ascending loop of Henle. The
net result is a reduction in the reabsorption of the ions and consequently water
through osmosis. Examples of loop diuretics are furosemide, bumetanide, torsemide, and ethacrynic acid. Diuresis can be augmented with concomitant use of thiazide diuretics through sequential nephron blockade as they work more distally in the
nephron at the distal convoluted tubule. Thiazide diuretics inhibit the sodium-chloride cotransporter to also decrease sodium reabsorption but to a lesser degree than
loop diuretics. Examples include metolazone, hydrochlorothiazide, and chlorothiazide. In some instances, ultraltration or renal replacement therapy may be necessary to reduce preload.
Afterload reduction is benecial in scenarios with elevated right ventricular
afterload or elevated pulmonary vascular resistance (PVR). In the setting of an
intermediate-high or high-risk PE, thrombolytics with alteplase or tenecteplase may
be indicated to decrease RV afterload [5]. Group 1 PH, or pulmonary arterial hypertension (PAH), has the most well- established therapies to reduce afterload. The
three main pathways in pharmacologic management of PAH are endothelin, nitric
oxide, and prostacyclin [13–15]. Endothelin-1 normally acts on endothelin receptor
A to cause vasoconstriction and cell proliferation and on endothelin receptor B to
cause vasodilation and antiproliferation. Endothelin receptor antagonists such as
bosentan, ambrisentan, and macitentan competitively inhibit endothelin-1.
Phosphodiesterase type 5 inhibitors include sildenal and tadalal. They prevent
the breakdown of cyclic guanosine monophosphate (cGMP) in pulmonary vascular
smooth muscle, thereby potentiating pulmonary vascular smooth muscle relaxation
and pulmonary vascular bed vasodilation. Riociguat is a soluble guanylate cyclase
stimulator and sensitizes endogenous soluble guanylate cyclase by stabilizing nitric
oxide-soluble guanylate cyclase binding. The resultant effect increases cyclic guanosine monophosphate, which inuences vascular tone, proliferation, brosis, and
inammation. Riociguat is also approved for the treatment of group 4 PH patients
who have residual CTEPH after surgical treatment or are deemed inoperable [16].
Prostacyclins mimic endogenous prostacyclin (PGI
) and cause direct vasodilation
2
of pulmonary and systemic arterial vascular beds, inhibition of platelet aggregation,
and antiproliferative effects. Prostacyclins are available in different dosage formulations and can be administered intravenously [epoprostenol (Flolan®, Veletri®),
treprostinil (Remodulin®)], subcutaneously [treprostinil (Remodulin®), orally [epoprostenol (Iloprost®), treprostinil (Orenitram®)], or inhaled [treprostinil (Tyvaso®)].
Initial combination therapy is now the standard of care for PAH to ideally target the
different pathways [17, 18].
Lastly, augmentation of right ventricular contractility can also be utilized.
Addressing the underlying insult of right ventricular failure is important; however,
inotropic support may be utilized in the interim. Inotropes will increase forward
ow in situations of inadequate cardiac output [2, 9, 10]. Milrinone is a phosphodiesterase III (PDE III) inhibitor. Inhibition of PDE III prevents the breakdown of
cyclic adenosine monophosphate (cAMP) and guanosine monophosphate (cGMP).
cAMP leads to phosphorylation of calcium ion channels in the sarcoplasmic reticulum and increasing calcium availability in the myocytes. This manifests as increased
322
cardiac contractility. Subsequently, PDE III inhibition increases calcium reuptake
into the sarcoplasmic reticulum and improves myocardial relaxation. Additionally,
PDE III inhibition prevents cGMP metabolism in the vascular smooth muscle,
resulting in dilation of the arteries and veins. Dobutamine stimulates beta-1 adrenergic receptors in the myocardium to increase contractility and heart rate. It also
stimulates beta-2 receptors in the peripheral vasculature, causing vasodilation.
Milrinone has more potent pulmonary and systemic vasodilatory effects compared
to dobutamine, leading to more profound reductions in right ventricle end-diastolic
pressures. Consequently, due to milrinone’s potent vasodilatory effects and longer
half-life, it is more likely to incite hypotension.
A. S. Jutba
12.4.3 Mechanical Circulatory Support (MCS)
If all pharmacological options have been optimized and exhausted, MCS can be
considered. Patient criteria for eligibility vary by institution. Timing of cannulation
or implantation and device selection are crucial to minimize end-organ damage and
maximize the chances of recovery. Device selection also depends on the anticipated duration of support. Extracorporeal membrane oxygenation (ECMO) is a
form of life support where deoxygenated blood from the vasculature is circulated
outside of the body by a mechanical pump, gets saturated with oxygen through an
oxygenator, and then gets recirculated back into the body. Venoarterial (VA)
ECMO bypasses the heart and lungs and provides respiratory and hemodynamic
support. The typical recommended duration of ECMO is 5–10days due to its associated complications such as infection, thrombus formation, and limb hypoperfusion [10, 13]. A right ventricular assist device (RVAD) is a device surgically or
percutaneously implanted to assist with right ventricular contractility to the pulmonary artery. RVADs have more data for prolonged use up to months, though they
are only approved for up to 4weeks [19]. Due to the temporary nature of MCS,
these devices only serve as a bridge therapy to either recovery or cardiac
transplantation.
12.5 Pulmonary Hypertension
Pulmonary hypertension, among many other diseases, can progress to right ventricular (RV) failure. Pulmonary hypertension (PH) is a complex disease state that
has a direct impact on the RV.The gold standard for diagnosing PH is a right heart
catheterization. The 2022 European Society of Cardiology and European
Respiratory Society Guidelines for the Diagnosis and Treatment of Pulmonary
Hypertension dene PH as a mPAP 20mmHg at rest. Other pertinent hemodynamic measurements include PVR and PCWP, both of which are utilized to differentiate between precapillary PH and isolated postcapillary PH [13–15].