Alaa Ateya Mohammed

Terms have been used to characterize AHF in the literature, including:

“acute heart failure syndromes” (AHFSs),

“acute(ly) decompensated heart failure” (ADHF),

“acute decompensation of chronic heart failure” (ADCHF),

“hospitalization for heart failure” (HHF).

Acute Heart failure Definition: AHF can be defined as:

“ The new onset or recurrence of symptoms and signs of heart failure requiring urgent or emergent therapy and resulting in seeking unscheduled care or hospitalization.”

Although the designation “acute” in the nomenclature suggests a sudden onset of symptoms, many patients may have a more subacute course, with gradual worsening of symptoms that ultimately reach a level of severity sufficient to seek unscheduled medical care.

Scope of the Problem

The overall number of hospitalizations for heart failure continues to grow as a consequence of:

Aging of the population,

Improved survival after acute MI,

Effective prevention of SCD.

Preserved vs Reduced Ejection Fraction

Unexpectedly high prevalence of HFpEF in AHF

HFpEF are more likely to be older, to be female, and to havea history of hypertension, less likely underlying CAD

The in-hospital mortality for patients with HFpEF appearsto be lower than that for patients with depressed LVejection fraction (LVEF), but postdischargerehospitalization rates are similarly high for bothgroups.

Comorbid Conditions with AHFVery common

represent diseases that are risk factors for the development of heart failure and also can complicate diagnosis and management.

Hypertension is the most prevalent 60%

CAD 50%

Dyslipidemia > 30%

Diabetes mellitus

Other conditions that are the result of the vascular injury produced by these diseases, such as Stroke, PVD, CKD

COPD 30%(confounds the presenting symptoms dyspnea)

Atrial fibrillation 30-40% (can both precipitate AHF and complicate its management)

PATHOPHYSIOLOGY

clinical signs and symptoms

( congestion or end-organ dysfunction, or

both)

Amplifying mechanisms

initiating

mechanisms or

Triggers

underlying substrate

Underlying Substrate may be one of 1. In most patients with AHF, the original substrate is one

of chronic compensated heart failure, followed by decompensation with development of AHF.

2. No previous history of heart failure but exhibit an abnormal substrate (e.g., those with stage B heart failure associated with asymptomatic LV dysfunction) with a first presentation of heart failure (de novo heart failure)

3. No previous history of heart failure in whom AHF develops because of sudden changes in ventricular function from an acute insult such as myocardial infarction or acute myocarditis.

Initiating mechanisms vary according to, and interact with, the underlying substrate

Maybe cardiac or extracardiac.

For patients with normal substrate (normal myocardium), a substantial insult to cardiac performance (e.g., acute MI, myocarditis) is required to lead to the clinical presentation of AHF.

For patients with abnormal substrate at baseline (e.g., asymptomatic LV dysfunction), smaller perturbations (e.g., poorly controlled hypertension, atrial fibrillation, or ischemia) may precipitate an AHF episode.

For patients with a substrate of compensated or stable chronic heart failure, medical or dietary noncompliance, drugs such as nonsteroidal anti-inflammatory agents or thiazolidinediones, and infectious processes all are common triggers for decompensation.

“Amplifying Mechanisms”

These include:

Neurohormonal and inflammatory activation,

Ongoing myocardial injury with progressivemyocardial dysfunction,

Worsening renal function,

Interactions with the peripheral vasculature

“all of which may contribute to the propagation andworsening of the AHF episode”

Congestion Systemic or pulmonary congestion, most often the

result of a high LV diastolic pressure, dominates theclinical presentation in most patients hospitalized forAHF

Gradual increases in intravascular volume lead tosymptoms of congestion and clinical presentation, andnormalization of volume status with diuretic therapyresults in restoration of homeostasis. Although thismechanism may be operative in some patients(particularly those with frank noncompliance withsodium restriction or diuretic therapy), this is

“oversimplification”.

Increasing interest in the concept of

volume redistribution rather than volume retentionas a mechanism of decompensation in heart failure

Clinical congestion and hemodynamic congestion

Although patients present with signs and symptoms of systemic congestion such as dyspnea, rales, elevated jugular venous pressure, and edema, this state often is preceded by so-called hemodynamic congestion, defined as high LV diastolic pressures without overt clinical signs.

Similarly, clinical congestion may resolve with treatment but hemodynamic congestion may persist, leading to a high risk of rehospitalization.

hemodynamic congestion may contribute to theprogression of heart failure because it may result in:

Wall stress,

(RAAS) and sympathetic nervous system (SNS) activation.

Myocyte loss and increased fibrosis.

Abnormal processing of the natriuretic peptides

Elevated diastolic filling pressures may decrease coronaryperfusion pressure, resulting in subendocardial ischemiawith further exacerbation of cardiac dysfunction.

Increased LV filling pressures also can lead to a morespherical

shape, contributing to worsening mitral regurgitation.

Pathologic remodeling

Myocardial Function Although a variety of extracardiac factors play

important roles in AHF, impairments of cardiac function (systolic, diastolic, or both) remain central to our understanding of this disorder.

Changes in systolic function and decreased arterialfilling can initiate a cascade of effects that areadaptive in the short term but maladaptive whenelevated chronically, including stimulation of theSNS and the RAA. (vasoconstriction, sodium andwater retention, increase and redistribution fromother vascular beds, increases in diastolic fillingpressures)

In patients with underlying CAD, initial defects in systolic function may initiate a vicious circle of decreasing coronary perfusion, increased myocardial wall stress, and progressively worsening cardiac performance. Increased LV filling pressures and changes in LV geometry can worsen functional mitral regurgitation, further decreasing cardiac output.

Approximately half of patients with AHF have relativelypreserved systolic function.

Of importance, abnormalities in diastolic function arepresent in patients with both preserved and impairedejection fraction.

The impairment of the diastolic phase may be related topassive stiffness or abnormal active relaxation of the leftventricle, or both.

Hypertension, tachycardia, and myocardial ischemia canfurther impair diastolic filling. All of these mechanismscontribute to higher LV end-diastolic pressures, which arereflected back to the pulmonary capillary circulation.

Diastolic dysfunction alone may be insufficient to lead toAHF, but it serves as the substrate on which otherprecipitating factors (such as atrial fibrillation, coronaryartery disease, or hypertension) lead to decompensation.

The availability of sensitive assays for circulating cardiac troponins has led to substantial evolution of our understanding of the role of myocardial injury in the pathophysiology of heart failure.

Circulating cardiac troponins are elevated in a large proportion of patients with AHF, even in the absence of clinically overt myocardial ischemia.

30% had persistent elevation of troponin at 30 days

Associated with increased risk of both in-hospital and postdischarge events

The precise mechanisms mediating myocardial injury in AHF are

poorly defined: Increased myocardial wall stress, Increased myocardial oxygen demand, Decreased coronary perfusion pressure, endothelial dysfunction, Activation of the neurohormonal and inflammatory axes, Activation of platelets, Altered calcium handling.

All may contribute to myocyte injury even in absence of CAD

Specific therapeutic interventions that may increase myocardial oxygen demand (such as positive inotropic agents) or decrease coronary artery perfusion pressure (such as some vasodilators) may exacerbate myocardial injury and further contribute to the cycle of decompensation.

Renal Mechanisms The kidney plays two fundamental roles relative to the

pathophysiology of heart failure:1) Modulates loading conditions of the heart by controlling

intravascular volume2) Responsible for neurohormonal outputs (i.e., the RAAS system)

Baseline measures of renal function also are well-established risk factors for poor outcomes in AHF

Additionally, worsening renal function during AHF therapy in thesetting of persistent congestion—often termed the “cardiorenalsyndrome”—has been associated with poor outcomes

Although often assumed to be related to low cardiac output and renal blood flow, careful hemodynamic studies have confirmed that: “The strongest predictor of worsening renal function in heart failure patients relates to elevated central venous pressure, which is reflected back to the renal veins and leads directly to changes in glomerular filtration rate.”

Diuretics may exacerbate renal dysfunction throughincreasing neurohormonal activation and vasoconstriction,although in many cases effective diuresis improves renalfunction by decreasing central venous pressure.

Newer biomarkers that may distinguish changes in renal function (as reflected by serum creatinine or cystatin C) from acute kidney injury (as reflected by markers such as urinary neutrophil gelatinase– associated lipocalin[NGAL]) may allow better differentiation of worsening renal function during AHF hospitalization

Vascular Mechanisms Increasing appreciation for the importance of the vasculature

not only as an underlying cause of cardiac dysfunction (i.e., atherosclerosis, hypertension) but also as a central component of the pathogenesis of AHF

Abnormalities of endothelial function related to nitric oxide–dependent regulation of vascular tone

Arterial stiffness

Peripheral vasoconstriction in the setting of AHF redistributes blood centrally, increasing pulmonary venous congestion and edema.

This increased afterload causes greater ventricular wall stress and increased myocardial ischemia and cardiac arrhythmias

Effects of this vascular abnormality are amplified by LV diastolic dysfunction.

Neurohormonal and InflammatoryMechanisms Increased plasma concentrations of norepinephrine,

plasma renin activity, aldosterone, and endothelin-1 havebeen reported in patients with AHF; all of these axes areassociated with vasoconstriction and volume retention, whichcould contribute to myocardial ischemia and congestion, therebyexacerbating cardiac decompensation.

Proinflammatory cytokines such as tumor necrosis factoralpha and interleukin-6 are elevated in patients with AHF

direct negative inotropic effects on the myocardium as well as increasing capillary permeability and inducing endothelial dysfunction.

Stimulates the release of the potent procoagulant tissue factor and endothelin-1, which can lead to further myocardial suppression, disruption of the pulmonary alveolar-capillary barrier, and increased platelet aggregation and coagulation (potentially worsening ischemia)

AHF Groups

1. Decompensated heart failure:

This group is composed of patients with worsening signs and symptoms of congestion on a background of chronic heart failure.

may be acute, subacute, or indolent, with gradually worsening symptoms over days to weeks.

Either preserved or reduced ejection fraction, but cardiac output generally is preserved and blood pressure is within the normal range.

Overall, this group represents the largest proportion of patients hospitalized for AHF.

2. Acute hypertensive heart failure:Hypertension is increasingly recognized as a common feature of the AHF

presentation, with 50% of patients presenting with systolic blood pressure (SBP) higher than 140 mm Hg and 25% with SBP higher than 160 mm Hg.

hypertension may be triggered by a high sympathetic tone related to dyspnea and accompanying anxiety (reactive hypertension)

OR acute hypertension with accompanying changes in afterload may be a trigger for decompensation. Both of these mechanisms may be operative in a given patient,

cause-and-effect relationships may be difficult to discern with precision

patients in whom acute hypertensive heart failure are more likely to have preserved systolic function

Sudden onset of symptoms Frank pulmonary edema with evident rales and florid congestion

on the chest radiograph is much more common in this group of patients than in those with more gradual onset of symptoms, probably related to differences in LV compliance, acuity of pressure changes, and pulmonary lymphatic capacity.

3. Cardiogenic shock:

This group presents with signs and symptoms

of organ hypoperfusion despite adequate preload

SBP often (although not always) is decreased, and evidence of frank or impending end-organ dysfunction (renal, hepatic, central nervous system) is common.

This type of AHF is relatively uncommon (4% )

Less common AHF clinical scenarios as:

isolated right-sided heart failure

high-output heart failure

AHF Clinical Triggers:

In the OPTIMIZE-HF registry, 61% of enrolled subjects had anidentifiable clinical precipitant:

Pulmonary processes Myocardial ischemia Arrhythmias (e.g. AF) Worsening renal function was responsible for the highest in-

hospital mortality rate (8%), Nonadherence to diet or medication OR

Uncontrolled HTN was associated with a much betterprognosis (<2% in-hospital mortality for each).

Others: Thyroid disease, Anemeia

More than one precipitant was identified in a substantialminority of the study population.

Biomarkers The natriuretic peptides are a family of important counterregulatory hormones in

heart failure with vasodilatory and other effects In AHF, both brain natriuretic peptide (BNP) and N-terminal pro–brain natriuretic

peptide (NT-proBNP) have an important role in the differential diagnosis inpatients presenting in the emergency department with dyspnea

BNP threshold of 100 pg/mL maximized sensitivity and specificity todifferentiate dyspnea that ultimately confirmed to be due to AHF:

the negative predictive value of a BNP level less than 100 pg/mL was particularlyhigh (89%),

the positive predictive value of this threshold was (79%)

NT-proBNP has similar diagnostic value, although the appropriate cut pointsare higher overall and vary with age

False positives (e.g., caused by myocardial infarction or pulmonary embolism) False negatives (primarily caused by obesity, which results in lower NP levels for a

given degree of heart failure) Natriuretic peptide levels tend to be lower in patients with HFpEF than those with

reduced systolic function

D.D.Non-Cardiogenic Pulmonary Edema

MANAGEMENT OF THE PATIENT WITH ACUTE HEART FAILURE Establish the diagnosis,

Treat life-threatening abnormalities,

Initiate therapies to rapidly provide symptom relief,

Identify the cause and precipitating triggers.

General Approaches to Therapy ofAcute Heart FailureTargeting Congestion The current general approach focuses on the

successful treatment of clinical and hemodynamiccongestion, while limiting effects on myocardial orend-organ function, identifying addressable triggers,and optimizing proven long-term therapies

Incorporates information from three main aspects of the patient’s clinical presentation:

blood pressure, volume status, and renal function

1) Blood Pressure Most patients present with elevated blood pressures

and consequently will benefit from and safely toleratevasodilator therapy.

Vasodilators may decrease preload by reversingvenous vasoconstriction and the related centralvolume redistribution from the peripheral andsplanchnic venous systems, and reduce afterloadby decreasing arterial vasoconstriction with aresultant improvement in cardiac and renal function.

Hypotension (SBP below 85 to 90 mm Hg) is a poorprognostic sign in patients with AHF.

Asymptomatic hypotension, as an isolated finding in theabsence of congestion and poor peripheral or centralperfusion, does not require emergent treatment.

Inotropic therapy may be indicated for persistentsymptomatic hypotension or evidence of hypoperfusion inthe setting of advanced systolic dysfunction.

In general, the use of vasoconstrictors, such as highdosedopamine, phenylephrine, epinephrine, andnorepinephrine, should be avoided unless such agents areabsolutely necessary for management of refractorysymptomatic hypotension or hypoperfusion

2) Volume Status Most patients with AHF have evidence of volume overload

Intravenous diuretics remain the foundation of AHFtherapy.

Patients with clinically evident congestion typically have 4to 5 liters of excess volume, and amounts greater than 10 Lare not uncommon.

The choice of diuretic regimen is influenced by theamount and rapidity of the desired fluid removal and therenal function.

Diuresis addresses the underlying abnormality andfrequently alleviates symptoms and signs of elevated fillingpressures.

However, intravenous vasodilator therapy may providemore rapid relief in highly symptomatic patients withevidence of pulmonary congestion. In fact, many patientswith hypertensive AHF may require minimal diuretics.

Careful attention to volume status is critical, becausepatients’ symptoms of congestion may resolve despitepersistent hemodynamic congestion (i.e., elevated fillingpressures).

Hospital discharge before hemodynamic congestion is fullytreated appears to be a common cause of rehospitalization

3) Renal Function Approximately two thirds of patients present with at

least moderate renal insufficiency.

This deficit may reflect preexisting kidney disease or may be a manifestation of the worsening heart failure.

Abnormal renal function typically is associated with some

degree of diuretic resistance, and higher doses of diuretics or

other strategies may be needed.

The important clinical problem of worsening renal function during AHF therapy, the cardiorenal syndrome

Diuretics

Loop diuretics are the primary pharmacologic agents for treatment of volume overload in patients with AHF

Rapid symptom relief in most patients

This group of agents (furosemide, torsemide, bumetanide, and ethacrynic acid)

intravenous administration avoids variable bioavailability and allows for rapid onset ofaction (typically within 30 to 60 minutes)

Based on the results of the DOSE study, initial doses of approximately 2.5 timesthe outpatient dose should be considered for patients on chronic oraldiuretic therapy, with underlying renal dysfunction, or with severe volume overload.

Titration should be rapid with doubling of the dose until an effectiveresponse is noted.

With significant volume overload (>5 to 10 liters) or diuretic resistance,a continuous intravenous infusion can be considered.

Vasodilators In the absence of hypotension, vasodilators can be used as first-line agents in

combination with diuretics in the management of patients with AHF to improve congestive symptoms

Include the organic nitrates (nitroglycerin [NTG] and isosorbide dinitrate), sodium nitroprusside (SNP), and nesiritide.

All of these drugs act by activating soluble guanylate cyclase (sGC) in the smooth muscle cells, leading to higher intracellular concentrations of cyclic guanosine monophosphate (cGMP) and consequent vessel relaxation

used with caution in patients who are preload- or afterload-dependent (e.g., severe diastolic dysfunction, aortic stenosis, coronary artery disease), because they may cause severe hypotension.

Blood pressure (BP) should be monitored frequently and the drug discontinued if symptomatic hypotension develops.

Nitrates

Organic nitrates are one of the oldest therapeuticagents for management of AHF.

These agents are potent venodilators, producingrapid decreases in pulmonary venous and ventricularfilling pressures and improvement in pulmonarycongestion, dyspnea, and myocardial oxygen demandat low doses

At slightly higher doses and in the presence ofvasoconstriction, nitrates also are arteriolarvasodilators, reducing afterload and increasing cardiacoutput

Nitrates are relatively selective for epicardial, compared tointramyocardial, coronary arteries, resulting in increasedcoronary blood flow and making them useful for patients withconcomitant active myocardial ischemia.

Organic nitrates may also be administered orally, sublingually,or by spray, allowing for convenient emergent treatmentbefore establishing intravenous access

The dose may initially be titrated to the goal of immediatesymptom relief, but a blood pressure reduction of at least 10mm Hg in mean arterial pressure with a SBP greater than 100mm Hg may be preferable.

The nitrate dose may need to be reduced if SBP is 90 to 100mmHg and often will need to be discontinued with SBP below90 mm Hg.

Limitations of organic nitrates:

Tolerance that typically develops within 24 hours

Headache is the most common adverse effect (20%)

Symptomatic hypotension (5%) but generally resolveswhen nitrate therapy is discontinued.

In view of the risk of severe hypotension withpotentially catastrophic consequences, the recent useof phosphodiesterase-5 inhibitors (sildenafil, tadalafil,and vardenafil) should be ruled out beforeadministration of nitrates

Oxygen In patients with severe hypoxemia (oxygen saturation

[SaO2] <90%), oxygen administration isrecommended.

Although oxygen saturation on presentation is inverselyrelated to short-term mortality, inhaled oxygen (FiO2 ≥0.4)may cause detrimental hemodynamic effects (such ashyperoxia-induced vasoconstriction) in patients withsystolic dysfunction, so it is not routinely recommendedfor patients without hypoxemia.

In patients with obstructive pulmonary disease, highconcentrations of inhaled oxygen should not be used, toavoid the risk of respiratory depression and worseninghypercarbia.

(NIPPV) & (CPAP) Noninvasive ventilation (NIV) with continuous

positive airway pressure(CPAP) or noninvasiveintermittent positive-pressure ventilation(NIPPV) wasassociated with greater improvement in patient-reported dyspnea, heart rate, acidosis, andhypercapnea after 1 hour of therapy,

although it was not associated with a 7-day mortalitybenefit or with decreased need for intubation whencompared with standard oxygen therapy.

CPAP CPAP typically is initiated with a positive end-expiratory pressure

(PEEP) of 5 to 7.5 cm H2O, titrated to 10 cm H2O as needed for dyspnea relief and improvement in O2 saturation.

Contraindications: immediate need for endotracheal intubation (inability to protect the

airway, life-threatening hypoxia) lack of patient cooperation (altered sensorium, unconsciousness,

anxiety, inability to tolerate mask)

Caution is indicated in patients with : Cardiogenic shock, RV failure, and Severe obstructive airway disease.

Potential side effects and complications anxiety, claustrophobia, dry mucous membranes, worsening RV failure, hypercapnea, pneumothorax, and aspiration

Morphine may be useful in patients with severeanxiety or distress but should be used cautiously oravoided, especially in the presence of hypotension,bradycardia, advanced atrioventricular block, or CO2retention.

Morphine use has been associated with increasedlikelihood of mechanical ventilation, requirementfor intensive care unit (ICU) admission, prolongedhospital stay, and death

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