Chapter 25: Heart Failure Syndromes in the Critical Care Setting

Heart failure (HF) is a global clinical syndrome which occurs when the metabolic demands of the body are not met by the circulation due to impairment of cardiac structure and function. Patients typically present with symptoms of progressive dyspnea, decreased exercise tolerance, and may or may not have signs of volume overload and congestion. The final diagnosis of HF must be made by a comprehensive clinical assessment and is not determined by a solitary laboratory value or radiological test.^1,2,3,4,5

HF may occur with or without the presence of left ventricular (LV) systolic dysfunction and thus it is widely categorized into 2 separate entities, namely, HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Though different investigators and societies have used different definition of HFrEF and HFpEF, the current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Heart Failure Guidelines define HFrEF as patients with an LV ejection fraction of 40% or lower; these patients often have varying degrees of diastolic dysfunction as well. Oral HF therapies (beta-blockers, angiotensin converting enzyme inhibitors, mineralocorticoid receptor antagonists, hydralazine, and nitrates) have been extensively validated to provide a quality of life and mortality benefit by many randomized-control trials in patients with chronic HFrEF.

HFpEF includes patients with a left ventricular ejection fraction (LVEF) of 50% or higher and such patients may comprise up to 50% of the entire HF population. HFpEF is described by clinical signs of volume overload, preserved or normal LVEF, and diastolic dysfunction, typically demonstrated by Doppler echocardiography or cardiac catheterization. Patients with HFpEF tend to be older women with hypertension, and other prevalent comorbidities in this group include coronary artery disease, obesity, diabetes mellitus, and atrial fibrillation. To date, no oral HF therapies are proven to demonstrate mortality benefit in this heterogeneous category.

Acute heart failure (AHF) is the most common cause of hospitalization in patients more than 65 years old. The relative incidence of heart failure in women is lower than that of men, however, due to their longer life expectancy woman represent half the cases of heart failure. The incidence of heart failure increases dramatically with population age. Additionally, the incidence of heart failure admissions to US hospitals has been increasing significantly due to the aging population, improved therapies, and survival for acute myocardial infarction as well as improved drug and device therapies for chronic heart failure. Hospitalization is a key prognostic event in patients with heart failure with reduced ejection fraction as it is predictive of a 30% mortality rate in 1 year and a 50% risk of recurrent hospitalization in 6 months.

History

Obtaining and performing a thorough history and physical examination are critical in reaching an accurate diagnosis of AHF and determining the cause of acute decompensation. The major elements of history that should be queried included changes in exercise tolerance, increase in baseline body weight, symptoms of ongoing cardiac ischemia, adherence to, and recent changes in heart failure medications, and signs or symptoms of infection. It is well known that signs and symptoms of heart failure (ie, weight gain, development of peripheral edema, dyspnea, and on exertion) can begin days to even weeks prior to hospital admission. Specific historical information can estimate if AHF involves right- or left-sided cardiac failure. Symptoms of left-sided AHF include dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, while symptoms of right-sided failure may include early satiety and leg edema.

Physical Examination

Although patients with AHF often have a reduced cardiac output, hypotension may not be present. According to the ADHERE registry (a national registry of AHF admissions at 263 hospitals in the United States) the majority of patients with AHF present with a systolic blood pressure (SBP) of greater than 140 mm Hg. This maintenance of blood pressure is due to a catecholamine-mediated increase in systemic vascular resistance. Narrow pulse pressure may be a marker of severe LV dysfunction and tachycardia may be present as a compensatory response or due to ongoing cardiac ischemia. The level of the jugular venous pulsation (JVP) can be used to estimate the central venous pressure and serves as an important bedside measure of intravascular volume. Cardiac auscultation is critical as it can point toward structural and arrhythmic causes of AHF and signs of congestion can be confirmed by pulmonary examination. It is important to note that patients with chronic HF may not have signs of pulmonary congestion due to compensatory lymphatic drainage. Extremities should be examined for warmth or coolness as an indirect measure of perfusion.

Chest X-Ray and Electrocardiogram

Chest radiography is crucial as it cannot only confirm the presence and severity of pulmonary edema, but may also reveal other characteristics of cardiac disease. The cardiac silhouette should be examined for enlargement, size of the pulmonary artery may indicate elevated pulmonary arterial pressures, increased mediastinum width can point to aortic pathology, and the presence of any cardiovascular implantable electronic devices or prosthetic heart valves would indicate preexisting disease. The electrocardiogram is essential to determine if AHF is related to ischemia and arrhythmia and should be serially monitored in patients admitted with acute coronary syndromes.

Laboratory Analysis

Laboratory data can provide more clues in determining the causes of AHF including anemia, thyroid disease, infection, and biomarkers, such as sodium and brain natriuretic peptides cannot only assist in determining volume status, but may also have prognostic value. Renal function is a sensitive marker of perfusion and intravascular volume, but it should be used in conjunction with the overall clinical assessment, since a decrease in creatinine clearance may occur from reduced cardiac output from either a drop or rise in intravascular volume, direct renal toxicity, or postrenal obstruction. Liver function test abnormalities may be related to congestive hepatopathy or ischemia from severely reduced cardiac output.

Clinical Assessment

The overall clinical assessment is aimed toward placing patients with AHF into one of 4 categories (Figure 25–1) based on their volume and perfusion status, and determining the acute precipitants of AHF. For patients with evidence of intravascular volume overload described as “wet” (elevated JVP, pulmonary rales, and peripheral edema) decongestive therapies such as diuretics or ultrafiltration can be administered to reduce intracardiac filling pressures and reduce dyspnea. If there are signs of reduced perfusion (such as decreased urine output, worsening renal function, and cool extremities) patients are considered “cool” and in the absence of hypotension, therapies are geared toward augmenting cardiac output by reducing afterload (oftentimes with nitrates and hydralazine). Routine use of inotropic agents without a definitive low output state and end organ failure is generally not indicated, since these medications can increase myocardial oxygen demand and can promote arrhythmias, and outcomes data from randomized trials and registry data typically demonstrate worse outcomes with inotropic therapy compared to vasodilator therapy.

The appropriate use of right heart catheterization in patients with AHF is a subject of considerable controversy. The ESCAPE trial, in which AHF patients were randomized to management with a pulmonary artery catheter (PAC) or careful clinical assessment, demonstrated no mortality benefit or decrease in length of hospitalization with PAC; the trial also demonstrated increased adverse events in the PAC arm driven principally by catheter related infections. Based on these results routine use of PAC in stable AHF patients is not recommended. The 2013 ACCF/AHA Heart Failure Guidelines recommend PAC monitoring for patients in respiratory distress or with clinical evidence of impaired perfusion in whom intracardiac filling pressures cannot be determined from clinical assessment, as well as in patients who are failing (ie, still symptomatic, worsening renal function, and hypotensive) initial empiric therapy based on best clinical assessment. Figure 25–2 shows the typical intravascular and intracardiac pressure profiles of common AHF syndromes.

Echocardiography is indicated to confirm a new diagnosis of AHF and in those with a significant clinical change from baseline. However, there is limited value in obtaining serial echocardiograms without a significant clinical alteration. This noninvasive modality is a cornerstone for diagnosing pathology involving the pericardium, heart valves, ventricular function, cardiac masses, and congenital defects. In cases of valvular pathology, valve area, valvular gradient, and regurgitant severity can be calculated to determine lesion severity, prognosis and drive further clinical management. Echocardiography can also provide supplementary information about intracardiac pressures in specific cardiac chambers to assist in determination of intravascular volume. For example, in a nonintubated patient if the inferior vena cava is noted to be dilated (> 2 cm) and not collapsing with respiration, the CVP is generally elevated beyond 10 mm Hg. Moreover, pulmonary artery and left sided pressures can be estimated by Doppler echocardiography of tricuspid regurgitation (TR) and mitral inflow, respectively. TR velocities greater than 3 m/s may indicate pulmonary hypertension and diastolic mitral inflow E wave velocities greater 0.12 m/s coupled with a prolonged deceleration time are present with elevated left atrial pressure. Diastolic dysfunction can also be graded by echocardiography.

In addition to improving loading conditions, it is paramount to address the underlying cause of AHF. In cases of acute coronary syndrome, cardiac catheterization is usually indicated to define coronary anatomy and determine either a percutaneous or surgical revascularization strategy. Management of regurgitant valvulopathy typically involves reduction of loading conditions, while stenotic lesions may need surgical intervention. Infections can raise metabolic demand to leading to AHF, especially in patients with reduced LV function and should be promptly treated with antibiotics. Another common scenario is uncontrolled hypertension leading to acute LV diastolic dysfunction and pulmonary edema. Intravenous agents, such as nitroprusside or nitroglycerin, can be administered to reduce blood pressure and diuretics can be given to reduce congestive symptoms. If AHF is caused by persistent tachyarrhythmias, that is, tachycardia-induced cardiomyopathy, then cardioversion may be indicated and an electrophysiologic consultation may be sought to determine optimal pharmacologic or ablative strategies for maintaining sinus rhythm. Dietary and pharmacologic nonadherence are common and recurrent causes of AHF in patients with preexisting chronic HF. In such cases, it is critical to educate patients on appropriate dietary modifications and address any psychosocial or financial problems that may preclude further compliance with HF medications. Please see Table 25–1 for additional precipitants of AHF.

Myocardial dysfunction can occur in patients with severe sepsis and is characterized by a reduction in ejection fraction and stroke volume. Cardiac output may be reduced or even normal due to a significant reduction in SVR. Cardiovascular dysfunction during sepsis can increase mortality up to 70% to 90%, in comparison to a 20% mortality in patients with sepsis without cardiovascular involvement. Although several biochemical mechanisms, such as upregulation of endothelin-1, higher expression of inducible nitric oxide synthase leading to free radical toxicity, activation of coagulation pathways and monocyte infiltration have been associated with sepsis cardiomyopathy, the precise mechanism of cardiac dysfunction remains elusive. Management rests upon treating the underlying infectious source and supporting the cardiovascular system.

BNP is a biomarker which has had an increasingly important role in the management of acute as well as chronic heart failure. Originally described in porcine brain extract (and hence “brain natriuretic peptide” or BNP), in human biology it is principally secreted by ventricular myocytes in response to increased ventricular filling pressures and ventricular stretch. The molecule is secreted as an inactive peptide pro-BNP, and is then lysed into the biologically active BNP as well as the biologically inert amino terminal BNP (NT-BNP). The biologically active BNP acts as a balanced veno- and arteriolar vasodilator and also has direct renal effects, which promote natriuresis and diuresis. Both of the cleaved molecules are used in modern chemistry laboratories for BNP levels.

BNP testing was well validated in emergency room settings in the Breathing Not Properly trial, where BNP testing was demonstrated to be useful in establishing the diagnosis of heart failure in the acutely dyspneic patient. Use of BNP in the critical care setting can be more complicated, as in addition to heart failure, there are many cardiac and noncardiac causes of elevated BNP in hospitalized patients, including but not limited to myocarditis, acute coronary syndrome, pulmonary embolism and sepsis (Table 25–2). BNP levels can be falsely low in very obese patients, and are also lower in HFpEF patients compared to HFrEF patients. Additionally, BNP levels are elevated in those with renal insufficiency compared to those without renal insufficiency. Finally, higher BNP levels are associated with a higher risk of mortality in both acute and chronic heart failure populations.

Sodium Nitroprusside

Sodium nitroprusside (SNP) is a potent vasodilator, with balanced action in the arteriolar and venous beds. It has a very short (seconds to minutes) half-life, and produces a dramatic increase in cardiac output, decrease in pulmonary capillary wedge pressure (PCWP), and decrease in mitral regurgitant fraction; this is typically associated with a decrease in mean arterial pressure. The initial dose is 10 mcg/min, with up titration to as high as 350 mcg/min. Since the coronary vasodilatory properties of SNP can promote coronary steal and ischemia in those with significant unrevascularized coronary artery disease, it is not recommend in patient with active ischemia. The metabolism of SNP leads to the release of nitric oxide and cyanide. The symptoms of cyanide toxicity include nausea, abdominal discomfort and dysphoria. As there can be accumulation of cyanide and thiocyanate, caution must be used in patients with renal and hepatic dysfunction.

Nitroglycerin

Nitroglycerin is a potent venodilator, producing rapid decreases in pulmonary congestion, left ventricular end diastolic pressure, LV wall stress, and myocardial oxygen consumption. It has coronary vasodilatory effects as well, making it a good option for patient with ongoing ischemia. Initial intravenous dose is typically 20 mcg/min, with a doubling of the dose every 5 to 15 minutes. Other options for administration include sublingual tablets and sprays as well as topical pastes. Major side effects include hypotension and headache.

Nesiritide

Nesiritide is recombinant B-type natriuretic peptide. It has balanced venous and arteriolar actions, and modestly enhances diuresis through direct renal effects. The dose starts at 0.01 mcg/kg/min. Major side effects include headache and hypotension. The ASCEND trial randomized 7141 patients with ADHF to either standard care or nesiritide plus standard of care. Nesiritide demonstrated a modest, statistically nonsignificant improvement in dyspnea; however, there was a higher rate of hypotension in the nesiritide arm of the trial. Importantly, there was no significant change in the rate of death, rehospitalization, or renal function in the nesiritide arm. Though there may be a role for nesiritide in some special populations (ie, diuretic resistant patients), the results of the ASCEND trial do not support the routine use of nesiritide in acute decompensate heart failure.

Milrinone

Milrinone is a positive inotropic agent as well as a vasodilator. It is a phosphodiesterase 3 inhibitor, and its mechanism of action is the inhibition of the breakdown of cyclic adenosine monophosphate (cAMP) in cardiac myocytes, leading to the increase of cAMP-mediated Ca++ in the myocyte and hence enhanced myocyte contractility. Similarly, in the vascular smooth muscle, its action is that of increasing cAMP-mediated contractile protein phosphorylation, leading to vascular relaxation. The hemodynamic changes seen with milrinone include an increased cardiac output, decreased SVR, reduced PCWP, and typically a mild decrease in mean arterial pressure. The half-life is approximately 2.4 hours, and it is renally cleared. The largest randomized clinical trial involving milrinone was the OPTIME-CHF trial, which randomized ADHF patients to either milrinone or placebo. Milrinone did not significantly decrease hospitalization length of stay, and did lead to significantly more hypotension and atrial arrhythmias. Use of milrinone is typically reserved patient with evidence of severely reduced cardiac output and end organ damage.

Dobutamine

Dobutamine is a direct beta-1 agonist, which produces positive inotropic and chronotropic effects. The mechanism of action is the binding of the beta-1 receptor, leading to phosphorylation of protein kinase A, which ultimately leads to an increase in intracellular cAMP and Ca++, leading to enhanced myocardial contractility. There is also a modest alpha and beta-2 effect, which causes mild peripheral vasodilation; in the context of increasing cardiac output, this can cause a variable effect on mean arterial pressure. The major side effects of dobutamine are atrial and ventricular tachyarrhythmias. There is no equivalent large, randomized trial experience with dobutamine in AHF as there is with milrinone, however registry data of AHF patients suggest worse outcomes with dobutamine and hence its use is limited to patients with poor response to diuretics and vasodilators and patients in overt cardiogenic shock.

Dopamine

Dopamine is a naturally occurring compound that plays an important role in many aspects of human body homeostasis, including major roles in neural, cardiovascular, and renal physiology. Dopamine has variable effects on different receptors at different doses; conventionally at low doses (0-2 mcg/kg/min), there is preferential dopamine receptor activation leading to enhanced renal artery vasodilation and enhanced renal perfusion; at 2 to 10 mcg/kg/min, there is enhanced norepinephrine release, leading to enhanced myocardial contractility and mild peripheral vasoconstriction; at doses above 10 mcg/kg/min, there is preferential alpha adrenergic receptor activation causing peripheral vasoconstriction and an increase in mean arterial pressure. In the context of treatment of AHF, dopamine is often used at low or “renal” dose in diuretic resistant patients, or at higher doses in those with frank cardiogenic shock. The limited clinical trial data evaluating the use of “renally dosed” dopamine in heart failure has been mixed. The most recent trial examining this issue (ROSE trial) randomized 360 AHF patients with renal dysfunction to either usual care or renally dosed dopamine (there was an additional low-dose nesiritide arm of the trial); the trial did not demonstrate a significant benefit of dopamine infusion in terms of urine output or change in renal function. Based on prior trial data, renally dosed dopamine is currently given a IIb recommendation by the ACC/AHA Heart Failure guidelines to help enhance urine output and renal perfusion in AHF patients.

Ultrafiltration

Ultrafiltration is a decongestive therapy in which water and small solutes are moved across a semipermeable membrane to reduce volume overload. Potential benefits of ultrafiltration over intravenous diuretics include more effective removal of sodium, minimal effects on serum electrolytes, decreased neurohormonal activation, and adjustable and potentially very rapid fluid removal rates. The outcomes in prospective heart failure trials in which patients were randomized to ultrafiltration versus diuretic therapy have varied. In the UNLOAD trial, 200 AHF patients were randomized to diuretics versus ultrafiltration; the ultrafiltration arm demonstrated greater fluid loss at 48 hours and a decrease in heart failure admissions in 90 days, with similar safety profile as diuretics. The CARESS-HF trial randomized AHF patients with cardiorenal syndrome to ultrafiltration or diuretics and failed to demonstrate a benefit with ultrafiltration. The cost, need for vascular access, need for nursing training and support are all potential barriers to ultrafiltration in clinical practice. Identifying the most appropriate patients for ultrafiltration therapy is an area of controversy and active clinical research.

Mechanical Circulatory Support

In cases of severe AHF, which is refractory to medical therapy, temporary circulatory support (TCS) can be utilized to improve end organ perfusion. TCS ranges from percutaneously inserted devices, such as intra-aortic balloon pump, tandem heart, and Impella which are able to augment cardiac output by up to 5 L/min. In cases of complete hemodynamic collapse or severe right ventricular failure, venoarterial extracorporeal membrane oxygenation can be placed to completely bypass the cardiopulmonary circulation. Additional surgically placed TCS includes semidurable continuous-flow ventricular assist devices, such as CentriMag. TCS can serve as a “bridge to recovery” or as a “bridge to decision” in patients who may need implantation of permanent LV assist devices or cardiac transplantation.