High-Output Cardiac Failure

Etiology

Causes of high-output cardiac failure can be simplified into two main categories: (1) there is an increase in the body’s demand for blood from increased metabolism or (2) there is a bypass of the arteriolar and capillary bed causing an increased flow into venous circulation from a lack of resistance, leading to increased oxygen consumption and a low systemic vascular resistance, respectively.[1][2] These processes both lead to an increase in cardiac output, either by cardiac remodeling or tachycardia and chronic plasma volume overload. Etiologies can further be characterized as metabolic, myocardial, mechanical vascular, or a combination of these. A single study conducted by Reddy et al. studied the etiologies of high-output cardiac failure, reporting common causes of obesity (31%), liver disease (23%), arteriovenous shunts (23%), lung disease (16%), and myeloproliferative disorders (8%).[1]

Metabolic

Several specific metabolic disease processes can increase metabolic demand, causing an increase in cardiac output.

Hyperthyroidism causes an increase in thyroid hormone affecting both the cardiac and systemic tissue.[5] Cardiac effects of thyroid hormone eventually lead to increased contractility and heart rate, while increased systemic metabolism leads to the creation of increased cellular waste products, causing a reduction in systemic vascular resistance.[5][6] Untreated, hypercontractility, tachycardia, and volume overload lead to the development of cardiomyopathy and hypertrophy.[7]

Myeloproliferative disorders also have been associated with high-output cardiac failure. They are linked to increased cellular metabolism and high cell turnover.[1] This causes a state of increased metabolic demand and decreased systemic vascular resistance, leading down a path to high-output cardiac failure if there are no intervention mechanisms such as those discussed in pathophysiology.[1]

Myocardial

Myocardial etiologies largely reflect diseases that have a direct myocardial effect but generally have multifactorial pathophysiology involving metabolic and vascular effects as well. An example of this is hyperthyroidism, where thyroid hormones have a global effect including a direct effect on myocardial tissue.

Sepsis causes a global inflammatory response to an infection, causing a wide range of hemodynamic changes and phases.[2][8] Patients usually present with an initial hypovolemic phase requiring volume resuscitation, however afterward, patients are in a hyperdynamic phase with high cardiac output and a low systemic vascular resistance consistent with high-output cardiac failure.[8] This is largely driven by inflammatory cytokines, causing a systemic vasodilatory effect in the setting of adequate myocardial function; however, subsequent phases of sepsis usually lead to depression in myocardial function.[2][8]

Thiamine is an essential vitamin used in the formation of thiamine pyrophosphate, an essential cofactor used in metabolism for energy production. Severe thiamine deficiency causes beriberi, which results from a buildup of pyruvate and lactate in the blood that leads to systemic vasodilation. Additionally, Ikram published a case series regarding cardiac beriberi showing that thiamine deficiency affects cardiac myocytes directly and describing vacuolation and intercellular edema with myofiber hypertrophy, fibrosis, and cellular infiltration in histopathology.[9] This causes an increased venous return and thus a high cardiac output, eventually leading to cardiomyopathy. If left untreated, symptoms of heart failure suggesting a decompensated state become evident.

Chronic lung disease is associated with high-output cardiac failure, largely with right-sided heart failure. Chronic hypoxia and hypercapnia drive a reduced systemic arterial resistance, leading to chronic volume overload, while pulmonary vascular constriction causes increased right heart remodeling; the left heart remains largely functional and produces a high cardiac output.[1]

Peripheral Vascular Effects

These effects are largely due to the bypass of the arteriolar and capillary bed, leading to increased direct flow into venous circulation. In the systemic vascular system, the majority of resistance is in the arteriolar system, considering the collective decrease in radius among all of the arterioles and thus decreasing flow into the venous circulation. If the arteriolar system is bypassed, flow increases to the venous circulation causing an increased venous return to the heart, eventually leading to cardiac volume overload.

Arteriovenous fistulas (AVF), either congenital or acquired, cause a shunt from an artery to a vein, bypassing the resistance of the arteriolar and capillary system. This causes an increased flow of blood to the heart, requiring an increase in heart rate and stroke volume, leading to increased cardiac output.[1] Congenital etiologies involve the formation of large or numerous hemangiomas or telangiectasias. Acquired etiologies include traumatic, iatrogenic formation (eg, puncture wounds, AVF formation for hemodialysis, transjugular intrahepatic portosystemic shunting procedure, arterial puncture for catheterization) or development of skeletal disorders causing several, minute AVF formations in response to extensive bone turnover.[10][11]

Liver cirrhosis is associated with arteriovenous shunts and decreased systemic vascular resistance.[1] Mechanisms of impaired clearance of vasoactive substances and bacterial translocation have been described as the driving force for decreased systemic vascular resistance.[11][12][13] This decrease in systemic vascular resistance is so severe that the increase in cardiac output is not sufficient, leading to a decompensated high-output cardiac failure.

The mechanism for obesity as an etiology is not well defined; however, it is associated with excessive vasodilation. Mechanisms of reduced arterial resistance secondary to vasoactive adipokines have been described in the literature.[14] Obesity also has a direct effect on cardiac function by alternating myocardial metabolism due to increased insulin resistance.[15] It has been shown in animal models that increased fatty-acid oxidation in cardiac myocytes can lead to left ventricular dysfunction; however, exact mechanisms are unknown.[15] 

Other etiologies that are less defined but mentioned in the literature include erythroderma, carcinoid syndrome, mitochondrial diseases, acromegaly, and Paget disease of bone. Stress, exercise, fever, and pregnancy are all contributors; however, they are not defined as direct causes of high-output cardiac failure.

Epidemiology

Heart failure is very common. It is stated to be the cause of millions of office visits per year and is the most common diagnosis of hospitalized patients. In the United States, it is published that more than 500,000 new cases are diagnosed per year, and the current prevalence is about 5 million.[16] This includes all forms of heart failure, including systolic and diastolic dysfunction as well as high-output cardiac failure. However, isolated high-output cardiac failure is a far less common form of heart failure, and the exact incidence and prevalence rates are not known.[1] This may be because high-output cardiac failure is secondary to other underlying pathologies and may or may not be identified appropriately. Furthermore, the prevalence and incidence of high-output cardiac failure are likely related to conditions that result in a high-output state.

Pathophysiology

The pathophysiology of high-output cardiac failure is largely unique to the underlying etiology. However, they all are characterized by having a low systemic vascular resistance, decreased arterial-venous oxygen gradient, and an elevated cardiac output. The latter is somewhat confusing, but even in the setting of an elevated cardiac output, the output is not sufficient to the body’s required demand, leading to clinical heart failure. The decreased supply of blood causes similar neurohormonal alterations seen in other causes of heart failure, with activation of the renin-angiotensin-aldosterone system (RAAS), adrenergic nervous system, and an excess of antidiuretic hormone. These systems are in place to increase intravascular blood volume in acute and subacute settings. However, chronic activations cause a progressive decline in cardiac function. Simply, in an attempt to compensate for hemodynamic burdens, the heart undergoes hypertrophy and remodeling to maintain contractility and reduction of wall stress by dilatation. Over time, the dilatation exceeds and holds more volume of blood that can be effectively pumped, causing heart failure.[1]

The goal of the adrenergic system is to increase cardiac output, which in high-output cardiac failure is already elevated, by increasing contractility (i.e., stroke volume) and heart rate while maintaining systemic blood pressure by causing vasoconstriction. Activated by baroreceptors in the carotid sinus and aortic arch, a decrease in transmission by these receptors in response to low blood pressure causes an increase in sympathetic stimulation. This attributes to ventricular hypertrophy and cardiac remodeling.[1]

The RAAS is activated by an increase in renin in response to decreased renal artery perfusion and the adrenergic nervous system. The release of renin leads to increased circulating angiotensin II, causing an increase in aldosterone secretion from the adrenal cortex and stimulating thirst in the hypothalamus. Aldosterone increases sodium reabsorption, causing increased water retention at the level of the kidneys in attempts to increase intravascular volume and thereby augmenting preload. An increase in preload allows for increased cardiac output via the Frank-Starling mechanism; however, in an already weak heart, this mechanism does not augment cardiac output as much as it causes excessive hypervolemia, leading to peripheral edema and pulmonary congestion seen in clinical heart failure.

Antidiuretic hormone (ADH) is activated in response to angiotensin II and baroreceptors, causing an increase in water retention at the level of the kidneys. Additionally, the antidiuretic hormone can contribute to vasoconstriction as well.

History and Physical

As with any initial evaluation, a thorough history and physical is paramount. In patients with high-output cardiac failure, history regarding chronic medical conditions can facilitate in determining the underlying etiology of high output cardiac failure.[1] Similar to other forms of heart failure, patients can present with complaints of progressively worsening fatigue, swelling, or dyspnea, either at rest or exertion, that is classically positional and worse when supine. Some may present with complaints of palpitation or heart racing as well. On physical exam, tachycardia, pulmonary and peripheral edema, and jugular venous distention can present. Contrasting to other forms of heart failure, in high-output cardiac failure, patients have a wide pulse-pressure and warm extremities secondary to a low systemic vascular resistance. The cardiac examination would be most notable for, if present, a bounding point of maximal impulse, systolic flow murmurs, and additional heart sounds S3 or even an S4. S3 sounds are secondary to blood filling a compliant ventricle from passive filling, which is heard in early diastole. S4 sounds are secondary to blood filling a noncompliant ventricle from atrial contraction, which is heard in late diastole and may be findings in heart failure that has progressed.

Further physical signs are related to the underlying etiologies. At times, the cardiac symptoms of high-output cardiac failure are secondary and somewhat incidental, as patients come with presenting symptoms of the underlying disease.

Hyperthyroidism presents with a wide range of symptoms. Relative to the heart, patients can present with tachycardia, palpitations, and dyspnea from hyperthyroidism alone, even in the absence of high output cardiac failure. Physical exam findings can include fever, eyelid retraction and lid lag, tremor, hyperreflexia, hyperactivity, enlarged thyroid gland with possible tenderness, and exophthalmos with periorbital edema in addition to cardiac findings.

Myeloproliferative disorders can show a wide range of findings in addition to cardiac findings. Fever, fatigue, dyspnea, increased bleeding episodes (e.g., epistaxis, bruising), with signs of splenomegaly and peripheral blood smear abnormality specific to the myeloproliferative disorder.

Sepsis presents on a wide spectrum, from fever, chills, fatigue, loss of appetite, palpitations to altered mentation, and even coma secondary to acute systemic vasodilation. A physical exam can show fever, tachycardia, tachypnea, and warm extremities in the first presenting stages of sepsis with further symptoms, depending on the source of infection. Further stages of sepsis can cause a worsening myocardial dysfunction, eventually leading to a left ventricular failure and causing systolic heart failure.

Berberi usually presents with a history of a malnourished, alcoholic, dieting, or bariatric patient. Patient presentation depends on the form of beriberi, characterized by either dry or wet beriberi. Relative to the heart, dry beriberi is separated from wet beriberi by symptoms of heart failure. Patients often present with complaints of dyspnea, orthopnea, palpitations, and peripheral swelling, with respective physical exam findings of clinical heart failure. Additional signs of beriberi are burning pain in the extremities, muscle weakness, and possible fall secondary to peripheral neuropathy with both sensory and motor involvement.

Chronic lung disease usually involves a patient with a smoking history, who has already been diagnosed with progressive lung disease; however, chronic lung disease can be diagnosed on initial presentation of worsening dyspnea, cough, and wheezing. Relative to the heart, when patients have chronic lung disease it often results in right-sided heart failure secondary to pulmonary hypertension. Isolated right-sided heart failure can lead to clinical symptoms and signs of peripheral swelling with pitting edema, positive jugular venous distention, parasternal heave, fixed split S2, and possible S3 or S4 heart sound.

Arteriovenous fistulas (AVF) can either be congenital or acquired. Usually, congenital AVF presents with diffuse hemangiomas from childhood (e.g., hereditary hemorrhagic telangiectasia or Osler-Weber-Rendu syndrome) with associated bleeding episodes from mucocutaneous or gastrointestinal sources. Acquired AVFs can be iatrogenic or traumatic with the respective history. Often, acquired iatrogenic AVFs are formed intentionally for hemodialysis access or secondary to a complication. All of these, if causing high-output cardiac failure, cause symptoms of progressive dyspnea, orthopnea, and swelling, with respective physical exam findings of heart failure. Patients with AVFs, especially for heart disease access, also have findings of palpable thrills and audible bruits over the AVF itself.

Patients with liver cirrhosis present with a wide spectrum of symptoms. History is notable for causes of liver cirrhosis if already diagnosed, such as alcohol abuse, viral hepatitis, obesity, autoimmune disease to name a few. Initial symptoms of the presentation can be very nonspecific to symptoms of decompensated liver disease. Fatigue, weakness, generalized unwellness, increased swelling, dyspnea, abdominal distention, yellowing of skin and eyes, confusion, and even gastrointestinal bleeding can be presenting symptoms. Physical exam findings are just as variable in liver cirrhosis and highly dependent on the severity of liver disease and if in a decompensated state. Relative to the heart, patients have physical exam findings of clinical heart failure in addition to decompensated liver cirrhosis.

Patients with obesity have a high body mass index (BMI), defined as a BMI greater than or equal to 30 kg/m2, with severe obesity indicated by a BMI of greater than or equal to 40 kg/m2. A physical exam is largely specific to, as well as limited by, an obese habitus. Relative to the heart, physical exam findings of clinical heart failure with tachycardia may be evident.

Evaluation

The diagnostic evaluation for high-output cardiac failure is important, but determining the underlying etiology is paramount as management changes. The first step in diagnosing heart failure is based on the initial history and physical. Aside from the history and physical exam, initial laboratory testing and imaging should be obtained. The use of natriuretic peptide levels is highly beneficial when the diagnosis of heart failure is not clear, with elevated levels suggesting heart failure. Electrocardiogram and a transthoracic echocardiogram also should be obtained. Findings of clinical heart failure in the setting of a high output cardiac state give the diagnosis of high-output cardiac failure. In contrast to other forms of heart failure, high-output cardiac failure has the presence of high cardiac output and/or cardiac index.[1]

The final step in evaluation is to determine the cause of high-output cardiac failure. Depending on the initial presentation and physical exam, diagnostic studies will differ. The history and physical will strongly dictate which further testing is necessary.

Treatment / Management

Management begins with the acute intervention of heart failure. Depending on the severity, treatment should be directed towards acute respiratory failure from volume overload and hypotension if present. The initial management can range from intermittent diuretic therapy and oxygen supplementation to continuous diuretic infusion, non-invasive positive pressure ventilation, or intubation. If hypotension and decreased organ perfusion are evident, inotropic medications are warranted. Once patients are stabilized and are no longer in a decompensated state, management can be directed at the underlying etiology. The treatment for specific etiologies is only briefly described further.

Treatment of hyperthyroidism is focused on symptomatic therapy with the goal to decrease the circulating thyroid hormones, either by medications and/or the use of radiotherapy or surgery if necessary. Myeloproliferative diseases are treated according to the specific underlying disease and may involve hematopoietic cell transplantation depending on the severity. Treatment is largely variable, depending on the disease and severity of symptoms. Sepsis treatment is guided by the Surviving Sepsis Campaign guidelines and involves early recognition, immediate and aggressive intravenous fluid resuscitation, and antibiotic therapy with an investigation to determine the source of infection. Thiamine deficiency causing beriberi is treated with thiamine replacement for a minimum of 2 weeks. Chronic lung disease is a progressive disease with treatment catered to the underlying pulmonary disease. In general, hypoxia and hypercapnia are addressed, and management is symptomatic therapy and slowing the progression of the underlying disease. Acquired AVFs are treated with either closure or reduction of blood flow. It is more pertinent in patients on hemodialysis, who need access; however, if presenting with high-output cardiac failure, it may be necessary to close, and alternative access sites should be obtained. Treatment of congenital AVFs can involve medical therapy, invasive embolization, or surgical excision, depending on the exact cause. Liver cirrhosis that is advanced enough to cause high-output cardiac failure is end-stage and treatment involves liver transplantation. Medical therapy has a role in fluid management for hypervolemia, involving the use of combined loop diuretics and anti-mineralocorticoids, which may limit the flow through shunts.

Differential Diagnosis

Clinical heart failure is a diagnosis based on a patient's history and physical on initial assessment. Though the type may not be clear, most patients present very similarly, if not the same. Hypervolemia, dyspnea on rest or exertion, orthopnea, and fatigue are the general symptoms of heart failure. Different types of heart failure include heart failure with reduced ejection fraction and heart failure with preserved ejection fraction and can be differentiated from high-output cardiac failure by measuring the cardiac output and/or cardiac index and low systemic vascular resistance.

Prognosis

The prognosis of high-output cardiac failure is dependent on the cause of the condition. As referenced above, Reddy published a retrospective analysis of patients with high-output cardiac failure, reporting an increased 3-mortality rate compared to the control group (subjects free of heart failure). The study reports a hazard ratio of 3.4 (1.6 to 7.6). The study further stated that among patients with high-output cardiac failure, causes related to obesity had the lowest 5-year mortality at 19%, compared to liver disease (58%), and heart failure associated with shunt formation (59%) which carried the highest 5-year mortality.[1]