501

SECTION I — Preventive CardiologySECTION II — Coronary Artery DiseaseSECTION III — Interventional CardiologySECTION IV — Cardiac ImagingSECTION V — Valvular Heart DiseaseSECTION VII — Heart FailureSECTION VII — Cardiac ElectrophysiologySECTION VIII — Right Heart and Pulmonary CirculationSECTION IX — Pediatric CardiologySECTION X — Cardiac SurgerySECTION XI — Miscellaneous

Chapter 60High-Output Heart Failure: Diagnosis and ManagementDHARMENDRA JAIN  •  GEETHA SUBRAMANIAN  •  AVIRAJ C.  •  BALAJI V.L.

low-output HF but clinical evidence and published guidelines have not focused on high-output HF.

PATHOPHYSIOLOGY OF HEART FAILURE

A high cardiac output has been defined as being .8 L/min or a cardiac index .3.9 L/min/m2 (see ref 4).The high cardiac output state in an individual and associated clinical HF with or without presence of underlying heart disease is associated with several pathologies (Fig. 60-1). Reduced systemic vascular

INTRODUCTION

Heart failure (HF) is a global clinical problem with an estimated 10 million patients suffering from HF across Europe1. According to American Heart Asso-ciation, approximately 5.7 million Americans of all ages have HF2. Westernization in the developing world is probably responsible for development of this problem of HF in epidemic proportions3. Low-output cardiac failure has been well studied and has been the focus of most of the guidelines written on HF. Various drugs are available supported by hun-dreds of randomized clinical trials for treatment of

Expansion of plasma volume

increased cardiac output

with/without undrlying ↓myocadial reserve/pathology

high output heart failure

Increased vasodilatation

e.g.liver cirrhosis, chronic anemia

Increased microvascular

density

Arteriovenous shunting

e.g.pulomonary or systemic A-V fisula

Increased metabolism

hyperthyroidism

Increased body mass

e.g.obesity

Low systemic vascular

resistance e.g.pregnacy,carcinoid

Figure 60-1.  Pathophysiology of high-output heart failure.

502 SECTION VII — Heart Failure

resistance due to systemic A-V shunting or periph-eral vasodilatation or both remains the underlying main physiological dysregulation in high-output HF. This leads to a fall in systemic arterial blood pressure which leads to salt and water retention through chronically activated sympathetic nervous system, renin–angiotensin–aldosterone system stimulation and antidiuretic hormone release. The neurohormonal activation despite low systemic vascular resistance, results in increased renovascu-lar resistance associated with reduced renal blood flow and glomerular filtration rate, with retention of salt and water. Chronically, increased salt and water leads to volume overload and high-output cardiac condition5. It is also associated with in-creased oxygen consumption due to increased metabolic demand and low arterial-venous oxy-gen content difference which may vary according to underlying aetiology. In a study of 120 patients with high-output HF, oxygen consumption was highest in the myeloproliferative disorder, whereas presence of liver disease was associated with low-est arterial-venous oxygen content difference and lowest systemic vascular resistance6. Other mecha-nisms contributing to development of low vascu-lar resistance or vasodilation include low viscosity in severe anaemia, release of endotoxins in sepsis, vasodilation due to release of nitric oxide, nonde-activation of vasodilator molecules in liver disease and development of multiple small A-V fistulas in the lung in liver cirrhosis. A persistent high- output state sometimes leads to ventricular dilata-tion and/or hypertrophy. The associated persis-tent tachycardia and development of functional valvular abnormalities, lead to adverse cardiac re-modelling and development of heart disease or deterioration of underlying cardiac pathology and culmination in HF.

DIAGNOSIS

SYMPTOMS AND SIGNS

Congestive heart failure (CHF) presents with variable symptoms and signs including dyspnoea, increased fatigability, tachypnoea, tachycardia, pulmonary rales and peripheral oedema. The signs and symp-toms as seen in high-output HF are due to systemic and pulmonary venous congestion. The other obvi-ous signs include raised jugular venous pressure and pleural effusion. The patients usually have warm peripheries due to low systemic vascular resistance and peripheral vasodilatation. A good history tak-ing and meticulous clinical examination may clinch the diagnosis and clue to underlying aetiology.

TABLE 60-1  CAUSES OF HIGH-OUTPUT HEART FAILURE

Vasodilation Arteriovenous Shunting

• Chronic anaemia• Chronic obstructive pul-

monary disease and chronic hypercapnia

• Thyrotoxicosis• Sepsis• Beriberi heart disease• Pregnancy• Obesity• Hepatic disease (e.g. 

cirrhosis)• Carcinoid syndrome• Skin disorders like psori-

asis

• Systemic arteriovenous fistula congenital, acquired or iatro-genic (e.g. haemodialysis fis-tula, bullet injury, postfemoral puncture)

• Multiple small arteriovenous shunts (e.g. hereditary haemorrhagic telangiectasia, Paget disease or renal cell carcinoma)

• Multiple myeloma• Albright disease• Hepatic disease• Carcinoid syndrome

Common findings on physical examination in patients with high-output HF include sinus tachy-cardia, bounding pulse and venous hum at neck or inguinal area, hyperdynamic apex, ejection systolic murmur and S3. The signs of increased left ven-tricular stroke volume like Traube’s sign, Quincke’s pulse and a systolic bruit over the carotids may be elicited on examination of the arteries.

AETIOLOGY

In a Mayo Clinic series of 120 patients diag-nosed as high-output HF, the most common causes were morbid obesity (31%), liver disease (22.5%), A-V shunts (22.5%), lung disease (16%) and myelo-proliferative disorders (8%) (see ref 6).

Causes of high-output failure have been summa-rized in Table 60-1.

INVESTIGATIONS

Electrocardiogram and chest radiography are useful tools to assess for cardiac enlarge-ment and pulmonary vascular pattern. Presence of pulmonary A-V fistula may be seen on the chest X-ray. ECG helps in picking up other causes of HF like myocardial infarction.

Echocardiography: In high-output states, it dem-onstrates dilated cardiac chambers with preserved or above normal left ventricular ejection fraction (.50%). Despite ‘normal’ left ventricular systolic function, high-output HF may be present. It is valu-able test in initial assessment of HF patients and ruling out conditions like patent ductus arteriosus and significant AR as cause for high cardiac output.

503Chapter 60  —  High-Output Heart Failure: Diagnosis and Management

Arterial and venous blood gas analysis: High SvO2 (.75%) has been shown to be associated with a high cardiac output state while a low SvO2 (,65%) is seen with an inadequate cardiac out-put. Low systemic saturation is seen in patients presenting with low cardiac output HF.

Biomarkers and other studies in HF: BNP and NT-proBNP may be elevated in low-output as well as high-output HF and troponins will be negative in the absence of myocardial ischaemia. Thyroid stimulating hormone will be depressed with elevated T3, T4 in hyperthyroidism. Liver and renal biochemical parameters and ultra-sound will reveal the presence or absence of un-derlying renal or hepatic dysfunction. Other tests can be carried out according to suspicion of un-derlying aetiology leading to high-output cardiac failure based on history, clinical examination and above tests.

SPECIFIC CONDITIONS ASSOCIATED WITH HIGH-OUTPUT HEART FAILURE

ANAEMIA7,8

Heart has to increase cardiac output to maintain tis-sue perfusion and oxygenation in severe chronic anaemia. There is increased renal and vascular nitric oxide synthase activity and low blood viscosity re-sulting in peripheral vasodilatation, low systemic vascular resistance and associated neurohormonal activation and HF7. Only in very severe anaemia, i.e. haemoglobin less than 5 g/dL, HF may develop in the absence of underlying heart disease and attempt must be made to find out other associated comor-bidities like renal or liver dysfunction and underly-ing myocardial disease like valvular abnormality or reduced functional reserve. Treatment includes eval-uating for and treating the type of anaemia, packed blood RBCs or whole blood to treat anaemia itself. Blood transfusion should be slow and under diuretic cover if required to avoid the pulmonary oedema.

SYSTEMIC ARTERIOVENOUS FISTULA9–18

Arteriovenous (A-V) fistulas may be congenital or acquired. Acquired cause includes trauma like bullet or knife injury and may be iatrogenic also due to procedures like percutaneous arterial puncture, sur-gically created fistula in upper limb in haemodialy-sis patients, iliac A-V fistula after lumbar disk sur-gery and transjugular intrahepatic portosystemic shunting (TIPS). The most common iatrogenic

cause, however rare, is arteriovenous fistula develop-ing after arterial puncture for cardiac catheteriza-tion. It has a reported incidence of 0.01%–0.02% of all catheterizations. The patient may present clini-cally anytime between 2 days to several months postcatheterization. Surgical or endovascular repair leads to resolution of the HF. There is decrease in the systemic vascular resistance and an increase in heart rate and stroke volume postrepair, as the blood from a high-pressure artery is shunted to a low-pressure vein while bypassing the capillary beds. Number and size of the communication decide the clinical outcome. Wide pulse pressure and sinus tachycardia denotes a significant A-V fistula. An A-V fistula is diagnosed by the local swelling, warmth and a con-tinuous ‘machinery murmur’ with a thrill over the fistulas when it is located near the surface with positive Nicoladoni-Branham sign, i.e. transient oc-clusion of a fistula is associated with decrease in heart rate, increase in arterial pressure and lowering of venous pressure. This may sometimes lead to an increase in the size of limb (Parkes Weber syn-drome). Congenital A-V fistulae, as seen in hepatic endotheliomas, lung and/or liver involvement in hereditary haemorrhagic telangiectasia involving the mucous membranes, gastrointestinal tract, and skin of the lips, nose, and finger tips (Osler–Weber–Rendu disease) are associated with a hyperdynamic circulation and subsequent HF. Arteriovenous malformations occur in the lung in about 15% of patients and less frequently in liver leading to high-output HF. History of epistaxis, recurrent gas-trointestinal bleeding, unexplained haematuria, haemoptysis or family history of bleeding in a pa-tient presenting with high-output HF should lead to strong suspicion for this disorder. A review of 27 patients with hepatic haemangiomatosis observed that 23 of them had concurrent cutaneous haeman-giomas and 25 had HF as suggested by the clinical triad of multiple enlarging cutaneous haemangiomas, hepatomegaly and HF. HF is also seen to be associated with diffuse A-V malformations in Klippel–Trénaunay syndrome. The most accepted treatment is aimed at surgical excision of the causative shunt. However, this may not be always feasible as many lesions are diffi-cult to localize precisely while others are so extensive as to prevent complete excision.

SKELETAL DISORDERS AND PAGET DISEASE19–23

Patients with polyostotic fibrous dysplasia (McCune–Albright syndrome), Paget disease and multiple myeloma present with a high cardiac output probably

504 SECTION VII — Heart Failure

due to presence of multiple minute A-V fistulas in the bony lesions with more than 15%–20% of the skeleton involvement required to cause significant shunting and lowering of peripheral vascular resis-tance and high-output HF. Rapid bone formation and resorption in Paget disease, multiple myeloma and fibrous dysplasia (Albright disease) are associ-ated with increased blood flow within the bone and the surrounding limb tissue leading to arteriove-nous shunting and high-output HF.

CHRONIC HYPERCAPNIA24

Chronic hypercapnia leads to salt and water reten-tion due to vasodilatation which causes systemic hypotension and adverse neurohormonal changes. This is commonly seen in chronic obstructive pul-monary disease and cor pulmonale. The fluid reten-tion may be associated with normal or increased cardiac output.

HYPERTHYROIDISM25–31

Thyroid hormones have positive effect on sympa-thoadrenal activation which is then associated with an increase in the heart muscle contractility, myo-cardial oxygen demands and consumption and en-hanced endothelium-dependent vasodilation with increase in cutaneous blood flow up to three times or greater than that in euthyroid controls leading to hyperdynamic circulatory state and high-output cardiac failure. Clinical diagnosis is clinched by findings of tachycardia at rest and during sleep, systolic hypertension with a widened pulse pressure, a ‘scratchy’ mid-systolic murmur (Means–Lerman scratch) along the left sternal border, exophthal-mos, stare, fine tremor of the outstretched hands and moist skin. High clinical suspicion is required in apathetic hyperthyroidism seen in older patients, in which usual manifestations of thyrotoxicosis may be absent. All these conditions, i.e. volume overload, increased muscle contractility and in-creased heart rate lead to the development of car-diac hypertrophy and dilatation in hyperthyroid patients. Hyperthyroidism may cause tachycardia-mediated cardiomyopathy and atrial fibrillation leading to worsening of haemodynamics. Beta blockers are useful in these patients as they lead to a reduction in their heart rate, cardiac output and pulse pressure towards normal. However, they should be administered cautiously since there may be a further reduction in myocardial contractility in some patients, especially those with impaired left ventricular systolic function.

SEPSIS32–34

Infection is associated with a increased release of factors such as tumour necrosis factor-alpha, inter-leukin-1,6, nitric oxide synthase and other proin-flammatory cytokines. The end result is sometimes significant systemic vasodilatation culminating in arterial hypotension and high-output failure.

BERIBERI HEART DISEASE35–38

It is seen in patients with severe long-term (.3 months) deficiency of the B vitamin thiamine. It is seen in chronic alcoholics due to poor dietary intake of thiamine, malabsorption conditions, patients’ receiving enteral nutrition, dialysis and other causes of chronic protein–calorie malnutrition. Beriberi disease can be of ‘dry’ form, with neurologic mani-festations or of ‘wet’ form, with cardiovascular in-volvement. Beriberi heart disease is associated with high-output HF along with oedema, fatigue and general malaise. Seven diagnostic criteria proposed for diagnosis include 3 or more months of thiamine-deficient diet, enlarged heart with normal sinus rhythm, dependent oedema, signs of neuritis, pel-lagra or both, minor electrocardiographic changes such as nonspecific ST-T wave changes, no other identifiable cause for heart disease and response to thiamine. High-output HF occurs due to arteriolar and cutaneous vasodilatation leading to a reduced systemic vascular resistance. Laboratory diagnosis requires estimation of increase in thiamine pyro-phosphate effect (TPPE), decrease in blood thiamine concentration or a decrease in red cell transketolase activity. The treatment includes up to 100 mg of thiamine intravenously and 25 mg/day for 2 weeks.

OBESITY39–41

Morbid obesity is associated with an increased risk of high-output HF; however, the exact pathogenesis is not clear. This risk is evident in both sexes. Ele-vated BMI is associated increased haemodynamic load, neurohormonal activation, increased oxida-tive stress leading to altered left-ventricular remod-elling. The rising epidemic of obesity worldwide is likely to increase the prevalence of obesity cardio-myopathy over time.

RENAL DISEASE42,43

The most common causes of high-output HF in chronic kidney disease patients are an arteriovenous (A-V) dialysis fistula and anaemia. Other aetiologies

505Chapter 60  —  High-Output Heart Failure: Diagnosis and Management

include acquired intrarenal A-V fistulas associated with trauma, postrenal biopsy or renal cell carcinoma and congenital renal arteriovenous malformation. Salt and water retention leading to volume expansion may also contribute to this condition. In acute postin-fectious glomerulonephritis, the renin–angiotensin–aldosterone system is suppressed and serum natri-uretic peptide concentrations are markedly elevated leading to oedema and hypertension due to volume expansion. Use of diuretics and dialysis can reverse these changes with fluid removal.

CIRRHOSIS44–46

Cirrhosis is associated with low blood pressure, sys-temic vasodilation, increased cardiac output and signs of reduced tissue perfusion. The increased car-diac output is seen due to splanchnic vasodilation and the development of intrahepatic, mesenteric and sometimes intrapulmonary A-V shunting. The condi-tion is associated with low urinary sodium excretion and increased plasma levels of renin, aldosterone and vasopressin. Liver transplantation improves the car-diac index and haemodynamics.

MISCELLANEOUS CAUSES47–50

There are several known causes of high-output HF, all leading to peripheral vasodilatation and decreased peripheral vascular resistance including pregnancy, acromegaly, carcinoid syndrome, polycythaemia vera, beta-thalassaemia intermedia, mitochondrial disease, anagrelide use and aortocaval fistula. Symp-tomatic management for HF and treatment of the underlying condition is indicated.

TREATMENT

Symptomatic management of HF is advised. In cases with volume overload, dietary restriction of salt and water and diuretics is given. Vasodilator therapies, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and beta blockers should not be given in patients with low systemic vascular resistance, as they may lead to further deterioration. In patients with increased systemic vascular resistance, intravenous vasocon-strictor adrenergic drugs, like noradrenaline, ephedrine, metaraminol and phenylephrine, may be useful as short-term adjuncts in acute settings while treatment of the underlying aetiology is ongoing. However, prolonged treatment leads to

reduced vital organ perfusion and tachycardia due to beta-adrenergic receptor activation (e.g. ephed-rine) and is not recommended.

Use of weight reduction therapies including bariatric surgeries in morbidly obese patients, transfusion of blood and treating cause of severe anaemia, thiamine supplementation in beriberi, antithyroid drugs in thyrotoxicosis and thyroidec-tomy in selected cases, bisphosphonates in Paget disease, growth hormone supplementation in ac-romegaly, percutaneous or surgical intervention for congenital or acquired arteriovenous fistulas and liver transplantation in liver cirrhosis are ex-amples of treatment directed at correcting the ae-tiology as discussed above. Arteriography with selective embolization or surgical excision has been shown to reverse the failure in select cases of giant cutaneous haemangiomas and HF51. Modifi-cation or even closure may be required for A-V fistula causing high-output HF created for haemo-dialysis patients. In one report of 15 patients with upper extremity dialysis fistulas, temporarily closing the fistula lowered the cardiac output by 0.3–11 L/min (see ref 10). Thus, treatment of high-output HF should be directed at correcting the cause if possible.

CONCLUSION

High-output HF, though uncommon, is an impor-tant cause of clinical HF associated with increased mortality. It must be considered in patients present-ing with dyspnoea, congestion and a normal ejec-tion fraction. The main pathophysiology is vasodi-lation and decrease in peripheral vascular resistance leading to activation of neurohormones including renin–angiotensin–aldosterone axis and antidi-uretic hormone and subsequent salt and water re-tention. Most common causes are morbid obesity, arteriovenous shunts – congenital or acquired, se-vere anaemia, renal and liver disease and acutely in septic shock. Physical findings include warm ex-tremities, bounding pulse and wide pulse pressure. A meticulous physical examination along with ap-propriate laboratory and diagnostic tests, including cardiac imaging, helps to define the particular cause and underlying cardiac reserve or associated pathol-ogy. Vasodilator therapies proven for low-output HF should not be used. Treatment of high-output HF includes salt and water restriction, judicious use of diuretics and correcting the cause of the high out-put or low systemic vascular resistance.

506 SECTION VII — Heart Failure

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