Cardiac Cachexia

Cardiac cachexia is a syndrome of involuntary, non-oedematous weight loss of more than 5% over 12 months or less in chronic heart failure (or body mass index under 20 kg/m2 if prior weight is unknown), together with reduced muscle strength, fatigue, anorexia, low fat free mass index or abnormal biochemistry.

It affects about 10 to 15% of patients with chronic heart failure, and more in advanced disease. It is independently associated with higher mortality, and low body mass index in heart failure carries a worse prognosis than obesity.

The usual setting is advanced heart failure with reduced or preserved ejection fraction, often with right heart failure, chronic kidney disease or lung disease.

Pathophysiology.

Neurohormonal activation (sympathetic, renin-angiotensin-aldosterone) and chronic inflammation (TNF-alpha, interleukin-6, C-reactive protein) drive a catabolic state with muscle and fat wasting and anabolic resistance.

Gut oedema impairs absorption, hepatic congestion reduces appetite, and early satiety, nausea and drug effects reduce intake. Insulin and growth hormone resistance, hypogonadism, and reduced physical activity add to loss of lean mass.

Muscle wasting reduces exercise capacity and ventilatory efficiency, creating a cycle of inactivity and further wasting.

Visible loss of fat and temporal and limb muscle wasting, usually hidden by oedema, so dry weight must be estimated. Anorexia, early satiety, fatigue, weakness, low serum albumin, and signs of congestion. Weight loss may be masked by fluid retention, so weight loss after diuresis is a key clue.

• Document dry weight and weight history, body mass index, mid-arm muscle circumference and grip strength; dual energy X-ray absorptiometry or bioimpedance for fat free mass where available.
• Blood tests: full blood count, ferritin and transferrin saturation, C-reactive protein, albumin, creatinine and eGFR, liver tests, thyroid function, glucose or HbA1c, vitamin B12 and folate, HIV test, and urine protein.
• Exclude other causes of weight loss: tuberculosis, HIV, malignancy, thyrotoxicosis, malabsorption, depression, diabetes, drug effects (digoxin, metformin, SGLT2 inhibitor), and chronic kidney or liver disease.
• Echocardiography and NT-proBNP to define heart failure severity.
• Nutritional screening with a validated tool and swallowing assessment where needed.

Differential diagnosis.

• Malignancy, tuberculosis and HIV-associated wasting.
• Thyrotoxicosis and malabsorption.
• Advanced chronic kidney, liver or lung disease.
• Depression, drug induced anorexia and sarcopenia of ageing.

Treat the cause. Optimise heart failure therapy with an ACE inhibitor or ARNI, evidence based beta blocker, mineralocorticoid antagonist and SGLT2 inhibitor as tolerated, and treat congestion to keep a stable dry weight. Treat iron deficiency, anaemia, thyroid disease and depression. Review drugs for anorexia and gastrointestinal effects.

Nutrition.

• Energy intake 30 to 35 kcal/kg daily and protein 1.2 to 1.5 g/kg daily (reduce protein in advanced kidney disease), in small frequent meals with energy dense oral supplements; dietitian review. Avoid severe sodium restriction (under 2 g daily) in cachexia because it worsens intake.
• Enteral feeding for failure of oral intake; parenteral nutrition only when enteral feeding is impossible.
• Vitamin D, thiamine and micronutrient replacement where deficient.

Iron deficiency (ferritin under 100 microgram/L, or 100 to 299 microgram/L with transferrin saturation under 20%): ferric carboxymaltose 500 to 1000 mg intravenously by haemoglobin and body weight using the product dosing table, repeated at 6 weeks and at 3 and 6 months as needed (maximum single dose 1000 mg, or 20 mg/kg); or ferric derisomaltose 20 mg/kg (maximum 1000 mg) as a single infusion over at least 20 minutes. Check ferritin and transferrin saturation at 3 months; phosphate after ferric carboxymaltose in repeated doses.

Exercise. Supervised aerobic and resistance training 2 to 3 times each week improves muscle mass and function.

Drugs not advised. Megestrol acetate and corticosteroids as appetite stimulants (fluid retention, thrombosis and adrenal suppression), anabolic steroids and growth hormone (no benefit in heart failure), and thalidomide. Testosterone replacement is considered only for proven symptomatic hypogonadism. Anamorelin and other ghrelin agonists are investigational.

Advanced care. Early palliative care input, goals-of-care discussion and consideration of advanced therapies. Severe cachexia (body mass index under 18 kg/m2) carries higher mortality after transplantation or ventricular assist device implantation, and nutritional rehabilitation first can improve outcomes.

Monitoring. Dry weight, body mass index, and appetite at every visit; albumin, C-reactive protein, haemoglobin, ferritin and creatinine every 3 months; grip strength and functional testing every 3 to 6 months.

Referral and escalation. Refer to a heart failure service with dietetic input. Refer for malignancy or tuberculosis workup when there is fever, night sweats or haemoptysis with weight loss, weight loss of over 5 kg in a month, or dysphagia. In patients taking digoxin, check for toxicity (anorexia, nausea, visual disturbance, bradycardia).

Special groups.

• Older adults: screen for sarcopenia, dysphagia and polypharmacy; protein and resistance exercise are central.
• Kidney impairment: moderate protein restriction against malnutrition risk, with dietitian review; adjust iron dosing and monitor phosphate.
• Region specific: HIV and tuberculosis are important coexisting or competing causes of wasting in sub-Saharan Africa and should be tested for in every patient.