Stem cell therapy
Stem cell therapy remains a promising treatment for patients with left ventricular (LV) dysfunction caused by coronary ischemia/infarction. Intracoronary or intramyocardial injections of skeletal myoblasts or bone-marrow-derived mononuclear cells (BMSCs) have led to a modest improvement in cardiac performance in some studies, including improvement in the LVEF and reduction in the size of scar tissue and cardiac volume. However, the clinical effect of such therapies has not yet been proven. The therapy appears to be well tolerated in patients after recent myocardial infarction (MI), but a proarrhythmic effect of cell therapy has been observed in patients with chronic heart failure (HF).
The recent CHART-1 trial was the largest multicenter and multinational study of stem cell therapy in patients with ischemic cardiomyopathy, LVEF less than 35% and worsening HF (class III/IV within the preceding 12 months). The primary efficacy endpoint was neutral but the exploratory analyses suggested a benefit (trends in reduction of clinical endpoints, and improvement in quality of life and physical fitness) in a large subset of the population defined by the degree of LV dilation and a lower number of injections.
In addition, intracoronary administration of BMSCs seems to be associated with improvements in cardiac contractile and microvascular function in patients with dilated cardiomyopathy. Intensive work in this and other areas (including the type of cell used, and the method and time of delivery) continues. However, stem cell therapy is not yet ready to become a mainstay of clinical practice.
Phrenic nerve stimulation in patients with central sleep apnea
This is an alternative approach to the treatment of patients with central sleep apnea (CSA), designed to restore a physiological breathing pattern throughout sleep. It uses a fully implantable system with transvenous leads designed for the long-term application of transvenous phrenic nerve stimulation (The Remedē System, Respicardia). The system is fully automated, thereby eliminating patient non-adherence. It works by stimulating the diaphragm during sleep to stabilize gas exchange and maintain normal breathing. It has recently been shown to stabilize the breathing pattern, reduce the number of apneic events, improve oxygen saturation and increase end-tidal carbon dioxide without suppressing the intrinsic drive to breathe. Future large studies in patients with HF and CSA are awaited.
Patiromer – a new treatment for chronic hyperkalemia
Hyperkalemia is common in patients receiving HF medications such as angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor blockers (ARBs), spironolactone or eplerenone, and often limits their use. Management of hyperkalemia in these patients is often challenging and comprises dietary restriction and dose reduction or withdrawal of the offending agent. Potassium-binding resins, such as resonium A (sodium polystyrene sulfonate) and calcium resonium (calcium polystyrene sulfonate) are commonly used in the management of chronic hyperkalemia. However, high quality evidence of the effectiveness of these agents is lacking. Furthermore, they can cause serious or intolerable gastrointestinal adverse events ranging from gastric irritation to (rarely) ischemic colitis, gastrointestinal obstruction, ulceration, perforation or necrosis.
Patiromer is a non-absorbable compound that predominantly binds to potassium in the colon and exchanges it for calcium. The most common adverse effects are constipation (11%) and hypokalemia (3%). Short-term studies have confirmed its efficacy in maintaining normokalemia in patients treated with HF medications.
Subcutaneous furosemide
Furosemide, the loop diuretic used to treat congestive HF, is licensed for use in oral and intravenous forms (see pages 96–7). For patients with recurrent fluid overload, intravenous administration in a hospital setting is the only licensed choice, although in some countries off-label subcutaneous furosemide has been used for several years in the palliative care setting. A new formulation of subcutaneous furosemide that uses a dedicated sc2Wear™ infusor pump has been developed. The drug pH has been reduced to a neutral level to minimize the risk of local irritation or discomfort.
Subcutaneous furosemide allows greater flexibility of administration, avoids the need for intravenous placement and potentially reduces the cost of care. Ongoing studies are awaited to establish its application and cost-effectiveness in patients with chronic HF.
Key points – clinical trials and developments
• Stem cell therapy has demonstrated a modest improvement in cardiac performance in some studies, but the clinical effect of such therapies has not yet been proven.
• A fully implantable, automated, phrenic nerve stimulation system is an alternative approach to the treatment of patients with central sleep apnea. Early findings are promising, and the results of ongoing trials in patients with HF are awaited.
• In short-term studies, patiromer, a non-absorbable compound that predominantly binds to potassium in the colon and exchanges it for calcium, has demonstrated efficacy in managing hyperkalemia in patients treated with HF medications.
• A new formulation of subcutaneous furosemide delivered via a dedicated device has been developed.
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