6.1 Medical Management
Management of CaHD presents several challenges, with most of these predicated on balancing the control of the neuroendocrine tumour (NET) and its cardiac manifestations. This task necessitates a multidisciplinary team (MDT) effort, involving cardiologists, cardiac surgeons, NET specialists, anesthesiologists, and radiologists.32 The primary goal is to tailor a management plan that addresses both the cardiac complications and the underlying NET, ensuring a comprehensive care strategy for patients.
With respect to managing heart failure symptoms in CaHD, this revolves around vigilant monitoring and the judicious use of diuretics.19 For asymptomatic patients, a watchful waiting strategy is employed until symptoms manifest. The development of right-sided heart failure symptoms, particularly peripheral edema, necessitates the introduction of loop or thiazide diuretics and aldosterone antagonists.19 Despite their efficacy, the potential for intravascular volume depletion and reduced cardiac output warrants cautious use. Other pharmacological agents like digoxin and angiotensin-converting enzyme inhibitors have been explored, though their specific efficacy in CaHD remains to be fully established.32
Understandably, reducing 5-HT secretion from the NET is crucial, employing both medical and interventional strategies. Somatostatin analogues like octreotide and lanreotide have been instrumental in this regard.33 Notably, the PROMID and CLARINET studies expanded treatment criteria to include asymptomatic patients, demonstrating these drugs’ anti-proliferative potential and positive effects on progression-free survival.34,35 Octreotide LAR and lanreotide AG, for instance, are administered in doses up to 30 mg and 120 mg every four weeks, respectively, with potential dose adjustments for refractory cases.26 At the same time, peptide receptor radionuclide therapy (PRRT), particularly with yttrium 90Y-edotreotide and Lutetium-DOTATATE, targets advanced NETs with somatostatin receptor-positive lesions.36 A prospective study highlighted that while only 4% of patients showed objective response, 70% exhibited no disease progression for a median of 18 months.36 Additionally, symptom improvement was reported in a majority of patients, underscoring PRRT’s role in managing CaHD, albeit with considerations for amino-acid and fluid infusions during treatment.
Emerging treatments like telotristat ethyl and everolimus present new avenues for managing CaHD. Telotristat ethyl, in particular, has shown promise in phase II and III trials, with significant reductions in bowel movement frequency and serotonin levels in patients inadequately responding to somatostatin analogues.37 For instance, a phase III trial reported that 44% and 42% of patients on telotristat etiprate experienced a durable response, compared to only 20% on placebo.38 Everolimus, studied in the RADIANT-2 trial, while not primarily focused on CaHD, demonstrated a significant reduction in 5-HIAA levels, offering an indirect benefit in managing the disease.26 However, its use demands caution due to potential side effects and considerations around surgical interventions.