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.