6.2. Surgical Management
Valve replacement surgery is the most effective treatment for managing symptomatic CaHD, significantly improving patient outcomes. The criteria and optimal timing for such surgery, however, remain subjects of debate. Consensus says that the indications for valve replacement surgery are symptomatic right heart failure, in conjunction with either progressive right ventricular enlargement or a decline in right ventricular systolic function, irrespective of the presence of symptoms.26The decision-making process for valve replacement should be predicated upon a thorough evaluation by a multidisciplinary team, taking into account comprehensive operability, the oncological status, and cardiac functionality. Surgical interventions have shown not only to alleviate symptoms of RHF but also to reverse right ventricular remodelling. Studies highlight the postoperative symptomatic improvement and survival benefits. For instance, a study by Mokhles et al. involving 19 patients showed a significant improvement in functional capacity one year post-valve replacement, with survival rates at 1- and 5-year follow-ups standing at 71% and 43%, respectively.39
Predominant surgical interventions include tricuspid valve replacement (TVR) and, less frequently, pulmonary valve replacement (PVR). Survival outcomes post-combined TVR and PVR surpass those of surgeries excluding PVR, thus advocating for the former as the preferred surgical intervention for the majority of patients (unless there is significant pulmonary valve involvement).40 In cases requiring intervention on both the tricuspid and pulmonary valves, combined valve replacement has been successfully performed, with reported median survival times extending from six to eleven years post-operation.1 Additionally, although balloon valvuloplasty has been attempted in patients deemed unsuitable for surgery, its utility is limited due to the high recurrence rate of valvular disease and the potential for concurrent TV and PV regurgitation.15
The selection of the valve prosthesis type remains a subject of debate, with no large comparative studies available. Initial preferences leaned towards mechanical prostheses to avoid the presumed risk of damage to bioprosthetic valves from vasoactive substances.1However, the protective potential of somatostatin analogs and other antitumor therapies against carcinoid plaque deposition on tissue valves has been recognized, shifting some opinion in favour of bioprosthetic valves. While bioprosthetic valves are susceptible to early degeneration from carcinoid-related fibrosis, this risk can be mitigated with effective postoperative control of neuroendocrine activity. Therefore, despite the potential for thrombosis, bioprosthetic valves generally do not require lifelong anticoagulation—typically, a three to six-month course suffices.26 Conversely, mechanical valves offer durability but necessitate lifelong anticoagulation, increasing the risk of bleeding and potentially complicating future interventions. In instances of bioprosthetic valve deterioration, Transcatheter Valve Implantation emerges as a logical subsequent treatment step.15
As often is the case with most surgical interventions, they are not devoid of risks. In the perioperative phase, the anaesthetist confronts challenges specific to CaHD, including the risk of carcinoid crisis, bleeding, and the potential onset of low cardiac output syndrome attributed to right ventricular (RV) failure.41 To mitigate these potential complications, an infusion of short-acting octreotide is initiated 12-24 hours prior to surgery and maintained throughout the perioperative period for three days, supplemented, if necessary, by the administration of catecholamines and histamine-releasing drugs.41 The paramount importance of bleeding management mandates that surgeons and anesthesiologists meticulously assess and refine surgical techniques, implement autologous blood recovery systems, and focus on the optimization of postoperative coagulation.40 Notably, the operative risk has decreased from 20% in the 1980s to 10% in more recent years, marking a significant advancement.15
Furthermore, partial hepatic resection and tumour debulking are generally reserved for patients with metastatic disease localised to a specific hepatic lobe.42 Indeed, liver resection is correlated with a diminished risk of CaHD cardiac progression, underscoring its critical role in the surgical management of CaHD.43 In select scenarios of metastatic carcinoid disease confined to the liver, patients might also be eligible for liver transplantation and the excision of the primary tumour.
Future Prospects/Recommendations:
As the healthcare field advances its understanding of CaHD, the trajectory for future management and research is set towards improving patient outcomes with a focus on innovation and personalised care. Advances in diagnostic modalities promise a new era where early detection and precise characterization of CaHD become the norm. The development of advanced imaging techniques such as 3D echocardiography and cardiac MRI, alongside specific biomarkers for early disease detection, are anticipated to revolutionise the diagnostic landscape of CaHD, enabling earlier and more targeted interventions.24,31
The exploration into the genetic and molecular bases of CaHD holds the potential to identify novel therapeutic targets. Uncovering the mechanisms behind serotonin-mediated valvular disease could pave the way for therapies that prevent or significantly reduce valvular fibrosis, moving beyond the current pharmacological approaches that primarily manage symptoms.1 In tandem with molecular research, the quest for innovative therapeutic agents that specifically address the pathophysiological processes of CaHD is critical. This includes not only drugs that effectively manage serotonin levels but also those that can inhibit fibrosis or offer cardioprotective effects without the drawbacks of existing treatments.
Surgical treatment of CaHD is also poised for advancement, with a focus on developing new valve prostheses and exploring minimally invasive and transcatheter interventions. The design of valve prostheses that are resistant to serotonin-induced fibrosis or mechanical valves that minimise thrombosis risk could significantly improve patient prognosis.7 Additionally, minimally invasive techniques could offer viable alternatives for high-risk patients, reducing perioperative complications and broadening treatment options.45 Furthermore, personalised treatment strategies are imperative for the future of CaHD management, advocating for treatments tailored to individual genetic profiles, disease severity, and therapeutic responses. This approach necessitates the creation of comprehensive databases and the application of advanced analytics, ensuring treatments are both effective and minimised for side effects. Integral to this personalised approach is the reinforcement of multidisciplinary care models, emphasising coordinated, patient-centred management across specialties to optimise treatment timing and patient care.
In addition, the establishment of patient registries and the commitment to long-term follow-up will provide critical insights into disease progression, treatment efficacy, and quality of life. These registries are essential for facilitating large-scale studies and validating new management strategies. International collaboration and the development of consensus guidelines based on the latest evidence will also play a pivotal role in advancing global standards of care for CaHD, ensuring patients everywhere have access to the best possible outcomes.45 Although the ideal scenario would involve a multicenter, randomised survival study, the rarity of CaHD and logistical challenges render this prospect unlikely.
Conclusion:
CaHD presents significant challenges in cardiac pathology associated with neuroendocrine tumours, characterised by valvular dysfunction due to serotonin-induced fibrosis. Central to its management are advancements in diagnostic modalities such as echocardiography and cardiac MRI, which have significantly enhanced the ability to diagnose the disease early and accurately. The management strategy for CaHD has evolved into a comprehensive approach, incorporating both medical and surgical treatments. Medical therapies, including somatostatin analogues and newer pharmacological options, aim to control symptoms and slow disease progression. However, surgical valve replacement remains a well-researched option for those with advanced symptomatic disease, offering symptomatic relief and improved survival. Ultimately, the goal in managing CaHD is to improve both survival and the quality of life of affected patients through early decision, tailored treatment strategies and ongoing research to refine and discover new therapeutic options.