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Background:

Risk stratification in chronic valvular regurgitation remains challenging. In carcinoid heart disease (CaHD), optimal surgical strategy and prognostic determinants are incompletely defined. In asymptomatic severe primary mitral regurgitation (PMR), current guideline thresholds based on left ventricular ejection fraction and end-systolic diameter may fail to detect early myocardial dysfunction. This thesis aimed to refine risk stratification using multimodality imaging and functional assessment.

Methods and Results:

Paper I analysed 60 consecutive patients undergoing valve surgery for CaHD (1986–2019). Thirty-day mortality was 12% overall (8% in the last decade). Combined tricuspid and pulmonary valve replacement (TVR+PVR) was associated with longer survival compared with isolated TVR. Echocardiographic (TTE) assessment of the pulmonary valve was challenging and may underestimate disease severity. NT-proBNP and 5-HIAA independently predicted outcome. Bioprosthetic valve durability was satisfactory.

Papers II–IV prospectively evaluated patients with asymptomatic severe PMR. In Paper II (n=47), myocardial external efficiency (MEE) assessed by ¹¹C-acetate PET was reduced in proportion to regurgitation severity and independently associated with subsequent mitral valve surgery during follow-up. In Paper III (n=48), impaired ventilatory efficiency assessed by cardiopulmonary exercise testing (CPET)—particularly an elevated VE/VCO₂ ratio at the anaerobic threshold—independently predicted mitral valve surgery beyond peak VO₂ and guideline-based echocardiographic thresholds. In Paper IV (n=49), comprehensive baseline imaging with TTE and cardiovascular magnetic resonance (CMR) demonstrated that volumetric parameters, especially indexed left ventricular end-diastolic volume (LVEDVi), were associated with outcome. In contrast, short-term (1-year) serial changes provided limited additional prognostic value. CMR-derived myocardial extracellular volume and histologically quantified myocardial fibrosis from perioperative biopsies were low or only mildly increased, suggesting limited irreversible myocardial injury at the time of surgery.

Conclusions:

In CaHD, valve surgery was associated with acceptable perioperative risk and prolonged survival, and combined TVR+PVR may be advantageous. Pulmonary valve disease may be underestimated by TTE, supporting the use of complementary imaging when needed. In asymptomatic severe PMR, MEE, ventilatory efficiency, and comprehensive baseline volumetric imaging may provide incremental prognostic information beyond conventional parameters. These findings support a multimodality approach to improve risk stratification and timing of intervention.