End-stage valvular heart disease requiring heart transplantation: risk profile, surgical modifiers, and myocardial pathology

Figures

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  VHD, valvular heart disease; HTx, heart transplantation. Among patients transplanted for end-stage VHD, we assessed clinical and pathological features and factors associated with time intervals to HTx. Genetic variants were associated with earlier onset, while associations with time-to-HTx were not statistically significant in this limited transplanted cohort.

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  Fig. 1. Inclusion and Exclusion Criteria. HTx, heart transplantation; TTE/TEE, transthoracic/transesophageal echocardiography; CMR, cardiac magnetic resonance; VHD, valvular heart disease; NIDCM, non-ischemic dilated cardiomyopathy; DCM, dilated cardiomyopathy; MR/AR, mitral regurgitation/aortic regurgitation; ICM, ischemic cardiomyopathy; HCM, hypertrophic cardiomyopathy; DbCM, diabetic cardiomyopathy; ARVC, arrhythmogenic right ventricular cardiomyopathy; RCM, restrictive cardiomyopathy; CHD, congenital heart disease; LVNC, left ventricular noncompaction; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVFS, left ventricular fractional shortening

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  Fig. 2. Kaplan–Meier analyses of event timing and time intervals to heart transplantation in end-stage valvular heart disease. A Female patients underwent HTx at an earlier age than male patients. B Patients with the HF phenotype underwent HTx earlier than those with the malignant ventricular arrhythmia phenotype. C Patients with congenital valvular heart disease underwent HTx earlier than those with acquired disease. D Following MACEs, patients without prior cardiac valvular surgery progressed to HTx earlier than those who had undergone surgery. E–F Patients with gene mutations developed symptoms earlier, but their age at HTx was similar to that of patients without mutations. MACEs were defined as HF or malignant ventricular arrhythmia events

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  Fig. 3. Kaplan–Meier analyses of event timing and surgery-related intervals in patients with end-stage valvular heart disease and a history of prior cardiac valvular surgery. A Patients with gene mutations developed symptoms at an earlier age than those without mutations. B Patients with congenital valvular heart disease underwent cardiac valvular surgery earlier than those with acquired valvular heart disease. C Patients who underwent cardiac valvular surgery after the occurrence of major adverse cardiovascular events (MACEs) proceeded to heart transplantation earlier than those who underwent surgery before MACEs. MACEs were defined as heart failure or malignant ventricular arrhythmia events

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  Fig. 4. Pathological manifestations of patients with end-stage valvular heart disease in heart transplantation cohort. A Schematic illustration of the six anatomical regions selected for pathological sampling, including the left ventricular anterior wall (LVAW), left ventricular lateral wall (LVLW), left ventricular posterior wall (LVPW), interventricular septum (IVS), right ventricular anterior wall (RVAW), and right ventricular posterior wall (RVPW). B Representative Masson’s trichrome staining images of the six sampled cardiac regions. C–E Bar plots showing the proportions of myocardium (C), fibrosis (D), and adipose tissue (E) across the six cardiac regions in patients with malignant arrhythmia (MA), refractory heart failure (HF), and mixed phenotype. F Donut charts summarizing the regional composition of myocardium, fibrosis, and adipose tissue across the six cardiac regions in the three clinical phenotypes. The inner ring represents the six anatomical regions, and the outer ring shows the relative proportions of myocardium, fibrosis, and adipose tissue in each region. MA, malignant arrhythmia; HF, heart failure; Figure 4A was created with BioRender.com

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  Fig. 5. Natural history of patients with valvular heart disease progressing to heart transplantation. MACEs, major adverse cardiovascular events; ICD, implantable cardioverter-defibrillator; CRT-D, cardiac resynchronization therapy device