Left ventricular fibrosis and CMR tissue characterization of papillary muscles in mitral valve prolapse patients.

PURPOSE: Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies. METHODS: MVP patients with indication for surgery due to severe mitral regurgitation (n = 19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE). CMR T1 mapping was performed on 21 healthy volunteers as controls. LV inferobasal myocardial biopsies were obtained in MVP patients and compared to CMR findings. RESULTS: MVP patients (54 ± 10 years old, 14 male) had a dark-appearance of the PM with higher native T1 and extracellular volume (ECV) values compared with healthy volunteers (1096 ± 78ms vs. 994 ± 54ms and 33.9 ± 5.6% vs. 25.9 ± 3.1%, respectively, p < 0.001). Seventeen MVP patients (89.5%) had fibrosis by biopsy. BB-LGE + in LV and PM was identified in 5 (26.3%) patients, while DB-LGE + was observed in LV in 9 (47.4%) and in PM in 15 (78.9%) patients. DB-LGE + in PM was the only technique that showed no difference with detection of LV fibrosis by biopsy. Posteromedial PM was more frequently affected than the anterolateral (73.7% vs. 36.8%, p = 0.039) and correlated with biopsy-proven LV fibrosis (Rho 0.529, p = 0.029). CONCLUSIONS: CMR imaging in MVP patients referred for surgery shows a dark-appearance of the PM with higher T1 and ECV values compared with healthy volunteers. The presence of a positive DB-LGE at the posteromedial PM by CMR may serve as a better predictor of biopsy-proven LV inferobasal fibrosis than conventional CMR techniques.

Left Ventricular Fibrosis and CMR Tissue Characterization of Papillary Muscles in Mitral Valve Prolapse Patients.

Purpose: Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies. Methods: MVP patients with indication for surgery due to severe mitral regurgitation (n=19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE). CMR T1 mapping was performed on 21 healthy volunteers as controls. LV inferobasal myocardial biopsies were obtained in MVP patients and compared to CMR findings. Results: MVP patients (54±10 years old, 14 male) had a dark-appearance of the PM with higher native T1 and extracellular volume (ECV) values compared with healthy volunteers (1096±78ms vs 994±54ms and 33.9±5.6% vs 25.9±3.1%, respectively, p<0.001). Seventeen MVP patients (89.5%) had fibrosis by biopsy. BB-LGE+ in LV and PM was identified in 5 (26.3%) patients, while DB-LGE+ was observed in LV in 9 (47.4%) and in PM in 15 (78.9%) patients. DB-LGE+ in PM was the only technique that showed no difference with detection of LV fibrosis by biopsy. Posteromedial PM was more frequently affected than the anterolateral (73.7% vs 36.8%, p=0.039) and correlated with biopsy-proven LV fibrosis (Rho 0.529, p=0.029). Conclusions: CMR imaging in MVP patients referred for surgery shows a dark-appearance of the PM with higher T1 and ECV values compared with healthy volunteers. The presence of a positive DB-LGE at the posteromedial PM by CMR may serve as a better predictor of biopsy-proven LV inferobasal fibrosis than conventional CMR techniques.

Quantification of regurgitation in mitral valve prolapse with four-dimensional flow cardiovascular magnetic resonance.

BACKGROUND: Four-dimensional cardiovascular magnetic resonance (CMR) flow assessment (4D flow) allows to derive volumetric quantitative parameters in mitral regurgitation (MR) using retrospective valve tracking. However, prior studies have been conducted in functional MR or in patients with congenital heart disease, thus, data regarding the usefulness of 4D flow CMR in case of a valve pathology like mitral valve prolapse (MVP) are scarce. This study aimed to evaluate the clinical utility of cine-guided valve segmentation of 4D flow CMR in assessment of MR in MVP when compared to standardized routine CMR and transthoracic echocardiography (TTE). METHODS: Six healthy subjects and 54 patients (55 ± 16 years; 47 men) with MVP were studied. TTE severity grading used a multiparametric approach resulting in mild/mild-moderate (n = 12), moderate-severe (n = 12), and severe MR (n = 30). Regurgitant volume (RVol) and regurgitant fraction (RF) were also derived using standard volumetric CMR and 4D flow CMR datasets with direct measurement of regurgitant flow (4DFdirect) and indirect calculation using the formula: mitral valve forward flow - left ventricular outflow tract stroke volume (4DFindirect). RESULTS: There was moderate to strong correlation between methods (r = 0.59-0.84, p < 0.001), but TTE proximal isovelocity surface area (PISA) method showed higher RVol as compared with CMR techniques (PISA vs. CMR, mean difference of 15.8 ml [95% CI 9.9-21.6]; PISA vs. 4DFindirect, 17.2 ml [8.4-25.9]; PISA vs. 4DFdirect, 27.9 ml [19.1-36.8]; p < 0.001). Only indirect CMR methods (CMR vs. 4DFindirect) showed moderate to substantial agreement (Lin's coefficient 0.92-0.97) without significant bias (mean bias 1.05 ± 26 ml [- 50 to 52], p = 0.757). Intra- and inter-observer reliability were good to excellent for all methods (ICC 0.87-0.99), but with numerically lower coefficient of variation for indirect CMR methods (2.5 to 12%). CONCLUSIONS: In the assessment of patients with MR and MVP, cine-guided valve segmentation 4D flow CMR is feasible and comparable to standard CMR, but with lower RVol when TTE is used as reference. 4DFindirect quantification has higher intra- and inter-technique agreement than 4DFdirect quantification and might be used as an adjunctive technique for cross-checking MR quantification in MVP.

Quantification of regurgitation in mitral valve prolapse with automated real time echocardiographic 3D proximal isovelocity surface area: multimodality consistency and role of eccentricity index.

Three-dimensional transthoracic echocardiography (3D-TTE) provides a semi-automated proximal isovelocity surface area method (3D-PISA) to obtain quantitative parameters. Data assessing regurgitation severity in mitral valve prolapse (MVP) are scarce, so we assessed the 3D-PISA method compared with 2D-PISA and cardiovascular magnetic resonance (CMR) and the role of an eccentricity index. We evaluated the 3D-PISA method for assessing MR in 54 patients with MVP (57 ± 14 years; 42 men; 12 mild/mild-moderate; 12 moderate-severe; and 30 severe MR). Role of an asymmetric (i.e. eccentricity index ≥ 1.25) flow convergence region (FCR) and inter-modality consistency were then assessed. 3D-PISA derived regurgitant volume (RVol) showed a good correlation with 2D-PISA and CMR derived parameters (r = 0.86 and r = 0.81, respectively). The small mean differences with 2D-PISA derived RVol did not reach statistical significance in overall population (5.7 ± 23 ml, 95% CI - 0.6 to 12; p = 0.08) but differed in those with asymmetric 3D-FCR (n = 21; 2D-PISA: 72 ± 36 ml vs. 3D-PISA: 93 ± 47 ml; p = 0.001). RVol mean values were higher using PISA methods (CMR 57 ± 33 ml; 2D-PISA 73 ± 39 ml; and 3D-PISA 79 ± 45 ml) and an overestimation was observed when CMR was used as reference (2D-PISA vs. CMR: mean difference: 15.8 ml [95% CI 10-22, p < 0.001]; and 3D-PISA vs. CMR: 21.5 ml [95% CI 14-29, p < 0.001]). Intra- and inter-observer reliability was excellent (ICC 0.91-0.99), but with numerically lower coefficient of variation for 3D-PISA (8%-10% vs. 2D-PISA: 12%-16%). 3D-PISA method for assessing regurgitation in MVP may enable analogous evaluation compared to standard 2D-PISA, but with overestimation in case of asymmetric FCR or when CMR is used as reference method.

Grading of aortic regurgitation by cardiovascular magnetic resonance and pulsed Doppler of the left subclavian artery: harmonizing grading scales between imaging modalities.

Transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) are current standard for assessing aortic regurgitation (AR). Regurgitant fraction (RF) can also be estimated by Doppler examination of the left subclavian artery (LSA-Doppler). However, a comparison of AR grading scales using these methods and a TTE multiparametric approach as reference is lacking. We evaluated the severity of AR in 73 patients (58 ± 15 years; 57 men), with a wide spectrum of AR of the native valve. Using a recommended TTE multiparametric approach the AR was divided in none/trace (n = 12), mild (n = 23), moderate (n = 12), and severe (n = 26). RF was evaluated by LSA-Doppler (ratio between diastolic and systolic velocity-time integrals) and by CMR phase-contrast imaging (performed in the aorta 1 cm above the aortic valve); the grading scales were then calculated. There were a good correlation between all methods, but mean RF values were greater with TTE compared with LSA-Doppler and CMR (39 ± 16% vs. 35 ± 18% vs. 32 ± 20%, respectively; p < 0.037). Mean differences in RF values between methods were significant in the groups with mild and moderate AR. Grading scales that best defined the TTE derived AR severity using CMR were: mild, < 21%; moderate, 22 to 41%; and severe, > 42%; and using LSA-Doppler: mild, < 29%; moderate, 30 to 44%; and severe, > 45%. RF values for AR grading using TTE, LSA-Doppler and CMR correlate well but differ in groups with mild and moderate AR when using a recognized multiparametric echocardiographic approach. Clinical prospective studies should validate these proposed modality adjusted grading scales.

Multi-biomarker mortality prediction in patients with aortic stenosis undergoing valve replacement.

OBJECTIVES: The prognostic value of biomarkers in aortic stenosis (AS) remains understudied. We investigated whether a combination of biomarkers related to cardiovascular stress, inflammation, and damage is associated with mortality in patients with severe AS undergoing surgical aortic valve replacement (SAVR). METHODS: From a prospective registry of patients with severe AS referred for SAVR, 499 participants (mean age, 68 ± 8.5 years; 292 male) with available preoperative echocardiograms and biomarker data were included. Preoperative concentrations of NT-pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein were dichotomized as high or low, according to calculated cut-off values. RESULTS: The mean follow-up time was 775 ± 410 days; 25 patients died. Only patients with elevated levels of all three biomarkers (n = 55) showed increased mortality [hazard ratio (HR), 7.26; 95% confidence interval (CI), 2.52-20.93; p < 0.001; reference group, no elevated biomarkers, n = 159]. Patients with elevated levels of the three biomarkers had higher 3-year all-cause mortality (24% vs. 4.5%); this remained true after multivariable adjustment (HR, 4.08; 95% CI, 1.87-8.87; p < 0.001). Patients with EuroSCOREs (logES) >3.0% tended to exhibit a higher risk of all-cause mortality (HR, 2.19; 95% CI, 0.98-4.87; p = 0.055); the mortality rate was 12-fold higher when logES >3 was combined with the three elevated biomarkers. This combination also showed a net reclassification improvement of 33% and significant likelihood-ratio test results. CONCLUSIONS: A multiple biomarker approach might be useful for predicting postoperative mid-term mortality in patients with severe AS undergoing SAVR. Further large-scale prospective validation should be performed.

Reversibility of severe mitral valve regurgitation after left ventricular assist device implantation: single-centre observations from a real-life population of patients.

OBJECTIVES: This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. METHODS: Of the 234 patients who received LVAD therapy in our centre during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7-28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283-848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. RESULTS: We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). CONCLUSIONS: Preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival.

Quantification of Aortic Valve Regurgitation by Pulsed Doppler Examination of the Left Subclavian Artery Velocity Contour: A Validation Study with Cardiovascular Magnetic Resonance Imaging.

BACKGROUND: Reflux of the aortic regurgitation (AR) causes an increased diastolic reverse flow in the aorta and its branching vessels. We aimed to evaluate the feasibility and accuracy of Doppler measurements in the left subclavian artery (LSA) for quantification of AR in a cardiovascular magnetic resonance imaging (CMR) validation study. METHODS: Systolic and diastolic flow profiles of the LSA (subclavicular approach) were evaluated prospectively by use of pulsed wave Doppler in 59 patients (55.5 ± 15 years; 44 men), 47 with a wide spectrum of AR and 12 as control group. Using CMR phase-contrast sequences (performed 1 cm above the aortic valve), the AR was divided into three groups: mild, regurgitant fraction (RF) < 20% (n = 17); moderate, RF 20%-40% (n = 10); and severe, RF > 40% (n = 20). The LSA Doppler-derived RF was calculated as the ratio between diastolic and systolic velocity-time integrals (VTI). RESULTS: Quality LSA Doppler signal could be obtained in all cases. Patients with CMR severe AR had higher values of LSA Doppler-derived RF (51% ± 9% vs 36% ± 11% vs 16% ± 8%; P < .0001). LSA Doppler showed a good correlation with CMR, with a sensitivity of 95%, specificity of 89%, and diagnostic accuracy for severe AR of 91.5%. Finally, Bland-Altman plots showed agreement in the group with moderate to severe AR (mean bias = -2.2% ± 8%, 95% CI, -17.7 to 13.3; P = .145) but differed in mild AR. CONCLUSIONS: Measurements of the RF for quantification of AR using LSA Doppler are comparable to those of CMR, highlighting the potential role of LSA Doppler as an adjunctive technique to assess the severity of AR.

Advanced symptoms are associated with myocardial damage in patients with severe aortic stenosis.

BACKGROUND: Once aortic stenosis (AS) is severe, patients develop symptoms at different stages. Indeed, symptom status may correlate poorly with the grade of valve narrowing. Multiple pathophysiological mechanisms, other than valvular load, may explain the link between AS and symptom severity. We aimed to describe the relationship between the severity of symptoms and the characteristics of a cohort of patients with severe AS already referred for aortic valve replacement (AVR). METHODS: We analyzed 118 consecutive patients (70±9 years, 55% men) with severe AS referred for AVR. We identified 84 patients with New York Heart Association (NYHA) I-II, and 34 with NYHA III-IV symptoms. Clinical and echocardiographic parameters were compared between these two groups. Left ventricular ejection fraction (LVEF), global longitudinal peak systolic strain (GLPS), NT-pro-B-type natriuretic peptide (BNP), and high-sensitive troponin T (hs-TNT) were determined at the time of admission. RESULTS: AS severity was similar between groups. Compared with the NYHA I-II group, patients in NYHA III-IV group were older and more likely to have comorbidities, worse intracardiac hemodynamics and more LV damage. Variables independently associated with NYHA III-IV symptomatology were the absence of sinus rhythm, higher E/e' ratio, and increased hs-TNT. GLPS showed a good correlation not only with hs-TNT as a marker of myocardial damage, but also with markers of increased afterload imposed on LV, being not directly related with advanced symptoms. CONCLUSIONS: Advanced symptoms in patients with severe AS referred for AVR are associated with worse intracardiac hemodynamics, absence of sinus rhythm, and more myocardial damage. It supports the concept of transition from adaptive LV remodeling to myocyte death as an important determinant of symptoms of heart failure.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa as a complication after minimally invasive mitral valve repair.

Pseudoaneurysm of the mitral-aortic intervalvular body is a rare condition, which has been reported as a result of endocarditis, chest trauma or cardiac surgery. We describe here the first case after minimally invasive mitral valve repair. Such a complication may be overlooked in the early postoperative echocardiographic study and may lead to fistula formation, compression of adjacent structures, infection, or rupture. Both computed tomography and echocardiography provide a detailed anatomy of the pseudoaneurysm and its communication with the left ventricular outflow tract.

Current indications for surgical repair in patients with bicuspid aortic valve and ascending aortic ectasia.

Preventive surgical repair of the moderately dilated ascending aorta/aortic root in patients with bicuspid aortic valve (BAV) is controversial. Most international reference centers are currently proposing a proactive approach for BAV patients with a maximum ascending aortic/root diameter of 45 mm since the risk of dissection/rupture raises significantly with an aneurysm diameter >50 mm. Current guidelines of the European Society of Cardiology (ESC) and the joint guidelines of the American College of Cardiology (ACC)/American Heart Association (AHA) recommend elective repair in symptomatic patients with dysfunctional BAV (aortic diameter ≥45 mm). In asymptomatic patients with a well-functioning BAV, elective repair is recommended for diameters ≥50 mm, or if the aneurysm is rapidly progressing (rate of 5 mm/year), or in case of a strong family history of dissection/rupture/sudden death, or with planned pregnancy. As diameter is likely not the most reliable predictor of rupture and dissection and the majority of BAV patients may never experience an aortic catastrophe at small diameters, an overly aggressive approach almost certainly will put some patients with BAV unnecessarily at risk of operative and early mortality. This paper discusses the indications for preventive, elective repair of the aortic root, and ascending aorta in patients with a BAV and a moderately dilated-or ectatic-ascending aorta.