Sex differences in myocardial remodeling and extracellular volume in aortic regurgitation.

Whether sex differences exist in the cardiac remodeling related to aortic regurgitation (AR) is unclear. Cardiac magnetic resonance (CMR) is the current non-invasive reference standard for cardiac remodeling assessment and can evaluate tissue characteristics. This prospective cohort included patients with AR undergoing CMR between 2011 and 2020. We excluded patients with confounding causes of remodeling. We quantified left ventricular (LV) volume, mass, AR severity, replacement fibrosis by late Gadolinium enhancement (LGE), and extracellular expansion by extracellular volume fraction (ECV). We studied 280 patients (109 women), median age 59.5 (47.2, 68.6) years (P for age = 0.25 between sexes). Women had smaller absolute LV volume and mass than men across the spectrum of regurgitation volume (RVol) (P ≤ 0.01). In patients with ≥ moderate AR and with adjustment for body surface area, indexed LV end-diastolic volume and mass were not significantly different between sexes (all P > 0.5) but men had larger indexed LV end systolic volume and lower LV ejection fraction (P ≥ 0.01). Women were more likely to have NYHA class II or greater symptoms than men but underwent surgery at a similar rate. Prevalence and extent of LGE was not significantly different between sexes or across RVol. Increasing RVol was independently associated with increasing ECV in women, but not in men (adjusted P for interaction = 0.03). In conclusion, women had lower LV volumes and mass than men across AR severity  but their ECV increased with higher regurgitant volume, while ECV did not change in men. Indexing to body surface area did not fully correct for the cardiac remodeling differences between men and women. Women were more likely to have symptoms but underwent surgery at a similar rate to men. Further research is needed to determine if differences in ECV would translate to differences in the course of AR and outcomes.

Regional Replacement and Diffuse Interstitial Fibrosis in Aortic Regurgitation: Prognostic Implications From Cardiac Magnetic Resonance.

OBJECTIVES: This study used cardiac magnetic resonance (CMR) to assess left ventricular (LV) remodeling in chronic aortic regurgitation (AR) to identify both forms of myocardial fibrosis and examine its association with clinical outcomes. BACKGROUND: Chronic AR leads to LV remodeling, which is associated with 2 forms of myocardial fibrosis: regional replacement fibrosis that is directly imaged by late gadolinium enhancement (LGE) CMR; and diffuse interstitial fibrosis, which can be inferred by T1 mapping techniques. METHODS: Patients with chronic AR who were undergoing contrast CMR with T1 mapping for valve assessment from 2011 to 2018 were enrolled. Patients with a confounding etiology of myocardial fibrosis were excluded. In addition to quantification of AR severity and LV volumetrics, LGE and T1 mapping pre- and post-contrast were performed to measure extracellular volume (ECV) and indexed ECV (iECV). Patients were followed up longitudinally to assess for the composite event of death and the need for aortic valve replacement. RESULTS: A total of 177 patients with isolated chronic AR were included (66% males, median age 58 years [IQR: 47.0-68.0 years]) with a median follow up of 2.5 years (IQR: 1.07-3.56 years). The iECV significantly increased with AR severity (P < 0.001), whereas ECV and replacement fibrosis did not (P = NS). On multivariate analysis, iECV remained associated with the composite event (P = 0.01). On Kaplan-Meier analysis stratified by AR regurgitant fraction (RF) and iECV, patients with AR RF severity ≥30% and iECV ≥24 mL/m2 demonstrated the highest event rate. CONCLUSIONS: Among CMR biomarkers of fibrosis, iECV was more closely associated than replacement fibrosis or ECV with survival free of aortic valve replacement.

Natural History of Functional Tricuspid Regurgitation Quantified by Cardiovascular Magnetic Resonance.

BACKGROUND: Quantitation of tricuspid regurgitant (TR) severity can be challenging with conventional echocardiographic imaging and may be better evaluated using cardiovascular magnetic resonance (CMR). OBJECTIVES: In patients with functional TR, this study sought to examine the relationship between TR volume (TRVol) and TR fraction (TRF) with all-cause mortality. METHODS: We examined 547 patients with functional TR using CMR to quantify TRVol and TRF. The primary outcome was all-cause mortality. Thresholds for mild, moderate, and severe TR were derived based on natural history outcome data. RESULTS: During a median follow-up of 2.6 years (interquartile range: 1.7 to 3.3 years), there were 93 deaths, with an estimated 5-year survival of 79% (95% confidence interval [CI]: 73% to 83%). After adjustment of clinical and imaging variables, including RV function, both TRF (adjusted hazard ratio [AHR] per 10% increment: 1.26; 95% CI: 1.10 to 1.45; p = 0.001) and TRVol (AHR per 10-ml increment: 1.15; 95% CI: 1.04 to 1.26; p = 0.004) were associated with mortality. Patients in the highest-risk strata of TRVol ≥45 ml or TRF ≥50% had the worst prognosis (AHR: 2.26; 95% CI: 1.36 to 3.76; p = 0.002 for TRVol and AHR: 2.60; 95% CI: 1.45 to 4.66; p = 0.001 for TRF). CONCLUSIONS: This is the first study to use CMR to assess independent prognostic implications of functional TR. Both TRF and TRVol were associated with increased mortality after adjustment for clinical and imaging covariates, including right ventricular ejection fraction. A TRVol of ≥45 ml or TRF of ≥50% identified patients in the highest-risk strata for mortality. These CMR thresholds should be used for patient selection in future trials to determine if tricuspid valve intervention improves outcomes in this high-risk group.

Usefulness of Mitral Regurgitant Volume Quantified Using Magnetic Resonance Imaging to Predict Left Ventricular Remodeling After Mitral Valve "Correction".

MRI studies have shown a tight correlation between mitral regurgitant volume and left ventricular end-diastolic volume (LV EDV) in patients with primary chronic mitral regurgitation (MR). They have also shown a tight correlation between regurgitant volume and the decrease in LVEDV following mitral valve surgery. The purpose of this study is to validate an empiric calculation that can be used preoperatively to predict the amount of left ventricular remodeling following mitral valve correction. This is a prospective multicenter study of 63 (61 ± 13 years, male 65%) patients who underwent an MRI before and after mitral valve correction. Pre and postmitral valve correction ventricular volumes and ejection fractions were quantified. The predicted change in LV EDV was empirically calculated as mitral regurgitant volume/left ventricular ejection fraction. The observed change in LV EDV was compared to the predicted change in LV EDV. The LVEDV decreased in 61 (97%) patients following mitral valve correction (237 ± 66 ml vs 164 ± 46 ml, p <0.0001). Correlation between the observed and predicted change in LVEDV was good for the entire cohort (r = 0.77, p <0.0001) and excellent in patients with <10 ml of residual MR (r = 0.87, p <0.0001). This tight correlation was seen in both patients with primary (0.86, p <0.0001) and secondary MR (0.97, p <0.0001) and <10 ml of residual MR. Multivariate predictors of LV remodeling were MR volume, primary MR, and LVESV. In conclusion cardiac MRI volumetric measurements accurately predict LV remodeling following mitral valve correction. This finding supports the notion that MRI accurately quantifies the severity of chronic mitral regurgitation and a cardiac MRI should be strongly considered before mitral valve correction.

Between a Rock and a Hard Place: Idiopathic Cardiac Osseous Metaplasia Complicating Severe Mitral Regurgitation.

A 77-year-old woman presented for assessment of symptomatic mitral regurgitation. Multimodality cardiac imaging revealed severe mitral regurgitation secondary to mitral valve prolapse. Significant mitral annular calcification with dramatic intramyocardial calcification was also incidentally discovered. She was then given a diagnosis of idiopathic cardiac osseous metaplasia and was managed conservatively. (Level of Difficulty: Advanced.).