Assessing Regurgitation Severity, Adverse Remodeling, and Fibrosis with CMR in Aortic Regurgitation.

PURPOSE OF REVIEW: Cardiac magnetic resonance (CMR) is emerging as a valuable imaging modality for the assessment of aortic regurgitation (AR). In this review, we discuss the assessment of AR severity, left ventricular (LV) remodeling, and tissue characterization by CMR while highlighting the latest studies and addressing future research needs. RECENT FINDINGS: Recent studies have further established CMR-based thresholds of AR severity and LV remodeling that are associated with adverse clinical outcomes, and lower than current guideline criteria. In addition, tissue profiling with late gadolinium enhancement (LGE) and extracellular volume (ECV) quantification can reliably assess adverse myocardial tissue remodeling which is also associated with adverse outcomes. The strengths and reproducibility of CMR in evaluating ventricular volumes, tissue characteristics, and regurgitation severity position it as an excellent modality in evaluating and following AR patients. Advanced CMR techniques for the detection of tissue remodeling have shown significant potential and merit further investigation.

Aortic Regurgitation: Review of the Diagnostic Criteria and the Management Guidelines.

PURPOSE OF REVIEW: The evaluation of aortic regurgitation (AR) has advanced from physical examination and angiography towards evidence based non-invasive quantitative methods, primarily with echocardiography and more recently with cardiac magnetic resonance (CMR). This review highlights the guidelines and recent evidence in the diagnosis and management of AR; and outlines future areas of research. RECENT FINDINGS: Contemporary large cohorts of AR patients studied with echocardiography and CMR suggest that the left ventricular remodeling and systolic function triggers for intervention may be lower than previously recommended in the guidelines and emphasize the importance of LV volumes in risk stratification. Important gaps of knowledge in the quantitation of AR severity and patient risk stratification were fulfilled recently. Potential thresholds for intervention using ventricular volumes and CMR quantitative findings were recently described. The criteria for what constitutes hemodynamically significant AR and the optimal timing of intervention AR deserve further study.

Now You See Me Now You Don't: Subaortic Membrane Causing a Diagnostic Dilemma.

Subaortic stenosis secondary to subaortic membrane is the second most common form of left ventricular outflow tract obstruction. We present the case of a 70-year-old male patient who presented with a 6-week history of progressive signs of heart failure. Multimodality imaging was required to confirm the presence of a subaortic membrane. (Level of Difficulty: Beginner.).

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.

Acute and Long-Term Scar Characterization of Venous Ethanol Ablation in the Left Ventricular Summit.

BACKGROUND: Venous ethanol ablation (VEA) can be effective for ventricular arrhythmias from the left ventricular summit (LVS); however, there are concerns about excessive ablation by VEA. OBJECTIVES: The purpose of this study was to delineate and quantify the location, extent, and evolution of ablated tissue after VEA as an intramural ablation technique in the LVS. METHODS: VEA was performed in 59 patients with LVS ventricular arrhythmias. Targeted intramural veins were selected by electrograms from a 2F octapolar catheter or by guide-wire unipolar signals. Median ethanol delivered was 4 mL (IQR: 4-7 mL). Ablated areas were estimated intraprocedurally as increased echogenicity on intracardiac echocardiography (ICE) and incorporated into 3-dimensional maps. In 44 patients, late gadolinium enhancement cardiac magnetic resonance (CMR) imaged VEA scar and its evolution. RESULTS: ICE-demonstrated increased intramural echogenicity (median volume of 2 mL; IQR: 1.7-4.3) at the targeted region of the 3-dimensional maps. Post-ethanol CMR showed intramural scar of 2.5 mL (IQR: 2.1-3.5 mL). Early (within 48 hours after VEA) CMR showed microvascular obstruction (MVO) in 30 of 31 patients. Follow-up CMR after a median of 51 (IQR: 41-170) days showed evolution of MVO to scar. ICE echogenicity and CMR scar volumes correlated with each other and with ethanol volume. Ventricular function and interventricular septum remained intact. CONCLUSIONS: VEA leads to intramural ablation that can be tracked intraprocedurally by ICE and creates regions of MVO that are chronically replaced by myocardial scar. VEA scar volume does not compromise septal integrity or ventricular function.

Coronary microvascular health in symptomatic patients with prior COVID-19 infection: an updated analysis.

AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with endothelial dysfunction. We aimed to determine the effects of prior coronavirus disease 2019 (COVID-19) on the coronary microvasculature accounting for time from COVID-19, disease severity, SARS-CoV-2 variants, and in subgroups of patients with diabetes and those with no known coronary artery disease. METHODS AND RESULTS: Cases consisted of patients with previous COVID-19 who had clinically indicated positron emission tomography (PET) imaging and were matched 1:3 on clinical and cardiovascular risk factors to controls having no prior infection. Myocardial flow reserve (MFR) was calculated as the ratio of stress to rest myocardial blood flow (MBF) in mL/min/g of the left ventricle. Comparisons between cases and controls were made for the odds and prevalence of impaired MFR (MFR < 2). We included 271 cases matched to 815 controls (mean ± SD age 65 ± 12 years, 52% men). The median (inter-quartile range) number of days between COVID-19 infection and PET imaging was 174 (58-338) days. Patients with prior COVID-19 had a statistically significant higher odds of MFR <2 (adjusted odds ratio 3.1, 95% confidence interval 2.8-4.25 P < 0.001). Results were similar in clinically meaningful subgroups. The proportion of cases with MFR <2 peaked 6-9 months from imaging with a statistically non-significant downtrend afterwards and was comparable across SARS-CoV-2 variants but increased with increasing severity of infection. CONCLUSION: The prevalence of impaired MFR is similar by duration of time from infection up to 1 year and SARS-CoV-2 variants, but significantly differs by severity of infection.

Relation of Left Ventricular Diastolic Function to Global Fibrosis Burden: Implications for Heart Failure Risk Stratification.

BACKGROUND: Left ventricular (LV) diastolic function is primarily assessed by means of echocardiography, which has limited utility in detecting fibrosis. Cardiac magnetic resonance (CMR) readily detects and quantifies fibrosis. OBJECTIVES: In this study, the authors sought to determine the association of LV diastolic function by echocardiography with CMR-determined global fibrosis burden and the incremental value of fibrosis with diastolic function grade in prediction of total mortality and heart failure hospitalizations. METHODS: A total of 549 patients underwent comprehensive echocardiography and CMR within 30 days. Echocardiography was used to assess LV diastolic function, and CMR was used to determine LV volumes, mass, ejection fraction, replacement fibrosis, and percentage extracellular volume fraction (ECV). RESULTS: Normal diastolic function was present in 142 patients; the rest had diastolic dysfunction grades I to III, except for 18 (3.3%) with indeterminate results. The event rate was higher in patients with diastolic dysfunction compared with patients with normal diastolic function (33.4% vs 15.5; P < 0.001). The model including LV diastolic function grades II and III predicted composite outcome (C-statistic: 0.71; 95% CI: 0.67-0.76), which increased by adding global fibrosis burden (C-statistic: 0.74, 95% CI: 0.70-0.78; P = 0.02). For heart failure hospitalizations, the competing risk model with LV diastolic function grades II and III was good (C-statistic: 0.78; 95% CI: 0.74-0.83) and increased significantly with the addition of global fibrosis burden (C-statistic: 0.80; 95% CI: 0.76-0.85; P = 0.03). CONCLUSIONS: Higher grades of diastolic dysfunction are seen in patients with replacement fibrosis and increased ECV. Fibrosis burden as determined with the use of CMR provides incremental prognostic information to echocardiographic evaluation of LV diastolic function.

Influence of Cardiac Remodeling on Clinical Outcomes in Patients With Aortic Regurgitation.

BACKGROUND: Quantitative cardiac magnetic resonance (CMR) outcome studies in aortic regurgitation (AR) are few. It is unclear if volume measurements are beneficial over diameters. OBJECTIVES: This study sought to evaluate the association of CMR quantitative thresholds and outcomes in AR patients. METHODS: In a multicenter study, asymptomatic patients with moderate or severe AR on CMR with preserved left ventricular ejection fraction (LVEF) were evaluated. Primary outcome was development of symptoms or decrease in LVEF to <50%, development of guideline indications for surgery based on LV dimensions, or death under medical management. Secondary outcome was the same as the primary outcome, excluding surgery for remodeling indications. We excluded patients who underwent surgery within 30 days of CMR. Receiver-operating characteristic analyses for the association with outcomes were performed. RESULTS: We studied 458 patients (median age: 60 years; IQR: 46-70 years). During a median follow-up of 2.4 years (IQR: 0.9-5.3 years), 133 events occurred. Optimal thresholds were regurgitant volume of 47 mL and regurgitant fraction of 43%, indexed LV end-systolic (iLVES) volume of 43 mL/m2, indexed LV end-diastolic volume of 109 mL/m2, and iLVES diameter of 2 cm/m2. In multivariable regression analysis, iLVES volume of ≥43 mL/m2 (HR: 2.53; 95% CI: 1.75-3.66; P < 0.001) and indexed LV end-diastolic volume of ≥109 mL/m2 were independently associated with the outcomes and provided additional discrimination improvement over iLVES diameter, whereas iLVES diameter was independently associated with the primary outcome but not the secondary outcome. CONCLUSIONS: In asymptomatic AR patients with preserved LVEF, CMR findings can be used to guide management. CMR-based LVES volume assessment performed favorably compared to LV diameters.

Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.

BACKGROUND: The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. METHODS: We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. RESULTS: We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (P<0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; P<0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (P<0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (P value for trend <0.001), whereas they were unchanged across the spectrum of AR (P=0.24 and 0.42, respectively). CONCLUSIONS: Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

Medical Management of Aortic Disease: If They Don't Need Surgery, What Do They Need?

Management of aortic disease has evolved significantly over the past few decades. A preemptive diagnostic approach with a multidisciplinary team and shared decision-making has led to improved clinical outcomes. Surgery is the cornerstone of management for most aortic conditions; however, medical therapy is now an important adjunctive therapy in most if not all patients. Herein, we review the role and evidence behind medical management of patients with aortic disease.

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

Incremental prognostic value of positron emission tomography derived left ventricular mass.

BACKGROUND: Left ventricular hypertrophy has been shown to be an independent predictor of outcomes in patients with coronary artery disease (CAD). We aimed to determine the incremental prognostic value of positron emission tomography (PET) derived left ventricular mass (LVM) to clinical variables and myocardial flow reserve (MFR). METHODS: We included consecutive patients who had clinically indicated PET myocardial perfusion imaging for suspected or established CAD. Patients were followed from the date of PET imaging for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention/coronary artery bypass grafting 90 days after imaging). RESULTS: A total of 2357 patients underwent PET MPI during the study period (47% female, mean age 66 ± 12 years, 87% hypertensive, 47% diabetic, 79% dyslipidemia). After a mean follow-up of 11.6 ± 6.6 months, 141 patients (6.0%, 5.1 per 1000 person-year) experienced MACE (86 D/24 MI/39 PCI/9 CABG). In nested multivariable Cox models, LVM was not independently associated with outcomes (HR 1.00, P = .157) and had no incremental prognostic value (C index: 0.75, P = .571) over MFR and clinical variables. CONCLUSION: Our analysis shows that LVM provides no independent and incremental prognostic value over MFR and clinical variables.

Substrate Ablation by Multivein, Multiballoon Coronary Venous Ethanol for Refractory Ventricular Tachycardia in Structural Heart Disease.

BACKGROUND: Ablation of ventricular tachycardia (VT) in the setting of structural heart disease often requires extensive substrate elimination that is not always achievable by endocardial radiofrequency ablation. Epicardial ablation is not always feasible. Case reports suggest that venous ethanol ablation (VEA) through a multiballoon, multivein approach can lead to effective substrate ablation, but large data sets are lacking. METHODS: VEA was performed in 44 consecutive patients with ablation-refractory VT (ischemic, n=21; sarcoid, n=3; Chagas, n=2; idiopathic, n=18). Targeted veins were selected by mapping coronary veins on the epicardial aspect of endocardial scar (identified by bipolar voltage <1.5 mV), using venography and signal recording with a 2F octapolar catheter or by guidewire unipolar signals. Epicardial mapping was performed in 15 patients. Vein segments in the epicardial aspect of VT substrates were treated with double-balloon VEA by blocking flow with 1 balloon while injecting ethanol through the lumen of the second balloon, forcing (and restricting) ethanol between balloons. Multiple balloon deployments and multiple veins were used as needed. In 22 patients, late gadolinium enhancement cardiac magnetic resonance imaged the VEA scar and its evolution. RESULTS: Median ethanol delivered was 8.75 (interquartile range, 4.5-13) mL. Injected veins included interventricular vein (6), diagonal (5), septal (12), lateral (16), posterolateral (7), and middle cardiac vein (8), covering the entire range of left ventricular locations. Multiple veins were targeted in 14 patients. Ablated areas were visualized intraprocedurally as increased echogenicity on intracardiac echocardiography and incorporated into 3-dimensional maps. After VEA, vein and epicardial ablation maps showed elimination of abnormal electrograms of the VT substrate. Intracardiac echocardiography demonstrated increased intramural echogenicity at the targeted region of the 3-dimensional maps. At 1 year of follow-up, median of 314 (interquartile range, 198-453) days of follow-up, VT recurrence occurred in 7 patients, for a success of 84.1%. CONCLUSIONS: Multiballoon, multivein intramural ablation by VEA can provide effective substrate ablation in patients with ablation-refractory VT in the setting of structural heart disease over a broad range of left ventricular locations.

Cardiovascular magnetic resonance for suspected cardiac amyloidosis: where are we now?

Cardiac amyloidosis (CA) is an underdiagnosed form of restrictive cardiomyopathy leading to a rapid progression into heart failure. Evaluation of CA requires a multimodality approach making use of echocardiography, cardiac magnetic imaging (CMR), and nuclear imaging. With superior tissue characterization, high-resolution imaging, and precise cardiac assessment, CMR has emerged as a versatile tool in the workup of cardiac amyloidosis with a wide array of parameters both visual and quantitative. This includes late gadolinium enhancement patterns, T1/T2 mapping, and extracellular volume (ECV) measurement providing robust diagnostic accuracies, patient stratification, and prognostication. Recent advancements have introduced new measures able to identify early disease, track disease progression, and response to therapy positioning CMR as an instrumental imaging modality in the era of rising interest in CA screening and emerging effective therapies.

Left ventricular mass on positron emission tomography: Validation against cardiovascular magnetic resonance.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important clinical finding that is independently associated with mortality and cardiovascular events. We aimed to assess the interstudy variability of LV mass quantitation between PET and CMR. METHODS: Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. LV mass on PET was compared against LV mass on CMR using several statistical measures of agreement. RESULTS: A total of 105 patients (mean age 60 ± 14 years, 67.6% male) were included. The median (interquartile range, IQR) duration between CMR and PET was 47 (11-154) days. The median (IQR) LV mass values were 168.0 g (126.0-202.0) on CMR and 174.0 g (150.0-212.0) with PET (absolute mean difference 29.42 ± 25.3). There was a good correlation (Spearman ρ = 0.81, P < 0.001; Intraclass Correlation Coefficient 0.78, 95% CI 0.70-0.85, P < 0.001) with moderate limits of agreement (95% limits of agreement - 63.78 to 83.7.) Results were consistent, albeit with moderate correlation, in subgroups of patients with LVH, in patients with myocardial infarction, in patients with LV ejection fraction < 50%, and those with limited image quality. LV mass on PET tended to be underestimated at high values compared to CMR. CONCLUSION: We demonstrate good correlation and reproducibility of LV mass quantitation by PET against the reference standard of CMR across a wide range of normal and diseased hearts with a tendency of PET to underestimate mass at higher mass values.

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.