Chronic Severe Aortic Regurgitation Research Articles

Aortic Regurgitation: From Valvular to Myocardial Dysfunction.

Chronic aortic regurgitation (AR) leads to volume overload in the left ventricle (LV), which is well tolerated for years. In this condition, the LV usually dilates with minimal reduction in the ejection fraction (EF), even in the absence of symptoms. Echocardiography is the primary imaging test used to quantify AR. However, no single assessment of Doppler measures is accurate and precise in individual patients; therefore, the integration of multiple parameters is necessary. Recent guidelines recommend surgical treatment for severe AR in patients who are symptomatic or have an LVEF < 55% and an end-systolic diameter > 50 mm. Nevertheless, advances in imaging technology have improved the quantification of AR and the assessment of LV subclinical dysfunction. It is widely recognized that patients who undergo aortic valve replacement/repair (AVR) due to symptoms or a low LVEF experience worse outcomes than those undergoing AVR for non-Class I indications. In fact, subclinical irreversible myocardial damage may occur in clinically well-compensated and closely monitored patients while awaiting formal surgical indications. This condition could be prevented by the use of multimodal imaging parameters, in particular longitudinal LV strain and magnetic resonance imaging. In addition, better cut-off values for mortality predictors should be established. This review aims to identify simple models that integrate several echocardiographic and cardiac magnetic resonance-derived parameters to predict the optimal timing of surgical treatment in asymptomatic patients with chronic severe AR.

Rationale and design of the ELEANOR trial early aortic valve surgery versus watchful waiting strategy in severe asymptomatic aortic regurgitation, ACRONYM: ELEANOR

BackgroundThe optimal treatment of patients with severe symptomatic aortic regurgitation (AR) is state-of-the-art surgery. Asymptomatic patients with advanced left ventricular (LV) dilatation and/or impaired ejection fraction should undergo surgical treatment, but there is no guidelines consensus on cut-off values for this recommendation. Multimodality imaging has brought new tools for the accurate selection of asymptomatic patients at risk of early clinical deterioration, however, prospective and randomized data are pending. Cardiac magnetic resonance (CMR)-derived AR quantification along with LV remodeling assessment appears to be the most accurate tool for a selection of such patients at risk. Trial designThe objective of our prospective and multicenter study is to determine whether patients at risk of early clinical deterioration as per CMR assessment will benefit from early surgical treatment. The study is designed as a superiority trial to demonstrate that early surgical treatment is safe and more effective than the standard treatment. A total of 217 asymptomatic patients with severe AR, but without current guidelines-based surgical indication, will be enrolled across all centers. We expect 24 % of patients identified as high clinical risk and therefore eligible for 1:1 randomization to early surgical treatment within 3 months or a watchful waiting strategy. Follow-up will be annual. We expect a complete restoration of LV size and function along with improved quality of life and physical performance in a short-term follow-up of 12 months. The primary endpoint will be a composite safety and efficacy with all criteria mandatory: 15 % or larger reduction of baseline CMR-derived LV end-diastolic volume index, LV ejection fraction >50 %, and no major adverse cardiovascular events. The annual follow-up will continue for a minimum of 4 years until the required number of endpoints is achieved to show a statistically significant difference in cardiovascular morbidity and mortality in early surgically treated patients. ConclusionThe ELEANOR trial is the first multicenter randomized controlled study to compare early surgical treatment with a watchful waiting strategy in asymptomatic patients with chronic severe AR at high risk of early clinical deterioration as per CMR assessment but without guidelines-based indications for surgical treatment.

The Association Between Ascending Aortic and Left Ventricular Dimensions in Patients After Aortic Valve Replacement.

Aortic valve replacement (AVR) is often recommended for patients with severe aortic stenosis or chronic aortic regurgitation. These conditions result in remodeling of the left ventricle, including increased interstitial fibrosis that may persist even after AVR. These structural changes impact left ventricular (LV) mechanics, causing compromised LV diameter to occur earlier than reduced LV ejection fraction (LVEF). The aim of this study was to examine the effect of left ventricular end-diastolic diameter (LVEDD) and its role in aortic expansion one year after AVR. Sixty-three patients who underwent AVR were evaluated. All patients underwent standard transthoracic echocardiography, which included measurements of the ascending aorta, aortic root, LVEF, and LVEDD before the surgery and one year postoperatively. Correlations between these variables were calculated. All patients underwent AVR with either a mechanical or biological prosthetic aortic valve. Following AVR, there was a significant decrease in the dimensions of the ascending aorta and aortic root (both P=0.001). However, no significant changes were observed in LVEDD and LVEF. Correlations were found between the preoperative ascending aortic size and the preoperative and one-year postoperative LVEDD (r=0.419, P=0.001 and r=0.320, P=0.314, respectively). Additionally, there was a correlation between the postoperative ascending aortic size and the preoperative and one-year postoperative LVEDD (r=0.320, P=0.003 and r=0.136, P=0.335, respectively). The study findings demonstrate a significant correlation between the size of the aortic root and ascending aorta, before and after AVR. Additionally, a notable correlation was observed between postoperative LVEDD and the size of the aortic root.

Abstract 18806: How Well Does Left Atrial Remodeling Predict Adverse Outcomes in Patients With Chronic Severe Aortic Regurgitation?

Introduction: Aortic regurgitation (AR) leads to left ventricular (LV) remodeling by increasing LV load. We recently showed that LV dimensions, widely adopted marker of severe AR, are not reliable predictors of adverse CV outcomes in older patients and female sex. Here we sought to study the effects of chronic severe AR on left atrial (LA) size and function as a prognostic adjunct to LV dimensions. Methods: Adult patients with ≥3+ AR on routine surveillance with serial echocardiograms between 1/2010 and 12/2016 were included in this study. We assessed longitudinal trends of LA volume indexed to body surface area (LAVI) and LA reservoir strain (LAr) stratified by age and sex. Clinical endpoints included the occurrence of heart failure hospitalization, urgent aortic valve surgery, or all-cause mortality and were used to assess the prognostic value of our studied parameters. Results: A total of 525 patients with 1,687 serial echocardiograms conducted over a median (IQR) follow-up duration of 2.0 (1.0-3.6) years were included. As shown in figure 1, we observed a substantial increase in LAVI (1.0 [95% CI: 0.76-1.2] mL/m2 per year of follow-up) and a decrease in LAr (-1.3% [95% CI: -1.6 to -0.92%]) over the study period. There was no significant interaction related to sex or age (p ≥0.17). 210 adverse events were recorded and were significantly predicted by both LA parameters. Optimal discriminatory threshold for LAVI was determined to be 37 mL/m2 and LAr at 35% and were both found to be consistent across categories of sex and age. Conclusions: This study indicates that LA remodeling, unlike LV remodeling, shows a similar rate of progression across different categories of sex and age among patients with chronic severe AR. Furthermore, LA parameters provide an added prognostic value over LV parameters and may therefore be better suited to inform the timing of AR intervention.

Echocardiographic Monoplane Left Ventricular Volumes to Assess Remodeling in Chronic Severe Aortic Regurgitation

Echocardiographic Monoplane Left Ventricular Volumes to Assess Remodeling in Chronic Severe Aortic Regurgitation

Value of Speckle Tracking Echocardiography Combined with Stress Echocardiography in Predicting Surgical Outcome of Severe Aortic Regurgitation with Markedly Reduced Left Ventricular Function.

Predicting outcomes of surgical aortic valve replacement (AVR) in patients with chronic severe aortic regurgitation (AR) and markedly reduced left ventricular (LV) function remains a challenge. This study aimed to explore the preoperative echocardiographic index that could predict the recovery of LV systolic function after surgery in patients with chronic severe AR and reduced left ventricular ejection fraction (LVEF). The study group consisted of 50 patients diagnosed with chronic severe AR ( 6 months) and significantly reduced LVEF (18~35%, average 26.2 5.3%). Low-dose dobutamine stress echocardiography (DSE) was performed before surgery. Only patients with an absolute increase in LVEF 8% during DSE were referred for surgical AVR. During following up (over six months to one year after surgery), the patients were divided into two groups by postoperative LVEF ( or 40%). DSE- and speckle tracking echocardiography (STE)-derived LV functional parameters were compared between groups to identify predictors of post-operative improvement in LVEF. A total of 38 patients underwent AVR. One patient died before discharge. Post-surgical LV size and LVEF improved markedly after surgery in all patients (n = 37). Pre-surgical LV end-systolic diameter, baseline global longitudinal strain (GLS) and peak GLS were better in the group with LVEF 40% (n = 18; p 0.05, t test). Baseline GLS and peak GLS correlated moderately with post-surgery LVEF (R = -0.581, p 0.001; R = -0.596, p 0.001; respectively). Logistic regression analysis demonstrated baseline GLS and peak GLS were the independent predictors of post-surgery improvement of LVEF. Peak GLS had the highest prediction value (area under the curve = 0.895, sensitivity and specificity: 89.5% and 77.8%, respectively), with a cutoff value of -9.4%. This study shows that STE combined with DSE can provide sensitive quantitative indices for predicting improvement of LV systolic function after AVR in patients with chronic severe AR and significantly decreased LVEF.

Can Measuring the 'Dual Anchors of Aorta' Enhance the Success Rate of TAVR?-A Single-Center Experience.

Chronic severe aortic regurgitation (AR) has a poor long-term prognosis, especially among old-age patients. Considering their advancing age, the surgical approach of aortic valve replacement may not always be the best alternative modality of treatment in such patients. Therefore, this study's primary goal was to provide an initial summary of the medium- and short-term clinical effectiveness of transcatheter aortic valve replacement (TAVR) guided by accurate multi-detector computed tomography (MDCT) measurements in patients with severe and chronic AR, especially in elderly patients. The study enrolled retrospectively and prospectively patients diagnosed with severe AR who eventually underwent TAVR procedure from January 2019 to September 2022 at Fuwai cardiovascular Hospital, Beijing. Baseline information, MDCT measurements, anatomical classification, perioperative, and 1-year follow-up outcomes were collected and analyzed. Based on a novel anatomical categorization and dual anchoring theory, patients were divided into four categories according to the level of anchoring area. Type 1, 2, and 3 patients (with at least two anchoring regions) will receive TAVR with a transcatheter heart valve (THV), but Type 4 patients (with zero or one anchoring location) will be deemed unsuitable for TAVR and will instead receive medical care (retrospectively enrolled patients who already underwent TAVR are an exception). The mean age of the 37 patients with severe chronic AR was 73.1 ± 8.7 years, and 23 patients (62.2%) were male. The American Association of Thoracic Surgeons' score was 8.6 ± 2.1%. The MDCT anatomical classification included 17 cases of type 1 (45.9%), 3 cases of type 2 (8.1%), 13 cases of type 3 (35.1%), and 4 cases of Type 4 (10.8%). The VitaFlow valve (MicroPort, Shanghai, China) was implanted in 19 patients (51.3%), while the Venus A valve (Venus MedTech, Hangzhou, China) was implanted in 18 patients (48.6%). Immediate TAVR procedural and device success rates were 86.5% and 67.6%, respectively, while eight cases (21.6%) required THV-in-THV implantation, and nine cases (24.3%) required permanent pacemaker implantation. Univariate regression analysis revealed that the major factors affecting TAVR device failure were sinotubular junction diameter, THV type, and MDCT anatomical classification (p < 0.05). Compared with the baseline, the left ventricular ejection fraction gradually increased, while the left ventricular end-diastolic diameter remained small, and the N-terminal-pro hormone B-type natriuretic peptide level significantly decreased within one year. According to the results of our study, TAVR with a self-expanding THV is safe and feasible for patients with chronic severe AR, particularly for those who meet the criteria for the appropriate MDCT anatomical classification with intact dual aortic anchors, and it has a significant clinical effect for at least a year.

Clinical Profile and Outcomes of Patients With Pure Aortic Regurgitation Who Underwent Surgical Aortic Valve Replacement

Surgical aortic valve replacement (SAVR) remains the standard of care for patients with chronic severe aortic regurgitation (AR). The introduction of a dedicated transcatheter heart valve for AR has fueled interest in using transcatheter aortic valve replacement to treat patients with isolated AR. We aimed to characterize the profile and outcomes of patients with symptomatic severe AR who underwent isolated SAVR. We conducted a retrospective, observational study of patients who underwent isolated SAVR for symptomatic severe AR at our institution. The primary outcome was in-hospital all-cause mortality. Patients were followed up with 30-day clinical and echocardiographic assessment. A total of 979 patients who underwent SAVR for severe AR between January 2015 and June 2021 were screened for eligibility, of whom 112 patients (11.4%) underwent isolated SAVR for symptomatic severe AR and were included in this analysis. Approximately 25% of patients were deemed to be at intermediate or high risk (n=26 of 112). The primary outcome occurred in 2.7% of patients (n=3 of 112). In-hospital stroke occurred in 2.7% of patients (n=3 of 112), and new-onset atrial fibrillation occurred in 32.1% (n=36 of 112). At 30-day follow-up, all-cause mortality occurred in 3.6% of patients (n=4 of 112), and 0.8% (1 of 112) had >mild AR. In conclusion, in a tertiary referral center, the number of patients who underwent isolated SAVR for pure AR represented a small fraction of the overall SAVR patients. The vast majority were low risk and younger when compared with patients with severe aortic stenosis. SAVR yielded excellent short-term mortality and echocardiographic improvements.

Marfan Syndrome: an uncommon cause of heart failure with late presentation and management challenges in a Nigerian (case report)

Marfan syndrome is an autosomal dominant disorder with life-threatening cardiovascular complications. It is an uncommon cause of heart failure in our environment. We hereby highlight a case of Marfan syndrome presenting with heart failure, challenges of late presentation and management of Marfan syndrome in our environment. A 56-year-old man with a 4-year history of hypertension presented with 3 months history of exertional dyspnoea and orthopnoea. He had associated musculoskeletal abnormalities and reduced vision since childhood. No family history of Marfan syndrome. Examination revealed features of severe chronic aortic regurgitation, bilateral supero-nasally dislocated lenses, kyphoscoliosis, positive thumb and wrist signs. The resting electrocardiogram showed left ventricular hypertrophy with strain pattern. Ocular ultrasound confirmed bilateral ectopia lentis. Echocardiography revealed aortic root aneurysm, severe aortic regurgitation, left ventricular dilatation and reduced ejection fraction. The computed tomography (CT) aortogram revealed aortic root aneurysm, tortuous abdominal aorta, thoracolumbar scoliosis and pectus excavatum. Using revised Ghent's criteria, a diagnosis of Marfan syndrome in heart failure was made. Management was multidisciplinary with plans for aortic root replacement, family and genetic screening. He commenced beta blocker and angiotensin receptor blocker with symptomatic relief. He reportedly died at home after sudden onset tiredness. His management was hampered by late clinical presentation, difficulty assessing surgery and out of pocket health funding.

Optimal Management of Chronic Severe Aortic Regurgitation - How to Determine Cutoff Values for Surgical Intervention?

Aortic regurgitation (AR) is a common valvular heart disease, but the optimal timing of surgical intervention remains controversial. In the natural history of chronic severe AR, sudden death is rare, and the annual mortality rate is comparatively low. Considering the hemodynamic features of combined volume and pressure overload and long-term compensation in patients with chronic AR, symptoms related to AR do not frequently occur. Therefore, the progression of left ventricular (LV) dysfunction is a key factor in determining the timing of surgical intervention in patients with severe chronic AR. In addition to symptoms, an ejection fraction <50% and an LV endsystolic diameter (LVESD) >45 mm are appropriate cutoff values for surgical intervention in Japanese patients, whereas LV end-diastolic diameter is not a good indicator. An LVESD index of 25 mm/m2is controversial, because adjusting for body size may cause overcorrection in Japanese patients who have a small body size compared with Westerners. Accumulation of data from the Japanese population is indispensable for establishing guidelines on optimal management of patients with chronic AR.

Predictors of heart failure and all-cause mortality in asymptomatic patients with moderate and severe aortic regurgitation.

Class I indications for aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR) include AR attributable symptoms or left ventricular (LV) ejection fraction <50%. As noninvasive estimates of elevated LV filling pressures (LVFP's) have been noted to predict heart failure (HF) readmission and all-cause mortality (ACM) in HF patients, we hypothesize that elevated LVFP's may also be independent predictors of HF and ACM in chronic AR. We developed a single center patient database of moderate or greater AR diagnoses between 2003 and 2008 and followed each patient through January 2013. We included patients with >30 days follow-up with interpretable Doppler-echocardiograms. We recorded demographic variables, EuroScore II, incident HF and ACM, and Doppler-echo variables of LV size, systolic and diastolic function. Patients with severe AR (105 patients) and moderate AR (201 patients) had similar EuroScore II values and similar incident HF and ACM. For the 180 patients who developed HF, effective arterial elastance (aHR=1.70 (1.01-2.83), p=.041), LV end-diastolic dimension (aHR=1.83, (1.11-3.03), p=.0176), E/e' (aHR=3.04, (1.83-5.05), p<.0001), eccentric hypertrophy (EH) (aHR=2.39, (1.62-5.12), p=.0004), and tricuspid regurgitation (TR) velocity (aHR=5.75, (3.70-10.36), p<.0001) were independent predictors. For the 118 patients with ACM, EH (aHR=1.73, (1.02-3.28), p=.0414), systolic blood pressure (aHR=.58, (.33-.95), p=.0301), left atrial volume index (aHR=1.82, (1.06-3.06), p=.0293), E/e' (aHR=1.83, (1.07-3.08), p=.0280), and TR velocity (aHR=4.14, (2.22-6.49), p<.0001) were independent predictors. Elevated TR velocity and EH were strong markers of HF and ACM in patients with asymptomatic severe AR and in moderate AR.

Association of Left Ventricular Remodeling Assessment by Cardiac Magnetic Resonance With Outcomes in Patients With Chronic Aortic Regurgitation

Chronic aortic regurgitation (AR) causes left ventricular (LV) volume overload, which results in progressive LV remodeling negatively affecting outcomes. Whether cardiac magnetic resonance (CMR) volumetric quantification can provide incremental risk stratification over standard clinical and echocardiographic evaluation in patients with chronic moderate or severe AR is unknown. To compare LV remodeling measurements by CMR and echocardiography between patients with and without heart failure symptoms and to verify the association of remodeling measurements of patients with chronic moderate or severe AR but no or minimal symptoms with clinical outcomes receiving medical management. This multicenter retrospective cohort study included consecutive patients with at least moderate chronic native AR evaluated by 2-dimensional transthoracic echocardiography and CMR examination within 90 days from each other between January 2012 and February 2020 at Allina Health System. Data were analyzed from June 2021 to January 2022. Clinical evaluation and risk stratification by CMR. The end point was a composite of death, heart failure hospitalization, or progression of New York Heart Association functional class while receiving medical management, censoring patients at the time of aortic valve replacement (when performed) or at the end of follow-up. Of the 178 included patients, 119 (66.9%) were male, 158 (88.8%) presented with no or minimal symptoms (New York Heart Association class I or II), and the median (IQR) age was 58 (44-69) years. Compared with patients with no or minimal symptoms, symptomatic patients had greater LV end-systolic volume index (LVESVi) by CMR (median [IQR], 66 [46-85] mL/m2 vs 42 [30-58] mL/m2; P < .001), while there were no significant differences by echocardiography (LVESVi: median [IQR], 38 [30-58] mL/m2 vs 27 [20-42] mL/m2; P = .07; LV end-systolic diameter index: median [IQR], 21 [17-25] mm/m2 vs 18 [15-22] mm/m2; P = .17). During the median (IQR) follow-up of 3.3 (1.6-5.8) years, 50 patients with no or minimal symptoms receiving medical management developed the composite end point, which, in multivariate analysis adjusted for age and EuroSCORE II, was independently associated with LVESVi of 45 mL/m2 or greater and aortic regurgitant fraction of 32% or greater, the latter adding incremental prognostic value to CMR volumetric assessment. In patients with chronic moderate or severe AR, patients presenting with heart failure symptoms have greater LVESVi by CMR than those with no or minimal symptoms. In patients with no or minimal symptoms, CMR quantification of LVESVi and AR severity may identify those at risk of death or incident heart failure and therefore should be considered in the clinical evaluation and decision-making of these patients.

Why are left ventricular linear internal diameters still so important for clinical decision-making to undergo surgery in asymptomatic patients with chronic severe aortic or primary mitral regurgitation?

Division of Cardiology, A.R.C., Policlinico San Giorgio, Via Gemelli 10, Pordenone, Italy Correspondence to Gian Luigi Nicolosi, MD, FESC, FACC, Division of Cardiology, A.R.C., Policlinico San Giorgio, Via Gemelli 10, Pordenone, Italy e-mail: [email protected] Received 24 September, 2021 Revised 21 November, 2021 Accepted 26 December, 2021

Utility of dobutamine stress echocardiography in aortic valve regurgitation and reduced left ventricular function.

Predictors for post-operative reverse remodeling in patients with severe aortic regurgitation (AR) and reduced left ventricular ejection fraction (LVEF) are unknown. We performed low-dose dobutamine stress echocardiography (DSE) in patients with severe AR and reduced LVEF to evaluate the relationship between contractile reserve (CR) and reverse remodeling after surgery. In 31 patients with chronic severe AR and reduced LVEF (LVEF<50%), we performed pre-operative DSE, assessed CR, and examined whether changes in preoperative DSE were associated with improvement of post-operative LVEF after aortic valve surgery. The pre-operative echocardiographic findings were as follows: left ventricular (LV) end-diastolic dimension: 67 ± 10mm, LV end-systolic dimension: 52 ± 13mm, and LVEF: 42 ± 8%. All patients underwent aortic valve surgery. Patients with pre-operative LVEF of ≥45% exhibited a significant increase in LVEF; however, patients with pre-operative LVEF of <45% showed no significant change. When we examined the results of DSE performed in patients with pre-operative LVEF of <45%, ΔLVEF of ≥6% (with CR) during DSE was related to an improvement in post-operative LVEF; ΔLVEF of ≥6% during DSE predicted an improvement in post-operative LVEF, with sensitivity 100%; specificity 78%; and area under curve (AUC) .92. DSE might be a helpful tool for predicting post-operative reverse remodeling in patients with severe AR and moderately reduced LVEF.

Non-invasive left ventricular myocardial work in patients with chronic aortic regurgitation and preserved left ventricular ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular global longitudinal strain (LV GLS) has been proposed as sensitive marker of myocardial damage in patients with chronic severe aortic regurgitation (AR) and preserved left ventricular ejection fraction (LVEF). However, LV GLS does not take into account the afterload. Non-invasive LV myocardial work is a novel parameter of LV myocardial performance, which integrates measurements of myocardial deformation and non-invasive blood pressure (afterload). Purpose The aims of this study were: 1) to assess non-invasive LV myocardial work in patients with chronic AR and preserved LVEF and its correlation with other echocardiographic parameters, 2) to evaluate changes of LV myocardial work after aortic valve replacement or repair (AVR) and 3) to assess the relationship between LV myocardial work and post-operative LV reverse remodeling. Methods This retrospective study included fifty patients (53 ± 16 years; 68% men) with moderate or severe chronic AR and preserved LVEF, who underwent AVR. Non-invasive LV myocardial work indices were measured at baseline and post-operatively (between 2 and 12 months after surgery) and compared with previously reported normal reference ranges. Results Based on normal reference values, patients with chronic AR and preserved LVEF had preserved or increased values of LV global work index (LV GWI) (84% and 16%, respectively) and LV global constructive work (LV GCW) (78% and 22%, respectively) (Figure 1). In addition, LV global work efficiency (LV GWE) was preserved in all patients, despite 16 (32%) subjects had impaired values of LV GLS (&amp;lt;16.7.% in men and &amp;lt;17.8% in women). LV GWI and GCW showed a positive correlation with markers of AR severity and parameters of LV systolic function. AVR results in a significant reduction of myocardial work indices (p &amp;lt; 0.0001), with the exception of LV global wasted work, that did not change (p = 0.29). According to normal reference ranges, 15 (30%) patients had impaired values of LV GWI and LV GCW post-operatively, while LV GLS was impaired in 37 (74%) patients. The post-operative impairment of LV GWI demonstrated a stronger association with reduced LV reverse remodeling, as compared to the impairment of LV GLS (Figure 2). Conclusions Compared to afterload-dependent echocardiographic parameters, non-invasive LV myocardial work indices allow a better understanding of myocardial performance and energetics in the setting of chronic AR with preserved LVEF and could improve risk stratification. Abstract Figure. Abstract Figure.

Magnetic resonance derived regurgitant fraction, 3D vena contracta area, and B-natriuretic peptide: the most accurate prognostic markers in patients with chronic asymptomatic aortic regurgitation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic 17-28265A. Background The optimal timing of surgical treatment is challenging in asymptomatic patients with severe aortic regurgitation (AR). A significant number of patients undergoing aortic valve surgery as per current guidelines have irreversible left ventricular (LV) myocardial damage with a negative impact on their long-term postoperative outcome. Purpose We aimed to determine the value of magnetic resonance-, advanced echocardiography–derived indices and serum B-natriuretic peptide level (BNP) to identify patients with chronic asymptomatic AR who are at risk of early disease progression. Methods We prospectively enrolled a group of asymptomatic patients with pure chronic severe AR, without an indication for surgical treatment as per the current guidelines, in a multicenter study. Baseline examination consisted of serum BNP level analysis, comprehensive echocardiography including 3D vena contracta area (VCA) and 2D global longitudinal strain (GLS), and a comprehensive MRI including regurgitant fraction (RF) measurement; all imaging data were analyzed in Corelab. Patient follow-up was every 6 months. The primary endpoint was a new guideline-directed indication for surgical treatment. Results In total, 129 patients were enrolled between 2015 and 2019, the endpoint occurred in 43 patients during a median follow-up of 1375 (IQR 1041-1783) days. Baseline clinical data did not differ between patients with the endpoint (surgical group) and stable patients (medical group). Baseline BNP levels were significantly higher in the surgical group (55 vs. 21 ng/L, P = 0.008). MRI-derived LV ejection fraction was not different (61 vs 61 %, P = 0.815) at baseline while both CMR-derived end-systolic and end-diastolic LV volumes were significantly higher in the surgical group (all P &amp;lt; 0.01). Both baseline 3D VCA and 2D GLS were different between the surgical and medical groups (33 vs. 25 mm2, P = 0.006 and 18 vs 19 %, P = 0.07). Magnetic resonance derived RF was significantly higher in the surgical group (46 vs 32 %) with P &amp;lt; 0.01. A combined model including independent markers such as BNP (cut-off &amp;gt; 31 ng/L), MRI RF (cut-off value &amp;gt; 34 %), 3D VCA (cut-off value 36 mm2) or 2D GLS (cut-off value &amp;lt; 17 %) showed the highest predictive accuracy (P = 0.002) to predict the primary endpoint. (Figure 1). Conclusion A combination of baseline parameters of AR severity (3D VCA, MRI-derived RF) and myocardial impairment (2D GLS, serum BNP level) present an accurate tool for the identification of patients with chronic asymptomatic AR who are at risk of early disease progression. Abstract Figure 1

Prognostic impact of the E/e′ ratio in patients with chronic severe aortic regurgitation undergoing aortic valve replacement

ObjectivesThe study objective was to evaluate the clinical implication of left ventricular diastolic dysfunction in patients with chronic severe aortic regurgitation undergoing aortic valve replacement. MethodsWe reviewed the medical records of 323 patients (age, 56.3 ± 14.1 years; 111 female) who underwent aortic valve replacement for chronic severe aortic regurgitation between 2005 and 2019. Left ventricular diastolic dysfunction was assessed by the ratio of peak left ventricular inflow velocity over mitral annular velocity (E/e′). The study end point was the composite of death and heart failure requiring hospital admission. ResultsThe E/e′ ratio was significantly correlated with age, left atrial dimension, left ventricular end-diastolic volume, mitral regurgitation grade, and tricuspid regurgitation grade (all P < .001). During follow-up (1748.3 patient-years), death and heart failure occurred in 36 patients (2.06/patient-year) and 9 patients (0.53/patient-year), respectively. In multivariable analysis, E/e′ ratio (per 5 increment, hazard ratio, 1.32; 95% confidence interval, 1.02-1.71; P = .03), age (hazard ratio, 1.06; 95% confidence interval, 1.03-1.10; P < .001), and left ventricular ejection fraction (hazard ratio, 0.94; 95% confidence interval, 0.90-0.98; P = .002) were independent predictors of death and heart failure. The 5-year heart failure–free survival was 94.9% ± 1.7% in patients with E/e′ less than 15% and 84.2% ± 4.2% in patients with E/e′ 15 or greater (P < .001). ConclusionsThe E/e′ ratio was significantly associated with adverse outcomes in patients with chronic severe aortic regurgitation undergoing aortic valve replacement and may be useful as a prognostic marker in such patients.

Noninvasive Left Ventricular Myocardial Work in Patients with Chronic Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction

Left ventricular (LV) global longitudinal strain (GLS) has been proposed as a sensitive marker of myocardial damage in patients with chronic severe aortic regurgitation (AR) and preserved LV ejection fraction (LVEF). However, LV GLS does not take into account the afterload. Noninvasive LV myocardial work is a novel parameter of LV myocardial performance, which integrates measurements of myocardial deformation and noninvasive blood pressure (afterload). The aims of this study were (1) to assess noninvasive LV myocardial work in patients with chronic AR and preserved LVEF and its correlation with other echocardiographic parameters, (2) to evaluate changes of LV myocardial work after aortic valve replacement or repair (AVR), and (3) to assess the relationship between LV myocardial work and postoperative LV reverse remodeling. Fifty-seven patients (53±16years; 67% men) with moderate or severe chronic AR and preserved LVEF treated by AVR were included. Noninvasive LV myocardial work indices were measured at baseline and postoperatively (between 2 and 12months after surgery) and compared with previously reported normal reference ranges. Based on normal reference values, patients with chronic AR and preserved LVEF had preserved or increased values of LV global work index (GWI; 82% and 18%, respectively) and LV global constructive work (GCW; 74% and 25%, respectively) and preserved LV global work efficiency (GWE). Left ventricular GWI and GCW showed a positive correlation with markers of AR severity and parameters of LV systolic function. Left ventricular GWI, GCW, and GWE decreased after AVR (P<.001), without changes in LV global wasted work (P=.28). The postoperative impairment of LV GWI, observed in 28% of patients, was closely associated with reduced LV reverse remodeling. Noninvasive myocardial work may allow better understanding of myocardial function and energetics than afterload-dependent echocardiographic parameters in chronic AR with preserved LVEF.

Assessment of Asymptomatic Severe Aortic Regurgitation by Doppler-Derived Echo Indices: Comparison with Magnetic Resonance Quantification.

Reliable quantification of aortic regurgitation (AR) severity is essential for clinical management. We aimed to compare quantitative and indirect echo-Doppler indices to quantitative cardiac magnetic resonance (CMR) parameters in asymptomatic chronic severe AR. Methods and Results: We evaluated 104 consecutive patients using echocardiography and CMR. A comprehensive 2D, 3D, and Doppler echocardiography was performed. The CMR was used to quantify regurgitation fraction (RF) and volume (RV) using the phase-contrast velocity mapping technique. Concordant grading of AR severity with both techniques was observed in 77 (74%) patients. Correlation between RV and RF as assessed by echocardiography and CMR was relatively good (rs = 0.50 for RV, rs = 0.40 for RF, p < 0.0001). The best correlation between indirect echo-Doppler and CMR parameters was found for diastolic flow reversal (DFR) velocity in descending aorta (rs = 0.62 for RV, rs = 0.50 for RF, p < 0.0001) and 3D vena contracta area (VCA) (rs = 0.48 for RV, rs = 0.38 for RF, p < 0.0001). Using receiver operating characteristic analysis, the largest area under curve (AUC) to predict severe AR by CMR RV was observed for DFR velocity (AUC = 0.79). DFR velocity of 19.5 cm/s provided 78% sensitivity and 80% specificity. The AUC for 3D VCA to predict severe AR by CMR RV was 0.73, with optimal cut-off of 26 mm2 (sensitivity 80% and specificity 66%). Conclusions: Out of the indirect echo-Doppler indices of AR severity, DFR velocity in descending aorta and 3D vena contracta area showed the best correlation with CMR-derived RV and RF in patients with chronic severe AR.

Layer-specific longitudinal strain detects transmural dysfunction in chronic severe aortic regurgitation before and after aortic valve surgery.

To assess if layer-specific longitudinal strain (LS) provides incremental diagnostic and prognostic value compared to global longitudinal strain (GLS) in patients with chronic severe aortic regurgitation (AR) scheduled for aortic valvesurgery. Forty-one patients were examined with speckle tracking echocardiography before surgeryalong with 15 healthy age-matched controls. Paired strain analyses before and after surgery were available in 31 patients. Layer-specific LS analysis enabled assessment of epicardial GLS (GLSepi), endocardial GLS (GLSendo), and conventional GLS. Strain parameters were indexed to end-diastolic volume (EDV; GLS/EDV) to account for increased preload. The prognostic value of layer-specific LS was evaluated using the primary outcome of persistent LV dilatation (LVEDV ≥ 175mL) three months after surgery. Absolute (GLS, GLSepi, GLSendo) and EDV-indexed layer-specific LS (GLS/EDV, GLSepi/EDV, GLSendo/EDV) were impaired in severe AR compared to controls at baseline (GLS:17.0 ± 3.2 vs. 20.6 ± 2.0; GLSepi:14.6 ± 2.8 vs. 18.1 ± 1.9; GLSendo:20.2 ± 3.7 vs. 23.8 ± 2.2%; GLS/EDV:0.09 ± 0.05 vs. 0.21 ± 0.05; GLSepi/EDV:0.08 ± 0.04 vs. 0.18 ± 0.04; GLSendo/EDV:0.11 ± 0.06 vs. 0.24 ± 0.05%/mL; all p < 0.001). In severe AR, GLS, GLSepi and GLSendo decreased after surgery whereas GLS/EDV, GLSepi/EDV and GLSendo/EDV increased (all p < 0.001). Impaired absolute and EDV-indexed layer-specific LS were all associated with the primary outcome (all p ≤ 0.01). Area under the curve analysis revealed similar prognostic value of GLSepi, GLSendo and GLS (GLS:0.86; GLSepi:0.87; GLSendo:0.86; p = n.s.). EDV-indexed LS did not improve the predictive value significantly (GLS/EDV:0.93; GLSepi/EDV: 0.93; GLSendo/EDV:0.92; p = n.s.). Layer-specific LS detects transmural dysfunction in chronic severe AR and predicts persistent LV dilation after surgery. Layer-specific LS or EDV-indexed LS does not provide incremental prognostic value compared to conventional GLS.