Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

BACKGROUND AND AIMS: Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. METHODS: A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. RESULTS: In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. CONCLUSIONS: Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

Retrograde Aortic Valve Migration During Transcatheter Aortic Valve Replacement for Aortic Regurgitation: A Case Report Highlighting the Importance of Prompt Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) Initiation.

Surgical aortic valve replacement (SAVR) is the recommended curative treatment for pure native aortic regurgitation (AR). However, some patients are not suitable for SAVR due to comorbidities or frailty. Transcatheter aortic valve replacement (TAVR) has been reported to offer a better prognosis than medical therapy in AR patients; thus, the use of TAVR for AR may increase in the future. However, the reduced calcification and annulus ring stiffness associated with TAVR may increase the risk of valve migration. Accumulating data on rescue measures in the event of valve migration is necessary. An 87-year-old female with a history of hypertension and persistent atrial fibrillation presented to our emergency department with dyspnea. The patient was diagnosed with congestive heart failure class IV, according to the New York Heart Association classification, necessitating urgent admission to our cardiac department. Due to the patient's high surgical risk (Society of Thoracic Surgeons (STS) score 9.17%, Euro2 score 9.55%, frailty 6), the heart team performed TAVR with a right femoral arterial approach. The patient was sedated, and pacing was initiated at 180 bpm. We placed an Edwards SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA) #23 (-1 mL volume, with attached balloon). During the post-deployment procedure, the aortic valve migrated retrogradely into the left ventricle (LV). Despite the occurrence of severe aortic valve regurgitation, the patient's vital signs remained stable. Five minutes after the migration of the aortic valve, venoarterial extracorporeal membrane oxygenation (VA-ECMO) was initiated. A second TAVR valve implantation was then performed. However, after the second valve implantation and the removal of the pre-shaped guidewire (Safari2 pre-shaped guidewire extra small, Boston Scientific, Marlborough, MA, USA), the migrated valve became stuck in the left ventricular outflow tract (LVOT) in a reverse position, resulting in severely limited left ventricular ejection. We increased the support provided by VA-ECMO, and surgical conversion to SAVR was performed without experiencing circulatory collapse. Surgical aortic valve replacement was initiated successfully, and withdrawal of the cardiopulmonary bypass (CPB) was performed without complications. The patient was extubated on the first postoperative day (POD), discharged from the ICU on POD 3, and transferred for rehabilitation on POD 27. In summary, the prompt introduction of VA-ECMO was important for avoiding complications and saving the patient's life following the retrograde migration of the TAVR valve.

A clinical case of Takayasu disease: emphasis on cardiac manifestations.

Takayasu arteriitis (TA) is a rare systemic vasculitis, affecting large vessels, cardiac valves and myocardium. Cardiac involvement is a major cause of morbidity and mortality in such patients. This publication presents a clinical case of a patient with severe aortic regurgitation combined with restrictive cardiomyopathy. It is emphasized that surgical treatment is associated with potential difficulties in patients with TA due to its inflammatory nature, disease activity and multiorgan involvement.

Aortic Regurgitation in Bicuspid Aortic Valve: The Role of Multimodality Imaging.

The evaluation of aortic regurgitation (AR) in bicuspid valve (BAV) is still a challenge because of the eccentricity of the jet, which may under/overestimate the regurgitation. The commonly used echocardiography parameters (such as vena contracta, pressure half-time, etc.) may not be useful in this kind of patient. A multimodality approach combining echocardiography, cardiac MRI, cardiac CT, and advanced technologies applied to non-invasive cardiac imaging (e.g., 4D flow and strain imaging) may be useful to better quantify regurgitation and to select patients suitable for valve replacement. This review provides an overview of the most recent insights about cardiovascular imaging tools and their utility in BAV evaluation, focusing on chronic regurgitation. We describe the role of multimodality imaging in both diagnosis and risk assessment of this disease, pointing out the advantages and disadvantages of the imaging techniques, aiming to provide a guide to clinicians and cardiovascular imaging specialists in choosing the best imaging tools to use.

Considerations in the Diagnosis and Management of Pulmonary Hypertension Associated With Left Heart Disease.

Pulmonary hypertension associated with left heart disease (PH-LHD) remains the most common cause of pulmonary hypertension globally. Etiologies include heart failure with reduced and preserved ejection fraction and left-sided valvular heart diseases. Despite the increasing prevalence of PH-LHD, there remains a paucity of knowledge about the hemodynamic definition, diagnosis, treatment modalities, and prognosis among clinicians. Moreover, clinical trials have produced mixed results on the usefulness of pulmonary vasodilator therapies for PH-LHD. In this expert review, we have outlined the critical role of meticulous hemodynamic evaluation and provocative testing for cases of diagnostic uncertainty. Therapeutic strategies-pharmacologic, device-based, and surgical therapies used for managing PH-LHD-are also outlined. PH-LHD in advanced heart failure, and the role of mechanical circulatory support in PH-LHD is briefly explored. An in-depth understanding of PH-LHD by all clinicians is needed for improved recognition and outcomes among patients with PH-LHD.

Performance of Purpose-Built vs Off-Label Transcatheter Devices for Aortic Regurgitation: The PURPOSE Study.

BACKGROUND: Severe pure aortic regurgitation (AR) carries a high mortality and morbidity risk, and it is often undertreated because of the inherent surgical risk. Transcatheter heart valves (THVs) have been used off-label in this setting with overall suboptimal results. The dedicated "purpose-built" Jena Valve Trilogy (JVT, JenaValve Technology) showed an encouraging performance, although it has never been compared to other THVs. OBJECTIVES: The aim of our study was to assess the performance of the latest iteration of THVs used off-label in comparison to the purpose-built JVT in inoperable patients with severe AR. METHODS: We performed a multicenter, retrospective registry with 18 participating centers worldwide collecting data on inoperable patients with severe AR of the native valve. A bicuspid aortic valve was the main exclusion criterion. The primary endpoints were technical and device success, 1-year all-cause mortality, and the composite of 1-year mortality and the heart failure rehospitalization rate. RESULTS: Overall, 256 patients were enrolled. THVs used off-label were used in 168 cases (66%), whereas JVT was used in 88 (34%). JVT had higher technical (81% vs 98%; P < 0.001) and device success rates (73% vs 95%; P < 0.001), primarily driven by significantly lower incidences of THV embolization (15% vs 1.1%; P < 0.001), the need for a second valve (11% vs 1.1%; P = 0.004), and moderate residual AR (10% vs 1.1%; P = 0.007). The permanent pacemaker implantation rate was comparable and elevated for both groups (22% vs 24%; P = 0.70). Finally, no significant difference was observed at the 1-year follow-up in terms of mortality (HR: 0.99; P = 0.980) and the composite endpoint (HR: 1.5; P = 0.355). CONCLUSIONS: The JVT platform has a better acute performance than other THVs when used off-label for inoperable patients with severe AR. A longer follow-up is conceivably needed to detect a possible impact on prognosis.

Left ventricular reverse remodeling after aortic valve replacement or repair in bicuspid aortic valve with moderate or greater aortic regurgitation.

Objective: Bicuspid aortic valve (AV) patients with aortic regurgitation (AR) differ from tricuspid AV patients given younger age, greater left ventricle (LV) compliance, and more prevalent aortic stenosis (AS). Bicuspid AV-specific data to guide timing of AV replacement or repair are lacking. Methods: Adults with bicuspid AV and moderate or greater AR who underwent aortic valve replacement or repair at our center were studied. The presurgical echocardiogram, and echocardiograms within 3 years postoperatively were evaluated for LV geometry/function, and AV function. Semiquantitative AS/AR assessment was performed in all patients with adequate imaging. Results: One hundred thirty-five patients (85% men, aged 44.5 ± 15.9 years) were studied (63% pure AR, 37% mixed AS/AR). Following aortic valve replacement or repair, change in LV end-diastolic dimension and change in LV end-diastolic volume were associated with preoperative LV end-diastolic dimension (ß = 0.62 Δcm/cm; 95% CI, 0.43-0.73 Δcm/cm; P < .001), and LV end-diastolic volume (ß = 0.6 ΔmL/mL; 95% CI, 0.4-0.7 ΔmL/mL; P < .001), respectively, each independent of AR/AS severity (P = not significant). Baseline LV size predicted postoperative normalization (LV end-diastolic dimension: odds ratio, 3.75/cm; 95% CI, 1.61-8.75/cm, LV end-diastolic volume: odds ratio, 1.01/mL; 95% CI, 1.004-1.019/mL, both P values < .01) whereas AR/AS severity did not (P = not significant). Indexed LV end diastolic volume outperformed LV end-diastolic dimension in predicting postoperative LV normalization (area under the curve = 0.74 vs 0.61) with optimal diagnostic cutoffs of 99 mL/m2 and 6.1 cm, respectively. Postoperative indexed LV end diastolic volume dilatation was associated with increased risk of death, transplant/ventricular assist device, ventricular arrhythmia, and reoperation (hazard ratio, 6.1; 95% CI, 1.7-21.5; P < .01). Conclusions: Remodeling extent following surgery in patients with bicuspid AV and AR relates to preoperative LV size independent of valve disease phenotype or severity. Many patients with LV end-diastolic dimension below current surgical thresholds did not normalize LV size. LV volumetric assessment offered superior diagnostic performance for predicting residual LV dilatation, and postoperative indexed LV end diastolic volume dilatation was associated with adverse prognosis.

Rapid deployment aortic valve implantation in complex patients with infective endocarditis or aortic valve insufficiency.

BACKGROUND: New prosthetic valves and surgical approaches that shorten operation time and improve the outcome of patients with aortic valve (AV) infective endocarditis (IE) and AV insufficiency (AVI) are crucial. The aim of this study was to evaluate the outcome of patients with AV IE or AVI treated with the EDWARDS INTUITY Rapid-Deployment AV prosthesis for this off-label indication. METHODS: This single-centre retrospective study analyzed data from patients who underwent AV replacement with the EDWARDS INTUITY Rapid-Deployment AV prosthesis for AV IE or regurgitation. (n = 8 for IE and n = 6 for AVI). RESULTS: Heart-lung machine times were significantly shorter in the AVI group (111.3 ± 20.7 min) compared to the IE group (171.9 ± 52.4 min) (p = 0.02). Aortic cross-clamp followed a similar trend (73.7 ± 9.9 min for AVI vs. 113.4 ± 35.6 min for IE) (p = 0.02). The length of ICU stay was also shorter in the AVI group (3.8 ± 2.6 days) compared to the IE group (16.9 ± 8.9 days) (p = 0.005). Postoperative echocardiography revealed no paravalvular leakage or significant valvular dysfunction in any patient. One patient died postoperatively from aspiration pneumonia. CONCLUSION: The INTUITY valve demonstrates as a safe option for complex AV IE and AVI surgery. Further prospective studies with larger patient cohorts are necessary to confirm these findings and explore the long-term benefits of this approach.

Iatrogenic non-coronary leaflet perforation as a complication after robotic mitral valve repair.

Iatrogenic aortic regurgitation secondary to leaflet injury is a rare complication of mitral valve surgery. For the first time, we report a patient who had progressive aortic regurgitation due to non-coronary leaflet perforation after robotic mitral valve repair and required aortic valve repair 18 months after this initial surgery. As in our case, aortic regurgitation after mitral valve surgery may remain undiagnosed on intraoperative transesophageal echocardiography or undetected until the patient's discharge due to gradual enlargement of very small perforations over the postoperative course.

Prevalence and prognosis of aortic valve diseases in patients hospitalized with heart failure with mildly reduced ejection fraction.

AIMS: Data regarding the characterization and outcomes of patients with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) is scarce. This study investigates the characteristics and prognostic impact of native aortic valve diseases (AVD) in patients with HFmrEF. METHODS AND RESULTS: Consecutive patients hospitalized with HFmrEF (i.e. left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. The prognostic impact of native aortic valve stenosis (AS), aortic valve regurgitation (AR) and mixed AVD (MAVD) was investigated for the primary endpoint of long-term all-cause mortality during a median follow-up of 30 months. Kaplan-Meier, univariable and multivariable Cox proportional analyses were applied. From a total of 2106 patients hospitalized with HFmrEF, the prevalence of AS and AR was 16.5% and 31.2%, respectively (MAVD 7.8%). The presence of moderate/severe AS was associated with a higher risk of long-term all-cause mortality (44.8% vs. 28.7%; p = 0.001) and HF-related rehospitalization (18.6% vs. 12.0%; p = 0.001), even after multivariable adjustment (mortality: hazard ratio [HR] 1.320; 95% confidence interval [CI] 1.035-1.684; p = 0.025; HF-related rehospitalization: HR 1.570; 95% CI 1.101-2.241; p = 0.013). Interestingly, even mild AS was associated with increased risk of long-term all-cause mortality compared to patients without AS (HR 1.477; 95% CI 1.101-1.982; p = 0.009). In contrast, the presence of AR was not associated with long-term outcomes after multivariable adjustment. CONCLUSIONS: The presence of AS, but not AR, was independently associated with increased risk of all-cause mortality and HF-related rehospitalization in patients with HFmrEF. Even milder stages of AS were associated with impaired prognosis.

Prevalence and Prognostic Implications of Pulmonary Hypertension in Patients With Severe Aortic Regurgitation.

Background: Pulmonary hypertension (PH) has been shown to be associated with worse outcomes in patients with aortic regurgitation (AR) in small older studies. Objectives: The authors sought to evaluate the prevalence of PH in patients with severe AR, its impact on mortality and symptoms, and regression after aortic valve replacement (AVR). Methods: A total of 821 consecutive patients with chronic ≥ moderate-severe AR on echocardiography from 2004 to 2019 were retrospectively analyzed. PH was defined as right ventricular systolic pressure (RVSP) >40 mm Hg on transthoracic echocardiogram (mild-moderate PH: RVSP 40-59 mm Hg, severe PH: RVSP > 60 mm Hg). Clinical and echocardiographic data were extracted from the electronic medical record and echocardiographic reports. The diastolic function and filling pressures were manually assessed and checked, and the left ventricular (LV) volumes were traced by a level 3-trained echocardiographer. The primary objectives were prevalence of PH in patients with ≥ moderate-severe AR, its risk associations and impact on all-cause mortality as the primary outcome. Secondary outcomes were impact of PH on symptoms and change in RVSP at discharge post-AVR. Logistic and Cox proportional hazards regression were used to analyze these outcomes. Results: The mean age was 61.2 ± 17 years, and 162 (20%) were women. Mild-moderate PH was present in 91 (11%) patients and severe PH in 27 (3%). Larger LV size, elevated LV filling pressures, and ≥ moderate tricuspid regurgitation were associated with PH. During follow-up of 7.3 (6.3-7.9) years, 188 patients died. Compared to those without PH, risk of mortality was higher in mild-moderate PH (adjusted HR: 1.59 (95% CI: 1.07-2.36) (P = 0.021)) and severe PH (adjusted HR: 2.90 (95% CI: 1.63-5.15) (P < 0.001)). Symptoms were also more prevalent in those with PH (P = 0.004). Of 396 patients who underwent AVR during the study period, 57 had PH. AVR similarly improved survival in patients without and with PH (P for interaction = 0.23), and there was regression in RVSP (≥8 mm Hg drop) at discharge post-AVR in 35/57 (61%) patients with PH. Conclusions: PH was present in 14% of patients with AR and was associated with higher mortality and symptoms. The survival benefit of AVR was similar in patients without and with PH.

Aortic valve laceration following rotational atherectomy: a case report.

Background: Iatrogenic aortic valve injury during cardiovascular catheterization interventions is extremely rare. Severe aortic regurgitation that ensues can be catastrophic and the management is typically with surgical valve replacement or repair. Percutaneous management of native pure aortic regurgitation is difficult due to anatomical challenges and the limitations of current transcatheter heart valve technology to anchor in the absence of leaflet or annular calcification. Case Summary: An 82-year-old female underwent rotational atherectomy (RA) for a severely calcified stenosis of the left anterior descending artery. The patient was discharged well following placement of two drug eluting stents. She represented to hospital 7 days later with acute pulmonary oedema. Bedside transthoracic echocardiography demonstrated new, severe AR with preserved left ventricular size and function. Review of the prior percutaneous coronary intervention revealed significant trauma to the aortic valve during RA, with contrast seen refluxing into the LV during diastole, evolving throughout the procedure. Given the patient was not an operative candidate, an oversized transcatheter aortic valve was successfully implanted. In the post-operative setting, the patient suffered a stroke. Extensive hypoattenuated leaflet thickening (HALT) and thrombus was seen on dedicated 4D CT imaging. She made full neurological recovery and valve function returned to normal following a period of anticoagulation. Conclusion: Although iatrogenic aortic valve laceration is rare, this case highlights several important learning points including the importance of good guide catheter support during RA; the feasibility of Transcatheter Aortic Valve Replacement for pure native AR; and the detection and management of HALT.

Remedy of a deep downward shift of a valve using double snares and "sandwich" technique.

A 76-year-old man diagnosed with severe pure native aortic regurgitation (PNAR) underwent transcatheter aortic valve replacement (TAVR) due to high surgical risk. The computed tomography angiography showed no calcification and no stenosis of the aortic valve, with an annulus perimeter of 81.1 mm and sinus diameters of 35 to 38 mm.

Transcatheter closure of ruptured sinus of Valsalva type IV with misleading severe aortic regurgitation.

We present an unusual case of ruptured sinus of Valsalva (RSOV) in the right atrium, progressive exertional dyspnea, occasional epigastric heaviness, and palpitations. The examination revealed high-pitch continuous murmur. On transthoracic echocardiography, there was a ~5-6 mm size RSOV of non-coronary sinus into right atrium, continuous turbulent flow, and unusual presentation of severe central aortic regurgitation jet with holodiastolic flow reversal seen in the descending aorta. The sinus of Valsalva aneurysm is a rare pathology, which is generally asymptomatic. In this case it manifested through a rupture into the right atrium and needed to be closed to relieve the symptoms. Transcathter closure of RSOV was done by using Amplatzer duct occluding device, there was no residual shunt, and aortic regurgitation completely disappeared. Learning objective: This is a unique case in which ruptured sinus of Valsalva flow and holodiastolic flow reversal were confused with severe aortic regurgitation. Careful and detailed transthoracic echocardiography played a key role in correct diagnosis and proper management.

Asymptomatic, Incidental Quadricuspid Aortic Valve: A Case Report and Discussion of Management.

With its exceeding rarity, there is little research on the quadricuspid aortic valve (QAV) inherently to drive guideline-based management. This leaves physicians without evidence-based guidance on the management of such patients should they come across this finding on imaging or should they care for a symptomatic patient. This article describes the case of an incidentally identified QAV in a patient undergoing treatment for tuberculosis, which seemingly had bicuspid-appearing valve hemodynamics. Additionally, current literature is reviewed to describe classification, presentation, complications, and intervention, with additional exploration and commentary on the lack of guideline-based care.

Comparisons of noncoronary sinus pivot implantation (NCPI) and conventional method for transcatheter aortic valve replacement with self-expanding valve in pure aortic regurgitation (PAR).

BACKGROUND: As compared to treatment of aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) using the commercially available valves to treat pure aortic regurgitation (PAR) has a lower device success rate and higher complication rates. AIMS: The study compared the acute results between TAVR using a novel noncoronary sinus pivot implantation (NCPI) method and that using the conventional method, aiming to explore a more optimized and effective operation method for TAVR in PAR. METHODS: PAR patients who underwent TAVR with self-expanding valves in our center from September 2021 to September 2023 were enrolled were divided into the NCPI (group A, N = 16) and conventional method (group B, N = 39) groups. We analyzed the pre-operative evaluation parameters and procedural and postoperative data of the two subgroups. RESULTS: The total patients' mean age was 71.2 ± 8.7 years and most were male (61.8%), with a mean Society of Thoracic Surgeons score of 3.4 ± 1.9%. The device success rate of groups A and B was 100% and 71.8%, respectively. In group B, 48.7% had major adverse cardiac events (MACE); 46.2% patients had permanent pacemaker implantation or valve in valve implantation. None had MACE in group A. The noncoronary sinus implantation depth in NCPI was -1.1 + 1.0 and 4.2 + 3.7 mm in groups A and B (p < 0.001), respectively. CONCLUSIONS: TAVR with a self-expanding valve using the NCPI method had a higher procedure success rate and dramatically low complications than that using the conventional method in PAR patients.

Commissural alignment and the ACURATE neo2 transcatheter aortic valve: Impact on valve performance.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly being used to treat severe aortic stenosis in younger patients. Accordingly, lifetime management regarding future reintervention and coronary access is a concern. AIMS: To assess the impact of commissural alignment on ACURATE neo2 transcatheter aortic valve (TAV) performance. METHODS: COMALIGN-neo2 was an observational, retrospective study enrolling consecutive TAVR patients treated with the ACURATE neo2 (October 2021 to October 2022). The degree of commissural (mis)-alignment (CMA) with the native aortic valve commissures was determined and transvalvular gradient, effective orifice area, patient-prosthesis mismatch (PPM), and aortic regurgitation (AR) were assessed. RESULTS: Among 825 patients, the mean age was 80.7 years and 42% were female. Commissural alignment was achieved in 60% of cases; mild (26%), moderate (9%), and severe misalignment (5%) were found less often. Severe PPM occurred more frequently in patients with severe CMA (14.7%) compared to aligned valves (p = 0.034). By multivariate analysis, severe CMA (odds ratio [OR]: 3.12, 95% confidence interval [CI] [1.09-8.90]; p = 0.033) and lack of postdilatation (OR: 3.85, [1.33-11.1]; p = 0.012) were associated with severe PPM. Higher rates of ≥mild AR (51.4%) were found in TAVs implanted with severe CMA compared to aligned (34.3%), mildly (38.1%) or moderately (36.0%) misaligned TAVs (p = 0.030). Multivariate analysis identified severe CMA (OR: 2.05, [1.05-4.02]; p = 0.037) to be an independent predictor of ≥mild AR. CONCLUSIONS: COMALIGN-neo2 is the largest study to date assessing the impact of commissural alignment on acute TAV performance. Severe CMA with the ACURATE neo2 platform was associated with worse valve hemodynamics and increased risk for mild AR.