Anterior Leaflet Research Articles

Abstract 4137145: Aortic Stenosis in Pregnancy: A Multidisciplinary Team Approach

Introduction: The hemodynamic adaptations that occur during pregnancy can have significant effects on patients with aortic stenosis (AS). These changes can lead to structural changes identified on echocardiogram even during uncomplicated pregnancies. While some cases can be managed with medical therapy and activity modification, others may require valve intervention in the gestational period. Case: A 29-year-old female with history of congenital bicuspid aortic valve, G1P0 presented at 42+2 weeks of pregnancy and was admitted to cardiac intensive care unit for continuous hemodynamic monitoring via use of arterial line. Her prior aortic valve disease was treated by valve repair with valvotomy, removal of tissue from pseudo raphe, removal of calcified scar tissue from both commissures, and a mitral valve repair for closure of an iatrogenic tear in her anterior leaflet. She followed closely with maternal fetal medicine and cardiology but became symptomatic at week 28 with lightheadedness, shortness of breath and decreased exercise tolerance (NYHA Class II). By week 33 she noticed lower extremity edema. Despite recommendations for planned delivery, she opted to wait until full term for delivery. Surveillance echoes revealed rising velocities yet stable valve area by planimetry. She ultimately underwent an uncomplicated Cesarean delivery of baby boy in week 42. At 6 months post partum she had successful transcatheter aortic valve replacement. Discussion: As the severity of valvular disease worsens there is a higher risk of complications during pregnancy. In our case, aortic valve velocities were elevated due to the expected hemodynamic changes of pregnancy. Thus, echocardiography monitoring should be used to assess the left ventricle’s ability to tolerate and compensate for these changes, while intervening based on symptoms and NYHA classification. We highlight the importance of multidisciplinary collaboration for safe and successful delivery in patients with AS.

Abstract 4119116: Percutaneous Aspiration of Mitral Valve Endocarditis using the AngioVac Device

Case Description: A 68-year-old man with end-stage renal disease on dialysis, peripheral vascular disease with metatarsal amputations, atrial fibrillation and type 1 diabetes was admitted for foot osteomyelitis secondary to MSSA bacteremia. Transesophageal echocardiogram revealed mobile mitral valve vegetations up to 1.8cm on the atrial aspect of the posterior mitral valve leaflet which prolapsed through the mitral valve during diastole. Ejection fraction was 60% and there was trivial-mild mitral regurgitation without valvular destruction or peri-annular extension into the mitral annulus. MRI brain showed bilateral cerebral and cerebellar hemispheric infarcts, consistent with acute embolic stroke. He was at high risk for both recurrent embolism and operative mortality (STS risk score 51%) due to his comorbidities and risk of hemorrhagic conversion of stroke. After shared decision making, percutaneous aspiration of the mitral vegetation was performed with AngioVac (Fig). Cerebral embolism protection devices were deployed prior to AngioVac evacuation of the mass. There was no residual mitral regurgitation and only a small vegetation strand remained (Fig). Surgical pathology confirmed MSSA endocarditis. Blood cultures remained negative, and the patient did not suffer from recurrent embolic events. The patient underwent revision metatarsal amputation and was discharged with a 6-week course of IV cefazolin. Discussion: Infective endocarditis with high embolic risk is life-threatening and challenging to treat in patients with high surgical risk. We illustrate a case of percutaneous vegetation aspiration using the AngioVac device in our patient who suffered from embolic strokes due to MSSA mitral valve endocarditis. Meta-analyses have shown clinically successful debulking in 90% of cases, with 82% of patients able to clear bacteremia with AngioVac. Although most commonly used in right-sided lesions, percutaneous debulking of left-sided endocarditis with AngioVac and cerebral protection can be considered as a treatment strategy in select patients with prohibitive surgical risk.

Contemporary Outcomes of Degenerative Mitral Valve Surgery in a Regional Tertiary Care Center

Objective: As percutaneous mitral valve techniques become more prevalent, it is important to evaluate the contemporary outcomes of surgical mitral valve interventions. This study assessed the current results and procedural trends of mitral valve surgery for degenerative mitral regurgitation (DMR) at a regional tertiary care center. Methods: Data were analyzed from 693 consecutive DMR patients who underwent isolated mitral valve operations, with or without tricuspid valve repair and atrial fibrillation ablation between 2017 and 2024. The outcomes were defined according to MVARC criteria. The study endpoints included successful mitral valve repair, in-hospital results, and operative and long-term mortality. Logistic regression was applied to assess the impact of valve lesions and patient risk factors on the probability of valve repair. Survival was analyzed using Kaplan–Meier methodology. The follow up was 100% complete. Results: Mitral valve repair was performed in 90.9% of cases, with only 0.9% requiring the conversion to replacement due to unsuccessful repair. Posterior leaflet lesions had the highest success rate (93.4%), while anterior leaflet lesions had a lower rate (86.2%), with anterior pathology being a negative predictor of repair (OR 2.57, p = 0.02). The type of lesion (prolapse vs. flail), the commissural involvement, and the increased risk for SAM had no statistically significant impact on valve repair outcome. Less invasive transaxillary access was used in 63.2% of patients, and its adoption increased significantly (from 50.9% to 67.4% p = 0.03) over time, resulting in more frequent fast-track extubation and home discharges. The rate of in-hospital mortality was 0.6%, while the rate of 5-year survival was 95.5%. Conclusions: Contemporary surgical techniques for DMR lead to high repair rates and excellent recovery outcomes. Despite the rise in transcatheter options, our findings confirm that surgery remains the gold standard for most DMR patients.

Tricuspid Anterior and Posterior Patch (TRAPP) Repair of Functional Tricuspid Regurgitation

Objective: Annuloplasty is the most common strategy for repair of functional tricuspid regurgitation (FTR) but is not effective in patients with massive/torrential FTR or leaflet tethering. To address the deficits of tricuspid annuloplasty, TRicuspid Anterior and Posterior Patch (TRAPP) repair was developed, which is a pericardial patch augmentation of the anterior and posterior leaflets. Methods: To test this repair, a previously validated ex vivo model in an explanted porcine heart was used, wherein annular and leaflet geometry were evaluated using a 3-dimensional structured light scanner at 4 time points: (1) baseline, (2) induction of FTR, (3) annuloplasty repair, and (4) patch repair. Results: Compared with the regurgitant tricuspid valve, annuloplasty reduced annular circumference (13.7 to 9.5 cm) and area (13.7 vs 6.1 cm2), whereas TRAPP repair did not alter annular dimensions (circumference: 13.7 vs 13.5 cm; area: 13.7 vs 13.6 cm2). Annuloplasty increased leaflet tenting angles (anterior: 53.5° vs 41.0°; posterior: 59.7° vs 48.2°; septal: 38.9° vs 31.4°) whereas TRAPP repair relieved anterior and posterior leaflet tenting (anterior: 28.9° vs 41.0°; posterior: 34.9° vs 48.2°; septal: 33.2° vs 31.4°) and restored geometry comparable to the native tricuspid valve. Central coaptation lengths were greater with TRAPP repair than with annuloplasty for all 3 leaflets (anterior: 12.7 vs 9.5 mm; posterior: 12.2 vs 8.2 mm; septal: 7.4 vs 4.6 mm). Conclusions: Compared with annuloplasty, TRAPP repair yielded greater coaptation length, resolved leaflet tethering, and resulted in a larger annular area that may facilitate durable repair of advanced FTR, which previously would have required replacement.

Impella 5.5 as a bridge-to-surgery in acute ischemic mitral regurgitation post-percutaneous coronary intervention: a case report

BackgroundAcute ischemic mitral regurgitation (AIMR) is a significant complication of acute coronary syndrome that leads to severe and immediate hemodynamic deterioration and cardiogenic shock. Intra-aortic balloon pumps (IABP) are commonly used to support patients with AIMR as a bridge to surgery, though they may be insufficient in some cases.Case PresentationA 74-year-old male presented with two days of indigestion and evident hypoxia, and an electrocardiogram revealed inferior and lateral ST-elevation myocardial infarction. Angiography demonstrated severe two-vessel coronary disease with a 100% thrombotic occlusion of the second obtuse marginal artery (OM2, culprit lesion) and an 80% stenosis of the proximal left anterior descending artery (LAD). Despite stenting of OM2, the patient remained hypoxic and hypotensive, necessitating escalated support via an IABP. A follow-up echocardiogram revealed severe mitral regurgitation presumed to be AIMR secondary to a ruptured posteromedial papillary muscle with a flail anterior leaflet (A2). Despite aggressive supportive measures with the IABP, the patient’s hemodynamics continued to show cardiogenic shock and clinical status did not improve. However, the patient was required to abstain from surgery for a P2Y12 inhibitor therapy wash out period. Consequently, the IABP was upgraded to Impella 5.5 as bridge-to-surgery support on day 1 post-admission. Subsequently, the patient’s hemodynamics improved, and he underwent a combined mitral valve replacement and coronary artery bypass grafting surgery on day 7 post-admission without incident. The Impella was successfully explanted on day 25 post-admission. Delay in explant was due to hypotension and respiratory status despite normalizing hemodynamics and echocardiogram revealing recovered left ventricular ejection fraction. The patient developed bacterial pneumonia and acute respiratory distress syndrome and expired on day 27 post-admission.ConclusionAlthough IABP is standard for supporting AIMR patients as a bridge to surgery, it may not provide sufficient hemodynamic support. This case supports a growing body of evidence that alternative forms of hemodynamic support should be considered if the traditional therapeutic modalities for AIMR do not adequately support patients. Clinicians may consider upgrading IABP to Impella to provide increased hemodynamic support and maintain AIMR patient stability while awaiting cardiac surgery.

Significance of mitral annulus apparatus morphometry in patients with persistent atrial fibrillation

Abstract Background Few data about mitral valve apparatus components deformation in patients with persistent atrial fibrillation are available. Four-dimensional transesophageal echocardiography (4DTEE) is an ideal imaging technique to evaluate the complex morphology of the mitral valve apparatus. Purpose The study aimed to find some characteristics in patients presenting with persistent atrial fibrillation and if some of them could be indicative of relapse after cardioversion. Methods The study enrolled 133 patients with persistent atrial fibrillation and mild/moderate functional mitral regurgitation (FMR) before cardioversion. 101 of the patients were at the first persistent atrial fibrillation episode, and 32 with relapse. After performing two-dimensional transthoracic echocardiography (2DTTE), the study included only patients with mild/moderate FMR. 4D TEE permitted a detailed examination of the mitral annulus and valve leaflets, using an E95 machine for acquisition and an ECHOPAC 204 for image postprocessing with mitral valve quantification (MVQ) software. The studied measured: annulus area (AA)3D, annulus perimeter (AP), antero-posterior diameter (APD), posteromedial-anterolateral diameter (PM-ALD), commissural diameter (CD), inter-trigonal distance (ITd), non-planar angle (NPa), mitral-aortic angle (MAa), and for the leaflets, morphological measured parameters were: anterior leaflet area (ALA), posterior leaflet area (PLA), anterior leaflet length (ALL), posterior leaflet length (PLL), anterior leaflet angle (ALa), posterior leaflet angle (PLa), tenting height (TH), tenting area (TA), tenting volume), closure line length (CLL). Results 1. We found significant statistic differences between mitral annulus apparatus components in patients with (32) and without relapse (101) after initial cardioversion: AA 3D: 3.12 vs. 11.65 (p=0.003), AP: 13.23 vs. 12.1 (p=0.0001), APD: 3.76 vs. 3.45 (p=0.0003), PM-ALD: 4.21vs 3.93 (p=0.004), CD:4.17 vs. 3.89 (p=0.002), ITd: 2.82 vs 2.74 (p=0.2), NPa: 158.5 vs 155.2 (p=0.09), MAa: 122 vs 120,7 (p=0.5), ALA: 5.73 vs. 5.18 (p=0.006), PLA: 7.04 vs. 6.09 (p < 0.0001), ALL: 2.19 vs. 2.07 (p=0.036), PLL: 1,73 vs. 1,6 (p=0.03), ALa: 15.31 vs. 18.82 (p=0.002), PLa: 21.38 vs. 25.31 (p=0.01), TH: 0.83 vs. 0.63 (p=0.001), TA: 1.63 vs. 1.32 (p=0.007), TV: 2.75 vs. 2.13 (p=0.007). 2. We found correlations between mitral valve leaflets area and coaptation length in atrial fibrillation patients with (ALA: r=0.72, PLA r=0.65) and without relapse. (ALA: r=0.76, PLA r=0.64). Conclusions 1. 4D TEE identified a more significant mitral annulus and leaflet remodeling in atrial fibrillation patients with relapse after initial cardioversion than in atrial fibrillation patients admitted with a first atrial fibrillation episode. 2. Mitral valve leaflets area correlated with the coaptation length. 3. Mitral annulus complex morphology in patients with atrial fibrillation could be essential in predicting relapse after initial cardioversion.Mitral annulus parameters evaluationMitral leaflets parameters evaluation

Comparison of mitral valve apparatus anomalies between sarcomeric hypertrophic cardiomyopathy and Fabry disease cardiomyopathy

Abstract Background Despite different etiopathogenesis, Fabry disease (FD) cardiomyopathy and sarcomeric hypertrophic cardiomyopathy (HCM) share a similar hypertrophic phenotype. Cardiac magnetic resonance (CMR) plays a pivotal role in distinguishing between these two clinical conditions, thanks to the thorough morphological definition of the phenotype and non-invasive tissue characterization. A high prevalence of mitral apparatus anomalies has been previously described both in sarcomeric HCM and FD cardiomyopathy. Purpose This study systematically compares the morphology of the mitral apparatus in sarcomeric HCM and FD cardiomyopathy, to add new insights into differential diagnosis. Methods CMR images of 120 patients were retrospectively analyzed and divided as follows: healthy controls CTRL (n=40), HCM (n=40), and FD (n=40) with left ventricular hypertrophy (LVH). The analyses included the measurement of I) papillary muscles’ hypertrophy, expressed as the maximum diameter (D max) of the anterolateral (AL) and posteromedial (PM) papillary muscles (see Figure 1 A and B); II) the anteriorization of the anterolateral papillary muscle defined as the distance between the anterolateral papillary muscle and the anterior interventricular junction (Anteriorization of AL) (Fig. 1 C); III) the length of the anterior mitral leaflet (MVL length) (Fig. 1 D). All measurements were performed on cine-SSFP sequences in diastole. Results Compared to healthy controls, HCM and FD patients showed significant hypertrophy of both papillary muscles (p<0.001) and elongation of the anterior mitral leaflet (p<0.001). Both papillary muscles in FD patients showed greater hypertrophy compared to HCM patients (D max AL p=0.017 and D max PM p=0.039). No significant differences were observed between FD and HCM regarding MVL length (p=0.078). Compared to FD (p=0.028) and healthy controls (p<0.001), HCM patients showed greater anteriorization of the anterolateral papillary muscle. (Results are summarized in Table 1). Conclusions From the comparison of mitral valve apparatus anomalies between HCM and FD, it emerged that patients with FD cardiomyopathy show a higher degree of papillary muscle hypertrophy, while patients with sarcomeric HCM display a greater anterior displacement of the anterolateral papillary muscle. The systematic analysis of the morphology of mitral apparatus can be integrated in the differential diagnosis between these two pathologies.Fig.1 Representation of MeasurementsTable 1.Summary results table

True-MAD and pseudo-MAD in consecutive patients undergoing cardiovascular magnetic resonance

Abstract Background Mitral annulus disjunction (MAD) is a controversial imaging entity with uncertain clinical significance, which has been either considered a pathological entity potentially related to mitral valve prolapse (MVP) and sudden cardiac death or, on the contrary, a benign finding in normal hearts. Cardiovascular magnetic resonance (CMR) is poised to be the ideal imaging modality to assess MAD. Recently, a distinction between pseudo-MAD, present only in systole and secondary to juxtaposition of the billowing posterior leaflet on the adjacent left atrial wall, and true-MAD, where the insertion of the posterior leaflet is clearly displaced on the atrial wall either in diastole or in systole, has been suggested. Purpose We aimed to investigate the prevalence of pseudo-MAD and true-MAD in consecutive patients undergoing clinically-referred CMR. Methods This was a single-center retrospective study including consecutive patients referred to CMR from September 2023 to November 2023. Patients with feasible MAD assessment were included. MAD was defined as a ≥1 mm displacement between the left atrial wall-mitral valve leaflet junction hinge and the top of the left ventricular wall, measured from cine-CMR images in the three long-axis views. Pseudo-MAD and true-MAD were defined according to the presence of MAD only in systole or both in systole and diastole, respectively. MVP was defined as a systolic displacement ≥2 mm of one or both mitral valve leaflets above the annulus in 3-chamber view. Results Two-hundred-ninety patients (mean age 57±18 years; 181 men, 62%) were included. MVP and MAD were respectively found in 24 (8%) and 145 (50%) patients, of which 98 (34%) with true-MAD and 47 (16%) with pseudo-MAD. In all measurements, systolic MAD (2.6±1.3 mm) resulted equal to or greater than diastolic MAD (2.2±1.1 mm). The most frequent MAD location was the inferior wall in the two-chamber view (42%), whereas the rarest one was the inferolateral wall in the three-chamber view (17%). In patients with MVP, the prevalence of MAD was higher when considering all long-axis views (22 patients, 92%), of which 50% presented with true-MAD and 50% with pseudo-MAD. The extent of pseudo-MAD and true-MAD were both greater in patients with MVP (4.2±1.5 mm and 3.0±1.6 mm, respectively) than in those without MVP (2.3±1.0 and 2.1±0.9 mm; p<0.001 and p=0.007, respectively) in all locations. At the level of the inferolateral wall, the prevalence of MAD was 71% vs. 12% (p<0.001) in patients with vs. without MVP. Conclusions The presence of true-MAD was a common imaging finding in consecutive patients undergoing CMR, thus not resulting in a distinctive abnormal feature related to MVP or sudden cardiac death. Patients with MVP showed higher prevalence and extent of true-MAD and pseudo-MAD in all locations, in line with greater degeneration of the mitral annulus. Larger studies are needed to identify potential malignant characteristics of MAD.True-MAD (A,B) and pseudo-MAD (C,D).

Mitral valve phenotypes in SMAD3-related thoracic aortic disease: insights from the Montalcino Aortic Consortium

Abstract Background SMAD3 pathogenic variants (PV) predispose to heritable thoracic aortic aneurysms and dissections (HTAD). Mitral annular disjunction (MAD) associated with mitral valve prolapse (MVP) and mitral regurgitation (MR) was identified as a potential new marker of disease severity in Marfan syndrome. The prevalence and prognostic impact of these mitral phenotypes in other forms of HTAD are less known. Purpose We hypothesize that mitral abnormalities are increased in SMAD3-related HTAD and are associated with increased risk for valve and aortic complications. Methods The Montalcino Aortic Consortium (MAC) registry has enrolled participants with PV in 15 HTAD genes. Subjects >16 years old with complete imaging and clinical data were included in this study. MVP was defined according to current guidelines. MR was classified as mild, moderate, or severe. MAD was defined by a >3-millimeter gap between the posterior mitral valve leaflet hinge point and the inferolateral myocardium as confirmed by direct measurement of echocardiogram images. Frequencies of MVP, MR, and MAD were compared between MAC participants with SMAD3 PV and other HTAD PV. Associations between clinical and echo characteristics and the composite outcome of arrhythmia, aortic surgery, aortic dissection, or congestive heart failure was evaluated with multivariable logistic regression. Results In 671 MAC participants (129 with SMAD3 PV, 36 [IQR 19-51] years, 49% female), the prevalence of MVP was 15% and the prevalence of MR was 22%. Both MVP (31/129, 24%, vs. 67/542, 12%, OR 2.2 [1.4-3.6], P<0.001) and MR (40/129, 31%, vs. 108/542, 20%, OR 1.8 [1.2-2.8], P<0.006) were more common in participants with SMAD3 PV compared to other PV and were further enriched in cases with SMAD3 missense PV compared to loss of function PV (MR or MVP: 26/48, 54% vs. 7/30, 23%, OR 3.9 [1.4-10.8], P<0.007). Images were available from 238 MAC participants (67 with SMAD3 PV) to assess for MAD. MAD (29/67, 43%, vs. 28/171, 16%, OR 3.9 [2.1-7.3], P<0.0001), or the composite of MR, MVP, or MAD (42/67, 63%, vs. 69/171, 35%, OR 3.2 [1.8-5.7], P<0.0001) was more common with SMAD3 PV compared to other PV (Figure 1). Twelve participants with SMAD3 PV (18%) had prominent mitral phenotypes (>mild MR, >10 mm MAD, or MAD with MVP) but no significant aortic dilation (Z<3). When controlling for age and sex, MR or MVP, but not MAD, was independently associated with the composite outcome (OR 16 [2.4-110], Figure 2). Conclusion Mitral valve pathology, including MVP, MR, and MAD, is increased in individuals with SMAD3 PV compared to other HTAD PV. Prominent mitral phenotypes related to SMAD3 missense PV may identify a high-risk subgroup with adverse cardiovascular outcomes. Because congenital mitral disease may be the primary presenting feature of SMAD3 PV, genetic testing for HTAD should be considered for such patients, especially if they also have a family history of thoracic aortic disease.

Sex-based differences in anatomical and hemodynamic parameters and outcomes in patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation

Abstract Background This study aimed to assess sex differences in anatomical and hemodynamic parameters, and in procedure related outcomes, in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA). Methods 154 patients that underwent ASA in at our university hospital, between 2009 and 2021, were retrospectively included. Anatomical and hemodynamic parameters were collected from invasive catheterization before and during ASA, and from echocardiography (ECHO) examinations at maximum one week before ASA. Follow-up was conducted one year after ASA. The parameters analyzed were left ventricular (LV) volume, basal septal wall thickness (BSWT), anterior (AML) and posterior mitral leaflet (PML) length, minimal left ventricle outflow tract (LVOT) diameter, and LVOT pressure gradient at rest, prior to ASA, and prevalence of atrioventricular block after ASA. Linear and logistic regression models were used to assess the sex differences between the parameters. Results 50% of the patients were women. At the time of ASA, women were significantly older, had lower LV volume indexed for BSA in end-diastole (44 vs. 54 ml, p<0.001) and end-systole (18 vs. 23 ml, p=0.021), longer AML length indexed for BSA (13.7 vs. 11.6 mm, p<0.001) and PML length indexed for BSA (8.8 vs. 8.1 mm, p=0.018), smaller minimal LVOT diameter (4.6 vs. 4.9 mm, p=0.042), and higher LVOT pressure gradient at rest (49.3 vs. 32.5 mmHg, p=0.014), compared with men. The median follow-up was 364 days. Atrioventricular block (II or III) was more common among women (n=20, 26%) compared with men (n=10, 13%, p=0.045). Conclusions ECHO and invasive catheterization prior to ASA showed that women with HOCM presented with less favorable anatomical and hemodynamic pre-conditions, compared with men. At follow-up, women had a greater incidence of atrioventricular block after ASA. This strongly emphasizes the need for a sex-specific approach to optimize care and improve outcomes in patients with HOCM.

Residual mitral leaflet length independently indicates left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Abstract Background Due to its dynamic character, the diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive exercise testing. Mitral valve alterations represent structural parameters that are not affected by load or contractility and influence left ventricular outflow tract (LVOT) gradients. The residual portion of the mitral valve extending past its coaptation (RML) has been postulated as a necessity to exhibit LVOTO. Purpose This study aims to assess the impact of RML length on the likelihood of LVOTO in HCM patients. Methods This is a cross-sectional, multi-center, registry-based analysis conducted at two HCM referral centers. The study included HCM patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses. LVOTO was defined as resting or dynamic peak LVOT gradients ≥30 mmHg. Results Among 270 HCM patients studied (43% women, mean age 58±14 years), 131 patients (49%) exhibited LVOTO, with 76 (28%) having undergone septal reduction therapy (SRT). Patients with obstructive HCM exhibited a more pronounced end-diastolic interventricular septum (IVSd) thickness (2.2±0.4 vs. 1.8±0.5 cm; p<0.001) and higher left ventricular ejection fraction (LVEF) (65±9 vs. 62±10%; p=0.009) compared to those without LVOTO (nHCM). Obstructive HCM patients demonstrated longer anterior (29±4 vs. 26±4 mm; p<0.001), posterior (23±4 vs. 20±4 mm; p<0.001), and residual mitral leaflets (11±3 vs. 7±3 mm; p<0.001) than nHCM patients. Multivariable logistic regression analysis adjusting for age, IVSd thickness, LVEF, anterior, and posterior mitral leaflet length identified RML length as an independent predictor of LVOTO [OR=1.47 (95% CI 1.30-1.66); p<0.001]. The area under the receiver-operating characteristic curve for RML length in identifying LVOTO was 0.82 (95% CI 0.77-0.87). RML length ≥9 mm demonstrated 73% sensitivity and 77% specificity in identifying obstructive HCM patients. Notably, these results remained statistically significant in sensitivity analyses selectively performed in HCM patients who had previously undergone SRT as well as in those who were SRT-naïve, respectively. Conclusions This study indicates RML length as an independent predictor of LVOTO in HCM patients. Moreover, RML length demonstrated high diagnostic accuracy in identifying LVOTO among HCM patients. Prospective studies are warranted to assess the added value of RML length in the diagnostic work-up of HCM patients.Figure:Diagnostic Accuracy of RML

Correlation of prosthesis position on mid-term pacing burden in patients with new permanent pacemaker after TAVI

Abstract Background Prior studies suggest a strong correlation of the final prosthesis position on the occurrence of new conduction disturbances resulting in permanent pacemaker (PPM) implantation after transcatheter aortic valve implantation (TAVI). A high burden right ventricular pacing (PPM stimulation rate of > 20 %) is associated with poor long-term outcomes. So far, data about predictors influencing the PPM stimulation rate after TAVI are scarce. Purpose Thus, the purpose of this study was to evaluate the influence of the three-dimensional transcatheter heart valve (THV) position, as well as device landing zone characteristics or peri-/post-procedural factors on the stimulation rate in patients with new implanted PPM as TAVI complication. Materials: We evaluated the final THV position of 387 patients (106 with self-expanding Evolut R THV, 281 with balloon-expandable Sapien 3 THV) using fusion imaging of pre- and post-TAVI computed tomography angiography (CTA) to obtain a three-dimensional reconstruction of the THV within the native annulus region. The length of the THV above and below the native annulus was measured within the fused images to assess the implantation depth. PPM stimulation rates were examined pre-discharge and after 3 months. Patient’s clinical long-term outcome was evaluated over 5 years via standardized questionnaire as well as contacting general practitioners. Results Out of the 387 patients 112 (29%) received a new PPM pre-discharge after TAVI between 2014 and 2022. They were grouped into patients with stimulations rate below and above 20%. A stimulation rate > 20% in the PPM control before discharge and after three months was detected in 69 % and 67 % of them, respectively. Using uni- and multivariate logistic regression analysis, only new occurred third degree atrioventricular blocks (p=0.007) was identified as predictor for high burden right ventricular pacing after PPM-implantation as well as after 3 months. The implantation depth of the THV showed no influence on the PPM stimulation rate – neither the mean value nor the exact implantation depth adjacent the left, right and non-coronary cusp (P=0.455, P=0.108 and P=0.932, respectively). There were no significant differences regarding MACE between both groups during long-term follow-up; only the degree of dyspnea 5 years after TAVI was significantly higher in patients with a stimulation rate > 20% (p=0.01). Conclusion We detected no correlation of the exact three-dimensional THV position on mid-term pacing burden in 112 patients implanted with a new PPM after TAVI using CTA fusion imaging. Only a new occurred third degree atrioventricular block was a predictor for a high burden right ventricular pacing (stimulation rate >20%). These results provide important insights into which patients actually require PPM implantation after TAVI.

Prevalence, characteristics, and long-term outcomes of patients with mitral annular disjunction undergoing surgery for degenerative mitral regurgitation

Abstract Background Mitral valve prolapse (MVP) is associated with progressive mitral regurgitation (MR) requiring surgical repair. A subset of patients with MVP may also suffer from malignant ventricular arrhythmias (VAs), especially in the presence of mitral annular disjunction (MAD). Purpose To assess the prevalence, associated characteristics, and long-term outcomes of patients with MVP with and without MAD undergoing mitral valve surgery for degenerative MR. Methods Patients with MVP and moderate-to-severe or severe degenerative MR undergoing mitral valve surgery between 2010-2022 at a university hospital in Sweden were included. MAD length was measured on echocardiograms at end-systole from the insertion of the posterior leaflet on the detached mitral annulus to the border of the bulging left ventricle. Patient demographics and clinical outcomes were collected from medical records. The primary endpoint consisted of VAs, defined as sustained- or non-sustained ventricular tachycardia or high burden of premature ventricular complexes causing hospitalizations or ablation or identified at Holter monitoring. Other endpoints included sudden cardiac death, all-cause mortality, new onset postoperative atrial fibrillation, stroke, mitral valve reoperation, endocarditis, new or worsened heart failure, myocardial infarction and implantation of permanent pacemaker or cardiac defibrillator. Results Of 599 patients undergoing mitral valve surgery, 96 (16%) had preoperative MAD, with a median (Q1, Q3) MAD length of 8.0 (5.0-10.0) mm. Compared with patients without MAD, patients with MAD were younger (55 vs 63 years), more likely to be female (31% vs 17%), to have diffuse myxomatous valve disease (66% vs 25%) and bileaflet prolapse (57% vs 17%). Most patients underwent mitral valve repair (84% vs 80%). No patient had residual MAD after surgical repair. At a mean follow up time of 5.8 ± 3.5 years after mitral valve repair, VAs were more common in patients with pre-operative MAD (10% vs 2% (adjusted HR 4.52, 95% CI 1.57-13.0)) (Figure 1). There were no significant differences in the risks of other clinical outcomes. Conclusions MAD was associated with almost a 5-fold increased long-term risk of VAs after mitral valve repair despite successful anatomical correction of MAD. These findings highlight the importance of increased awareness of VAs in patients with MAD also after mitral valve surgery.

Identification of left ventricular flow features in healthy and pathological conditions

Abstract Background In the presence of mitral valve diseases or following surgical interventions, the hemodynamics in the left ventricle (LV) are significantly altered [1]. These maladaptive intraventricular hemodynamic alterations can stimulate a cascade of events leading to progressive adverse LV remodeling and eventual heart failure [2]. Qualitative and quantitative evaluation of LV flow features may provide a potential for sensitive risk stratification of clinical cardiac function [3]. Purpose The purpose of this study is to identifying LV flow features using in vitro experiments under both normal and pathological conditions, including mitral regurgitation (MR), mitral valve replacement with bioprosthetic/mechanical valve, and transcatheter mitral valve edge-to-edge repair (TEER). Methods We utilized a biohybrid approach to construct the in vitro experimental platform, where the native mitral valve (including chordae tendineae and papillary muscles) and aortic valve from porcine were combined with a 3D-printed silicon LV (figure 1). To ensure comparability across different conditions, we maintained consistency by utilizing the same native valve and 3D-printed LV. For pathological conditions, we cut the chordae tendineae in A2 zone to induce the severe degenerative MR, and TEER was performed on this prolapsed valve by placing two clips in A2-P2 zone. Then, the anterior leaflet of valve was cut, and a bioprosthetic valve and mechanical valve were sutured to mitral annulus to simulate surgical valve replacement, respectively. Left ventricular flow fields were measured using four-dimensional particle image velocimetry (4D-PIV) technique, with vector interval of 0.9 mm in all the spatial directions and temporal resolution of 10 ms. Results Significant differences in mean flow field were observed among healthy and pathological conditions (figure 2). Firstly, the vortex orientation was clockwise in healthy, MR, bioprosthetic valve replacement, and TEER conditions, which could accompany the redirection of blood flows towards the aortic valve. However, the replacement with a mechanical valve resulted in an alteration in vortex orientation from clockwise to counterclockwise. Secondly, the position of the center of the vortex changed in pathological conditions, with the center of the vortex closest to the apex and the left ventricle outflow tract in the healthy condition. Thirdly, the maximum Reynolds shear stress (RSS), which may be responsible for thrombus formation, significantly increased after TEER procedure and bioprosthetic valve replacement. Conclusions This study demonstrates significant changes in LV hemodynamics across different conditions. The flow features, including vortex orientations, vortex positions and the RSS, may potentially become crucial considerations for the optimization of artificial valves and mitral valve repair devices.Figure 1 Figure 2

Zebrafish arterial valve development occurs through direct differentiation of second heart field progenitors.

Bicuspid Aortic Valve (BAV) is the most common congenital heart defect, affecting at least 2% of the population. The embryonic origins of BAV remain poorly understood, with few assays for validating patient variants, limiting the identification of causative genes for BAV. In both human and mouse, the left and right leaflets of the arterial valves arise from the outflow tract cushions, with interstitial cells originating from neural crest cells and the overlying endocardium through endothelial-to-mesenchymal transition (EndoMT). In contrast, an EndoMT-independent mechanism of direct differentiation of cardiac progenitors from the second heart field (SHF) is responsible for the formation of the anterior and posterior leaflets. Defects in either of these developmental mechanisms can result in BAV. Although zebrafish have been suggested as a model for human variant testing, their naturally bicuspid arterial valve has not been considered suitable for understanding human arterial valve development. Here, we have set out to investigate to what extent the processes involved in arterial valve development are conserved in zebrafish and ultimately, whether functional testing of BAV variants could be carried out. Using a combination of live imaging, immunohistochemistry and Cre-mediated lineage tracing, we show that the zebrafish arterial valve primordia develop directly from SHF progenitors with no contribution from EndoMT or neural crest, in keeping with the human and mouse anterior and posterior leaflets. Moreover, once formed, these primordia share common subsequent developmental events with all three aortic valve leaflets. Our work highlights a conserved ancestral mechanism of arterial valve leaflet formation from the SHF and identifies that development of the arterial valve is distinct from that of the atrioventricular valve in zebrafish. Crucially, this confirms the utility of zebrafish for understanding the development of specific BAV subtypes and arterial valve dysplasia, offering potential for high-throughput variant testing.

Source Localization and Classification of Pulmonary Valve-Originated Electrocardiograms Using Volume Conductor Modeling with Anatomical Models.

Premature ventricular contractions (PVCs) are a common arrhythmia characterized by ectopic excitations within the ventricles. Accurately estimating the ablation site using an electrocardiogram (ECG) is crucial for the initial classification of PVC origins, typically focusing on the right and left ventricular outflow tracts. However, finer classification, specifically identifying the left cusp (LC), anterior cusp (AC), and right cusp (RC), is essential for detailed preoperative planning. This study aims to improve the accuracy of cardiac waveform source estimation and classification in 27 patients with PVCs originating from the pulmonary valve. We utilized an anatomical human model and electromagnetic simulations to estimate wave source positions from 12-lead ECG data. Time-series source points were identified for each measured ECG waveform, focusing on the moment when the distance between the estimated wave source and the pulmonary valve was minimal. Computational analysis revealed that the distance between the estimated wave source and the pulmonary valve was reduced to less than 1 cm, with LC localization achieving errors under 5 mm. Additionally, 74.1% of the subjects were accurately classified into the correct origin (LC, AC, or RC), with each origin demonstrating the highest percentage of subjects corresponding to the targeted excitation origin. Our findings underscore the novel potential of this source localization method as a valuable complement to traditional waveform classification, offering enhanced diagnostic precision and improved preoperative planning for PVC ablation procedures.

Comparing surgical techniques and results of secondary ischemic mitral regurgitation: a state-of-the-art literature review.

Surgery for mitral valve disease is a developing area with a wide range of surgical options. There is growing evidence on the best approach for secondary ischemic mitral regurgitation (SIMR) when the pathology is within the ventricle. The goal of this literature review is to provide a comprehensive comparison of surgical treatments for SIMR. The initial screening process included PubMed, Medline and Embase to identify randomized controlled trials, propensity-matched observational series, meta-analyses and unmatched observational series. The terms used were 'mitral valve disease', 'secondary mitral regurgitation', 'secondary ischemic mitral regurgitation', 'functional mitral regurgitation', 'restrictive mitral annuloplasty', 'subvalvular repair', 'Trans Catheter Edge to Edge Repair and echocardiography coupled with secondary mitral regurgitation', 'secondary ischemic mitral regurgitation', and 'functional mitral regurgitation'. Six strategies have been identified for treating SIMR. These include mitral valve replacement (MVR), restrictive mitral annuloplasty, surgical revascularisation (with and without mitral annuloplasty), subvalvular procedures [papillary muscle (PM) approximation, PM relocation, ring and string procedure], procedures directly targeting the mitral valve (edge-to-edge repair and anterior leaflet enlargement), and transcatheter heart valve therapy. There is a deficiency of robust empirical data to enable meaningful comparisons between MVR, mitral valve repair (including subvalvular repair), and transcatheter mitral valve procedure. This review will definitively analyze the current outcomes of transcatheter mitral valve procedure using the edge-to-edge mitral valve repair technique and standard surgical mitral valve procedures in patients with secondary mitral regurgitation (MR). In addition, the seminar highlights the role of left ventricular assist devices in managing SIMR. It discusses the advantages and limitations of each intervention. Currently, there is no consensus on the optimal management strategy for patients with SIMR. Therefore, a multidisciplinary cardiac team should manage patients with secondary MR to ensure the best outcome by matching the ideal intervention with the patient.

Isolated prolapse of the posterior mitral valve leaflet: phenotypic refinement, heritability and genetic etiology.

Isolated posterior leaflet mitral valve prolapse (PostMVP), a common form of MVP, often referred as fibroelastic deficiency, is considered a degenerative disease. PostMVP patients are usually asymptomatic and often undiagnosed until chordal rupture. The present study aims to characterize familial PostMVP phenotype and familial recurrence, its genetic background, and the pathophysiological processes involved. We prospectively enrolled 284 unrelated MVP probands, of whom 178 (63%) had bi-leaflet MVP and 106 had PostMVP (37%). Familial screening within PostMVP patients allowed the identification of 20 families with inherited forms of PostMVP for whom whole genome sequencing was carried out in probands. Functional in vivo and in vitro investigations were performed in zebrafishand in Hek293T cells. In the 20 families with inherited form of PostMVP, 38.8% of relatives had a MVP/prodromal form, mainly of the posterior leaflet, with transmission consistent with an autosomal dominant mode of inheritance. Compared with control relatives, PostMVP family patients have clear posterior leaflet dystrophy on echocardiography. Patients with PostMVP present a burden of rare genetic variants in ARHGAP24. ARHGAP24 encodes the filamin A binding RhoGTPase-activating protein FilGAP and its silencing in zebrafish leads to atrioventricular regurgitation. In vitro functional studies showed that variants of FilGAP, found in PostMVP families, are loss-of-function variants impairing cellular adhesion and mechano-transduction capacities. PostMVP should not only be considered an isolated degenerative pathology but as a specific heritable phenotypic trait with genetic and functional pathophysiological origins. The identification of loss-of-function variants in ARHGAP24 further reinforces the pivotal role of mechano-transduction pathways in the pathogenesis of MVP. Isolated posterior mitral valve prolapse (PostMVP), often called fibro-elastic deficiency MVP, is at least in some patients, a specific inherited phenotypic traitPostMVP has both genetic and functional pathophysiological origins Genetic variants in the ARHGAP24 gene, which encodes for the FilGAP protein, cause progressive Post MVP in familial cases, and impair cell adhesion and mechano-transduction capacities.

Ring only repair of bileaflet mitral valve prolapse with mitral regurgitation: Insights from computational modeling

This study evaluates the efficacy of annuloplasty repair as a standalone procedure for treating bileaflet mitral valve prolapse with mitral regurgitation (MR). Various flexible ring bands for MR of different severities were compared to assess their biomechanical impact and treatment outcomes. Computational beating heart models, based on the Living Heart Human Model, were utilized to simulate annuloplasty repairs. Repairs using bands of varying lengths were modeled on moderate and severe MR cases, considering bileaflet mitral valve prolapse. Key parameters, including regurgitant orifice area (ROA), prolapse severity, coaptation length, leaflet position, and deformation, were computed to compare conditions before and after implantation. Annuloplasty repairs effectively reduced the ROA in both moderate and severe MR cases, achieving complete sealing in selective instances. Additionally, annuloplasty repair corrected bileaflet prolapse, with prolapse severity decreasing as the annular size increased. Successful coaptation was indicated by the expansion of each leaflet’s contact area distribution and percentage in contact with the opposing leaflet. The risk of systolic anterior motion, that may obstruct the left ventricular outflow tract, was minimized, as the anterior leaflet was directed towards the posterior position. In conclusion, annuloplasty repair alone can effectively treat MR when an appropriate band length is selected. It facilitates a significant reduction in ROA, correction of bileaflet prolapse, and improvement in leaflet coaptation. These findings have important clinical implications, potentially offering a less complex surgical treatment avenue and reducing complications in the management of MR.

Impact of Non-Valvular Atrial Fibrillation on Mitral Valve Anatomic Features: A Study of Three-Dimensional Mitral Valve by Transesophageal Echocardiography and Automatic Analysis Software.

Mitral regurgitation (MR) is frequently observed in non-valvular atrial fibrillation (NVAF) patients and is a significant risk factor for its progression. This study aims to investigate the three-dimensional anatomical characteristics of the mitral valve (MV) in patients with different types of NVAF to elucidate the underlying mechanisms of MR. A retrospective analysis was conducted on 82 paroxysmal atrial fibrillation patients (PAF group) and 66 persistent atrial fibrillation patients (PerAF group) who underwent real-time three-dimensional transesophageal echocardiography (RT 3D-TEE) before initial ablation. Additionally, 30 patients undergoing RT 3D-TEE for the assessment of patent foramen ovale were selected as the control group. Basic echocardiographic variables were measured, left atrioventricular volume and strain parameters were calculated using automated software (Dynamic-HeartModel and AutoStrain). MV anatomic features were analyzed using the 4D-MV Assessment software (TomTec Imaging Systems). The maximum left atrial volume (LAVmax) was highest in the PerAF group, followed by the PAF and control groups, with statistically significant differences (p<0.01). Left atrial reservoir strain (LASr) showed an opposite trend, being the lowest in the PerAF group (p<0.01). The proportion of moderate to severe MR was significantly higher in the PerAF group (27.3%) compared to the PAF group (11.0%) (p<0.01). Compared to controls, the AF groups exhibited mitral annular (MA) dilation, flattening of the MA plane, and increased leaflet area (all p<0.05). Correlation analysis between effective regurgitant orifice area (EROA) and left atrioventricular structure and function parameters, as well as various annular parameters, showed that EROA was significantly correlated with left ventricular end-diastolic volume (LVEDV), LAVmax, LASr, anterior and posterior diameter, annular area, ratio of annular height to commissural diameter (AH/CD ratio), posterior leaflet area, posterior leaflet length, and the C-shaped annulus length (all p<0.05). Significant remodeling of the MV apparatus occurs in NVAF patients, with more pronounced changes in PerAF patients, contributing to a higher incidence of moderate to severe MR. RT 3D-TEE-based MV automated assessment offers significant advantages in accurately diagnosing MV remodeling and supporting the evaluation of MR in NVAF patients.