The preferable position for quantifying left ventricular diameter by transthoracic echocardiography.

BACKGROUND: In quantifying left ventricular (LV) diameter, which position for echocardiographic measurements, mitral valve tip level (MV-tip) or LV mid level (LV-mid), more accurately represents the LV volume is unclear. Furthermore, which factor affects the measurement error also has not been elucidated. METHODS: We enrolled 150 patients without myocardial infarction and local asynergy who underwent echocardiography and cardiac magnetic resonance imaging (CMRI). Echocardiographic LV diastolic diameter (LVDD) and LV systolic diameter (LVDS) were measured at both MV-tip and LV-mid, and the LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were quantified using CMRI. We quantified the degree of aortic wedging as the angle between the anterior wall of the aorta and the ventricular septal surface (ASA). RESULTS: The average LVDD was smaller and average LVDS larger when measured at the MV-tip than at the LV-mid. In regression analyses, the correlation coefficient between LVDD and LVEDV was larger at LV-mid (R = 0.89) than at MV-tip (R = 0.82), and the correlation coefficient between LVDS and LVESV also larger at LV-mid (R = 0.93) than MV-tip (R = 0.87). ASA, Valsalva diameter, left atrial diameter, patient height, and LV mass significantly affected the echocardiographic measurement error, but no factor affected the measurement error when quantifying LVDD at the LV-mid level. CONCLUSIONS: The echocardiographic LV diameter measured at LV-mid has a stronger correlation with LV chamber size derived from CMRI than measurements at MV-tip. The LVDD measured at the LV-mid level is not affected by other factors.

5-Year Outcomes of Anterior Mitral Leaflet Laceration to Prevent Outflow Obstruction.

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is a common, often fatal complication of transcatheter mitral valve replacement (TMVR). Laceration of the anterior mitral leaflet to prevent outflow obstruction (LAMPOON) was safe and effective at preventing LVOT obstruction at 30 days in the National Heart, Lung, and Blood Institute LAMPOON trial. OBJECTIVES: The authors report the 5-year trial outcomes. METHODS: The National Heart, Lung, and Blood Institute LAMPOON trial was a prospective, multicenter, single-arm safety and feasibility study of LAMPOON and transseptal SAPIEN 3 TMVR in annuloplasty rings (valve-in-ring) or native mitral annular calcification (MAC) (valve-in-MAC). All subjects had high predicted risk for LVOT obstruction. Subjects were not excluded for excessive frailty or comorbidity. The primary endpoints were technical success and safety at 30 days. Secondary clinical and echocardiographic endpoints were assessed at 1 year and clinical follow-up at 5 years. RESULTS: Thirty subjects were enrolled between June 2017 and June 2018, equally between the valve-in-MAC and valve-in-ring arms. At 30 days, LAMPOON was successful in all 30 subjects, with no strokes, 1 (3%) death, and 1 (3%) moderate LVOT obstruction. Eighteen (65%) survived to 1 year, and 7 (25%) survived to 5 years. Six (20%) were hospitalized for heart failure in the first year. From baseline to 1 year, there was a 24-point improvement in Kansas City Cardiomyopathy Questionnaire score and a 60-m improvement in 6-minute walk distance. There was no significant change in N-terminal pro-brain natriuretic peptide. At 1 year, LVOT gradients remained low. CONCLUSIONS: LAMPOON enabled TMVR despite the risk for LVOT obstruction. There were no long-term complications associated with LAMPOON. The selection of inoperable patients limited assessment of long-term survival following TMVR. (NHLBI DIR LAMPOON Study: Intentional Laceration of the Anterior Mitral Leaflet to Prevent Left Ventricular Outflow Tract Obstruction During Transcatheter Mitral Valve Implantation; NCT03015194).

Outcomes Following Transcatheter Mitral Valve Replacement Using Dedicated Devices in Patients With Mitral Annular Calcification.

BACKGROUND: Patients with mitral regurgitation (MR) and morphologic presence of relevant mitral annular calcification (MAC) represent a challenging phenotypic subset with limited treatment options. OBJECTIVES: The aim of this study was to assess the feasibility of transcatheter mitral valve replacement (TMVR) using dedicated devices for the treatment of MAC patients. METHODS: Consecutive patients with symptomatic MR receiving TMVR and with available computed tomography data from the CHOICE-MI (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency) multicenter registry were stratified by the presence of none or mild mitral annular calcification (MACnone/mild) vs moderate or severe mitral annular calcification (MACmod/sev). RESULTS: Among 279 eligible patients (median age = 76.0 years [Q1-Q3: 71.0-81.0 years], EuroSCORE II = 6.2% [Q1-Q3: 3.9%-12.1%]), 222 (79.6%) presented with MACnone/mild and 57 (20.4%) with MACmod/sev. Patients with MACmod/sev had a higher prevalence of extracardiac arteriopathy (P = 0.011) and primary MR (P < 0.001). Although the technical success rate and the extent of MR elimination did not differ, TMVR treatment in MACmod/sev patients was associated with higher rates of postprocedural bleeding complications (P = 0.02) and renal failure (P < 0.001). Functional improvement at the 1- and 2-year follow-up did not differ between groups. At the 2-year follow-up, there were no differences between patients with MACmod/sev and MACnone/mild regarding all-cause mortality (38.5% vs 37.7%; P = 0.76), cardiovascular mortality (21.3% vs 24.9%; P = 0.97), and all-cause mortality or heart failure hospitalization (52.4% vs 46.7%; P = 0.28) CONCLUSIONS: TMVR in patients with MACmod/sev is associated with higher rates of postprocedural complications but similar rates of survival, MR resolution, and functional improvement compared to MACnone/mild. Further studies are necessary to define the role of dedicated TMVR devices in this population. (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency Registry [CHOICE-MI]; NCT04688190).

Image-based simulation of mitral valve dynamic closure including anisotropy.

Simulation of the dynamic behavior of mitral valve closure could improve clinical treatment by predicting surgical procedures outcome. We propose here a method to achieve this goal by using the immersed boundary method. In order to go towards patient-based simulation, we tailor our method to be adapted to a valve extracted from medical image data. It includes investigating segmentation process, smoothness of geometry, case setup and the shape of the left ventricle. We also study the influence of leaflet tissue anisotropy on the quality of the valve closure by comparing with an isotropic model. As part of the anisotropy analysis, we study the influence of the principal material direction by comparing methods to obtain them without dissection. Results show that our method can be scaled to various image-based data. We evaluate the mitral valve closure quality based on measuring bulging area, contact map, and flow rate. The results show also that the anisotropic material model more precisely represents the physiological characteristics of the valve tissue. Furthermore, results indicate that the orientation of the principal material direction plays a role in the effectiveness of the valve seal.

Hospital and Surgeon Surgical Valvar Volume and Survival after Multi-Valve Cardiac Surgery in Medicare Beneficiaries.

OBJECTIVE: Long-term outcomes after multi-valve cardiac surgery remain under-evaluated. METHODS: Medicare administrative claims from 2008-2019 identified beneficiaries undergoing multi-valve surgery. Operative characteristics were doubly-adjudicated using International Classification of Diseases and Current Procedural Technology codes. A multivariable flexible parametric model evaluated predictors of survival; regression standardization was performed to predict standardized survival probabilities (SSP) at varying percentiles of annual valvar volume. RESULTS: Of 476,092 cardiac surgeries involving the aortic (AVS), mitral (MVS), or tricuspid (TVS) valve, 63,083 (13.3%) were identified as involving multi-valve surgery: 22,884 MVS+TVS, 30,697 AVS+MVS, 3,443 AVS+TVS and 6,059 AVS+MVS+TVS. Surgery occurred at 1,157 hospitals by 2,922 surgeons. Annual valvar volume (total AVS+MVS+TVS) was tallied for surgeons and hospitals. Median survival varied substantially by type of multi-valve surgery: 8.09 [7.90-8.24] years in MVS/TVS, 6.65 [6.49-6.81] years in AVS/MVS, 5.77 [5.37-6.13] in AVS/TVS, and 6.02 [5.64-6.38] in AVS/MVS/TVS. SSPs were calculated across combined hospital/surgeon volume percentiles; the median SSP increased with increasing percentile of combined hospital/surgeon volume: 5%tile: 5.77 [5.58,5.98], 25%tile: 6.18 [6.07,6.28], 50%tile: 6.56 [6.44,6.68], 75%tile: 6.86 [6.75,6.97], and 95%tile: 7.58 [7.34,7.83] years, respectively. CONCLUSIONS: Survival varied significantly by type of multi-valve surgery, worsened with addition of concomitant interventions and improved substantially with increasing annual hospital and surgeon volume. Hospital volume was associated with an improved early hazard for death that abated beyond 3 months post-surgery), while surgeon volume was associated with an improved hazard for death that persisted even beyond the first post-operative year. Consideration should be given to referring multi-valve cases to high-volume hospitals and surgeons.

Left ventricular outflow tract obstruction after transcatheter mitral valve replacement: a case report with a multifaceted approach.

An 83-year-old woman was admitted to our center because of heart failure. Transthoracic echocardiography revealed severe mitral annular calcification resulting in a double mitral valve lesion. After discussion by the heart team, transcatheter mitral valve replacement with Tendyne (Abbott Structural, Santa Clara, CA, USA) was performed. Despite having a predicted neo-left ventricular outflow tract (LVOT) above the cut-off value, the patient developed clinically significant LVOT obstruction (LVOTO) refractory to medical treatment. This situation is often treated before the intervention, and dealing with LVOTO afterward can be challenging. After taking the patient's anatomy into consideration, we decided to perform alcohol septal ablation. Applying a combined strategy of medical treatment and intervention led to success. In this case report, we discuss this event and the strategies available for preventing and managing the condition.

Serotonin transporter deficiency in mice results in an increased susceptibility to HTR2B-dependent pro-fibrotic mechanisms in the cardiac valves and left ventricular myocardium.

Increased serotonin (5HT) concentration and signaling, can lead to pathological remodeling of the cardiac valves. We previously showed that a reduction of the 5HT transporter (SERT) expression in the mitral valve (MV) contributes to the progression of degenerative MV regurgitation (MR). We sought to investigate the myocardial and valvular phenotype of SERT-/- mice in order to identify remodeling mechanisms specific to the MV and left ventricular (LV) remodeling. Using 8- and 16-week-old WT and SERT-/- mice we show that male and female animals deficient of SERT have pathological remodeling of the cardiac valves, myocardial fibrosis, diminished ejection fraction and altered left ventricular dimensions. In the MV and intervalvular area of the aortic valve (AV)-MV, gene expression, including Col1a1 mRNA, was progressively altered with age up until 16 weeks of age. In contrast, in the AV and myocardium, most gene expression changes occurred earlier and plateaued by 8 weeks. To explore basal differences in susceptibility to remodeling stimuli among cardiac valves, valve interstitial cells (VIC) were isolated from AV, MV, tricuspid valve (TV), pulmonary valve (PV) and fibroblasts (Fb) from the myocardial apex from 16 weeks old wild type (WT) mice. After 24h stimulation with 10µM of 5HT, the gene expression of Col1a1 and Acta2 were upregulated in MVIC to a higher degree than in VIC from other valves and Fb. Treatment with TGFß1 similarly upregulated Cola1 and Acta2 in MVIC and AVIC, while the increase was milder in right heart VIC and Fb. Experiments were also carried out with human VIC. In comparison to mice, human left heart VIC were more sensitive to 5HT and TGFß1, upregulating COL1A1 and ACTA2; TGFß1 upregulated HTR2B expression in all VIC. Our results support the hypothesis that a deleterious cardiac effect of SERT downregulation may be mediated by increased susceptibility to HTR2B-dependent pro-fibrotic mechanisms, which are distinct among VIC populations and cardiac fibroblasts, regardless of SERT activity. Given that HTR2B mechanisms involved in VIC and myocardial remodeling response are due to both 5HT and also to downstream related TGFß1 and TNFα activity, targeting HTR2B could be a therapeutic strategy for dual treatment of MR and LV remodeling.

Evaluating Mitral TEER in the Management of Moderate Secondary Mitral Regurgitation Among Heart Failure Patients.

BACKGROUND: Moderate secondary mitral regurgitation (SMR) represents a subgroup of heart failure (HF) patients with treatment restricted to medical therapy. Outcomes in patients with moderate SMR treated with mitral transcatheter edge-to-edge repair (M-TEER) are less well known. OBJECTIVES: The aim of this study was to assess the safety and effectiveness of M-TEER in subjects with moderate SMR using the EXPANDed studies. METHODS: One-year outcomes in subjects from the EXPANDed studies (EXPAND [A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices] and EXPAND G4 [A Post-Market Study Assessment of the Safety and Performance of the MitraClip G4 System] MitraClip studies) with baseline moderate SMR (2+), per echocardiographic core laboratory (ECL) assessment, were compared with subjects with baseline severe SMR (≥3+). RESULTS: There were 335 subjects with moderate SMR and 525 with severe SMR at baseline per ECL review. Baseline characteristics were similar between the 2 subgroups. After treatment with M-TEER, significant MR reduction was achieved in both groups. Significant left ventricular (LV) reverse remodeling was observed through 1 year, with a >20 mL decrease in LV end-diastolic and end-systolic volumes on average in the moderate SMR group. Significant 1-year improvements in NYHA functional class (>78% NYHA functional class I or II) and quality of life (>20 points on the Kansas City Cardiomyopathy Questionnaire-Overall Summary) were observed in subjects with moderate SMR. Similarly, low rates of major adverse events, all-cause mortality, and HF hospitalizations were observed between the 2 subgroups through 1 year. CONCLUSIONS: In the EXPANDed studies, subjects with moderate SMR treated with M-TEER had improvements similar to subjects with severe SMR in quality of life and positive LV remodeling at 1 year. Future studies are needed to evaluate if M-TEER would be beneficial for HF patients with moderate SMR.

Stretch of the papillary insertion triggers reentrant arrhythmia: an in silico patient study.

Background: The electrophysiological mechanism connecting mitral valve prolapse (MVP), premature ventricular complexes and life-threatening ventricular arrhythmia is unknown. A common hypothesis is that stretch activated channels (SACs) play a significant role. SACs can trigger depolarizations or shorten repolarization times in response to myocardial stretch. Through these mechanisms, pathological traction of the papillary muscle (PM), as has been observed in patients with MVP, may induce irregular electrical activity and result in reentrant arrhythmia. Methods: Based on a patient with MVP and mitral annulus disjunction, we modeled the effect of excessive PM traction in a detailed medical image-derived ventricular model by activating SACs in the PM insertion region. By systematically varying the onset of SAC activation following sinus pacing, we identified vulnerability windows for reentry with 1 ms resolution. We explored how reentry was affected by the SAC reversal potential ( E SAC ) and the size of the region with simulated stretch (SAC region). Finally, the effect of global or focal fibrosis, modeled as reduction in tissue conductivity or mesh splitting (fibrotic microstructure), was investigated. Results: In models with healthy tissue or fibrosis modeled solely as CV slowing, we observed two vulnerable periods of reentry: For E SAC of -10 and -30 mV, SAC activated during the T-wave could cause depolarization of the SAC region which lead to reentry. For E SAC of -40 and -70 mV, SAC activated during the QRS complex could result in early repolarization of the SAC region and subsequent reentry. In models with fibrotic microstructure in the SAC region, we observed micro-reentries and a larger variability in which times of SAC activation triggered reentry. In these models, 86% of reentries were triggered during the QRS complex or T-wave. We only observed reentry for sufficiently large SAC regions ( > = 8 mm radius in models with healthy tissue). Conclusion: Stretch of the PM insertion region following sinus activation may initiate ventricular reentry in patients with MVP, with or without fibrosis. Depending on the SAC reversal potential and timing of stretch, reentry may be triggered by ectopy due to SAC-induced depolarizations or by early repolarization within the SAC region.

Predictive value of left atrial volumes assessed using real-time three-dimensional echocardiography for pulmonary hypertension in dogs with myxomatous mitral valve disease.

Introduction: Left atrial volume (LAV) obtained using real-time three-dimensional echocardiography (RT3DE) is an independent predictor of post-capillary pulmonary hypertension (PH) in humans; however, no studies have investigated LAV obtained using RT3DE as a predictor of post-capillary PH in dogs with myxomatous mitral valve disease (MMVD). Therefore, we aimed to evaluate the clinical applicability of LAV obtained using RT3DE compared to that obtained using two-dimensional echocardiography (2DE) in dogs with MMVD, with or without PH. Methods: Medical records and echocardiographic images of 237 privately owned dogs with naturally occurring MMVD with or without PH were retrospectively reviewed. A total of 49 privately owned dogs with naturally occurring MMVD, with or without PH, were finally included (35 MMVD without PH, 14 MMVD with PH). The LAV and left ventricular volumes were obtained using 2DE and RT3DE. Echocardiographic parameters were analyzed to identify independent predictors of post-capillary PH. Results: We found that the left atrial and left ventricular volumes obtained using 2DE and RT3DE indexed to body weight and several 2DE-derived variables were univariately associated with post-capillary PH. Furthermore, multivariable logistic regression analysis revealed that the RT3DE minimum LAV indexed to body weight (LAVi min) was the only significant independent predictor of post-capillary PH (odds ratio, 12.86; 95% confidence interval [CI], 2.40-68.99; p = 0.003), with the highest area under the curve value of 0.86 (95% CI, 0.75-0.96; p < 0.001). Discussion: In conclusion, LAV indexed to body weight obtained using 2DE and RT3DE, can be a useful predictor of post-capillary PH in dogs with MMVD. In particular, the RT3DE LAVi min was observed to be the strongest predictor of post-capillary PH.

Papillary Muscle Maneuvers: Pathophysiology-based Approach in Secondary Mitral Regurgitation.

The treatment of secondary mitral regurgitation (SMR) remains challenging despite the implementation of modern heart failure medication and established catheter-based techniques. Only a subgroup of SMR patients benefit from mitral valve (MV) intervention, and the long-term prognostic benefit of different therapeutic approaches in SMR remains controversial. A literature search was conducted through PubMed and Embase databases to identify relevant studies addressing the pathophysiological background for papillary muscle maneuvers in SMR and currently available surgical techniques. Furthermore, the studies evaluating patients' selection criteria for papillary muscle maneuvers were specifically considered. Articles were selected based on quality and relevance. Over the last two decades, papillary muscle maneuvers have evolved as a pathophysiology-based treatment strategy to address left ventricular (LV) remodeling in SMR. In particular, patients with severe leaflet tenting and moderate heart failure phenotype seem to benefit most from papillary muscle maneuvers that improve LV geometry and thereby the durability of MV repair. We conclude that papillary muscle maneuvers are an evolving pathophysiology-based treatment strategy of ventricular SMR which target papillary muscle displacement due to LV remodeling.

First-in-Man Use of Intraoperative Electrophysiological Mapping to Evaluate the Efficacy of the EnCompass Clamp During a Cox-IV Maze Procedure.

This case report describes the first-in-man use of intraoperative electrophysiological (EP) mapping to evaluate the efficacy of the EnCompass clamp (AtriCure, Inc., Mason, OH) during a Cox-IV Maze procedure. A 53-year-old male with paroxysmal atrial fibrillation and severe mitral valve regurgitation underwent mitral valve repair with concomitant surgical ablation for atrial fibrillation. Intraoperative 3D EP mapping was performed using the Abbott EnSite Precision system (Abbott Inc., Chicago, IL) before ablation, after initial radiofrequency ablation with the AtriCure EnCompass clamp, and after the full Cox-IV Maze procedure was completed. The pre-ablation map showed approximately 80-85% high voltage areas in the posterior left atrial wall. Initial ablation with the EnCompass clamp reduced high voltage areas to 30-35%. The final map following the Cox-IV Maze procedure demonstrated near-complete electrical silence, with only 5-10% of the atrial surface retaining high voltage activity. This represents an estimated 88% reduction in high-voltage areas from baseline. The patient had an uncomplicated postoperative course apart from one episode of postoperative atrial fibrillation requiring direct current (DC) cardioversion. This case demonstrates the utility of intraoperative EP mapping in guiding and confirming the efficacy of surgical ablation procedures, as well as the effectiveness of combining the EnCompass clamp with a full Cox-IV Maze in achieving comprehensive atrial electrical isolation. The EnCompass clamp can be used for ablations with a beating heart, thus reducing the aortic cross-clamp time and therefore minimizing the total myocardial ischemia time.

Skin, Heart, and CNS Involvement in Granulomatosis With Polyangiitis: A Case Report.

We discuss the case of a 60-year-old male who presented with ankle pain, a necrotic rash, and progressive weakness in both lower limbs and the right upper limb. An infectious workup of the skin lesions came back negative. Additionally, his kidney function tests indicated an acute kidney injury. This prompted investigations for vasculitis etiologies, which revealed a positive cytoplasmic antineutrophil cytoplasmic autoantibody (c-ANCA). His neurological deficits were also investigated, and imaging suggested embolic infarcts. Cardiac imaging showed valve vegetations and blood culture showed a lack of growth suggestive of a noninfective nature of these lesions. Based on all these findings, a kidney biopsy was obtained and demonstrated pauci-immune segmental vasculitis consistent with ANCA-associated glomerulonephritis. As such, the patient showed improvement with heavy pulse steroid and immunomodulator therapy. Although skin, heart, and CNS involvement have been previously reported with ANCA-associated vasculitis, it is rare, especially together, and can prove a diagnostic challenge. Therefore, it is important to consider vasculitis etiology in patients presenting similarly. In addition, this case highlights the overlapping clinical picture between infective endocarditis and vasculitis with valvular involvement, making differentiation between the two challenging.

A rare case of inferior sinus venosus atrial septal defect and concomitant hypoplasia of the posterior mitral valve leaflet.

Inferior sinus venosus atrial septal defect (SVASD) is the rarest form of the atrial septal defect (ASD) and can sometimes go unnoticed. Although this defect can be associated with other congenital anomalies, its association with hypoplasia of the posterior mitral leaflet is extremely rare. In this case, we present a woman with a history of surgery for an ostium secundum ASD who exhibited persistent right heart chamber dilation. Echocardiography revealed hypoplasia of the posterior mitral leaflet, and cardiac magnetic resonance (CMR) imaging confirmed the presence of a previously undetected inferior sinus venosus ASD.

Similar Outcomes in Males and Females Undergoing Surgery for Infective Endocarditis.

Background: Sex-based differences in mortality have been previously observed in patients with surgically treated infective endocarditis. We sought to evaluate the risk factors leading to this difference. Methods: A retrospective cohort from three centers in Israel comprising 376 surgically treated patients, comparing short- and long-term mortality rates and risk factors between female and male patients. Results: Compared to male patients, female patients had higher rates of hypertension (62% vs. 48%), higher rates of Gram-negative infections (20% vs. 11%), and more mitral valve replacement (55% vs. 42%). Diabetes and age were the most significant predictors for mortality and did not differ between female and male patients. In-hospital mortality rates did not differ between female and male patients (29% vs. 26%), and the difference in long-term mortality was not statistically significant (46% vs. 36% p = 0.088). Conclusions: No statistical difference was observed in short- and long-term mortality between female and male patients, most likely due to a lack of difference in the rates of important risk factors such as diabetes and age. Mortality rates decreased in the last 10 years, and a good prognosis is observed for patients surviving the initial 30 days after surgery.