Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial.

BACKGROUND: Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding. METHODS: The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100 units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100 units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2 to 5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. CONCLUSIONS: Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation. CLINICAL TRIALS REGISTRATION NUMBER: The study protocol is registered at ClinicalTrials.gov, identifier NCT05305612.

Understanding transcatheter edge-to-edge repair "knobology": Advanced catheter steering for different scenarios of transseptal puncture.

Following the introduction in the latest European and American guidelines, transcatheter edge-to-edge repair has become a valid alternative to surgery for ineligible patients. Among the available technologies, MitraClip (Abbott) was the first to be introduced for the percutaneous treatment of mitral regurgitation with the edge-to-edge technique. Although its safety and effectiveness has been widely demonstrated, the optimal procedural results are highly dependent from operators' experience. In this manuscript, we provide a full guide of advanced steering maneuvers of MitraClip in different scenarios of transseptal puncture.

Clinical characteristics and outcomes of alcohol septal ablation in the era of transcatheter valve interventions.

BACKGROUND: The clinical efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) have been well-established; however, less is known about outcomes in patients undergoing preemptive ASA before transcatheter mitral valve replacement (TMVR). AIMS: The goal of this study is to characterize the procedural characteristics and examine the clinical outcomes of ASA in both HCM and pre-TMVR. METHODS: This retrospective study compared procedural characteristics and outcomes in patient who underwent ASA for HCM and TMVR. RESULTS: In total, 137 patients were included, 86 in the HCM group and 51 in the TMVR group. The intraventricular septal thickness (mean 1.8 vs. 1.2 cm; p < 0.0001) and the pre-ASA LVOT gradient (73.6 vs. 33.8 mmHg; p ≤ 0.001) were higher in the HCM group vs the TMVR group. The mean volume of ethanol injected was higher (mean 2.4 vs. 1.7 cc; p < 0.0001). The average neo-left ventricular outflow tract area increased significantly after ASA in the patients undergoing TMVR (99.2 ± 83.37 mm2 vs. 196.5 ± 114.55 mm2; p = <0.0001). The HCM group had a greater reduction in the LVOT gradient after ASA vs the TMVR group (49.3 vs. 18 mmHg; p = 0.0040). The primary composite endpoint was higher in the TMVR group versus the HCM group (50.9% vs. 25.6%; p = 0.0404) and had a higher incidence of new permanent pacemaker (PPM) (25.5% vs. 18.6%; p = 0.3402). The TMVR group had a higher rate of all-cause mortality (9.8% vs. 1.2%; p = 0.0268). CONCLUSIONS: Preemptive ASA before TMVR was performed in patients with higher degree of clinical comorbidities, and correspondingly is associated with worse short-term clinical outcomes in comparison to ASA for HCM patients. ASA before TMVR enabled percutaneous mitral interventions in a small but significant minority of patients that would have otherwise been excluded. The degree of LVOT and neoLVOT area increase is significant and predictable.

Optimizing transseptal puncture guided by three-dimensional mapping: the role of a unipolar electrogram in a needle tip.

AIMS: A three-dimensional electroanatomic mapping system-guided transseptal puncture (3D-TSP), without fluoroscopy or echocardiography, has been only minimally reported. Indications for 3D-TSP remain unclear. Against this background, this study aims to establish a precise technique and create a workflow for validating and selecting eligible patients for fluoroless 3D-TSP. METHODS AND RESULTS: We developed a new methodology for 3D-TSP based on a unipolar electrogram derived from a transseptal needle tip (UEGM tip) in 102 patients (the derivation cohort) with intracardiac echocardiography (ICE) from March 2018 to February 2019. The apparent current of injury (COI) was recorded at the muscular limbus of the foramen ovalis (FO) on the UEGM tip (sinus rhythm: 2.57 ± 0.95 mV, atrial fibrillation: 1.92 ± 0.77 mV), which then disappeared or significantly reduced at the central FO. Changes in the COI, serving as a major criterion to establish a 3D-TSP workflow, proved to be the most valuable indicator for identifying the FO in 99% (101/102) of patients compared with three previous techniques (three minor criteria) of reduction in atrial unipolar or bipolar potential and FO protrusion. A total of 99.9% (1042/1043) patients in the validation cohort underwent successful 3D-TSP through the workflow from March 2019 to July 2023. Intracardiac echocardiography guidance was required for 6.6% (69/1042) of patients. All four criteria were met in 740 patients, resulting in a 100% pure fluoroless 3D-TSP success rate. CONCLUSION: In most patients, fluoroless 3D-TSP was successfully achieved using changes in the COI on the UEGM tip. Patients who met all four criteria were considered suitable for 3D-TSP, while those who met none required ICE guidance.

Septal venous channel perforation during left bundle branch area pacing: a prospective study.

AIMS: To characterize the diagnosis, frequency, and procedural implications of septal venous channel perforation during left bundle branch area pacing (LBBAP). METHODS AND RESULTS: All consecutive patients undergoing LBBAP over an 8-month period were prospectively studied. During lead placement, obligatory septal contrast injection was performed twice, at initiation (implant entry zone) and at completion (fixation zone). An intuitive fluoroscopic schema using orthogonal views (left anterior oblique/right anterior oblique) and familiar landmarks is described. Using this, we resolved zonal distribution (I-VI) of lead position on the ventricular septum and its angulation (post-fixation angle θ). Subjects with and without septal venous channel perforation were compared. Sixty-one patients {male 57.3%, median age [interquartile range (IQR)] 69.5 [62.5-74.5] years} were enrolled. Septal venous channel perforation was observed in eight (13.1%) patients [male 28.5%, median age (IQR) 64 (50-75) years]. They had higher frequency of (i) right-sided implant (25% vs. 1.9%, P = 0.04), (ii) fixation in zone III at the mid-superior septum (75% vs. 28.3%, P = 0.04), (iii) steeper angle of fixation-median θ (IQR) [19 (10-30)° vs. 5 (4-19)°, P = 0.01], and (iv) longer median penetrated-lead length (IQR) [13 (10-14.8) vs. 10 (8.5-12.5) mm, P = 0.03]. Coronary sinus drainage of contrast was noted in five (62.5%) patients. Abnormal impedance drops during implantation (12.5% vs. 5.7%, P = NS) were not significantly different. CONCLUSION: When evaluated systematically, septal venous channel perforation may be encountered commonly after LBBAP. The fiducial reference framework described using fluoroscopic imaging identified salient associated findings. This may be addressed with lead repositioning to a more inferior location and is not associated with adverse consequence acutely or in early follow-up.

Tailored Planning of Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease characterized by abnormal thickening of the myocardium caused by myocardial disarray and interstitial fibrosis. HCM is associated with sudden cardiac-related events, such as ventricular fibrillation, tachycardia, and syncope. Moreover, left ventricular or midcavity obstruction due to the thickened myocardium can result in severe heart failure and mortality in patients with HCM. Surgical myectomy is a standard treatment option for patients with symptomatic obstructive HCM; however, it is a complex procedure that requires careful planning and execution to avoid complications, such as residual flow obstruction, persistent obliteration of the left ventricular cavity in systole, or iatrogenic ventricular septal defects. Therefore, a thorough understanding of the mechanics of HCM and precise evaluation of the location and extent of the hypertrophic myocardium to be removed are crucial for preoperative planning. Multiphase cardiac CT postprocessing is important for preoperative evaluation and planning of surgical myectomy in patients with HCM. In this review, the authors highlight use of multiphase cardiac CT with step-by-step postprocessing methods to simulate successful surgical myectomy. The transaortic surgeon's view on end-diastolic phase images accurately represents the surgical field. Moreover, myocardial segmentation can be used to generate volume-rendered images and three-dimensional printing. CT evaluation can also assist in identifying concurrent abnormalities, such as mitral valve or papillary muscle abnormalities. In addition to CT, other imaging modalities for preoperative evaluation of HCM and postmyectomy evaluation methods are presented. ©RSNA, 2023 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Association between postoperative nadir platelet count and postoperative cardiovascular complications following septal myectomy in patients with hypertrophic cardiomyopathy: a retrospective cohort study.

BACKGROUND: Platelet count is associated with cardiovascular risk and mortality in several cardiovascular diseases, but the association of the nadir platelet counts post-septal myectomy with the cardiovascular complication risk in hypertrophic obstructive cardiomyopathy patients remains unclear. METHODS: This retrospective cohort study reviewed all adult patients who underwent septal myectomy at a single tertiary referral center over a 5-year period. Postoperative nadir platelet count was defined as the lowest platelet count in the first 4 postoperative days or until hospital discharge. The composite outcome included cardiovascular death, myocardial infarction, heart failure, malignant arrhythmia, cardiac tamponade, and major bleeding events within 30 days postoperatively. Univariable and multivariable logistic regression and restricted cubic spline models were used to assess the association between postoperative nadir platelet count and the 30-day postoperative cardiovascular complication risk. RESULTS: Among the 113 enrolled patients, 23 (20.4%) developed cardiovascular events within 30 days postoperatively. The incidence of postoperative cardiovascular complications was significantly higher in patients with a nadir platelet count ≤ 99 × 109/L than in those with a nadir platelet count > 99 × 109/L (33.3% vs. 7.1%, crude risk ratio: 4.67, 95% confidence interval: 1.69-12.85, P < 0.001). Multivariable logistic regression revealed that postoperative nadir platelet count was negatively associated with 30-day postoperative cardiovascular complications (adjusted odds ratio: 0.97; 95% confidence interval: 0.95-0.99; P = 0.005) and the association was linear (Pnonlinearity = 0.058) after full adjustment. The association between nadir platelet count and cardiovascular complications within 30 days post-surgery was consistent in all predefined subgroups (Pinteraction > 0.05). CONCLUSION: The postoperative nadir platelet count was significantly associated with the 30-day post-myectomy risk of cardiovascular complications in hypertrophic obstructive cardiomyopathy patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04275544).

Intracardiac echocardiography guided electrified J-wire trans-septal puncture: A prospective randomized controlled trial.

BACKGROUND: Application of electrocautery to a J-wire is used to perform transseptal puncture (TSP), but with limited evidence supporting safety and efficacy. We conducted a prospective randomized controlled trial to evaluate the safety and efficacy of this technique. METHODS: Two hundred consecutive patients were randomized in a 1:1 fashion to either the ICE-guided electrified J-wire TSP group or a conventional Brockenbrough (BRK) needle TSP group. The TSP was performed with a 0.032″ guidewire under 20 W, "coag" mode and was compared to TSP using the BRK needle. The primary safety endpoints were complications related to TSP. The primary efficacy endpoints included the TSP success rate, the total TSP time, and the total procedure time. RESULTS: All patients complete the procedure safely. The electrified J-wire TSP group had a significantly shorter TSP time than BRK needle TSP group. The total procedure time, number of TSP attempts required to achieve successful LA access, width of the intra-atrial shunt at the end of ablation were similar between the two groups. The incidence of new cerebral infarction detected by MRI were similar between the two groups (3/32 patients in the J-wire TSP group and 2/26 patients in conventional BRK TSP group, p = .82). And no difference in the incidence of residual intra-atrial shunt (4.3% vs. 6%, p = .654) during the 3-month's follow up. CONCLUSION: Using an electrified J-wire for TSP under the guidance of ICE appears to be as safe as and more efficient than conventional BRK needle TSP, which may be especially useful in the era of non-fluoroscopy AF ablation.

Long-Term Clinical Outcome After Alcohol Septal Ablation and Its Periprocedural Predictive Factors in Japan　- A Retrospective Observational Study.

BACKGROUND: Evidence is limited regarding long-term clinical outcomes after alcohol septal ablation (ASA) for patients with hypertrophic obstructive cardiomyopathy and its periprocedural predictive factors in Japan.Methods and Results: This retrospective observational study included 44 patients who underwent ASA between 1998 and 2022 in a single center. We evaluated the periprocedural change in variables and long-term clinical outcomes after the procedure. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. The secondary outcome was all-cause death. Using multivariable Poisson regression with robust error variance, we predicted underlying periprocedural factors related to primary outcome development. ASA decreased the median pressure gradient at the left ventricular outflow tract from 88 to 33 mmHg and reduced moderate or severe mitral regurgitation (MR), present in 53% of patients before ASA, to 16%. Over a median 6-year follow-up, the cumulative incidence of the primary outcome at 5 and 10 years was 16.5% and 25.6%, respectively. After multivariable analysis, moderate or severe MR after ASA was significantly associated with the primary outcome (relative risk 8.78; 95% confidence interval 1.34-57.3; P=0.024). All-cause mortality after ASA was 15.1% and 28.9% at 5 and 10 years, respectively. CONCLUSIONS: This study presents long-term clinical outcomes after ASA in Japan. Moderate or severe MR after ASA was significantly associated with the composite of cardiovascular death or hospitalization for heart failure.

Bilateral septal pacing in combination with coronary venous pacing for cardiac resynchronization therapy.

BACKGROUND: Conventional right ventricular pacing combined with coronary venous pacing (CVP) is a mainstay for cardiac resynchronization therapy (CRT). However, QRS duration of conventional CRT may be frequently more than 130 ms. This study aimed to evaluate the effectiveness of QRS narrowing by bilateral septal pacing (BSP) in combination with CVP for CRT (BSP-CRT). METHODS: Fourteen patients with QRS > 130 ms of conventional CRT after failure of physiological conduction system pacing were enrolled. Electrophysiologic characteristics were compared among different modes of CRT during procedure. BSP which was defined as capture of both sides of interventricular septum manifested as shortened R wave peak time without a right bundle branch block QRS pattern. RESULTS: BSP-CRT were successfully achieved in 85.7% (12/14) patients. QRS duration at baseline was 185 ± 13 ms and significantly narrowed to 156 ± 9 ms during conventional CRT (n = 14, P < .001), to 143 ± 7 ms during left ventricular septal pacing (LVSP) in combination with CVP for CRT (LVSP-CRT) (n = 9, P < .001), and further to 122 ± 10 ms during BSP-CRT (n = 12, P < .001). Notably, among 7 patients in whom both LVSP and BSP were achieved, BSP-CRT outperformed LVSP-CRT at QRS narrowing by 16% (P < .001). At 3-month follow-up, left ventricular ejection fraction improved from 29 ± 6% to 41 ± 8% (P < .001). CONCLUSIONS: BSP-CRT resulted in superior acute electrical synchronization to conventional CRT and might be considered as an alternative to conventional CRT with QRS more than 130 ms.

[Surgery for obstructive hypertrophic cardiomyopathy: challenge and future].

After more than 60 years of development, with the deepening of the pathophysiological understanding of obstructive hypertrophic cardiomyopathy, the extent and resection thickness of myectomy have increased significantly. Myectomy combined with the correction of anomalies of the mitral valve apparatus has become the standard treatment of obstructive hypertrophic cardiomyopathy. Only a few centers worldwide can routinely perform it due to the difficulty. Because of the advances of new drugs and interventional therapy, the development of surgical treatment faces many challenges. At the same time, generations of cardiovascular surgeons are constantly trying to promote septal myectomy, including developing devices and the surgical field, as well as improving surgical planning by advanced technology. At present, the superior long-term efficacy of septal myectomy has been confirmed. It is necessary to work together to promote the treatment of hypertrophic obstructive cardiomyopathy, so as to guard people's health.

[Efficacy of alcohol septal ablation in mildly symptomatic or severely symptomatic patients with hypertrophic obstructive cardiomyopathy].

Objective: To compare the prognosis of mildly or severely symptomatic patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent alcohol septal ablation (ASA). Methods: This retrospective study cohort consisted of patients with OHCM who received ASA treatment in Beijing Anzhen Hospital, Capital Medical University from March 2001 to August 2021. These patients were divided into mildly and severely symptomatic groups according to the severity of clinical symptoms. Long-term follow-up was conducted, and the following data were collected: duration of follow-up, postoperatire treatment, New York Heart Association (NYHA) classification, arrhythmia events and pacemaker implantation, echocardiographic parameters, and cause of death. Overall survival and survival free from OHCM-related death were observed, and the improvement of clinical symptoms and resting left ventricular outflow tract gradient (LVOTG) and the incidence of new-onset atrial fibrillation were evaluated. The Kaplan-Meier method and log-rank test were used to determine and compare the cumulative survival rates of the different groups. Cox regression analysis models were used to determine predictors of clinical events. Results: A total of 189 OHCM patients were included in this study, including 68 in the mildly symptomatic group and 121 in the severely symptomatic group. The median follow-up of the study was 6.0 (2.7, 10.6) years. There was no statistical difference in overall survival between the mildly symptomatic group (5-year and 10-year overall survival were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year overall survival were 94.2% and 83.9%, respectively, P=0.405); there was also no statistical difference in survival free from OHCM-related death between the mildly symptomatic group (5-year and 10-year survival free from HCM-related death were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year survival free from HCM-related death were 95.2% and 92.6%, respectively, P=0.846). In the mildly symptomatic group, NYHA classification was improved after ASA (P<0.001), among which 37 patients (54.4%) were in NYHA class Ⅰ, and the resting left ventricular outflow tract gradient (LVOTG) decreased from 67.6 (42.7, 90.1) mmHg (1 mmHg=0.133 kPa) to 24.4 (11.7, 35.6) mmHg (P<0.001). In severely symptomatic group, NYHA classification was also improved post ASA (P<0.001), among which 96 patients (79.3%) improved by at least one NYHA classification, and the resting LVOTG decreased from 69.6 (38.4, 96.1) mmHg to 19.0 (10.6, 39.8) mmHg (P<0.001). The incidence of new-onset atrial fibrillation was similar between the mildly and severely symptomatic groups (10.2% vs. 13.3%, P=0.565). Cox multivariate regression analysis showed that age was an independent predictor of all-cause mortality in OHCM patients post ASA (HR=1.068, 95%CI 1.002-1.139, P=0.042). Conclusions: Among patients with OHCM treated with ASA, overall survival and survival free from HCM-related death were similar between mildly symptomatic group and severely symptomatic group. ASA therapy can effectively relieve resting LVOTG and improve clinical symptoms in mildly or severely symptomatic patients with OHCM. Age was an independent predictor of all-cause mortality in OHCM patients post ASA.

Transseptal access: A review of contemporary tools.

Transseptal left atrial catheterization is routinely used for many common catheter-based interventions. Tools for transseptal catheterization have advanced over the recent years. Such tools include imaging advances with intracardiac echocardiology as well as an array of needles, wires, and dilators to achieve transseptal access with greater ease and safety. This study will discuss the contemporary tools for transseptal catheterization and guidance for difficult cases.

Why is the patient still symptomatic after myectomy for HCM!

We describe the case of a young female patient with hypertrophic cardiomyopathy (HCM) with a dual chamber implantable cardioverter defibrillator (ICD), and complete heart block from a prior septal ablation procedure. Due to persistent left ventricular outflow tract (LVOT) obstruction and symptoms, she underwent surgical myectomy. Her exertional symptoms continued despite improved LVOT flow parameters. A comprehensive evaluation, including ICD interrogation, helped arrive at the correct diagnosis and treatment plan.

Real-world clinical outcomes of percutaneous transluminal septal myocardial ablation for patients with drug-refractory hypertrophic obstructive cardiomyopathy: results from a retrospective multicenter registry of non-high-volume centers.

Percutaneous transluminal septal myocardial ablation (PTSMA) is a well-established interventional therapy for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM) as an alternative to surgical myectomy. Although guidelines recommend that PTSMA should be performed in institutions with extensive experience, it is not centralized to such high-volume centers in real-world clinical practice. Thus, this study aimed to assess the feasibility of PTSMA in non-high-volume centers. We retrospectively examined patients with HOCM who underwent PTSMA between August 2012 and May 2020 at four institutions that experienced fewer than 20 cases of PTSMA procedures. The primary clinical endpoint was a composite of safety (all-cause death, electrical defibrillation for ventricular tachycardia or fibrillation, cardiac tamponade, permanent pacemaker implantation, and repeated interventions) and efficacy endpoints (repeated interventions [PTSMA or surgical myectomy]). Fifty-eight consecutive patients were enrolled. During the 30-day follow-up, no major clinical adverse events were noted except three patients (5.2%) requiring permanent pacemaker implantation for complete atrioventricular block. The percentage of patients with New York Heart Association functional class 1 or 2 significantly increased from 8.6 to 100% (p < 0.001). In the Cox proportional hazard model, left ventricular outflow tract pressure gradient at rest ≥ 30 mmHg (hazard ratio [HR] 6.56; 95% confidence interval [CI] 1.44-29.90; p = 0.015) and mitral regurgitation grade ≥ 3 (HR 10.75; 95% CI 1.81-63.79; p = 0.009) at the 30-day follow-up were associated with a composite of major clinical adverse events. The current study demonstrated that 58 patients who underwent PTSMA in non-high-volume centers had favorable 30-day clinical outcomes, with a primary composite endpoint rate of 5.2%. A prospective study with a larger sample size and longer follow-up is warranted to verify the safety and efficacy of PTSMA in non-high-volume centers.

Exercise Echocardiography following Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy.

OBJECTIVES: To investigate outcome after septal myectomy and to evaluate long-term hemodynamics with exercise echocardiography. METHODS: This study included 40 consecutive patients operated with septal myectomy for hypertrophic obstructive cardiomyopathy from January 1998 to August 2017 at Skane University Hospital, Lund, Sweden. Perioperative clinical data and echocardiography measurements were reviewed retrospectively. Patients (n = 36) who were alive and living in Sweden were invited for exercise echocardiography to evaluate exercise capacity and hemodynamics, of whom 19 patients performed exercise echocardiography. RESULTS: Overall survival was 100% at 1 year and 96% at 5 years following surgery. Preoperative median resting peak LVOT (left ventricular outflow tract) gradient was 80 mm Hg. Septum thickness was reduced from 22 ± 4 mm preoperatively to 16 ± 3 mm postoperatively (p < 0.001). During exercise echocardiography, the peak LVOT gradient was 8 mm Hg at rest, and increased to 13 mm Hg during exercise echocardiography (p = 0.002). None of the patients had dynamic LVOT obstruction during exercise echocardiography, and there was no clinically significant systolic anterior motion or severe mitral insufficiency during exercise. CONCLUSIONS: Long-term survival following septal myectomy is very good. At long-term follow-up, LVOT gradients were low and exercise echocardiography demonstrated good hemodynamics.

Hypertrophic Obstructive Cardiomyopathy: Discrepancy Between Hemodynamic Measurements in the Cardiac Laboratory and Operating Room Is to Be Expected.

OBJECTIVES: It is not uncommon to observe some discrepancy in hemodynamic values characterizing left ventricular outflow tract (LVOT) obstruction preoperatively and in the operating room in patients with hypertrophic obstructive cardiomyopathy. Interpretation of this discrepancy can be challenging. To clarify the extent of the discrepancy, the authors compared hemodynamic variables in patients undergoing septal myectomy at the time of preoperative and intraoperative evaluation. DESIGN: Retrospective study. SETTING: Single academic medical center. INTERVENTIONS: Medical records review, study group-173 patients. MEASUREMENTS AND MAIN RESULTS: While there was no statistically significant difference in resting peak LVOT gradients by preoperative transthoracic echocardiography (TTE) compared to intraoperative transesophageal echocardiography (46 mmHg [19-87 mmHg] v 36 mmHg [16-71 mmHg], p = 0.231), the former were higher compared to direct needle-resting LVOT gradient measurements before myectomy (49 mmHg [19-88 mmHg] v 32 mmHg [14-67 mmHg], p = 0.0022). The prevalence of systolic anterior motion was high (94.6% v 91.6%, P = 1.000) both on pre- and intraoperative evaluation. The incidence of moderate/severe mitral was higher intraoperatively (p < 0.0001). Pulmonary artery systolic pressures measured by pulmonary artery catheter provided higher values compared to preoperative TTE estimate (39 mmHg [34-45 mmHg] v 34 mmHg [28-41 mmHg], p < 0.0001). CONCLUSIONS: Discrepancy between hemodynamic measurements in the cardiac laboratory and operating room is common and generally should not affect planned patients' care. These changes in hemodynamics might be explained by preoperative fasting, anesthetic agents, volume shifts while supine, and positive-pressure ventilation, as well as the difference in measurement techniques.

Hypertrophic obstructive cardiomyopathy with a basal septal thickness of 16 mm or less: clinical characteristics and surgical results.

PURPOSES: To characterize the clinical features and surgical outcomes of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) in patients with only mild septal hypertrophy. METHODS: The clinical characteristics and surgical outcomes of 53 HOCM patients with a basal septal thickness ≤ 16 mm (mild group) were compared with those of 128 HOCM patients with a basal septal thickness > 16 mm (control group). RESULTS: The mild group had a greater prevalence of mitral subvalvular anomalies than the control group (79.2% vs. 6.3%, p < 0.001). Neither iatrogenic septal perforation nor inadequate septal myectomy was observed after myectomy in the mild group. There were no deaths during a median follow-up of 10 months. Transthoracic echocardiography 6 months after myectomy revealed a significant decrease in maximum gradients in both groups, from baseline 90.5 ± 21.5 mmHg to 10.3 ± 4.4 mmHg in the mild group (p < 0.001) and from 95.0 ± 22.0 mmHg to 12.0 ± 5.9 mmHg (p < 0.001) in the control group. Neither residual obstruction nor residual mitral regurgitation was recorded in the mild group. CONCLUSIONS: Symptomatic patients with hypertrophic obstructive cardiomyopathy and mild septal hypertrophy may have a higher prevalence of mitral subvalvular abnormalities. Mitral subvalvular management during myectomy can achieve outstanding results for these patients.

[Therapeutic effects of alcohol septal ablation in mildly symptomatic patients with hypertrophic obstructive cardiomyopathy].

Objective: To observe the therapeutic effects of alcohol septal ablation (ASA) in mildly symptomatic patients (NYHA class Ⅱ) with hypertrophic obstructive cardiomyopathy(HOCM). Methods: This retrospective study included 150 mildly symptomatic patients with HOCM hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from March 2001 to December 2017, consisting of medical therapy group (n=102) and ASA group (n=48). Baseline clinical data were collected, patients were followed up to a mean of 6.0 (3.5, 8.1) years. Overall and HCM-related mortality events (including chronic heart failure, atrial fibrillation related stroke, sudden cardiac death) were observed in the two groups. Moreover, the improvement of NYHA function classification and left ventricular outflow tract gradient (LVOTG) were also evaluated. Survival analysis was performed by Kaplan-Meier method. Results: Age of this cohort was (52.9±14.5)years, 92 cases(61.3%) were male. In the follow-up, LVOTG was reduced from (85.8±35.4)mmHg (1 mmHg=0.133 kPa) to (27.7±19.8)mmHg (P<0.001) in the ASA group, and from (66.3±35.0)mmHg to (56.5±27.7)mmHg in medical therapy group(P<0.01). At the last clinical follow-up, there were 32 patients (66.7%) whose LVOTG were<30 mmHg, septal thickness decreased from (20.3±3.8)mm to (16.1±3.4)mm (P<0.001), NYHA classification was also remarkably improved (P<0.001). New-onset atrial fibrillation tended to be lower in the ASA group compared to medical therapy group (9.3%(4/43) vs. 20.8%(20/96),P=0.096). Eleven patients (10.8%) in the medical therapy group and 2 patients (4.2%) in the ASA group died during the follow-up. One patient received pacemaker during the peri-procedural period, 1 patient was implanted with two-chamber pacemaker due to Ⅲ° atrioventricular block at 10 years after operation in the ASA group. Survival free of all-cause mortality of ASA group at 5 and 10 years was 97.9% and 97.9%, respectively, which was comparable to the medical therapy group (P=0.231). Survival free of HCM-related mortality was similar between the two groups (P=0.397). Conclusions: Compared with medical therapy in mildly symptomatic patients with HOCM, long-term survival rate is similar after ASA. Meanwhile, ASA can remarkably reduce LVOTG and improve the clinical status of the patients. Therefore, ASA may be used as an alternative therapy for mildly symptomatic HOCM patients.

SHROOM3 is downstream of the planar cell polarity pathway and loss-of-function results in congenital heart defects.

Congenital heart disease (CHD) is the most common birth defect, and the leading cause of death due to birth defects, yet causative molecular mechanisms remain mostly unknown. We previously implicated a novel CHD candidate gene, SHROOM3, in a patient with CHD. Using a Shroom3 gene trap knockout mouse (Shroom3gt/gt) we demonstrate that SHROOM3 is downstream of the noncanonical Wnt planar cell polarity signaling pathway (PCP) and loss-of-function causes cardiac defects. We demonstrate Shroom3 expression within cardiomyocytes of the ventricles and interventricular septum from E10.5 onward, as well as within cardiac neural crest cells and second heart field cells that populate the cardiac outflow tract. We demonstrate that Shroom3gt/gt mice exhibit variable penetrance of a spectrum of CHDs that include ventricular septal defects, double outlet right ventricle, and thin left ventricular myocardium. This CHD spectrum phenocopies what is observed with disrupted PCP. We show that during cardiac development SHROOM3 interacts physically and genetically with, and is downstream of, key PCP signaling component Dishevelled 2. Within Shroom3gt/gt hearts we demonstrate disrupted terminal PCP components, actomyosin cytoskeleton, cardiomyocyte polarity, organization, proliferation and morphology. Together, these data demonstrate SHROOM3 functions during cardiac development as an actomyosin cytoskeleton effector downstream of PCP signaling, revealing SHROOM3's novel role in cardiac development and CHD.