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We describe the echocardiographic features of a 22-year-old female with a giant aneurysm of membranous ventricular septum (AMVS). Both transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) demonstrated significant dilatation of the aortic annulus and severe aortic regurgitation. A giant aneurysm was detected extending from a large membranous ventricular septal defect (MVSD) to the anterior surface of the aortic root. Contrast-enhanced CT and three-dimensional CT revealed a giant aneurysm located below the aortic root and connected to the left ventricular outflow tract (LVOT). The diagnosis was confirmed by surgery and postoperative pathological examination., (© 2024. The Author(s).)

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach., (© 2024. The Author(s).)

Ventricular septation is a complex process which involves the major genes of cardiac development, acting on myocardial cells from first and second heart fields, and on mesenchymal cells from endocardial cushions. These genes, coding for transcription factors, interact with each other, and their differential expression conditions the severity of the phenotype. In this chapter, we will describe the formation of the ventricular septum in the normal heart, as well as the molecular mechanisms leading to the four main anatomic types of ventricular septal defects: outlet, inlet, muscular, and central perimembranous, resulting from failure of development of the different parts of the ventricular septum. Experiments on animal models, particularly transgenic mouse lines, have helped us to decipher the molecular determinants of ventricular septation. However, a precise description of the anatomic phenotypes found in these models is mandatory to achieve a better comprehension of the complex mechanisms responsible for the various types of VSDs., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The extent of heavy-metal-induced cardiotoxicity is proportional to the levels of metal bioaccumulation, and it was previously assumed that heavy metals accumulate uniformly in the myocardium. Therefore, the aim of this study was to investigate concentrations of metals and metalloids in two distant regions of the left ventricle (LV), the base of the LV, and apex of the LV using inductively coupled plasma mass spectrometry (ICP-MS). We also examined the potential correlation between metal levels and the thickness of the interventricular septum in twenty LV specimens (ten from the base of LV and ten from the apex of LV) from 10 individuals (mean age 75 ± 6 years). We found significantly higher concentrations of arsenic and lead in the LV apex compared to the base of the LV. We also found a positive correlation between the concentrations of arsenic in the myocardium of LV and the thickness of the interventricular septum. Our results indicate that arsenic and lead accumulate to a higher extent in the apex of the LV compared to the base of the LV. Therefore, future studies designed to measure levels of metals in heart muscle should consider non-uniform accumulation of metals in the myocardium.

Rationale: We report a rare case of hypertrophic cardiomyopathy (HCM) caused by a heterozygous variant in TTR gene., Patient Concerns: The proband had been vomiting without obvious inducement since the age of 27, accompanied by the expulsion of stomach contents. At the age of 28, she began to suddenly syncope., Diagnosis: Cardiac magnetic resonance showed thickening of the right ventricular lateral wall and ventricular septum. The left ventricular diastolic function was limited. Targeted Sanger sequencing validates the presence of mutation p.Leu75Pro in TTR gene., Interventions and Outcomes: After admission to hospital for syncope, she was given metoprolol tablets 25 mg bid, spironolactone tablets 20 mg qd, and trimetazidine 20 mg tid. Her symptoms improved after taking the medicine., Lessons: The results of this case show that HCM caused by TTR mutation is not easy to be identified and treatment is easy to be delayed. Therefore, high-risk patients with amyloidosis should be evaluated as soon as possible. Timely diagnosis of HCM caused by TTR mutation before irreversible organ damage is essential for proper treatment and better outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Presence of scar at the implantation-site is considered as a major factor in determining the success of left bundle branch pacing (LBBP). We aimed at analyzing the predictors of procedural failure in patients with scarred-left ventricle (LV) as demonstrated by cardiac-magnetic resonance-imaging (CMR)., Methods: This was a retrospective, observational single-center-study that included consecutive cardiomyopathy patients with LV-scar as demonstrated by late-gadolinium-enhancement (LGE) in CMR requiring LBBP. Procedural-failure was defined as the inability to penetrate the septum to reach the LV subendocardium RESULTS: A total of 25 cardiomyopathy patients demonstrated LGE in CMR and were included in the study. LBBP was successful in 16 patients (group-I; 64% acute-procedural-success). In the remaining 9 patients (group-II) lead could not be penetrated and hence biventricular-pacing was done. LBBP resulted in reduction in QRS-duration and improvement in LV ejection fraction in group-I patients during a mean follow-up of 11.2 ± 3.7 months. Computed-tomography-angiography after LBBP showed the successful lead deployment site (LBBP-Zone) as the overlapping areas of inferior aspect of antero-septum and superior aspect of infero-septum (segment 2/3; AHA-model) in short-axis view(figure-1C). CMR showed LGE in significantly more number of LV-segments and high scar-burden in group-II as compared to group-I (figure-1). A total scar score value of >1.0 predicted failure with 100%-sensitivity and 75%-specificity. CMR revealed transmural-scar in the LBBP-Zone in all patients in group-II (n = 9; 100%). Transmural scar in LBBP-Zone by CMR had 100%-sensitivity and 100%-specificity for predicting the procedural-failure., Conclusion: CMR helps in predicting the procedural failure of LBBP in patients with scarred LV. Presence of transmural-LGE in the LBBP-Zone predicts failure with high sensitivity and specificity., (© 2023 Wiley Periodicals LLC.)

Granular cell tumours are usually benign with a 1-2% incidence of malignancy. They are less sensitive to radiotherapy and chemotherapy and are treated by surgical excision. We report a case of a malignant granular cell tumour located at the interventricular septum., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Unexpected cardiac deaths are a current challenge to healthcare systems. In adults, coronary artery disease and acquired cardiomyopathies are the most frequent causes of sudden cardiac death while in younger than 35 years old, the main cause is represented by non-ischemic diseases, usually inherited. Nowadays, around 10%-15% of unexpected deaths remain without a definite cause of decease after a complete autopsy, then classified as deaths potentially due to an inherited arrhythmia. Discrete abnormalities in some of the heart measures have been considered as potential predictors or risk factors for sudden cardiac death. However, role of non-benign genetic variants in these scattered heart alterations remains to be clarified, especially if variants are classified of ambiguous role. Clinicians usually only take into consideration pathogenic variants for decision-making. It is yet unclear what the role of VUS genetic variants in modifying the anatomical parameters of the heart. We hypothesize that some heart measures might be influenced by polygenic components as some variants may individually confer minor risk but may actually produce additive effects when combined with others. Our aim was to investigate whether carrying non-benign rare variants in genes related to inherited arrhythmias may contribute to scattered cardiac alterations in anatomical normal hearts. The study is composed by 761 samples collected from autopsies of SD suffered by adults from 18 to 50 years of age who occurred in Catalonia (Spain) in a 9-year period. Complete medico-legal autopsy was performed to determine the cause of death. Molecular autopsy was performed as part of our forensic protocol, including genes associated with inherited diseases.To evaluate the effect of genetic rare variants into hearts measures we performed a linear regression model and data were presented as regression. This study showed, for the first time, that rare variants, regardless of significance (pathogenic, probably pathogenic or uncertain significance), may contribute to interventricular septum width in the structurally normal heart. While the cohort is based on sudden death cases, further studies and case-control studies will be necessary to conclude that the genetic determinants of septal thickness contributes to sudden cardiac death. We conclude that non-benign rare variants contribute to modify scattered septum width in structural normal hearts, being a potential risk factor of arrhythmia in genetic harbors. These evidence support the current recommendation in forensic protocols of including histologic analysis of septum when inherited arrhythmogenic disease is suspicious cause of decease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study aimed to investigate the impact of weight loss after laparoscopic sleeve gastrectomy (LSG) on cardiac structural and functional remodeling in obese Chinese. A total of 44 obese participants were enrolled consecutively. The physical, laboratory, electrocardiographic, and echocardiographic parameters of pre-and postoperative were recorded. The average follow-up time was 12.28 ± 5.80 months. The body mass index (BMI) of the patients with obesity was decreased from 41.6 ± 7.44 to 30.3 ± 5.73kg/m 2 ( P <0.001) after LSG. The systolic and diastolic blood pressure of the subjects was significantly reduced from 137.9 ± 15.7mmHg to 123.0 ± 16.0 and 83.4 ± 10.8 to 71.3 ± 11.7mmHg (P<0.001), respectively. The levels of fasting insulin and fasting blood glucose were significantly decreased (38.8 ± 32.1 to 8.43 ± 4.16 mU/L, P <0.001; 6.95 ± 2.59 to 4.64 ± 0.50mmol/L, P <0.001). Total cholesterol (TC, 4.66 ± 0.84 to 4.23 ± 0.75mmol/L, P<0.001) and triglyceride (TG, 1.92 ± 1.21 to 0.85 ± 0.30mmol/L, P<0.001) decreased significantly. Cardiovascular geometric parameters including aortic sinus diameter (ASD, 32.9 ± 2.83mm to 32.0 ± 3.10mm, P<0.05), left atrial diameter (LAD, 38.8 ± 4.03 to 36.2 ± 4.12mm, P<0.001), and interventricular septum thickness(IVS, 10.2 ± 0.93 to 9.64 ± 0.89mm, P<0.001) were significantly reduced. The ratio of weight loss (RWL) was positively correlated with the changes of LAD. The change of IVS was negatively correlated with the change of fasting blood glucose (GLU). Weight loss after LSG could effectively improve cardiac structural, but not functional, abnormality in obese Chinese., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Meng, Peng, Du, Zheng, Liu, Qu, Xu and Zhang.)

Sustained ventricular tachycardia (sVT), leading to sudden cardiac death, is one of the common manifestations in cardiac sarcoidosis (CS). Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been reported to be associated with sVT, the relationships of its localization to sVT have not been fully evaluated.To evaluate the localization of LGE and its relationships to sVT in patients with CS, we reviewed medical record of consecutive 31 patients with CS who underwent CMR. The localization of LGE was divided into four categories: Left ventricular (LV) septum, LV free wall, right ventricular (RV) septum, and RV free wall. We investigated the association of sVT with localization of LGE and other parameters including serum biomarkers LV ejection fraction on echocardiography and Fluorine-18-fluorodeoxyglucose (FDG) accumulation on positron emission tomography (PET) -CT.Of the studied population, 8 patients (25.8%) were known to present with sVT among 31 CS patients. LGE was observed in the RV free wall in 6 patients with sVT, whereas it was in 5 patients without sVT (75.0% versus 21.7%, P = 0.022). Univariate analysis showed that only LGE in the RV free wall was associated with sVT (odds ratio [OR]: 10.80; 95% confidence interval [CI]: 1.64-70.93, P = 0.013).LGE in the RV free wall was associated with sVT in patients with CS.

Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized lipodystrophy, GLD) or only some (partial lipodystrophy, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia., Objective: Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy., Methods: Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N = 27), and 3 to 5 years (N = 23) of metreleptin. Outcomes were echocardiograms, blood pressure (BP), triglycerides, A1c, and homeostasis model assessment of insulin resistance., Results: In GLD, metreleptin lowered triglycerides (median [interquartile range] 740 [403-1239], 138 [88-196], 211 [136-558] mg/dL at baseline, 1 year, 3-5 years, P < .0001), A1c (9.5 ± 3.0, 6.5 ± 1.6, 6.5 ± 1.9%, P < .001), and HOMA-IR (34.1 [15.2-43.5], 8.7 [2.4-16.0], 8.9 [2.1-16.4], P < .001). Only HOMA-IR improved in PLD (P < .01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8 ± 1.7, 9.1 ± 1.3, 8.3 ± 1.7 mm, P < .01), and LV mass (140.7 ± 45.9, 128.7 ± 37.9, 110.9 ± 29.1 g, P < .01), and increased septal e' velocity (8.6 ± 1.7, 10.0 ± 2.1, 10.7 ± 2.4 cm/s, P < .01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e' velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD., Conclusion: Metreleptin attenuated cardiac hypertrophy and improved septal e' velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined., (Published by Oxford University Press on behalf of the Endocrine Society 2021.)

Ventricular septal defects (VSDs) are the most common congenital heart defects (CHDs). Studies have documented that ISL1 has a crucial impact on cardiac growth, but the role of variants in the ISL1 gene promoter in patients with VSD has not been explored. In 400 subjects (200 patients with isolated and sporadic VSDs: 200 healthy controls), we investigated the ISL1 gene promoter variant and performed cellular functional experiments by using the dual-luciferase reporter assay to verify the impact on gene expression. In the ISL1 promoter, five variants were found only in patients with VSD by sequencing. Cellular functional experiments demonstrated that three variants decreased the transcriptional activity of the ISL1 promoter ( P < 0.05). Further analysis with the online JASPAR database demonstrated that a cluster of putative binding sites for transcription factors may be altered by these variants, possibly resulting in change of ISL1 protein expression and VSD formation. Our study has, for the first time, identified novel variants in the ISL1 gene promoter region in the Han Chinese patients with isolated and sporadic VSD. In addition, the cellular functional experiments, electrophoretic mobility shift assay, and bioinformatic analysis have demonstrated that these variants significantly alter the expression of the ISL1 gene and affect the binding of transcription factors, likely resulting in VSD. Therefore, this study may provide new insights into the role of the gene promoter region for a better understanding of genetic basis of the formation of CHDs and may promote further investigations on mechanism of the formation of CHDs.

Objective: To report on the feasibility of establishing a regional prenatal referral network for critical congenital heart defects (CHDs) and its impact on perinatal outcome of fetuses with transposition of the great arteries and intact ventricular septum (TGA-IVS) in low-resource settings., Methods: This was a retrospective study of consecutive fetuses with a diagnosis of TGA-IVS between January 2011 and December 2019 in Kochi, Kerala, India. A regional network for prenatal diagnosis and referral of patients with critical CHDs was initiated in 2011. Pregnancy and early neonatal outcomes were reported. The impact of the timing of diagnosis (prenatal or after birth) on age at surgery, perinatal mortality and postoperative recovery was evaluated., Results: A total of 82 fetuses with TGA-IVS were included. Diagnosis typically occurred later on in gestation, at a median of 25 (interquartile range (IQR), 21-32) weeks. The majority (78.0%) of affected pregnancies resulted in live birth, most (84.4%) of which occurred in a specialist pediatric cardiac centers. Delivery in a specialist center, compared with delivery in a local maternity center, was associated with a significantly higher rate of surgical correction (98.1% vs 70.0%; P = 0.01) and overall lower neonatal mortality (3.7% vs 50%; P = 0.001). The proportion of cases undergoing arterial switch operation after prenatal diagnosis of TGA-IVS increased significantly, along with the prenatal detection rate, over the study period (2011-2015, 11.1% vs 2016-2019, 29.4%; P = 0.001). Median age at surgery was significantly lower in the prenatally diagnosed group than that in the postnatally diagnosed group (4 days (IQR, 1-23 days) vs 10 days (IQR, 1-91 days); P < 0.001). There was no significant difference in postoperative mortality (2.0% vs 3.6%; P = 0.49) between the two groups., Conclusions: This study demonstrates the feasibility of creating a network for prenatal diagnosis and referral of patients with critical CHDs, such as TGA, in low-resource settings, that enables planned peripartum care in specialist pediatric cardiac centers and improved neonatal survival. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Interventricular septal hematoma is an extremely rare complication following congenital heart surgery. During cardiac surgery, interventricular septal hematomas can be detected only by intraoperative transesophageal echocardiography. Here, we report an interesting case of interventricular septal hematoma that was accidentally found in an infant following ventricular septal defect (VSD) closure., Case Presentation: Transesophageal echocardiography images were acquired from a 1-month-old boy after surgical repair of a large (6.5 mm) perimembranous outlet VSD with interventricular septal flattening. Surgical correction was performed with auto-pericardium and 7-0 Prolene sutures. The patient was successfully weaned from cardiopulmonary bypass, and transesophageal echocardiography showed no VSD leakage and good ventricular function. However, approximately 30 min later, two anechoic masses were found within the interventricular septum, which were suspected to be interventricular septal hematomas; the larger mass measured 1.51 [Formula: see text] 1.48 cm. The swollen interventricular septum showed decreased contractility and compressed both the right and left ventricles. However, there was no change in the size of hematomas or a significant hemodynamic instability for 30 min of observation. Therefore, expecting spontaneous resolution of the hematomas, the interventricular septum was not explored, and the patient was removed from cardiopulmonary bypass. On postoperative day 4, follow-up transthoracic echocardiography revealed thrombi filling the hematomas. The patient was discharged on postoperative day 15 and followed up with regular echocardiographic evaluations., Conclusions: We describe a unique case of interventricular septal hematoma after VSD closure. Surgical manipulation of perimembranous VSD and injury of the septal perforating artery may contribute to the development of an interventricular septal hematoma. Moreover, conservative treatment and serial echocardiographic evaluation generally show gradual hematoma resolution in hemodynamically stable patients. Pediatric cardiac anesthesiologists should be aware of this rare complication after VSD repair., (© 2021. The Author(s).)

Background: Multiple studies have addressed the importance of anteroseptal scar in patients with nonischemic cardiomyopathy. However, this pattern has never been fully evaluated in patients with prior myocarditis., Objective: The purpose of this study was to evaluate whether anteroseptal scar is associated with worse outcome in patients with prior myocarditis and how it affects the efficacy of catheter ablation (CA)., Methods: This was a retrospective study of consecutive patients with prior myocarditis and arrhythmic presentation. Cardiac magnetic resonance and electroanatomic voltage mapping were used to identify the scar pattern. Patients were referred for either CA or escalated antiarrhythmic drug (AAD) therapy. The main outcome was ventricular arrhythmia (VA)-free survival according to the presence of anteroseptal scar., Results: A total of 144 consecutive patients with prior myocarditis were included. Mean age was 42.1 ± 14.9 years, and 58% were men. Ejection fraction was normal in 73% of patients. Anteroseptal scar was present in 44% of cases. Sixty-one patients (42%) underwent CA. Overall, at 2-year follow-up, VA-free survival was 77% in the CA group. After CA, the mean number of AADs taken by each patient decreased from 1.8 to 0.9 per day (p<0.001). The presence of anteroseptal scar was found to be an independent predictor of VA relapse both in patients treated with CA (hazard ratio [HR] 3.6; 95% confidence interval [CI] 1.1-11.4; P = .03) and in the overall population (HR 2.0; 95% CI 1.2-3.5; P = .02) ., Conclusion: In patients with prior myocarditis and VA, the presence of anteroseptal scar negatively predicts outcomes irrespective of treatment strategy., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

An essential role for cilia in the pathogenesis of congenital heart disease (CHD) has emerged from findings of a large-scale mouse forward genetic screen. High throughput screening with fetal ultrasound imaging followed by whole exome sequencing analysis recovered a preponderance of cilia related genes and cilia transduced cell signaling genes among mutations identified to cause CHD. The perturbation of left-right patterning in CHD pathogenesis is suggested by the association of CHD with heterotaxy, but also by the finding of the co-occurrence of laterality defects with CHD in birth defect registries. Many of the cilia and cilia cell signaling genes recovered were found to be related to Hedgehog signaling. Studies in mice showed cilia transduced hedgehog signaling coordinates left-right patterning with heart looping and differentiation of the heart tube. Cilia transduced Shh signaling also regulates later events in heart development, including outflow tract septation and formation of the atrioventricular septum. More recent work has shown mutations in cilia related genes may also contribute to valve disease that largely manifest in adult life. Overall, these and other findings show cilia play an important role in CHD and also in more common valve diseases., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) on changes in cardiac sympathetic nervous (CSN) function remains unclear. Using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, we investigated the impact of PPM after TAVR on CSN activity.We enrolled 44 of 117 patients with severe aortic stenosis who underwent TAVR for analysis in the present study. We conducted 123I-MIBG scintigraphy at baseline and at about 9 months after TAVR. Differences between baseline and post-TAVR 123I-MIBG parameters were compared between cases with and without PPM.There were 17 and 27 patients with and without PPM, respectively. Those without PPM exhibited significantly decreased left ventricular mass index (122 ± 36 g/m 2 versus 108 ± 30 g/m 2 , P < 0.001) following TAVR, whereas those with PPM did not (117 ± 21 g/m 2 versus 110 ± 17 g/m 2 , P = 0.09). Significant improvements in delayed heart-to-mediastinum (H/M) ratio (2.8 ± 0.4 versus 3.0 ± 0.4, P = 0.004) and washout rate (WR) (33% ± 10% versus 24% ± 12%, P < 0.001) were observed after TAVR in patients without PPM but not in those with PPM. Multivariable linear regression analysis revealed PPM to be a negative predictor of improvements in delayed H/M ratio and WR.Delayed H/M ratio and WR improve significantly after TAVR in the absence of PPM, whereas these improvements are not observed in patients with PPM. Hence, the presence of PPM is a negative predictor of improvements in delayed H/M ratio and WR in patients undergoing TAVR.

Rationale: Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease and a common cause of sudden cardiac death, heart failure, atrial fibrillation and stroke. In families affected by HCM, genotyping is useful for identifying susceptible relatives. In the present study, we investigated the disease-causing mutations in a three-generation Chinese family with HCM using whole exome sequencing (WES)., Patient Concerns: The proband, a 50-year-old man, was diagnosed with HCM at the age of 41 years. He presented with an asymmetric hypertrophic interventricular septum and a maximum interventricular septum thickness of 18.04 mm. His third elder sister, niece and daughter were also clinically affected by HCM., Diagnosis: Autosomal dominant HCM., Interventions: Seven family members, including 4 affected members, accepted WES. The genetic variants were subsequently called using Genome Analysis Toolkit and annotated using the InterVar program. Following frequency filtration by the Genome Aggregation Database, the variants were evaluated using an in-house bioinformatics analysis pipeline., Outcomes: HCM was transmitted as an autosomal dominant trait in the family. An extremely rare stop gained mutation, rs796925245 (g.1:201359630G>A, c.835C>T, p.Gln279Ter) in the troponin T2 (TNNT2) gene was identified as the disease-causing mutation. The stop gained mutation was predicted to result in a truncated troponin T protein in cardiac sarcomere. An adolescent family member who had normal echocardiographic measurements was found to carry the same disease-causing mutation., Lessons: A novel nonsense TNNT2 mutation was identified as the HCM-causing mutation in this Chinese pedigree. Since HCM shows a low penetrance by clinical criteria in adolescents, the adolescent mutation carrier, who is still clinically unaffected, should be offered routine follow-ups and sport activity recommendations to prevent adverse events including sudden cardiac death in the future.

Background: It is still unclear whether growth hormone (GH) replacement is able to improve cardiovascular parameters in adults with GH deficiency (AGHD) from the updated clinical trials reported to date., Methods and Results: We systematically reviewed clinical trials of GH treatment on AGHD patients in recent decade, and evaluated the effects of GH on cardiovascular parameters assessed by echocardiography. 11 clinical trials were identified in 3 bibliographic databases. We conducted a combined analysis of effects on four aspects: General indicators: baseline heart rate (BHR), peak heart rate (PHR), systolic blood pressure (SBP), diastolic blood pressure (DBP); Cardiac structure: left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular interventricular septum (LVIS), left ventricular mass (LVM), left ventricular posterior wall (LVPW); Cardiovascular function: deceleration time of E wave (DT), E/A ratio (E/A), ejection fraction (EF), NT-BNP; Life quality: peak VO 2 , VE/VCO 2 slope. Overall effect size was used to evaluate significance, and weighted mean difference after GH treatment was given to appreciate size of the effect. GH treatment was associated with a significant increase in BHR (3.03[2.00, 4.06]), LVIS (0.50[0.43, 0.57]), LVPW (0.50[0.43, 0.57]), and EF (2.12[1.34, 2.90]). Overall effect sizes were negative significant for DBP (- 1.19[- 2.33, - 0.05]), LVEDV (- 9.84[- 16.53, - 3.15]), NT-BNP (- 206.34[- 308.95, - 103.72]), and VE/VCO2 slope (- 2.31[- 2.92, - 1.71])., Conclusions: As assessed by echocardiography, GH administration may improve the general vital signs and life quality of AGHD patients, based on the positive effect on BHR and negative effects on DBP and VE/VCO 2 slope. Also, GH treatment would influence the structure of heart with positive effects on LVIS, LVPW and negative effect on LVEDV, which together with the increase of EF and decrease of NT-BNP, then resulting in improving the systolic function of AGHD patients.

Objective: Via subclavian/jugular vein, successful puncture of interventricular septum (IVS) has been achieved transvenously. However, the approach was limited by acute entry-angle. The study was conducted to investigate a novel transcatheter puncture of IVS via femoral access and transfemoral-venous access to left ventricle (LV) through IVS., Methods: Via femoral artery, transcatheter puncture of mid-IVS was performed with a custom-made nickel-titanium needle and 6F-sheath in 16 healthy mini-swine. Then femoral arterio-venous circuit was established through IVS. After pre-dilation of IVS, a 20F-sheath was introduced into LV transvenously over-the-guidewire in 15 swine. Furthermore, transfemoral-venous TAVR was attempted with the approach in another swine. IVS was evaluated postoperatively and was further confirmed pathologically 2 months later., Results: All transcatheter puncture of IVS was performed successfully in LV and the mid-IVS thickness was 7.67 ± 0.98 mm. In all swine, femoral arterio-venous circuit was established via IVS, and a 20F-sheath was introduced into LV and aorta transfemoral-venously (entry-angle: 145.3 ± 12.2° in front view). After the procedure, there was one swine with moderate tricuspid-regurgitation and five swine with mild residual-shunt (2.6 ± 0.7 mm). Two months later, residual-shunt was still detected in three swine and the communication was confirmed pathologically. In other swine, no defect occurred and replacement-scar was identified along puncture-tract. In the swine underwent transfemoral-venous TAVR, prosthetic valve was deployed successfully with good function., Conclusions: Transfemoral transcatheter puncture of IVS is feasible and safe in a swine model, and large sheath can be introduced into LV transfemoral-venously using the novel access with the aid of vessel circuit., (© 2020 Wiley Periodicals, Inc.)

Clinical spectrum of hypertrophic cardiomyopathy (HC) has been expanded to include patients with mild or no thickening of the left ventricle (LV), who nevertheless have outflow tract obstruction at rest or after exercise, due to systolic anterior motion (SAM) and ventricular septal contact, with mitral valve elongation and papillary muscles anomalies. Apical ballooning mimicking a takotsubo syndrome (TS) wall motion pattern can occur in HC with mild septal thickening when latent obstruction becomes unrelenting. To define the prevalence of anatomic abnormalities characteristic of HC in patients diagnosed with TS, we analyzed echocardiograms of 44 unselected TS patients, age 67±12 years, 95% women including studies performed before the event (n = 11, median 515 days) and after recovery of left ventricular function (n = 33, median 92 days, interquartile range = 29 to 327) and compared the findings to 60 age and sexed matched controls. Analysis of echocardiograms was blinded to event timing, and patient vs. control status. During the ballooning event, 13 patients (30%) had SAM including 9 with LV outflow obstruction, peak gradients 71±40 mmHg, as well as: ventricular septal thickening (16 ± 4 mm), elongated anterior leaflets (30 ± 3mm), and increased mitral coaptation to posterior wall distance (17 ± 5 mm), consistent with diagnosis of the HC phenotype. Compared to 31 TS patients without SAM, study patients with SAM had longer anterior leaflets (30 ± 3 vs 26 ± 4 mm, p = 0.006), thicker septum (16 ± 4 vs 12 ± 3 mm), increased coaptation to posterior wall distance (17 ± 5 vs 14 ± 4 mm, p < 0.04) and reduced distance from coaptation to septum (19 ± 5 vs 27 ± 5, p < 0.001). In the 13 patients with SAM, morphologic characteristics of HC persisted after normalization of LV function. In conclusion, a subset of patients experiencing TS events demonstrates a constellation of morphologic abnormalities characteristic of HC that persist after recovery of LV wall motion. These findings suggest that dynamic outflow obstruction may cause apical ballooning in susceptible patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Basal septal hypertrophy (BSH) is commonly seen in patients with systemic hypertension and has been associated with increased afterload. The impact of localized hypertrophy on left ventricular (LV) and left atrial (LA) function is still unclear. Our aim is to investigate if BSH is a marker of a more pronounced impact of hypertension on cardiac function in the early stages of hypertensive heart disease. An echocardiogram was performed in 163 well-controlled hypertensive patients and 22 healthy individuals. BSH was defined by a basal-to-mid septal thickness ratio ≥1.4. LV dimensions and mass were evaluated. LV global and regional deformation was assessed by 2-dimensional (2D) speckle tracking echocardiography, and LV diastolic function by 2D and Doppler imaging. LA function was evaluated with phasic volume indices calculated from 2D and 3-dimensional volumes, as well as speckle tracking echocardiography. The population was 54% men, mean age 57 (53 to 60) years. BSH was seen in 20% (n = 32) of the hypertensive cohort. Patients with BSH showed decreased regional LV systolic deformation, impaired LV relaxation with a higher proportion of indeterminate LV diastolic function, and LA functional impairment defined by a reduction of reservoir strain and a change in LA functional dynamics. In conclusion, in well-controlled hypertension impairment of LV and LA function is present in patients with early LV remodeling and localized hypertrophy. BSH might be useful as an early marker of the burden of hypertensive heart disease., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

An 87-year-old man was hospitalized due to dyspnea and leg edema. He was diagnosed with heart failure due to anemia with a hemoglobin (Hb) concentration of 6.0 g/dL. Chest X-ray on admission revealed pleural effusion. He was transfused with 400 mL packed red blood cells, which elevated the Hb concentration to 8.6 g/dL. Spironolactone (25 mg/day) and furosemide (20 mg/day, intravenously) were initiated. Despite the negative fluid balance, the patient's dyspnea worsened. Chest X-ray on day 8 revealed pulmonary edema despite decreased pleural effusion. Transthoracic echocardiography (TTE) revealed a sigmoid-shaped interventricular septum and systolic anterior motion of the mitral valve, causing left ventricular outflow tract obstruction (LVOTO; peak pressure gradient, 96 mmHg). Pilsicainide (75 mg/day) was administered to reduce the LVOTO. In addition, furosemide administration was changed to continuous infusion with increased dose of 48 mg/day (2 mg/h). The patient's dyspnea finally abated, with X-ray on day 12 revealing marked reduction in pulmonary congestion. TTE on day 17 revealed marked reduction in LVOTO (peak pressure gradient, 21 mmHg). Hemodynamic change by diuretics in the setting of right-sided heart failure due to anemia and in the presence of LVOTO due to sigmoid septum could be the cause of pulmonary edema.

Objective: The current guidelines suggest alcohol septal ablation (ASA) is less effective in hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular hypertrophy, despite acknowledging that systematic data are lacking. Therefore, we analysed patients in the Euro-ASA registry to test this statement., Methods: We compared the short-term and long-term outcomes of patients with basal interventricular septum (IVS) thickness <30 mm Hg to those with ≥30 mm Hg treated using ASA in nine European centres., Results: A total of 1519 patients (57±14 years, 49% women) with symptomatic HOCM were treated, including 67 (4.4%) patients with IVS thickness ≥30 mm. The occurrence of short-term major adverse events were similar in both groups. The mean follow-up was 5.4±4.3 years and 5.1±4.1 years, and the all-cause mortality rate was 2.57 and 2.94 deaths per 100 person-years of follow-up in the IVS <30 mm group and the IVS ≥30 mm group (p=0.047), respectively. There were no differences in dyspnoea (New York Heart Association class III/IV 12% vs 16%), residual left ventricular outflow tract gradient (16±20 vs 16±16 mm Hg) and repeated septal reduction procedures (12% vs 18%) in the IVS <30 mm group and IVS ≥30 mm group, respectively (p=NS for all)., Conclusions: The short-term results and the long-term relief of dyspnoea, residual left ventricular outflow obstruction and occurrence of repeated septal reduction procedures in patients with basal IVS ≥30 mm is similar to those with IVS <30mm. However, long-term all-cause and cardiac mortality rates are worse in the ≥30 mm group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Lymphatic microvessel density (LMVD) contributes to fibrosis in patients with myocardial infarction. However, the role of LMVD in the process of myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) patients is unclear. We studied LMVD in ventricular septal (VS) samples from 52 individuals (42 was HOCM patients who underwent a transaortic extended septal myectomy, and 10 traffic accident victims), and examined the relationships between the LMVD stained immunohistochemically with lymphatic vessel endothelial hyaluronan receptor (LYVE-1) antibodies, collagen volume fraction (CVF), and clinical characteristics. Compared with traffic accident victims, LMVD was significantly increased in VS of HOCM patients (132.0 ± 49.0 VS 57.8 ± 48.8/mm 2 , p = 0.000). HOCM patients with syncope had higher level of LMVD than without syncope [166.7 (131.0-201.1) VS 116.4 (80.7-152.1)/mm 2 , p = 0.017], and LMVD were positively correlated with Log (CVF) (r = 0.431, p = 0.004). On multiple variables regression analysis, LMVD was independently associated with Log (CVF) (r = 0.379, p = 0.009) and syncope (r = 0.335, p = 0.020). In conclusions, the LYVE-1-positive lymphatics have close associations with VS fibrosis in HOCM patients.

This paper presents two cases of human hearts (a 75-year-old woman and an 88-year-old man) with double posterior descending arteries (PDA) of various sizes originating from the right coronary artery, mainly supplying the interventricular septum as well as the posterior walls of both heart ventricles in a different scope. In the analysis of the arterial vasculature, a range of aspects were considered, such as the point of exit of the right coronary artery, the course of the vessel, the range of the blood supply of the interventricular septum and both ventricles, as well as selected morphometric parameters that were simultaneously compared with one another. These atypical changes presented based on the example of the analyzed cases will certainly constitute a valuable source of information for cardiac surgeons and interventional cardiologists in planning operations.

Ventricular bands are strand-like intraventricular structures extending between adjacent papillary muscles; a papillary muscle and the ventricular wall or the interventricular septum and ventricular wall. Examination of the domestic dog right ventricle documented six ventricular band types. Eighty-five of the 89 examined hearts had at least one right ventricular band. In the current study, the right ventricle of the 85 dog hearts was re-examined for more than one ventricular band type. Seven patterns of multiple different bands were identified in the 24 dog hearts. The patterns (i.e., combinations) of different ventricular bands were grouped into three categories. Category 1 had five different patterns of bands. Each pattern had two different band types. Category 2 had one combination of three different bands. Category 3 had one combination of four different bands. The presence of right ventricular bands around the trabecula septomarginalis dextra was also documented. All 24 dog hearts with multiple ventricular bands had a trabecula septomarginalis dextra. The main goal of this study was documentation of multiple right ventricular band patterns. A secondary goal was documentation of the combined presence of these bands and a trabecula septomarginalis dextra. In the dog, the ventricular bands and trabecula are both thin, strand-like intraventricular structures with variable branching patterns before blending into the ventricular wall. The gross similarity of these structures and lack of information on their combined presence could precipitate their misidentification., (© 2019 Blackwell Verlag GmbH.)

Obesity is associated with additional left ventricular hypertrophy (LVH) in adults with hypertrophic cardiomyopathy (HCM). It is not known whether obesity can lead to further LVH in children with HCM. Echocardiographic LV dimensions were determined in 504 children with HCM. Measurements of interventricular septal thickness (IVST) and posterior wall thickness (PWT), and patients' weight and height were recorded. Obesity was defined as a body mass index (BMI) ≥ 99th percentile for age and sex. IVST data was available for 498 and PWT data for 484 patients. Patient age ranged from 2 to 20 years (mean ± SD, 12.5 ± 3.9) and 340 (68%) were males. Overall, patient BMI ranged from 7 to 50 (22.7 ± 6.1). Obesity (BMI 18-50, mean 29.1) was present in 140 children aged 2-19.6 (11.3 ± 4.1). The overall mean IVST was 20.5 ± 9.6 mm and the overall mean PWT was 11.0 ± 8.4 mm. The mean IVST in the obese patients was 21.6 ± 10.0 mm and mean PWT was 13.3 ± 14.7 mm. The mean IVST in the non-obese patients was 20.1 ± 9.5 mm and mean PWT was 10.4 ± 4.3 mm. Obesity was not significantly associated with IVST (p = 0.12), but was associated with increased PWT (0.0011). Obesity is associated with increased PWT but not IVST in children with HCM. Whether obesity and its impact on LVH influences clinical outcomes in children with HCM needs to be studied.

Introduction: Concealed structural abnormalities were detected by delayed enhancement - magnetic resonance imaging (DE-MRI) in patients with apparently idiopathic tachycardia of left ventricular (LV) origin. Basal septal fibrosis was evaluated as a potential arrhythmia substrate in patients with left ventricular outflow tract (LVOT) arrhythmias., Methods and Results: A total of 22 patients with LVOT arrhythmias, including frequent monomorphic premature ventricular complexes (PVCs) in 15 patients and ventricular tachycardia (VT) in 7 patients, underwent catheter ablation and DE-MRI. A total of 19 patients with frequent PVCs and 17 patients with idiopathic VT of other origin served as a control group. Basal septal intramural fibrosis as thin strip-shaped intramyocardial DE or as marked intramyocardial DE involving >25% of wall thickness was detected more frequently in patients with LVOT arrhythmias (41% and 32%) than in patients with non LVOT arrhythmias (14% and 3%). After successful ablation, 4/16 patients with basal septal intramural fibrosis and LVOT PVCs (n = 3) or LVOT VT (n = 1) compared with no patient without basal septal fibrosis experienced episodes of sustained VT with similar or different QRS morphology resulting in ICD therapy in three patients. Follow-up DE-MRI after PVC ablation (17 ± 7 months) revealed an increase in LV ejection fraction from 49 ± 5% to 56 ± 5% (n = 9) but the amount of septal DE remained unchanged., Conclusions: Basal septal intramural fibrosis may serve as the arrhythmia substrate in a substantial part of patients with premature ventricular complexes (PVCs) and VT originating from the LVOT and identifies patients with continued risk for VT recurrence after initially successful ablation of LVOT arrhythmias., (© 2019 Wiley Periodicals, Inc.)

Transcatheter mitral valve replacement (TMVR) is a promising strategy for patients with mitral valve disease and no surgical options. Left ventricular outflow tract (LVOT) obstruction is a life-threatening complication of TMVR. Although there are no commercially available devices to prevent LVOT obstruction, the risk of it can be reduced by careful preprocedure planning and the use of novel modifications to commercially available devices. This article summarizes current techniques to prevent LVOT obstruction with an emphasis on electrosurgical strategies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Dominant mutations of Gata4, an essential cardiogenic transcription factor (TF), were known to cause outflow tract (OFT) defects in both human and mouse, but the underlying molecular mechanism was not clear. In this study, Gata4 haploinsufficiency in mice was found to result in OFT defects including double outlet right ventricle (DORV) and ventricular septum defects (VSDs). Gata4 was shown to be required for Hedgehog (Hh)-receiving progenitors within the second heart field (SHF) for normal OFT alignment. Restored cell proliferation in the SHF by knocking-down Pten failed to rescue OFT defects, suggesting that additional cell events under Gata4 regulation is important. SHF Hh-receiving cells failed to migrate properly into the proximal OFT cushion, which is associated with abnormal EMT and cell proliferation in Gata4 haploinsufficiency. The genetic interaction of Hh signaling and Gata4 is further demonstrated to be important for OFT development. Gata4 and Smo double heterozygotes displayed more severe OFT abnormalities including persistent truncus arteriosus (PTA). Restoration of Hedgehog signaling renormalized SHF cell proliferation and migration, and rescued OFT defects in Gata4 haploinsufficiency. In addition, there was enhanced Gata6 expression in the SHF of the Gata4 heterozygotes. The Gata4-responsive repressive sites were identified within 1kbp upstream of the transcription start site of Gata6 by both ChIP-qPCR and luciferase reporter assay. These results suggested a SHF regulatory network comprising of Gata4, Gata6 and Hh-signaling for OFT development., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine the associations between transthoracic echocardiogram (TTE) cardiac structure/function measures and cardioembolic stroke (CES) and new-onset atrial fibrillation (AF) in patients without known AF., Methods: Inpatients at a single institution (2013-2015) with imaging-confirmed ischemic stroke, no AF, and TTE within the 1st week were included. TTE structure/function variables were abstracted. Stroke subtype (CES vs other) was defined according to Trial of Org 10172 in Acute Stroke Treatment, blinded to TTE results. New AF was defined as any duration of AF on ECG, telemetry, or event monitor. Separate multivariable logistic regression models defined associations between CES or new-onset AF and TTE measures, adjusting for demographic and vascular risk factors., Results: Of 322 participants (mean age 60 years), 55% were male and 56% African American. In adjusted models (odds ratio, 95% confidence interval), odds of CES increased per 0.1 cm increase in left atrial (LA) systolic diameter (1.06, 1.02-1.11), 1 cm/s in mitral E point velocity (1.03, 1.02-1.05), with presence of mitral valve dysfunction (3.78, 1.42-10.02), and with wall motion abnormality (2.00, 1.13-3.55). As ejection fraction increased (per 10%), odds of CES decreased (0.65, 0.53-0.79). New-onset AF was also associated with increasing LA systolic diameter (1.13, 1.04-1.22)., Conclusions: Cardiac structural changes independent of AF and detectable on TTE may be on the CES causal pathway. Confirming these results could have implications for future use of TTE and decisions about antithrombotic vs anticoagulant treatment., (© 2019 American Academy of Neurology.)

Background: We report on a 21-year-old patient with a giant symptomatic hydatid cyst of the interventricular septum, to whom a staged management approach was employed. Induction medical therapy led to a reduction in the size of the cyst, which was then completely removed via surgical excision., Case Presentation: A 21-year-old male Caucasian, with main complaints of fatigue and palpitations, was referred to our Centre due to a cystic formation in his left ventricle. The workup consisted of transthoracic echocardiography and cardiac magnetic resonance, which revealed a huge hydatid cyst in an active stage of disease, occupying the basal and mid part of the interventricular septum. Due to the size of the lesion and lack of viable myocardium in the affected area, the patient was declared inoperable and medical therapy was initiated. Serial echocardiography revealed a significant reduction in the size of the lesion and degradation to transitional and inactive stage, after which successful surgical excision of the cyst was performed. In the course of the medical treatment, the patient experienced sustained ventricular tachycardia causing loss of consciousness, which did not reoccur after surgical excision., Conclusion: Medical therapy can result in the degradation of a giant heart hydatid cyst, enabling surgical excision. Heart hydatid cyst can lead to potentially lethal arrhythmia irrespective of its size and stage, which does not reoccur after successful surgical excision.

Background: It is unclear how upper septal hypertrophy (USH) affects Doppler-derived left ventricular stroke volume (SV) in patients with AS. The aims of this study were to: (1) validate the accuracy of 3D transesophageal echocardiography (TEE) measurements of the left ventricular outflow tract (LVOT), (2) evaluate the differences in LVOT geometry between AS patients with and without USH, and (3) assess the impact of USH on measurement of SV., Methods: In protocol 1, both 3D TEE and multi-detector computed tomography were performed in 20 patients with AS [aortic valve area (AVA) ≤ 1.5 cm 2 ]. Multiplanar reconstruction was used to measure the LVOT short and long diameters in four parts from the tip of the septum to the annulus. In protocol 2, the same 3D TEE measurements were performed in AS patients (AVA ≤ 1.5 cm 2 , n = 129) and controls (n = 30). We also performed 2D and 3D transthoracic echocardiography in all patients., Results: In protocol 1, excellent correlations of LVOT parameters were found between the two modalities. In protocol 2, the USH group had smaller LVOT short and long diameters than the non-USH group. Although no differences in mean pressure gradient, or SV calculated with the 3D method existed between the two groups, the USH group had greater SV calculated with the Doppler method (73 ± 15 vs. 66 ± 15 ml) and aortic valve area (0.89 ± 0.26 vs. 0.73 ± 0.24 cm 2 ) than the non-USH group., Conclusions: 3D TEE can provide a precise assessment of the LVOT in AS. USH affects the LVOT geometry in patients with AS, which might lead to inaccurate assessments of disease severity.

Background: In chronic kidney disease (CKD), endothelin-1 (ET-1) always increases and there are changes in cardiac ultrasonography. In the present study, we aimed at investigating the role of serum ET-1 in predicting cardiac complications in patients with CKD., Methods: The level of serum ET-1 was measured by enzyme-linked immunosorbent assay (ELISA) and cardiac ultrasonography was performed in enrolled patients. Indexes of heart failure, such as left ventricular mass index, interventricular septum thickness and left ventricular end diastolic diameter, were measured in patients with CKD., Results: In the present study, we found that the level of serum ET-1 was significantly correlated with left ventricular mass index, interventricular septum thickness and left ventricular end diastolic diameter (p < .001) in non-dialysis patients with CKD., Conclusions: The results of the present study indicated that the level of serum ET-1 is closely related to the cardiac complications of CKD and is a useful predictor of cardiac complication.

Background: In patients with disabling symptoms caused by hypertrophic obstructive cardiomyopathy (HOCM), echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) could be a less invasive treatment option., Objectives: This study aimed to investigate the safety and efficacy of the PIMSRA for left ventricular outflow tract (LVOT) gradient reduction in HOCM., Methods: The study enrolled 15 patients with HOCM. These patients underwent electrocardiography, imaging, and blood biochemistry examination over 6 months of follow-up., Results: At 6 months of follow-up, patients showed significant reductions in peak LVOT gradients (resting gradient: from 88.00 [66.00] mm Hg to 11.00 [6.00] mm Hg; p = 0.001; stress-induced gradient: from 117.00 [81.00] mm Hg to 25.00 [20.00] mm Hg; p = 0.005) and interventricular septum (IVS) thickness (anterior IVS: from 25.00 [21.00] mm to 14.00 [12.00] mm; p = 0.001; posterior IVS: from 24.00 [21.00] mm to 14.00 [11.50] mm; p = 0.001). The reductions in IVS thickness and LVOT gradients were associated with improvement in New York Heart Association functional classification (from 3.00 [2.00] to 1.00 [1.00]; p < 0.001), total exercise time (from 6.00 [5.50] min to 9.00 [8.00] min; p = 0.007), and pro B-type natriuretic peptide levels (from 924.00 [370.45] pg/ml to 137.45 [75.73] pg/ml; p = 0.028). No patient had bundle branch block or complete heart block., Conclusions: PIMSRA is a safe and effective treatment approach for severe, symptomatic HOCM and results in sustained improvement in exercise capacity, persistent reduction in LVOT gradient, and sustained improvement in cardiac function., (Copyright © 2018 American College of Cardiology Foundation. All rights reserved.)