Retrofitting the Heart: Explaining the Enigmatic Septal Thickening in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is the most common genetic cardiac disease and is characterized by left ventricular hypertrophy. Although this hypertrophy often associates with sarcomeric gene mutations, nongenetic factors also contribute to the disease, leading to diastolic dysfunction. Notably, this dysfunction manifests before hypertrophy and is linked to hypercontractility, as well as nonuniform contraction and relaxation (myofibril asynchrony) of the myocardium. Although the distribution of hypertrophy in hypertrophic cardiomyopathy can vary both between and within individuals, in most cases, it is primarily confined to the interventricular septum. The reasons for septal thickening remain largely unknown. In this article, we propose that alterations in muscle fiber geometry, present from birth, dictate the septal shape. When combined with hypercontractility and exacerbated by left ventricular outflow tract obstruction, these factors predispose the septum to an isometric type of contraction during systole, consequently constraining its mobility. This contraction, or more accurately, this focal increase in biomechanical stress, prompts the septum to adapt and undergo remodeling. Drawing a parallel, this is reminiscent of how earthquake-resistant buildings are retrofitted with vibration dampers to absorb the majority of the shock motion and load. Similarly, the heart adapts by synthesizing viscoelastic elements such as microtubules, titin, desmin, collagen, and intercalated disc components. This pronounced remodeling in the cytoskeletal structure leads to noticeable septal hypertrophy. This structural adaptation acts as a protective measure against damage by attenuating myofibril shortening while reducing cavity tension according to Laplace Law. By examining these events, we provide a coherent explanation for the septum's predisposition toward hypertrophy.

Interventricular septal thickness on cardiac computed tomography as a novel risk factor for conduction disturbances in patients undergoing transcatheter aortic valve replacement.

AIMS: We examined whether thickness of the basal muscular interventricular septum (IVS), as measured by pre-procedural computed tomography (CT), could be used to identify the risk of conduction disturbances following transcatheter aortic valve replacement (TAVR). The IVS is a pivotal region of the electrical conduction system of the heart where the atrioventricular conduction axis is located. METHODS AND RESULTS: Included were 78 patients with severe aortic stenosis who underwent CT imaging prior to TAVR. The thickness of muscular IVS was measured in the coronal view, in systolic phases, at 1, 2, 5, and 10 mm below the membranous septum (MS). The primary endpoint was a composite of conduction disturbance following TAVR. Conduction disturbances occurred in 24 out of 78 patients (30.8%). Those with conduction disturbances were significantly more likely to have a thinner IVS than those without conduction disturbances at every measured IVS level (2.98 ± 0.52 mm vs. 3.38 ± 0.52 mm, 4.10 ± 1.02 mm vs. 4.65 ± 0.78 mm, 6.11 ± 1.12 mm vs. 6.88 ± 1.03 mm, and 9.72 ± 1.95 mm vs. 10.70 ± 1.55 mm for 1, 2, 5 and 10 mm below MS, respectively, P < 0.05 for all). Multivariable logistic regression analysis showed that pre-procedural IVS thickness (<4 mm at 2 mm below the MS) was a significant independent predictor of post-procedural conduction disturbance (adjOR 7.387, 95% CI: 2.003-27.244, P = 0.003). CONCLUSION: Pre-procedural CT assessment of basal IVS thickness is a novel predictive marker for the risk of conduction disturbances following TAVR. The IVS thickness potentially acts as an anatomical barrier protecting the underlying conduction system from mechanical compression during TAVR.

Successful repair of recurrent ventricular septal perforation after myocardial infarction using double patch technique via right ventriculotomy: a case report.

BACKGROUND: Post-myocardial infarction (MI) ventricular septal perforation (VSP) is a rare but life-threatening complication. Surgical repair is challenging and carries significant risks, particularly in the context of recurrent VSPs. This case study presents a patient with recurrent VSP after initial surgical repair following myocardial infarction. CASE PRESENTATION: A 65-year-old male were re-administered to our hospital due to recurrent VSP. He was during follow up after undergone emergency VSP closure surgery 2 months earlier, utilizing the bovine double patch technique via left ventriculostomy. The initial VSP was located in the apical part of the interventricular septum, while the recurrent VSP appeared in the upper middle portion of the interventricular septum (Fig. 1). As the previous patch remained intact, the second surgery employed the bovine double patch technique via right ventriculostomy. The patient's condition remained stable without the development of heart failure symptoms. CONCLUSION: Repairing recurrent VSPs remains a challenge, necessitating the mastery of appropriate approaches to achieve optimal outcomes. Further research and guidelines are required to refine management strategies for recurrent VSPs.

Aneurysms of Aortic Sinus of Valsalva Dissecting through the Interventricular Septum With Rupture into the Left Ventricle: Case Series and Literature Review.

Aneurysm of Aortic sinus of Valsalva (ASOV) dissecting into the interventricular septum (IVS) and rupturing into the left ventricle (LV) is a rare clinical diagnosis. Systemic inflammatory diseases like tuberculosis can aggravate this condition. We describe three cases of ASOV dissecting into the IVS and rupturing into the LV. All three patients underwent surgical intervention; two had a successful outcome. A literature review was conducted and19 previously reported cases were studied. The extent and direction of septal dissection determined the associated cardiac valvular and rhythm problems. Patch closure of the mouth of the aneurysm is the surgical method of choice. In the presence of multiple sinus tracts or if there is recurrence after surgical closure, aortic sinus or root replacement techniques have better outcomes.

The optimal slow pathway ablation site in atrioventricular nodal reentrant tachycardia cases with an inferiorly located His bundle.

INTRODUCTION: The optimal slow pathway (SP) ablation site in cases with an inferiorly located His bundle (HIS) remains unclear. METHODS AND RESULTS: In 45 patients with atrioventricular nodal reentrant tachycardia, the relationship between the HIS location and successful SP ablation site was assessed in electroanatomical maps. We assessed the location of the SP ablation site relative to the bottom of the coronary sinus ostium in the superior-to-inferior (SPSI), anterior-to-posterior (SPAP), and right-to-left (SPRL) directions. The HIS location was assessed in the same manner. The HIS location in the superior-to-inferior direction (HISSI), SPSI, SPAP, and SPRL were 17.7 ± 6.4, 1.7 ± 6.4, 13.6 ± 12.3, and -1.0 ± 13.0 mm, respectively. The HISSI was positively correlated with SPSI (R2 = 0.62; P < .01) and SPAP (R2 = 0.22; P < .01), whereas it was not correlated with SPRL (R2 = 0.01; P = .65). The distance between the HIS and SP ablation site was 17.7 ± 6.4 mm and was not affected by the location of HIS. The ratio of the amplitudes of atrial and ventricular potential recorded at the SP ablation site did not differ between the high HIS group (HISSI ≥ 13 mm) and low HIS group (HISSI < 13 mm) (0.10 ± 0.06 vs. 0.10 ± 0.06; P = .38). CONCLUSION: In cases with an inferiorly located HIS, SP ablation should be performed at a lower and more posterior site than in typical cases.

Staged Ventricular Septation of the Double-Inlet Ventricle: How-I-Do-It.

Ventricular septation of the double-inlet ventricle is a largely abandoned operation due to poor historical outcomes. However, there has been renewed interest in septation as an alternative to Fontan palliation given its long-term sequelae. As one of the few centers to revisit septation in the early 1990s, our institution has long-term data on a series of patients with a double-inlet ventricle who underwent biventricular repair. This manuscript is a summary of our approach to staged septation of the double-inlet ventricle, with a focus on patient selection criteria, surgical techniques, perioperative considerations on timing of interventions, and long-term results. We believe that septation of the double-inlet ventricle should be reconsidered in patients with suitable anatomy in light of the known complications of Fontan palliation.

Right Sinus of Valsalva Aneurysm Rupturing into the Right Atrium and Dissecting into the Interventricular Septum.

The right sinus of the Valsalva aneurysm (SVA) rupturing into the right atrium (RA) and dissecting into the interventricular septum (IVS) is rare. The disease can be definitively diagnosed using two-dimensional (2D) echocardiography and color Doppler ultrasonography. Real-time biplane imaging and three-dimensional (3D) echocardiography offer new perspectives for viewing and diagnosing this disease.

No cupid, just an arrow: a penetrating injury into the interventricular septum.

BACKGROUND: Penetrating cardiac injuries are rare but often fatal, with 16-55% mortality. We report a patient who suffered a non-fatal occupational cardiac injury. CASE PRESENTATION: A 47-year-old man was operating an ironworker machine. A thin 3-cm metal fragment catapulted from the machine piercing the chest wall and the right ventricular outflow tract (RVOT), burrowing into the interventricular septum (IVS). The patient remained hemodynamically stable and walked to the nearest hospital. ECG-gated computed tomography revealed the exact location of the fragment within the IVS, allowing for detailed preoperative planning. The fragment was removed through a sternotomy and an incision through the RVOT. The postoperative course was uneventful. CONCLUSIONS: This case underscores the value of detailed preoperative imaging and the wide spectrum of clinical scenarios of penetrating cardiac injuries.

Impact of renal denervation on cardiac remodeling in resistant hypertension: A meta-analysis.

Twelve studies involving 433 patients were included. After RDN treatment, LVMI decreased by 13.08 g/m2 (95% confidence interval [CI]: -18.38, -7.78; p < .00001), PWTd decreased by 0.60 mm (95% CI: -0.87, -0.34; p < .00001), IVSTd decreased by 0.78 mm (95% CI: -1.06, -0.49; p < .00001), and LVEF increased by 1.80% (95% CI: 0.71, 2.90; p = .001). However, there were no statistically significant improvements in LVIDd (95% CI: -1.40, 0.24; p = .17) and diastolic function (E/A) (95% CI: -0.04, 0.14; p = .28). Drug treatment for resistant hypertension (RH) is challenging. Renal denervation (RDN) is one of the most promising treatments for RH. Although studies have shown RDN can control blood pressure, the impacts of RDN on cardiac remodeling and cardiac function are unclear. This meta-analysis evaluated the effect of RDN on cardiac structure and function in patients with RH. PubMed, Embase, and Cochrane were used to conduct a systematic search. The main inclusion criteria were studies on patients with RH who received RDN and reported the changes in echocardiographic parameters before and after RDN. Echocardiographic parameters included left ventricular mass index (LVMI), end-diastolic left ventricular internal dimension (LVIDd), left ventricular end-diastolic posterior wall thickness (PWTd), end-diastolic interventricular septum thickness (IVSTd), E/A, and left ventricular ejection fraction (LVEF). Data was analyzed using RevMan. Twelve studies involving 433 patients were included. After RDN treatment, LVMI decreased by 13.08g/m2 (95%confidence interval [CI]: -18.38, -7.78, p < .00001), PWTd decreased by 0.60mm (95% CI: -0.87, -0.34, p < 0.00001), IVSTd decreased by 0.78mm (95% CI: -1.06, -0.49, p < .00001), and LVEF increased by 1.80% (95% CI: 0.71, 2.90, p = .001). However, there were no statistically significant improvements in LVIDd (95% CI: -1.40, 0.24, p = .17) and diastolic function (E/A) (95% CI: -0.04, 0.14, p =.28). This meta-analysis finds that RDN can improve left ventricular hypertrophy and ejection fraction in patients with RH but has no significant effect on LVIDd and diastolic function. However, more studies are warranted due to the lack of a strict control group, a limited sample size, and research heterogeneity.

Delivery catheter system carries more physiological right ventricular septal pacing than stylet system.

INTRODUCTION: The Mt. FUJI multicenter trial demonstrated that a delivery catheter system had a higher rate of successful right ventricular (RV) lead deployment on the RV septum (RVS) than a conventional stylet system. In this subanalysis of the Mt. FUJI trial, we assessed the differences in electrocardiogram (ECG) parameters during RV pacing between a delivery catheter system and a stylet system and their associations with the lead tip positions. METHODS: Among 70 patients enrolled in the Mt FUJI trial, ECG parameters, RV lead tip positions, and lead depth inside the septum assessed by computed tomography were compared between the catheter group (n = 36) and stylet group (n = 34). RESULTS: The paced QRS duration (QRS-d), corrected paced QT (QTc), and JT interval (JTc) were significantly shorter in the catheter group than in the stylet group (QRS-d: 130 ± 19 vs. 142 ± 15 ms, p = .004; QTc: 476 ± 25 vs. 514 ± 20 ms, p < .001; JTc: 347 ± 24 vs. 372 ± 17 ms, p < .001). This superiority of the catheter group was maintained in a subgroup analysis of patients with an RV lead tip position at the septum. The lead depth inside the septum was greater in the catheter group than in the stylet group, and there was a significant negative correlation between the paced QRS-d and the lead depth. CONCLUSION: Using a delivery catheter system carries more physiological depolarization and repolarization during RVS pacing and deeper screw penetration in the septum in comparison to conventional stylet system. The lead depth could have a more impact on the ECG parameters rather than the type of pacing lead.

Left coronary sinus of valsalva aneurysm dissecting into interventricular septum: a case report.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is an extremely rare condition, and its rupture causes acute symptoms such as chest pain and dyspnea. Ruptured SVA is frequently associated with other congenital defects. CASE PRESENTATION: A 37-year-old male presented with SVA originating from the left coronary sinus that ruptured into the interventricular septum. SVA was diagnosed by echocardiography, cardiac computed tomography and magnetic resonance imaging, and confirmed during the operation. CONCLUSIONS: SVA is a rare cardiac abnormality which can lead to severe clinical symptoms upon rupture. Immediate surgery is necessary to repair the ruptured SVA.

Fibrosis and expression of extracellular matrix proteins in human interventricular septum in aortic valve stenosis and regurgitation.

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.

Morphometrics predicts the differential regurgitant fraction in bilateral pulmonary arteries of patients with repaired tetralogy of fallot.

In patients with repaired tetralogy of Fallot (rTOF), the regurgitant fraction (RF) in left pulmonary artery (LPA) and right pulmonary artery (RPA) is usually unequal. The morphometrics may play a crucial role in this RF discrepancy. Cardiovascular MR of 79 rTOF patients and 20 healthy controls were retrospectively enrolled. Forty-four from the 79 patients were matched in age, sex and body surface area to the 20 controls and were investigated for: (1) phase-contrast flow of main pulmonary artery (MPA), LPA, and RPA; (2) vascular angles: the angles between the thoracic anterior-posterior line (TAPL) with MPA (θM-AP), MPA with RPA (θM-R), and MPA with LPA (θM-L); (3) cardiac angle, the angle between TAPL and the interventricular septum; (4) area ratio of bilateral lung and hemithorax regions. Compared with the 20 controls, the 44 rTOF patients exhibited wider θM-AP, sharper θM-L angle, and a smaller θM-L/θM-R ratio. In the 79 rTOF patients, LPA showed lower forward, backward, and net flow, and greater RF as compared with RPA. Multivariate analysis showed that the RF of LPA was negatively associated with the θM-L/θM-R ratio and the age at surgery (R2 = 0.255). Conversely, the RF of RPA was negatively associated with the left lung/left hemithorax area ratio and cross-sectional area (CSA) of LPA, and positively associated with CSA of RPA and MPA (R2 = 0.366). In rTOF patients, the RF of LPA is more severe than that of RPA, which may be related to the vascular morphometrics. Different morphometric parameters are independently associated with the RF of LPA or RPA, which may offer potential insights for surgical strategies.

Left ventricular eccentricity index to assess precapillary pulmonary hypertension in dogs.

INTRODUCTION: Interventricular septal flattening, frequently present in pulmonary hypertension (PH) can be quantified by the left ventricular eccentricity index (EI) measured at end-diastole (EId), end-systole (EIs) and at maximal septal flattening (EIm). In humans, EI correlates with invasive pulmonary arterial pressure. The aim of this study was to evaluate if EI correlates with parameters of right heart remodeling (RHR) and if EI is a quantitative marker of PH in dogs. MATERIALS AND METHODS: Left ventricular eccentricity indices were retrospectively measured in four groups (no, mild, moderate and severe PH) with interpretable tricuspid and/or pulmonary regurgitation. RESULTS: Ninety-seven dogs were included, with no (n = 29), mild (n = 13), moderate (n = 25) and severe (n = 30) PH. The intra- and inter-observer variability for EI measurements ranged from 2 % to 11 %. All EI were significantly elevated in severe compared to no, mild and moderate PH (P < 0.0005). In the moderate group, EIs and EIm were higher compared to the no PH group (P < 0.01). Tricuspid and pulmonary regurgitation pressure gradients and RHR parameters correlated with EId, EIs and EIm in all groups. Optimal cut-off values discriminating moderate and severe PH from no and mild PH were 1.24 (Sensitivity (Se) 60 %; Specificity (Sp) 90 %) for EId, 1.34 (Se 67 %; Sp 95 %) for EIs and 1.37 (Se 76 %; Sp 83 %) for EIm. CONCLUSIONS: Left ventricular eccentricity indices are reproducible echocardiographic variables increasing with severity of PH. Dogs with moderate and severe PH can be discriminated from dogs with no or mild PH using EIs and EIm.

Association between left bundle branch block and ventricular septal mid-wall fibrosis in patients with preserved left ventricular ejection fraction.

BACKGROUND: The left bundle branch block (LBBB) is associated with ventricular septal mid-wall fibrosis (SMF) in patients with dilated cardiomyopathy (DCM). However, whether LBBB is also associated with SMF in patients with preserved left ventricular ejection fraction (LVEF) remains unclear. METHODS: We performed a retrospective study of 210 patients with preserved LVEF (male, n = 116; female, n = 94; mean age, 44 ± 17 years). LBBB was defined as QRS duration ≥140 ms for men or ≥ 130 ms for women, QS or rS in V1-V2, mid-QRS notching or slurring in at least two leads (V1, V2, V5, V6, I, and aVL). SMF determined by late gadolinium-enhancement cardiovascular magnetic resonance was defined as stripe-like or patchy mid-myocardial hyper-enhancement in the interventricular septal segments. RESULTS: SMF was detected in 24.8% (52/210) of these patients. The proportion of patients with SMF with LBBB was higher than the proportion of patients with SMF without LBBB (58.3% vs. 20.4%; P < 0.001). In the forward multivariate logistic analysis, LBBB (OR, 4.399; 95% CI, 1.774-10.904; P = 0.001) and age (OR, 1.028; 95% CI, 1.006-1.051; P = 0.011) were independently associated with SMF. The presence of LBBB showed a sensitivity of 27%%, specificity of 94%, positive predictive value of 58%%, and negative predictive value of 80% for the detection of SMF. CONCLUSION: LBBB was significantly associated with SMF in hospitalized patients with preserved LVEF. Screening with a resting 12­lead ECG may help to identify patients who are at a high risk of the presence of SMF.

Right Ventricular Outflow Tract Obstruction by an Aneurysm of the Ventricular Membranous Septum: A Systematic Review of Case Reports.

We performed a literature search to identify the details of patients with right ventricular outflow tract obstruction caused by an aneurysm of the ventricular membranous septum in a perimembranous ventricular septal defect. Thirty-one cases with a median age of 29 years (range, 1-69 years) were studied. A right ventricle-pulmonary artery systolic pressure gradient ranged from 35 to 107 mm Hg (mean 69 mm Hg). An interventricular shunt was absent in eight patients: two children and six adults. It is necessary to monitor the size of an aneurysm of the ventricular membranous septum, whether or not an interventricular shunt is present.