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.

Characteristics and proposed mechanisms of QRS morphology observed during the left bundle branch pacing procedure.

BACKGROUND: In performing left bundle branch pacing (LBBP), various QRS morphologies are observed as the lead penetrates the ventricular septum (VS). This study aimed to evaluate these characteristics and infer the mechanism underlying each QRS morphology. METHODS: In 19 patients who met the strict criteria for LBB capture, we classified the QRS morphologies observed during the LBBP procedure into seven patterns, the first five of which were determined by the depth of penetration: right ventricular septal pacing (RVSP), intraventricular septal pacing (IVSP1 and IVSP2), endocardial side of left ventricular septal pacing (LVSeP), nonselective LBBP (NS-LBBP), selective LBBP (S-LBBP), and NS-LBBP with anodal capture. The parameters of the QRS morphologies in these seven patterns were evaluated. RESULTS: Among the first five patterns, stimulus-QRSend duration (s-QRSend) was the narrowest in IVSP1 rather than in NS-LBBP, and stimulus-to-peak of R wave in V6 (s-LVAT) was significantly shortened in two steps, from RVSP to IVSP1 (96 ± 11; 82 ± 8 ms, p < .01) and from LVSeP to NS-LBBP (76 ± 7; 60 ± 4 ms, p < .01). The late-R duration in V1 was significantly prolonged in the order of LVSeP, NS-LBBP, and S-LBBP (45 ± 7; 53 ± 10; 71 ± 15 ms, respectively, p < .01). CONCLUSIONS: s-QRSend was the narrowest in IVSP1 rather than in NS-LBBP among the QRS morphologies observed during lead penetration through the VS. The prolonged late-R duration in V1 and abrupt shortening of the s-LVAT in V6 may help determine LBB capture during lead penetration.

Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy.

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 ±â€…3.0, 6.5 ±â€…1.6, 6.5 ±â€…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 ±â€…1.7, 9.1 ±â€…1.3, 8.3 ±â€…1.7 mm, P < .01), and LV mass (140.7 ±â€…45.9, 128.7 ±â€…37.9, 110.9 ±â€…29.1 g, P < .01), and increased septal e' velocity (8.6 ±â€…1.7, 10.0 ±â€…2.1, 10.7 ±â€…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.

Left bundle branch pacing compared to left ventricular septal myocardial pacing increases interventricular dyssynchrony but accelerates left ventricular lateral wall depolarization.

BACKGROUND: Nonselective His-bundle pacing (nsHBp), nonselective left bundle branch pacing (nsLBBp), and left ventricular septal myocardial pacing (LVSP) are recognized as physiological pacing techniques. OBJECTIVE: The purpose of this study was to compare differences in ventricular depolarization between these techniques using ultra-high-frequency electrocardiography (UHF-ECG). METHODS: In patients with bradycardia, nsHBp, nsLBBp (confirmed concomitant left bundle branch [LBB] and myocardial capture), and LVSP (pacing in left ventricular [LV] septal position without proven LBB capture) were performed. Timings of ventricular activations in precordial leads were displayed using UHF-ECG, and electrical dyssynchrony (e-DYS) was calculated as the difference between the first and last activation. Duration of local depolarization (Vd) was determined as width of the UHF-QRS complex at 50% of its amplitude. RESULTS: In 68 patients, data were collected during nsLBBp (35), LVSP (96), and nsHBp (55). nsLBBp resulted in larger e-DYS than did LVSP and nsHBp [- 24 ms (-28;-19) vs -12 ms (-16;-9) vs 10 ms (7;14), respectively; P <.001]. nsLBBp produced similar values of Vd in leads V5-V8 (36-43 ms vs 38-43 ms; P = NS in all leads) but longer Vd in leads V1-V4 (47-59 ms vs 41-44 ms; P <.05) as nsHBp. LVSP caused prolonged Vd in leads V1-V8 compared to nsHBp and longer Vd in leads V5-V8 compared to nsLBBp (44-51 ms vs 36-43 ms; P <.05) regardless of R-wave peak time in lead V5 or QRS morphology in lead V1 present during LVSP. CONCLUSION: nslbbp preserves physiological LV depolarization but increases interventricular electrical dyssynchrony. LV lateral wall depolarization during LVSP is prolonged, but interventricular synchrony is preserved.

Electrophysiological Insights into Three Modalities of Left Bundle Branch Area Pacing in Patients Indicated for Pacing Therapy.

Left bundle branch pacing (LBBP) has been adopted as a new pacing therapy whether in routine pacing or patients with heart failure, but the criteria for a completely captured LBBP are too complicated and have a low success rate in routine clinical practice.Consecutive patients with pacing therapy indications were enrolled. Left bundle branch area pacing (LBBAP) was conducted, and the presence of LBB potential, paced QRS duration, stimulus to left ventricular activation time (Stim-LVAT), and LBB potential to left ventricular activation time (LBB po-LVAT) were determined and utilized to characterize LBBAP modalities. Pacing parameters and safety were assessed at 6-month follow-up. LBBAP succeeded in 95.6% of patients (103/106) who completed the 6-month follow-up. Complete LBBP was achieved in 21 (20%) patients, characterized with a short Stim-LVAT equal to LBB po-LVAT. Incomplete LBBP was achieved in 58 (56%) patients with a short Stim-LVAT equal to LBB po-LVAT at a high pacing output and a relatively longer Stim-LVAT at a low pacing output. Deep septal pacing (DSP) characterized with no LBB potential and a longer Stim-LVAT (83.3 ± 7.7 ms) than that in LBBP (71.37 ± 7.1 ms, P < 0.01 versus DSP) was observed in 24 (23%) patients. Complete LBBP had a longer total procedure time and longer fluoroscopic time than the other two groups.This study describes the similarities and differences in electrophysiological characteristics and the possible mechanisms of the different types of LBBAP, classified into 3 modalities in routine clinical practice, each with narrow paced QRS duration and stable parameters, indicating LBBAP can be a near-physiological pacing modality.

Cardiac hemodynamics in fetuses with transposition of the great arteries and intact ventricular septum from diagnosis to end of pregnancy: longitudinal follow-up.

OBJECTIVES: Little is known about cardiac hemodynamics in the fetus with transposition of the great arteries and intact ventricular septum (TGA-IVS). Better understanding of the fetal physiology in TGA-IVS would help to provide insights into specific clinical complications observed after birth, in particular neonatal hypoxia and pulmonary hypertension. The aim of this study was to assess cardiac hemodynamics in fetuses with TGA-IVS by performing systematic longitudinal echocardiographic follow-up from diagnosis to delivery. METHODS: This was a longitudinal retrospective study of fetuses referred between 2010 and 2018 to the Sainte-Justine University Hospital Centre. Complete assessment of cardiac hemodynamics was performed in fetuses with TGA-IVS at 18-22, 28-32 and 35-38 weeks' gestation, which were compared with normal fetuses matched for gestational age. The maximum diameter of the foramen ovale was measured using two-dimensional echocardiography under the guidance of color Doppler echocardiography. Fetal cardiac hemodynamics were analyzed according to postnatal preductal transcutaneous oxygen saturation (TcSO2 ) < 65% or ≥ 65%, as a neonatal outcome, in fetuses with TGA-IVS. RESULTS: In total, 59 fetuses with TGA-IVS and 160 normal fetuses were included. Global cardiac output was significantly higher in fetuses with TGA-IVS than in controls, mainly owing to higher global pulmonary output, while global systemic cardiac output did not differ between TGA-IVS fetuses and controls throughout pregnancy. Aortic flow (right ventricular output in fetuses with TGA-IVS, left ventricular output in controls) was significantly higher in fetuses with TGA-IVS than in normal fetuses. Ductal flow was significantly lower in fetuses with TGA-IVS at every timepoint, and this difference increased considerably after 28-32 weeks. In parallel, the diameter of the foramen ovale was significantly smaller in fetuses with TGA-IVS at 28-32 and 35-38 weeks, with a stagnation in growth after 28 weeks, compared with continuous growth in normal fetuses. Most of these cardiac hemodynamic anomalies in fetuses with TGA-IVS were already present at 18-22 weeks, and the differences became greater at 28-32 weeks' gestation. TGA-IVS neonates with TcSO2 < 65% had lower fetal left ventricular output, higher diastolic ductal retrograde flow and smaller foramen ovale at 28-32 weeks, compared with fetal values in those with postnatal TcSO2 ≥ 65%. CONCLUSIONS: Compared with normal fetuses, those with TGA-IVS undergo a complex redistribution of blood flow during the second half of pregnancy, with higher global pulmonary flow, lower ductal flow (with negative diastolic flow at the end of pregnancy) and a smaller foramen ovale. In addition, fetal cardiac hemodynamic anomalies observed at 28-32 weeks' gestation were associated with lower postnatal TcSO2 . These observations may provide a better understanding of premature closure of the foramen ovale and postnatal hypoxia that are specific to TGA-IVS physiology. © 2019 International Society of Ultrasound in Obstetrics and Gynecology.

Cardiovascular magnetic resonance imaging derived septal curvature in neonates with bronchopulmonary dysplasia associated pulmonary hypertension.

BACKGROUND: Bronchopulmonary dysplasia (BPD) associated with pulmonary hypertension (PH) is a significant source of morbidity and mortality in premature infants. Recent advances have allowed the use of cardiovascular magnetic resonance (CMR) in the assessment of respiratory and cardiac disease in infants with BPD. In adults and older pediatric patients, decreased CMR interventricular septal curvature correlates with increased mean pulmonary artery pressure and pulmonary vascular resistance. The current study sought to determine the relationship of CMR derived septal curvature in neonates with BPD and BPD-PH with a need for PH therapy. METHODS: Forty moderate or severe BPD and 12 mild BPD or control infants were imaged without contrast between 38 and 47 weeks post-menstrual age on a neonatal-sized, neonatal intensive care unit-sited 1.5 T CMR scanner. CMR indices including eccentricity index (CMR-EI) and septal curvature were measured and compared to BPD severity and clinical outcomes including hospital length of stay (LOS), duration of respiratory support, respiratory support level at discharge and PH therapy. RESULTS: CMR-EI was directly associated and septal curvature was inversely associated with BPD severity. In a univariate analysis, CMR-EI and septal curvature were associated with increased hospital LOS, duration of respiratory support, respiratory support at hospital discharge, and need for PH therapy. In multivariable analysis CMR-EI was associated with hospital LOS and duration of respiratory support and septal curvature was associated with respiratory support at hospital discharge. Septal curvature was the only clinical or CMR variable associated with need for PH therapy (R2 = 0.66, p = 0.0014) in multivariable analysis demonstrating improved discrimination beyond CMR-EI. CONCLUSIONS: CMR derived septal curvature correlates significantly with clinical outcomes including hospital LOS, duration of respiratory support, respiratory support level at hospital discharge, and PH therapy in neonates with BPD and BPD-PH. Further, CMR derived septal curvature demonstrated improved discrimination of need for PH therapy and respiratory support at discharge compared to clinical variables and other CMR indices, supporting septal curvature as a non-invasive marker of PH in this population with potential to guide management strategies.

Bipolar radiofrequency ablation for ventricular tachycardias originating from the interventricular septum: Safety and efficacy in a pilot cohort study.

BACKGROUND: Interest has grown in recent years in bipolar radiofrequency ablation (B-RFA). However, indications and outcome in patients with ventricular tachycardia (VT) are still to be defined. OBJECTIVE: The purpose of this study was to describe patient selection, safety and effectiveness of B-RFA, in a pilot cohort study of patients with nonischemic dilated cardiomyopathy (NIDCM) and drug-refractory VT. METHODS: We enrolled 21 patients with NIDCM (mean age 66±10 years; 18/21 (86%) men; left ventricular ejection fraction 35%±14%; 100% redo procedures) scheduled for a B-RFA procedure because of drug-refractory VT of suspected septal (interventricular septum [IVS]) origin. After electroanatomic mapping by using the CARTO®3 system, B-RFA was performed in all patients. Short- and long-term outcomes, including procedural success, major complications, and occurrence of major ventricular arrhythmias (MVAs), were evaluated at 25±8 months of follow-up (FU). RESULTS: Endocardial mapping showed IVS scar in all patients and extra-IVS in 7 patients (33%). B-RFA was performed at an average power of 33 W, for 60-90 seconds, over a 4.1 cm2 area, with 13±3 mm distance between catheters tips. The impedance drop was 27±4 Ω. The primary end point of noninducibility of the target clinical VT was obtained in 20 patients (95%). During FU, MVAs were documented in 7 patients (33%). FU MVAs occurred in all (100%) patients with extra-IVS localizations (7 of 7) or inflammatory nonischemic cardiomyopathy etiology (2 of 2). IVS thinning (tip-to-tip catheter distance < 5 mm) represented the only anatomical limitation to B-RFA. CONCLUSION: B-RFA is feasible in patients with NIDCM and drug-refractory VT of septal origin. Extra-IVS substrate and inflammatory NIDCM etiology were associated with an adverse outcome.

Modern mapping and ablation techniques to treat ventricular arrhythmias from the left ventricular summit and interventricular septum.

Managing arrhythmias from the left ventricular summit and interventricular septum is a major challenge for the clinical electrophysiologist requiring intimate knowledge of cardiac anatomy, advanced training and expertise. Novel mapping and ablation strategies are needed to treat arrhythmias originating from these regions given the current suboptimal long-term success rates with standard techniques. Herein, we describe innovative approaches to improve acute and long-term clinical outcomes such as mapping and ablation using the septal coronary venous system and the septal coronary arteries, alcohol ablation, coil embolization, and ablation of all early sites among others.

Basal Ventricular Septal Hypertrophy in Systemic Hypertension.

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.

Myocardial edema in paroxysmal permeability disorders: The paradigm of Clarkson's disease.

PURPOSE: Paroxysmal Permeability Disorders (PPDs) comprise a variety of diseases characterized by recurrent and transitory increase of endothelial permeability. Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a rare PPD that leads to an abrupt massive shift of fluids and proteins from the intravascular to the interstitial compartment. In some cases, tissue edema may involve the myocardium, but its role in the development of shock has not been elucidated so far. MATERIALS AND METHODS: Assessment of cardiac involvement during ten life-threatening ISCLS episodes admitted to ICU. RESULTS: Transthoracic echocardiographic examination was performed in eight episodes, whereas a poor acoustic window prevented cardiac ultrasound assessment in two episodes. Myocardial edema was detected by echocardiography in eight episodes and marked pericardial effusion in one-episode. Cardiac magnetic resonance showed diffuse myocardial edema in another episode. In one case, myocardial edema caused fulminant left ventricular dysfunction, which required extracorporeal life support. The mean septum thickness was higher during the shock phase compared to the recovery phase [15.5 mm (13.1-21 mm) vs. 9.9 mm (9-11.3 mm), p = .0003]. Myocardial edema resolved within 72 h. CONCLUSIONS: During early phases of ISCLS, myocardial edema commonly occurs and can induce transient myocardial dysfunction, potentially contributing to the pathogenesis of shock.

Programmed deep septal stimulation: A novel maneuver for the diagnosis of left bundle branch capture during permanent pacing.

INTRODUCTION: Permanent deep septal stimulation with capture of the left bundle branch (LBB) enables maintenance/restoration of the physiological activation of the left ventricle. However, it is almost always accompanied by the simultaneous engagement of the local septal myocardium, resulting in a fused (nonselective) QRS complex, therefore, confirmation of LBB capture remains difficult. METHODS: We hypothesized that programmed extrastimulus technique can differentiate nonselective LBB capture from myocardial-only capture as the effective refractory period (ERP) of the myocardium is different from the ERP of the LBB. Consecutive patients undergoing pacemaker implantation underwent programmed stimulation delivered from the lead implanted in a deep septal position. Responses to programmed stimulation were categorized on the basis of sudden change in the QRS morphology of the extrastimuli, observed when ERP of LBB or myocardium was encroached upon, as: "myocardial," "selective LBB," or nondiagnostic (unequivocal change of QRS morphology). RESULTS: Programmed deep septal stimulation was performed 269 times in 143 patients; in every patient with the use of a basic drive train of 600 milliseconds and in 126 patients also during intrinsic rhythm. The average septal-myocardial refractory period was shorter than the LBB refractory period: 263.0 ± 34.4 vs 318.0 ± 37.4 milliseconds. Responses diagnostic for LBB capture ("myocardial" or "selective LBB") were observed in 114 (79.7%) of patients. CONCLUSIONS: A novel maneuver for the confirmation of LBB capture during deep septal stimulation was developed and found to enable definitive diagnosis by visualization of both components of the paced QRS complex: selective paced LBB QRS and myocardial-only paced QRS.

Importance of Preoperative Computed Tomography Assessment of the Membranous Septal Anatomy in Patients Undergoing Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve.

BACKGROUND: Cardiac conduction disturbance (CD) is the most frequent complication following transcatheter aortic valve replacement (TAVR). This study examined whether the anatomy of the membranous septum (MS) could provide useful information about the risk of CD following TAVR with a balloon-expandable valve (BEV).Methods and Results:Among 132 consecutive patients, 106 (mean age, 85.6±5.1 years; 75 females) were included in the study. Using preoperative CT and angiography, MS length and implantation depth (ID) were assessed. The MS length minus the prosthesis ID was calculated (∆MSID). Correlation between CD, defined as new-onset left-bundle branch block (LBBB) or the need for permanent pacemaker (PPM) within 1 week after the procedure, and MS length were evaluated. A total of 19 patients (18%) developed CD following TAVR. MS length was significantly shorter in these patients than in those without CD (5.3±1.3 vs. 6.6±1.4; P<0.001), and was the important predictor of CD (odds ratio [OR]: 0.43, 95% confidence interval [CI]: 0.27-0.69, P<0.001). When considering the pre- and postprocedural parameters, the ∆MSID was smaller in patients with CD (-1.7±1.5 vs. 0.8±1.9, P<0.001), and emerged as the important predictor of CD (OR: 0.47, 95% CI: 0.33-0.69, P<0.001). CONCLUSIONS: Short MS is associated with an increased risk of CD after TAVR with BEV.

Dynamic unipolar voltage criteria of right ventricular septum for identifying left ventricular septal scar.

PURPOSE: The right ventricular (RV) septal unipolar voltage (UV) for predicting left ventricular (LV) septal scar wall thickness (WT) remains to be elucidated. METHODS: From 2013 to 2015, data obtained from RV and LV electroanatomic maps of 28 patients (mean age, 53 ± 16 years; 19 men [67.9%]) with/without identified LV septal scars were reviewed. Patients with an RV septal scar were excluded (n = 90). Direct measurement of septal WT was conducted (mean distance, 10.4 ± 3.3 mm). Patients in group 1 had a normal LV substrate, while those in group 2 had an LV septal scar. Fisher's linear discriminant formula was used to determine the dynamic UV criteria. RESULTS: A total of 552 points were collected: 323 in 12 patients from group 1 and 229 in 16 patients from group 2. The UV of the RV septum is capable of identifying the opposite LV endocardial bipolar scar and is proportional to the WT of the interventricular septum. In the absence of an RV endocardial scar, the formula of "RV septal cut-off value = 0.736 × WT - 0.117 mV" has better sensitivity and specificity for predicting the LV septal scar (0.96 vs. 0.68 and 0.91 vs. 0.80, respectively) than the predefined fixed criteria of 8.3 mV with a net reclassification improvement of 25.7% (P < 0.001). CONCLUSIONS: The combined measurement of UV and WT is more sensitive than the predefined fixed UV criteria for defining deep scars.

Elevated lymphatic vessel density measured by Lyve-1 expression in areas of replacement fibrosis in the ventricular septum of patients with hypertrophic obstructive cardiomyopathy (HOCM).

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/mm2, 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)/mm2, 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.

Left bundle branch area pacing is superior to right ventricular septum pacing concerning depolarization-repolarization reserve.

INTRODUCTION: Left bundle branch area pacing (LBBAP) has recently been reported to be a new physiological pacing strategy with clinical feasibility and safety. The present study aims to investigate depolarization-repolarization measures including QT interval, QT dispersion (QTD), and Tpeak-end interval (Tp Te ) in this novel LBBAP strategy. METHODS AND RESULTS: A total of 131 pacing-indicated patients were prospectively enrolled and randomized to the LBBAP group (n = 66) and right ventricular septum pacing (RVSP) group (n = 65). LBBAP was successfully achieved in 61 subjects with stable lead performance and comparable complications (ie, pocket hematoma, lead perforation, and dislodgement) compared with RVSP. Of the 61 patients with successful LBBAP, the mean LV peak activation time was 67.89 ± 6.80 ms, with the LBB potential mapped in 46 cases (75.4%). Electrocardiogram (ECG) indices were compared between these two groups before and after implantation. As a result, LBBAP yielded a narrower paced QRS duration (121.49 ± 9.87 ms vs 145.62 ± 8.89 ms; P < .001), shorter QT interval (434.16 ± 32.70 ms vs 462.66 ± 32.04 ms; P < .001), and QTc interval (472.44 ± 33.30 ms vs 499.65 ± 31.35 ms; P < .001), lower QTD (40.10 ± 8.68 ms vs 46.11 ± 10.85 ms; P = .001), and QTc D (43.57 ± 8.78 ms vs 49.86 ± 11.98 ms; P = .001), and shorter Tp Te (96.59 ± 10.76 ms vs 103.77 ± 10.16 ms; P < .001) than RVSP. However, Tp Te /QT ratio did not differ between these two groups (0.223 ± 0.026 vs 0.225 ± 0.022; P = .733). Furthermore, LBBAP displayed less increased QRS duration, QTc interval, QTD, QTc D, and a more shortened QT interval compared with RVSP (all P < .05). CONCLUSION: LBBAP proves to be a feasible and safe pacing procedure with better depolarization-repolarization reserve, which may predict lower risk of ventricular arrhythmia and sudden cardiac death.

What are the atrioventricular delays in right ventricular apical and septal pacing for optimal hemodynamics in patients with normal left ventricular function?

INTRODUCTION: There is a surge of interest in alternate site pacing to prevent pacing-induced left ventricular dysfunction. However, little is known regarding the appropriate atrioventricular (AV) delay between right ventricular (RV) septal and RV apical pacing for optimal hemodynamic benefit. OBJECTIVES: To determine the programmed values of atrial sensed and atrial paced AV delays in basal RV septal and apical RV pacing that results in the maximum delivered stroke volume (SV). METHODS: We calculated the Doppler-derived SV at various sensed and paced AV delays in 50 patients with complete AV block implanted with a dual-chamber pacemaker (group A: 25 RV apical pacing; group B: 25 RV septal pacing). The hemodynamic difference in terms of the SV between sensed and paced AV delay, corresponding to the site of RV pacing was then compared for statistical significance. RESULTS: In group A, maximal SV was derived at a sensed AV delay of 123.2 ± 11 ms and paced AV delay of 129.2 ± 10 ms, and in group B, at a sensed AV delay of 123.6 ± 8 ms and paced AV delay of and 132.8 ± 7 ms. At these intervals, there was no difference in the SV between septal and apical RV pacing (P = .28 and .22, respectively). CONCLUSION: The atrial sensed and atrial paced AV delays for septal and apical RV pacing for optimal hemodynamics are similar. For optimal hemodynamics, the atrial paced AV delay is longer than the atrial sensed AV delay.

Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy through non-left anterior descending septal perforators.

Percutaneous transluminal septal myocardial ablation (PTSMA) has become a significant treatment for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) despite maximal medical therapy. The target septal arteries usually arise from the left anterior descending artery (LAD). However, when septal perforators do not originate from the LAD, non-LAD septal perforators should be included as candidate-target septal branches that feed the hypertrophic septal myocardium, causing left ventricular outflow tract (LVOT) obstruction. Data pertaining to the procedure remain limited. We aimed to investigate PTSMA through the non-LAD septal perforators in patients with HOCM. In this case series review, we evaluated the baseline characteristics, echocardiographic features, and angiographic features, as well as symptoms and pressure gradient before and after PTSMA through the non-LAD septal perforators. Among 202 consecutive patients who underwent PTSMA for HOCM with LVOT obstruction, 21 had non-LAD septal branches that fed the hypertrophic septal myocardium and received alcohol ablation. Non-LAD septal perforators could be used as an alternative route for PTSMA in patients who experienced ineffective ablation of the septal branch that arises from the LAD. This unique procedure may improve response rates and overall outcomes of patients with HOCM.

Utility of the combination of simple electrocardiographic parameters for identifying mid-septal pacing.

INTRODUCTION: The electrocardiograms (ECG) criteria to anchor the lead to the right ventricular septum have not been established. This study aimed to identify ECG criteria of pacing at the right ventricular mid septum (RVMS) and investigate whether the paced QRS duration (pQRSd) from the RVMS was narrow. METHODS AND RESULTS: In 42 patients, ECG pacing at the basal anterior wall (BA), mid-anterior wall (MA), apex (AP), and mid septum (MS) was recorded. The pacing sites were validated by using right ventriculography and computed tomography. We estimated the ECG parameters and compared them among the four pacing sites. The combination of simple four paced-ECG parameters could reliably confirm the pacing at the RVMS. The area under the receiver-operating characteristics curve for the number of positive findings among the following: (a) positive QRS in lead aVL, (b) QRS notching in lead I, (c) precordial leads transition at less than V5, and (d) presence of isoelectric QRS in the inferior leads was 0.95 (95% confidence interval, 0.91-0.98) and the number of positive findings (≥3) had a sensitivity of 83.3% and a specificity of 93.7% for discriminating MS from the other sites. The pQRSd with three or more positive findings was significantly narrower than that with less than three positive findings (≥3: 137.4 ± 9.2 ms, <3: 151.8 ± 13.1 ms, P ≤ .05). CONCLUSION: The combination of ECG parameters can help identify right ventricular mid-septal pacing. The use of these parameters may enable the implantation of the pacing lead in the RVMS accurately and obtain a narrower QRS duration.

Improvement of abnormal systolic motion of the interventricular septum with cardiac resynchronization therapy.

BACKGROUND: There is no consensus in the literature regarding what is the responsible mechanism of left ventricular dyssynchrony; septal dyskinesia or late movement of left ventricle (LV) lateral wall. We aim to evaluate the abnormal systolic motion in each myocardial segment and the improvement of LV systolic function with pulsed tissue Doppler imaging (TDI) in patients undergoing cardiac resynchronization therapy (CRT) with left bundle branch block (LBBB). METHODS: A total of 26 patients undergoing CRT implantation with LBBB, wide QRS duration (≥120 ms), and low ejection fraction (EF) (<35%) were included. Pulsed TDI was taken from apical 4-chamber view and parasternal short axis view (PSAX). All echocardiographic parameters were measured when CRT is on and off. RESULTS: Systolic ejection time (ET) of anteroseptal and posterolateral wall of LV in PSAX was statistically significantly longer in CRT on group (321.6 ± 62.7 vs 237.5 ± 59.3 ms, P < .001; 323.9 ± 58.0 vs 289.4 ± 43.7 ms, P = .015, respectively). In apical 4-chamber view, septal annulus systolic ET is significantly longer in CRT on group than CRT off group (315.8 ± 57.2 vs 287.3 ± 42.2, P = .014). Also, there was a strong correlation between systolic ET of the septum in PSAX with aortic velocity time integral (VTI), QRS duration and EF (r = .587, P = .002; r = .479, P = .013; r = .440, P = .025; respectively). CONCLUSION: Circumferential contraction of septal myocardial fibers is improved with CRT and it is strongly correlated with increase of aortic VTI and shortening of QRS duration. These findings predict the deterioration of septal contraction as the main mechanism in patients with LBBB pattern and, CRT may improves myocardial contraction by correcting septal systolic motion.