Anomalous papillary muscles-Implications in the surgical treatment of hypertrophic obstructive cardiomyopathy.

OBJECTIVES: To categorize and assess the functional significance of anomalous papillary muscles in patients undergoing surgical management of obstructive hypertrophic cardiomyopathy. METHODS: We reviewed the records of operations for obstructive hypertrophic cardiomyopathy and identified 73 patients with an anomalous papillary muscle. Anomalous papillary muscles inserting directly into the body of the anterior mitral valve leaflet were classified as type I, those with both direct insertion into the body of the leaflet and attachment to the free edge of the anterior leaflet were categorized as type II, and anomalous papillary muscles inserting into the free edge of the anterior leaflet were grouped as type III. Additionally, we investigated detection rates by preoperative transthoracic echocardiography, intraoperative transesophageal echocardiography, and cardiac magnetic resonance imaging. RESULTS: The mean age of patients was 51.9 ± 12.3 years, and 49.3% were male. The anomalous papillary muscle was classified as type I in 31.5% of patients, type II in 35.6%, and type III in 32.9%. Only type I and type II anomalous papillary muscles contributed to left ventricular outflow tract obstruction. The anomalous papillary muscle was detected on preoperative transthoracic echocardiography in 11% of patients and by intraoperative transesophageal echocardiography in 27.4% of patients. No anomalous papillary muscles were identified on cardiac magnetic resonance imaging. All patients underwent septal myectomy with or without (n = 34) associated excision of the anomalous papillary muscle. Excision of the papillary muscles was more common in patients with type I and II (76.4% and 80.8%, respectively) when compared with type III (4.2%). Ten patients underwent mitral valve repair, and 1 patient had mitral valve replacement. CONCLUSIONS: Papillary muscle abnormalities are important findings in patients with obstructive hypertrophic cardiomyopathy but are not identified preoperatively in the majority of patients. Recognition of anomalous papillary muscles intraoperatively and understanding of the morphologic subtypes are critical to adequate gradient relief and preservation of mitral valve function. The optimum approach involves a transaortic extended septal myectomy associated with the resection of the anomalous papillary muscles in patients with type I and II anatomy.

Left ventricular remodeling after mitral valve repair and papillary muscle approximation.

BACKGROUND: Mitral valve repair with papillary muscle approximation (MVr-PMA) for severe secondary mitral regurgitation (MR) decreases MR recurrence compared with MVr alone. This study assessed the effects of MVr-PMA on left ventricular (LV) remodeling and shape, systolic function and strain mechanics. METHODS: Forty-eight patients who underwent MVr-PMA for severe secondary MR and had follow-up echocardiograms available for review were identified. Student's t-test, linear regression modeling, and receiver-operating characteristic curves were used in the statistical analyses. RESULTS: Median follow-up time was 14.9 months. MVr-PMA was associated with significant LV reverse remodeling with a smaller LV end-diastolic diameter, Systolic Sphericity Index, and interpapillary muscle distance at follow-up. Nine patients (18.8%) experienced moderate recurrent MR. When compared to recurrent MR patients at follow-up, those with durable MVr-PMA had a greater LV ejection fraction (32.8 vs. 22.0%, P=0.03), a smaller end-diastolic diameter (59.6 vs. 67.3 mm, P=0.03), Systolic Sphericity Index (0.35 vs. 0.47, P=0.03), and end-systolic interpapillary muscle distance (16.3 vs. 21.1 mm, P=0.03). A durable MVr-PMA also resulted in stable global longitudinal strain when compared with pre-operative values, while the recurrent MR group experienced a further decline (no recurrent MR: -8.4 vs. -7.5%; recurrent MR: -8.2 vs. -5.4%; P<0.05). A pre-operative LV end-diastolic diameter ≥ 64 mm was a discriminative predictor of MR recurrence (sensitivity=100%, specificity=51%, AUC=0.756, P=0.02). CONCLUSIONS: A durable MVr-PMA confers improved LV geometry and function, and stable LV mechanics. The extent of baseline LV remodeling identifies patients at risk for recurrent MR.

Ex Vivo Model of Ischemic Mitral Regurgitation and Analysis of Adjunctive Papillary Muscle Repair.

Ischemic mitral regurgitation (IMR) is particularly challenging to repair with lasting durability due to the complex valvular and subvalvular pathologies resulting from left ventricular dysfunction. Ex vivo simulation is uniquely suited to quantitatively analyze the repair biomechanics, but advancements are needed to model the nuanced IMR disease state. Here we present a novel IMR model featuring a dilation device with precise dilatation control that preserves annular elasticity to enable accurate ex vivo analysis of surgical repair. Coupled with augmented papillary muscle head positioning, the enhanced heart simulator system successfully modeled IMR pre- and post-surgical intervention and enabled the analysis of adjunctive subvalvular papillary muscle repair to alleviate regurgitation recurrence. The model resulted in an increase in regurgitant fraction: 11.6 ± 1.7% to 36.1 ± 4.4% (p < 0.001). Adjunctive papillary muscle head fusion was analyzed relative to a simple restrictive ring annuloplasty repair and, while both repairs successfully eliminated regurgitation initially, the addition of the adjunctive subvalvular repair reduced regurgitation recurrence: 30.4 ± 5.7% vs. 12.5 ± 2.6% (p = 0.002). Ultimately, this system demonstrates the success of adjunctive papillary muscle head fusion in repairing IMR as well as provides a platform to optimize surgical techniques for increased repair durability.

Spontaneous myogenic fasciculation associated with the lengthening of cardiac muscle in response to static preloading.

Force enhancement is one kind of myogenic spontaneous fasciculation in lengthening preload striated muscles. In cardiac muscle, the role of this biomechanical event is not well established. The physiological passive property is an essential part for maintaining normal diastole in the heart. In excessive preload heart, force enhancement relative erratic passive properties may cause muscle decompensating, implicate in the development of diastolic dysfunction. In this study, the force enhancement occurrence in mouse cardiac papillary muscle was evaluated by a microstepping stretch method. The intracellular Ca2+ redistribution during occurrence of force enhancement was monitored in real-time by a Flou-3 (2 mM) indicator. The force enhancement amplitude, the enhancement of the prolongation time, and the tension-time integral were analyzed by myography. The results indicated that the force enhancement occurred immediately after active stretching and was rapidly enhanced during sustained static stretch. The presence of the force and the increase in the amplitude synchronized with the acquisition and immediate transfer of Ca2+ to adjacent fibres. In highly preloaded fibres, the enhancement exceeded the maximum passive tension (from 4.49 ± 0.43 N/mm2 to 6.20 ± 0.51 N/mm2). The occurrence of force enhancement were unstable in each static stretch. The increased enhancement amplitude combined with the reduced prolongation time to induce a reduction in the tension-time integral. We concluded that intracellular Ca2+-synchronized force enhancement is one kind of interruption event in excessive preload cardiac muscle. During the cardiac muscle in its passive relaxation period, the occurrence of this interruption affected the rhythmic stability of the cardiac relaxation cycle.

The mechanism and prognosis of acute and late improvement in mitral regurgitation after cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) improves functional mitral regurgitation (MR); however, the mechanism and differences in acute and late improvement in MR are unclear. We aimed to evaluate the factors associated with the acute and late MR improvements and the prognosis of MR improvement after CRT. This retrospective study included 121 patients who underwent CRT implantation with full echocardiography assessment at baseline, 1 week, and 6 months after implantation. MR severity was classified into five grades (0: none to 4: severe). Two-dimensional speckle-tracking echocardiography with radial strain was used to assess dyssynchrony, and the time difference between the lateral and inferior segments at papillary muscle levels (TDlate-inf) was calculated. The MR improved 1 week and 6 months after CRT in 40 (33%) and 45 (37%) patients, respectively. On multivariate analyses, TDlate-inf (baseline-1 week) and SPWMD were independently associated with acute MR improvement. The %reduction in left ventricular end-systolic volume (LVESV) (baseline-6 months) and TDlate-inf (baseline-1 week) were independently correlated with late MR improvement. The patients with pre-MR grades 2-4 and improved MR after CRT showed significantly better prognosis in heart failure hospitalization. Cutoff values of ≥ 19.5 ms of the reduction of TDlate-inf and ≥ 30.8% of the %reduction of LVESV were significantly associated with the decrease in heart failure hospitalization. The improved interpapillary muscle activation time delay and volume reduction after CRT were associated with acute and late MR improvements. There may be different time course of recovery and distinct causes for late MR improvement.

Papillary Muscles Abnormalities in Athletes With Otherwise Unexplained T-Wave Inversion in the ECG Lateral Leads.

Background Papillary muscles (PMs) abnormalities may be associated with ECG repolarization abnormalities. We aimed to evaluate the relation between lateral T-wave inversion (TWI) and PMs characteristics in a cohort of athletes with no clinically demonstrable cardiac disease. Methods and Results We included 53 athletes (median age, 20 years; 87% men) with lateral TWI and no evidence of heart disease on clinical and cardiac magnetic resonance evaluation. A group of healthy athletes with normal ECG served as controls. We evaluated the PMs dimensions, such as diameters, area, volume, mass, and ratio between PMs and left ventricular mass, and the prevalence of PMs apical displacement. Compared with controls, athletes with TWI showed PMs hypertrophy with significantly increased PMs diameters, area, volume, and mass. The ratio between PMs and left ventricular mass was 4.4% in athletes with TWI and 3.0% in controls (P<0.001). A PMs/left ventricular mass ratio >3.5% showed 85% sensitivity and 76% specificity for differentiating between athletes with TWI and controls. Apical displacement of PMs was found in 25 (47%) athletes with TWI versus 9 (17%) controls (P=0.001). At multivariable analysis, PMs/left ventricular mass ratio and apical displacement remained independent predictors of TWI. Clinical outcome of the athletes with TWI and PMs abnormalities was uneventful despite continuation of their sports activity. Conclusions PMs hypertrophy and apical displacement may underlie otherwise unexplained lateral TWI in the athlete. Lateral TWI associated with PMs abnormalities appears as a distinct anatomo-clinical condition characterized by a favorable outcome.

Mavacamten decreases maximal force and Ca2+ sensitivity in the N47K-myosin regulatory light chain mouse model of hypertrophic cardiomyopathy.

Morbidity and mortality associated with heart disease is a growing threat to the global population, and novel therapies are needed. Mavacamten (formerly called MYK-461) is a small molecule that binds to cardiac myosin and inhibits myosin ATPase. Mavacamten is currently in clinical trials for the treatment of obstructive hypertrophic cardiomyopathy (HCM), and it may provide benefits for treating other forms of heart disease. We investigated the effect of mavacamten on cardiac muscle contraction in two transgenic mouse lines expressing the human isoform of cardiac myosin regulatory light chain (RLC) in their hearts. Control mice expressed wild-type RLC (WT-RLC), and HCM mice expressed the N47K RLC mutation. In the absence of mavacamten, skinned papillary muscle strips from WT-RLC mice produced greater isometric force than strips from N47K mice. Adding 0.3 µM mavacamten decreased maximal isometric force and reduced Ca2+ sensitivity of contraction for both genotypes, but this reduction in pCa50 was nearly twice as large for WT-RLC versus N47K. We also used stochastic length-perturbation analysis to characterize cross-bridge kinetics. The cross-bridge detachment rate was measured as a function of [MgATP] to determine the effect of mavacamten on myosin nucleotide handling rates. Mavacamten increased the MgADP release and MgATP binding rates for both genotypes, thereby contributing to faster cross-bridge detachment, which could speed up myocardial relaxation during diastole. Our data suggest that mavacamten reduces isometric tension and Ca2+ sensitivity of contraction via decreased strong cross-bridge binding. Mavacamten may become a useful therapy for patients with heart disease, including some forms of HCM.NEW & NOTEWORTHY Mavacamten is a pharmaceutical that binds to myosin, and it is under investigation as a therapy for some forms of heart disease. We show that mavacamten reduces isometric tension and Ca2+ sensitivity of contraction in skinned myocardial strips from a mouse model of hypertrophic cardiomyopathy that expresses the N47K mutation in cardiac myosin regulatory light chain. Mavacamten reduces contractility by decreasing strong cross-bridge binding, partially due to faster cross-bridge nucleotide handling rates that speed up myosin detachment.

PDE5 inhibition improves cardiac morphology and function in SHR by reducing NHE1 activity: Repurposing Sildenafil for the treatment of hypertensive cardiac hypertrophy.

Previously, we have shown that an increased cGMP-activated protein Kinase (PKG) activity after phosphodiesterase 5 (PDE5) inhibition by Sildenafil (SIL), leads to myocardial Na+/H+ exchanger (NHE1) inhibition preserving its basal homeostatic function. Since NHE1 is hyperactive in the hypertrophied myocardium of spontaneous hypertensive rats (SHR), while its inhibition was shown to prevent and revert this pathology, the current study was aimed to evaluate the potential antihypertrophic effect of SIL on adult SHR myocardium. We initially tested the inhibitory capability of SIL on NHE1 in isolated cardiomyocytes of SHR by comparing H+ efflux during the recovery from an acid load. After confirmed that effect, eight-month-old SHR were chronically treated for one month with SIL through drinking water. Compared to their littermate controls, SIL-treated rats presented a decreased NHE1 activity, which correlated with a reduction in its phosphorylation level assigned to activation of a PKG-p38 MAP kinase-PP2A signaling pathway. Moreover, treated animals showed a decreased oxidative stress that appears to be a consequence of a decreased mitochondrial NHE1 phosphorylation. Treated SHR showed a significant reduction in the pro-hypertrophic phosphatase calcineurin, despite slight tendency to decrease hypertrophy was detected. When SIL treatment was prolonged to three months, a significant decrease in myocardial hypertrophy and interstitial fibrosis that correlated with a lower myocardial stiffness was observed. In conclusion, the current study provides evidence concerning the ability of SIL to revert established cardiac hypertrophy in SHR, a clinically relevant animal model that resembles human essential hypertension.

Multipolar mapping for catheter ablation of premature ventricular complexes originating from papillary muscles in the structurally normal heart: a case series.

BACKGROUND: Previous studies on radiofrequency catheter ablation of premature ventricular complexes (PVCs) arising from the left ventricle (LV) papillary muscles (PM) show a modest procedural success rate with higher recurrence rate. Our study sought to explore the utility of using a multipolar mapping with a steerable linear duodecapolar catheter for ablating the PM PVCs. METHODS: Detailed endocardial multipolar mapping was performed using a steerable linear duodecapolar catheter in 6 consecutive PM PVCs patients with structurally normal heart. The clinical features and procedural data as well as success rate were analysed. RESULTS: LV endocardial electroanatomic mapping was performed in all patients via a retrograde aortic approach using a duodecapolar mapping catheter. All patients displayed a PVC burden with 16.2 ± 5.4%. Duodecapolar catheter mapping demonstrated highly efficiency with an average procedure time (95.8 ± 7.4 min) and fluoroscopy time (14.2 ± 1.5 min). The mean number of ablation applications points was 6.8 ± 1.9 with an average overall ablation duration of 6.1 ± 3.0 min. The values of earliest activation time during mapping using duodecapolar catheter were 37.8 ± 7.2 ms. All patients demonstrated acute successful ablation, and the PVC burden in all patients after an average follow-up of 8.5 ± 2.0 months was only 0.7%. There were no complications during the procedures and after follow-up. CONCLUSIONS: Mapping and ablation of PM PVCs using a duodecapolar catheter facilitated the identification of earliest activation potentials and pace mapping, and demonstrated a high success rate during follow-up.

Relations of Augmented Systolic Annular Expansion and Leaflet/Papillary Muscle Dynamics in Late-Systolic Mitral Valve Prolapse Evaluated by Echocardiography with a Speckle Tracking Analysis.

The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets.MV annulus systolic expansion, PMs' systolic superior shift, and MV leaflets' systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP.PMs' superior shift, MV leaflets' lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m2, 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m2, 6.8 ± 2.5 versus 5.7 ± 1.0 cm2/m2 and 1.6 ± 0.8 versus 0.1 ± 0.5 cm2/m2, P < 0.001, respectively). Multivariate analysis identified MV leaflets' lengthening and PMs' superior shift as independent factors associated with MV annular expansion.Conclusions: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets' lengthening and PMs' superior shift.

Outcomes of emergency or urgent mitral valve repair in patients with papillary muscle rupture and active infective endocarditis.

BACKGROUND: Emergency or urgent surgery is often required in patients with papillary muscle rupture and active mitral valve infective endocarditis. The aim of this study was to analyze the outcomes of patients with active endocarditis who underwent emergency or urgent mitral valve repair. METHODS: From 2005 to 2014, 154 ischemic mitral regurgitation patients and 41 infective endocarditis patients underwent mitral valve repair in our institution; 23 had emergency operations due to papillary muscle rupture, and 18 with active infective endocarditis underwent urgent surgery. RESULTS: Cardiopulmonary bypass time (141.4 ± 43.3 versus 145.3 ± 46.5 min) and crossclamp time (77.7 ± 34.1 versus 79.2 ± 33.0 min) were similar in the papillary muscle rupture and elective ischemic mitral regurgitation subgroups, and major postoperative complications were comparable. Hospital mortality was 17.4% in the papillary muscle rupture subgroup and 8.4% in the elective ischemic mitral regurgitation subgroup. Cardiopulmonary bypass time (103.6 ± 37.0 versus 75.5 ± 20.8 min) and crossclamp time (61.7 ± 21.2 versus 45.3 ± 18.0 min) were significantly longer in infective endocarditis patients. There were no major complications or hospital deaths. Eight years postoperatively, overall survival was 94.4% and 86.5% in the papillary muscle rupture and elective ischemic mitral regurgitation subgroups, respectively (p = 0.730). Overall survival was 100% in both infective endocarditis subgroups. CONCLUSION: The feasibility and effectiveness of emergency or urgent mitral valve repair in patients with papillary muscle rupture and active infective endocarditis are satisfactory. Early and mid-term outcomes are comparable to those of elective operations.

Intraventricular muscle bundle as a novel cause of left ventricular aneurysm.

BACKGROUND: There are a variety of causes of left ventricular aneurysm, but it is rarely due to a disturbance in intraventricular hemodynamics. To the best of our knowledge, there have been no reports of ventricular aneurysm at the left ventricular apex caused by an abnormal left ventricular muscle bundle. CASE PRESENTATION: We report two cases of patients with congenital abnormal left ventricular muscle bundles which caused disturbances in intraventricular hemodynamics. This process eventually led to a left ventricular aneurysm at the apex of the heart. In both cases, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) indicated ventricular aneurysm formation at the apex of the left ventricle. There were also abnormal muscular bundles connecting the ventricular septum and the posterior wall of the left ventricle. The only differences between these two cases were the comorbidities and severity of symptoms. CONCLUSION: Ventricular aneurysm at the apex of the left ventricle is common. However, it is rare for a ventricular aneurysm to form due to intraventricular hemodynamic disturbances caused by an abnormal muscle bundle as opposed to that due to original ventricular wall damage, which is more common. There is currently a lack of relevant studies on the treatment and prognosis of such patients. Whether surgical resection of a ventricular aneurysm leads to a better prognosis remains uncertain.

Evidence of 2 conduction exits of the moderator band: Findings from activation and pace mapping study.

BACKGROUND: The moderator band (MB) is an endocavitary structure with only 2 exits to the bulk of the ventricular myocardium. Whether this may lead to specific electrophysiological characteristics remains unknown. OBJECTIVE: The purpose of this study was to investigate electrocardiographic (ECG), activation, and pace mapping characteristics of MB-originated ventricular arrhythmias (VAs). METHODS: Mapping and ablation of MB-VAs were performed in 12 patients under the guidance of a 3-dimensional electroanatomic mapping system and intracardiac echocardiography and ECG, and mapping data were analyzed. Of these patients, 11 underwent pace mapping study of 6 sites around the MB and the QRS morphology was compared. RESULTS: The earliest activation site was free wall (FW) insertion in 8 patients (66.7%) and MB body in 4 patients (33.3%), preceding the QRS onset by 17.8±4.7 ms, and Purkinje-like potential was observed in 6 (50.0%). VAs were eliminated at the earliest activation site in the procedure, but recurrence was documented in 2 cases (16.7%) during a follow-up of 13.4±7.8 months. Pacing QRS complex from the MB was characterized by short QRS duration (P<.001), short intrinsicoid deflection time (P<.001), later precordial transition (P=.025), and notch on the descending limb of the inferior leads (P<.001) as compared with pacing from the adjacent anterior-lateral FW, and that notch could also differentiate MB from the anterior papillary muscle (P=.027). However, pacing QRS is identical between the MB body and the FW insertion in 11 of 11 patients and between the septal insertion and the MB body in 7 of 11 patients. CONCLUSION: Bidirectional conduction via the 2 exits during MB-VAs contributed to distinct ECG and electrophysiological characteristics, while pace mapping is of limited value in defining the ablation target.

QRS morphology in lead V1 for the rapid localization of idiopathic ventricular arrhythmias originating from the left ventricular papillary muscles: A novel electrocardiographic criterion.

BACKGROUND: Twelve-lead electrocardiogram (ECG) criteria have been developed to identify idiopathic ventricular arrhythmias (VAs) from the left ventricular (LV) papillary muscles (PAPs), but accurate localization remains a challenge. OBJECTIVE: The purpose of this study was to develop ECG criteria for accurate localization of LV PAP VAs using lead V1 exclusively. METHODS: Consecutive patients undergoing mapping and ablation of VAs from the LV PAPs guided by intracardiac echocardiography from 2007 to 2018 were reviewed (study group). The QRS morphology in lead V1 was compared to patients with VAs with a "right bundle branch block" morphology from other LV locations (reference group). Patients with structural heart disease were excluded. RESULTS: One hundred eleven patients with LV PAP VAs (mean age 54 ± 16 years; 65% men) were identified, including 64 (55%) from the posteromedial PAP and 47 (42%) from the anterolateral PAP. The reference group included patients with VAs from the following LV locations: fascicles (n = 21), outflow tract (n = 36), ostium (n = 37), inferobasal segment (n = 12), and apex (5). PAP VAs showed 3 distinct QRS morphologies in lead V1 93% of the time: Rr (53%), R with a slurred downslope (29%), and RR (11%). Sensitivity, specificity, positive predictive value, and negative predictive value for the 3 morphologies combined are 93%, 98%, 98%, and 93%, respectively. The intrinsicoid deflection of PAP VAs in lead V1 was shorter than that of the reference group (63 ± 13 ms vs 79 ± 24 ms; P < .001). An intrinsicoid deflection time of <74 ms best differentiated the 2 groups (sensitivity 79%; specificity 87%). CONCLUSION: VAs originating from the LV PAPs manifest unique QRS morphologies in lead V1, which can aid in rapid and accurate localization.

Lipid Emulsion Restoration of Myocardial Contractions After Bupivacaine-Induced Asystole In Vitro: A Benefit of Long- and Medium-Chain Triglyceride Over Long-Chain Triglyceride.

BACKGROUND: The relative efficacies of a long- and medium-chain triglyceride (LCT/MCT) emulsion and an LCT emulsion for treatment of bupivacaine (BPV)-induced cardiac toxicity are poorly defined. METHODS: After inducing asystole by BPV, varied concentrations (1%-12%) of either LCT/MCT (Lipofundin; B. Braun, Melsungen, Germany) or LCT emulsion (Intralipid; Fresenius Kabi, Upsala, Sweden) were applied to observe the recovery of stimulated contractile responses and contractile forces in either a recirculating or washout condition for 60 minutes, using guinea pig papillary muscles. The recirculation condition was used to demonstrate BPV binding by lipid emulsion. The washout condition was used to determine whether the time-dependent recovery of contraction is due to their metabolic enhancement. Oxfenicine, an inhibitor of carnitine palmitoyltransferase I in heart mitochondria, was used to evaluate the effect of each lipid emulsion on mitochondrial metabolic inhibition by BPV. To examine the effect of the lipid emulsion alone on contractility, either lipid emulsion was examined. BPV concentrations in solution and myocardial tissues were measured. RESULTS: In the recirculating condition, LCT/MCT emulsions (2%-12%) restored regular stimulated contractile responses in all muscles. Eight percent and 12% LCT/MCT emulsions led to complete recovery of contractile forces after 30 minutes. Meanwhile, LCT emulsions (4%-12%) did not restore regular stimulated contractile responses in some muscles (6, 3, and 2 in 9 muscles each in 4%, 8%, and 12% emulsions, respectively). Partial recovery, approximately 60%, of contractile forces was observed with 8% and 12% LCT emulsions. In the washout experiments, after asystole, LCT/MCT emulsions (1%-12%) restored contractility to baseline levels earlier and greater than LCT emulsion. Partial recovery, approximately 60%, was observed with a high concentration of LCT emulsion (12%). In the oxfenicine-pretreated group, the contractile recovery was enhanced with LCT/MCT emulsion but showed no change with LCT emulsion. Contractile depression by 40% was observed with high concentrations of LCT emulsion alone (8% and 12%), whereas no depression or enhanced contraction was observed with LCT/MCT emulsion (1%-12%) alone. Both types of lipid emulsions (2%-12%) caused concentration-related reductions of tissue BPV levels; LCT/MCT emulsions reduced tissue BPV levels slightly greater than LCT emulsion in a recirculating condition. CONCLUSIONS: An LCT/MCT emulsion was more beneficial than an LCT emulsion in terms of local anesthetic-binding and metabolic enhancement for treating acute BPV toxicity. The metabolic benefit of MCT, combined with the local anesthetic-binding effect of LCT, in an LCT/MCT emulsion may improve contractile function better than an LCT emulsion in an isolated in vitro animal myocardium model.

Ablation of the N terminus of cardiac essential light chain promotes the super-relaxed state of myosin and counteracts hypercontractility in hypertrophic cardiomyopathy mutant mice.

In this study, we focus on the molecular mechanisms associated with the A57G (Ala57-to-Gly57) mutation in myosin essential light chains (ELCs), found to cause hypertrophic cardiomyopathy (HCM) in humans and in mice. Specifically, we studied the effects of A57G on the super-relaxed (SRX) state of myosin that may contribute to the hypercontractile cross-bridge behavior and ultimately lead to pathological cardiac remodeling in transgenic Tg-A57G mice. The disease model was compared to Tg-WT mice, expressing the wild-type human ventricular ELC, and analyzed against Tg-Δ43 mice, expressing the N-terminally truncated ELC, whose hearts hypertrophy with time but do not show any abnormalities in cardiac morphology or function. Our data suggest a new role for the N terminus of cardiac ELC (N-ELC) in modulation of myosin cross-bridge function in the healthy as well as in HCM myocardium. The lack of N-ELC in Tg-Δ43 mice was found to significantly stabilize the SRX state of myosin and increase the number of myosin heads occupying a low-energy state. In agreement, Δ43 hearts showed significantly decreased ATP utilization and low actin-activated myosin ATPase compared with A57G and WT hearts. The hypercontractile activity of A57G-ELC cross-bridges was manifested by the inhibition of the SRX state, increased number of myosin heads available for interaction with actin, and higher ATPase activity. Fiber mechanics studies, echocardiography examination, and assessment of fibrosis confirmed the development of two distinct forms of cardiac remodeling in these two ELC mouse models, with pathological cardiac hypertrophy in Tg-A57G, and near physiologic cardiac growth in Tg-Δ43 animals.

Possible association of papillary muscle hypertrophy with the genesis of J-waves.

BACKGROUND: Although J-waves have been known to be associated with vulnerability to ventricular fibrillation, their electrophysiologic mechanism remains to be elucidated. The papillary muscles (PMs) of the left ventricle (LV) have been recognized as the target site of radiofrequency ablation for ventricular arrhythmias. However, the relationship between PM hypertrophy and J-waves has not been investigated. OBJECTIVE: To investigate the electrocardiographic characteristics, including the J-waves, in patients with solitary PM hypertrophy. METHODS: We studied 101 patients with PM hypertrophy without LV hypertrophy (PMH group) and 159 age- and sex-matched control subjects (control group). The parameters of the 12-lead electrocardiogram and the echocardiogram were compared between the two groups. RESULTS: Compared with the control group, the PMH group had significantly higher incidence (15% vs. 33%, p=0.001) and amplitude (0.17±0.06mV vs. 0.28±0.17mV, p<0.01) of J-waves; significantly longer QRS, QTc, and JTc intervals (p=0.0001, p<0.0001, and p<0.05, respectively); significantly greater Sokolow-Lyon index (p<0.001); and significantly greater LV wall thickness and LV mass index (p<0.0001 for each). Multivariate logistic regression analysis showed that only the PM hypertrophy was an independent predictor of the presence of J-waves. CONCLUSION: PM hypertrophy was related to the genesis of J-waves.

Impact of posteromedial papillary muscle infarction on mitral regurgitation during ST-segment elevation myocardial infarction.

The exact role of papillary muscle infarction (PMI) during the acute phase of acute ST-segment elevation myocardial infarction (STEMI) is not well understood, as existing data on the impact of PMI location is conflicting. We hypothesized that infarction of the posteromedial papillary muscle (PM-PMI) as determined by cardiac magnetic resonance imaging might be associated with an increased incidence of mitral valve regurgitation in the first week after STEMI. 242 patients with first STEMI underwent a late-enhancement (LGE-) cardiac magnetic resonance imaging within a median of 2 (IQR 2-5) days and echocardiography within 3 (IQR 2-5) days after primary angioplasty for the index event. PMI was scored based on short axis slices (AL-PMI: anterolateral PMI, PM-PMI, AL/PM-PMI: AL- and PM-PMI). Patients with PM-PMI had significantly higher odds (OR 2.62, p < 0.01) for the occurrence of mitral regurgitation than patients with no-PMI, AL-PMI or AL/PM-PMI. Furthermore, advanced age, non-anterior infarct location and longer pain-to-balloon time were identified as risk factors for the occurrence of mitral regurgitation. Binary logistic regression analysis revealed that PM-PMI is a predictor of mitral regurgitation independent of infarct location and age (OR 2.229, CI 1.078-4.903, p = 0.031). PM-PMI as determined by cardiac magnetic resonance imaging is an independent predictor of mitral regurgitation in the setting of acute STEMI. Our data might improve our understanding of the dynamic nature of functional mitral regurgitation.

Follow-Up After Catheter Ablation of Papillary Muscles and Valve Cusps.

OBJECTIVES: The goal of this study was to determine the impact of catheter ablation in the region of papillary muscles (PMs) and valvular cusps (VC) on mitral, tricuspid, or aortic valve function. BACKGROUND: Ventricular arrhythmias arising from PMs and VCs often require extensive catheter ablation. Little is known regarding the risk of valve dysfunction after radiofrequency catheter ablation of such arrhythmias. METHODS: A retrospective analysis was completed for 149 PM and VC VT/premature ventricular contraction (PVC) ablations from 2008 to 2018 at our institution. Patient and procedural details were collected for VT and PVC ablation cases involving PMs and VCs with available echocardiographic data pre-ablation and post-ablation (within 6 months). Degree of valvular regurgitation (VR) was graded from 0 (none) to 4 (severe), and significant valvular dysfunction was defined as a 2+ change in VR. RESULTS: Of 149 radiofrequency catheter ablation cases, there were 84 (56%) aortic valve cusp ablations, 60 (40%) left ventricular PM ablations, and 5 (3%) right ventricular PM ablations. There were no statistically significant differences between pre-ablation and post-ablation VR severity (p = 0.33). No patients had a 2+ grade change in VR severity when pre-ablation and post-ablation echocardiograms were compared. There were no significant sequelae requiring intervention in the post-ablation period. On follow-up of 36 ± 9 months, for those with a change in VR, the severity had improved to baseline or remained stable. CONCLUSIONS: Despite often-times extensive ablation on and around valvular networks, risk of longstanding or permanent valvular dysfunction after VT/PVC ablation is rare.