Left Ventricular Papillary Muscles Research Articles

Electrocardiographic characteristics and catheter ablation of premature ventricular complex- mediated ventricular fibrillation

Abstract Background Premature ventricular contractions (PVCs) can trigger ventricular fibrillation (VF) in patients with/or without structural heart disease. There are limited data on coexisting electrocardiographic (ECG) features and catheter ablation outcomes in these patients which could suggest the concomitant presence of an abnormal electrical and structural substrate. Purpose We investigated ECG and electroanatomic characteristics and clinical outcomes in patents who underwent catheter ablation of PVCs triggering VF. Methods We analyzed data from a consecutive series of patients who underwent catheter ablation between 08/2019 and 04/2023 for PVCs triggering VF. On the 12-lead ECG, we assessed the following abnormalities: (a) Early repolarization (ER) pattern in either inferior or lateral leads (Figure 1), or (b) QRS Notching of either the native sinus beat or PVC (Figure 2). Post-ablation follow up outcomes were collected using a combination of ICD interrogation, remote transmission and clinical follow up. Results The cohort included 15 patients: age 52.1±16.8 years, 46.7% females, and 26.7% presenting with VF storm. On average, there were 3.8 HV shocks/per patient from an ICD prior to the index ablation procedure (range: 0-19 shocks). On the 12-lead ECG, the mean coupling interval of the PVC leading to VF was 204±82 ms, and an overall narrow PVC morphology with a mean QRS duration of 107±17 ms. We observed early repolarization (ER) in 6 (40%) of the cohort. In most patients (n=11; 73.3%), at least one of the 2 ECG abnormalities were present. An endocardial-only approach was adequate in all patients, and during catheter ablation, Purkinje potentials were targeted in 10 (66%) of the patients. Based on activation and pace-mapping, the PVCs were localized to the following sites: (a) left ventricular (LV) septum in 11 (73.3%), (b) papillary muscles in 2 (13.3%), and (c) other sites such as the Moderator band and right ventricular outflow tract in the remaining 2 (13.3%) patients. The ablation locations on the LV septum extended from basal to mid-septum. After an average of 1.7 ablation procedures targeting PVC-triggering VF, 12 (80%) patients remained free of sustained ventricular arrhythmias and ICD shocks, over a mean follow up of 479±395 days. Conclusion In most patients with PVCs-triggering VF, there was an evidence of an ECG abnormality either in the form of an ER pattern or notching of either the Sinus QRS or the PVC complex on pre-ablation ECG. During ablation, Purkinje potentials and PVCs were mapped to and ablated in the region of the LV interventricular septum and papillary muscles. Over long-term follow up, catheter ablation seemed durable and effective in reducing VF episodes and ICD shocks.Presence of Early Repolarization patternPresence of a notching pattern in the Si

Catheter ablation of papillary muscle arrhythmias: procedural characteristics and long term outcome

Abstract Background Ventricular arrhythmias (VA) originating from the papillary muscles can occur both in patients with and without structural heart disease. Although catheter ablation is the treatment of choice, ablation success remains challenging and long-term outcomes for this origin of VA are still unsatisfactory. Methods and Results All patients undergoing catheter ablation for premature ventricular contractions or ventricular tachycardia between june 2009 and november 2022 were analyzed. 66 patients (26 female (39%), mean age 60±15 years) undergoing catheter ablation of VA originating from the papillary muscle were identified. 21/66 (32%) patients had a reduced or mildly reduced left ventricular ejection fraction at time of initial presentation. While mitral valve regurgitation was present in 32/66 (48%) patients, mitral valve prolapse was observed in only 2/66 (3%) patients. 6/66 (9%) patients presented with non-sustained ventricular tachycardia (VT) and 1/66 (2%) patient presented with sustainend VT prior to catheter ablation. 61/66 (92%) patients underwent ablation of PVCs of the left ventricular papillary muscles (22/66 (33%) patients anterolateral; 39 (59%) patients posteromedial). 5/66 patients underwent ablation of premature ventricular complex (PVC) originating from the papillary muscles of the right ventricle. In 13/66 (19.7%) patients only a retrograde approach was used, in 26/66 (39.5%) patients a retrograde and an additional transeptal approach and in only 10/66 (15.2%) patients solely a transeptal approach. Mean PVC QRS duration was 152.5 ± 3.5 msec. Ablation was acutely successful in 44/66 (67%) patients. Mean procedure time was 145.8 ± 63.7 minutes and mean number of radiofrequency applications was 21.3 ± 16.7 (25 to 55 Watts, 37764.2 ± 27824.1 Joules). Overall, procedural complications occurred in 4/66 (6%) patients Follow up data were obtained from Holter ECGs, review of medical records, patient consultation, or via structured follow-up within the prospective TRUST registry. All information was combined to assess recurrence of PVC/VT. Recurrence of VA originating from the papillary muscles occurred in 11/66 (17%) patients. 9/66 patients (14%) underwent re-ablation due to recurrence of VA originating from the papillary muscles after previous ablation procedures. Conclusion Catheter ablation of papillary muscle arrhythmias is associated with a single procedural success rate of 67% with a procedural complication rate of 6%. 14% of patients underwent re-ablation due to recurrence of papillary muscle arrhythmias.

Feasibility of an animal model for long-term mechanical circulatory support with Impella 5.5 implanted through carotid artery access in sheep.

Impella is a mechanical circulatory support device of a catheter-based intravascular microaxial pump for left ventricular support and unloading. However, nonclinical studies assessing the effects of the extended duration of left ventricular unloading on cardiac recovery are lacking. An animal model using Impella implanted with a less invasive procedure to enable long-term support is required. This study aimed to evaluate the feasibility of an animal model for long-term support with Impella 5.5 implanted through carotid artery access in sheep.Impella 5.5 was implanted in four sheep through the proximal region of the left carotid artery without a thoracotomy, and myocardial injuries were induced by coronary microembolization. Support by Impella 5.5 was maintained for 4 weeks, and the animals were observed. The position of Impella 5.5 and cardiac function was evaluated using cardiac computer tomography at 2 and 4 weeks after implantation.All four animals completed the 4-week study without major complications. The discrepancy in the Impella 5.5 flow rate between the conscious and anesthetized states was observed depending on the device's position. Animals in whom the inflow was above the left ventricular papillary muscle had a relatively high flow rate under the maximum performance level without a suction alarm during the conscious state. Pathological changes in the aortic valve were observed. Cardiac function under the minimum performance level was observed with no remarkable deterioration.The animal model with myocardial injuries supported for 4 weeks by Impella 5.5 implanted through carotid artery access in sheep was feasible.

Intoxicação por Nerium oleander em bovinos: uso de imuno-histoquímica para troponina C como método de diagnóstico auxiliar

ABSTRACT: Nerium oleander, also known as “espirradeira” in Brazil, is a shrub or small tree widely used as an ornamental plant in temperate and subtropical regions of the world. Ingestion of N. oleander can cause intoxication due to the presence of cardioactive glycosides, in both humans and animals. This study aims to report the epidemiological, clinical, postmortem, and immunohistochemical features of an outbreak of natural intoxication by N. oleander in cattle and the use of immunohistochemistry (IHC) for troponin C, for the first time, in this intoxication in the species. Twenty-eight cattle had access to pruned branches of N. oleander and 20 animals started presenting clinical signs of apathy, anorexia, ataxia, tachypnea, tremors, and recumbency ten hours after the consumption. Eight cattle progressed to death 48 hours after the clinical progression and one was submitted for necropsy. Macroscopic findings included petechiae and ecchymosis on the epicardium and endocardium. Histologically, there were multifocal areas of necrosis of individual or multiple cardiomyocytes, mainly in the left ventricular papillary muscle. Immunohistochemistry for troponin C revealed decrease or absence of cytoplasmic immunolabeling in necrotic cardiomyocytes. Although intoxication by N. oleander is uncommon in cattle, it should be considered as a differential diagnosis for other conditions that cause sudden or acute death in livestock and IHC for troponin C is an auxiliary tool in the identification of peracute and acute cardiac lesions.

Rats with Postinfarction Heart Failure: Effects of Propranolol Therapy on Intracellular Calcium Regulation and Left Ventricular Function

Patients with heart failure may live longer if they receive chronic treatment with beta-adrenergic blocking medications. Unresolved are the mechanisms underlying the beneficial effects and if they may be applied to ischemic heart failure. Rats (n = 28) underwent echocardiographic-Doppler exams one and six weeks following a simulated operation or myocardial infarction (MI). After the first echocardiography, rats were randomized to either no therapy or 500 mg/l of propranolol in their drinking water. The noninfected left ventricular (LV) papillary muscles were used to record isometric contractions and intracellular Ca transients simultaneously. Untreated MI rats had a restrictive LV diastolic filling pattern, decreased systolic function (13% ± 2%), and significant LV dilatation (10.6 ± 0.4 mm vs. 8.9 ± 0.3 mm, MI vs. control). The LV chamber diameters of the propranolol-treated MI rats were 10.6 ± 0.5 mm, and systolic performance (13% ± 2%). Higher LV end-diastolic pressures (27 ± 2 mmHg vs. 20 ± 3 mmHg) and a more constrained LV diastolic filling pattern (increased ratio of early to late filling velocities and faster E wave deceleration rate) were seen in the propranolol-treated animals. Papillary muscle contractility in untreated MI rats was lower (1.6 ± 0.3 g mm²). Furthermore, the inotropic response to isoproterenol was attenuated, and Ca transients were extended. During isoproterenol stimulation, beta-adrenergic blocking administration had no effect on force development (1.6 ± 0.3 g mm²) or the length of Ca transients. Rats with postinfarction heart failure receiving chronic propranolol treatment did not have improvements in systolic function or LV remodeling. Propranolol exacerbated LV diastolic pressures and filling patterns. Additionally, there was no discernible improvement in intracellular contractility following treatment, Calcium control, or beta-adrenergic sensitivity in the myocardium that is not infarcted).

Phosphorylation Mimetic of Myosin Regulatory Light Chain Mitigates Cardiomyopathy-Induced Myofilament Impairment in Mouse Models of RCM and DCM.

This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in essential (ELC, MYL3 gene) or regulatory (RLC, MYL2 gene) light chains of myosin. Phosphomimetic S15D-RLC was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild-type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by the S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted with fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared with those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM-treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.

Dark papillary muscles sign: a novel prognostic marker for cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background the prognostic role of left ventricular (LV) papillary muscle abnormalities in patients with preserved LV systolic ejection fraction (LVEF) is unknown. Aim to evaluate the prevalence and the clinical and prognostic impact of papillary muscle abnormalities by CMR in patients with ventricular arrhythmias, preserved LVEF with no cardiac disease. Methods 391 patients with >500/24h premature ventricular complexes and/or with non-sustained ventricular tachycardia (NSVT), preserved LVEF and no cardiac disease, were enrolled. Different features of LV papillary muscles were considered: supernumerary muscles, papillary thickness, the attachment, late gadolinium enhancement (LGE). The end-systolic hypointensity was defined when its measured signal intensity (SI) was lower than the SI of the septum in early post-contrast cine CMR images. Dark-Paps was defined when both the main papillary muscles had systolic hypointensity. Mitral valve prolapse, mitral annular disjunction (MAD), myocardial LGE were considered. The outcome of hard cardiac events was define as a composite of cardiac death, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) shock, sustained ventricular tachycardia (lasting ≥30 s at ≥100 beats/min). Results Dark-Paps was found in 79 (20%) patients and was more frequent in females. It was associated with higher prevalence of mitral valve prolapse and MAD. During a median follow-up of 2534 days, 22 hard cardiac events occurred. At Kaplan-Meier curve (Figure) analysis patients with Dark-Paps were at higher risk of events than those without (p<0.0001). Dark-Paps was significantly associated with hard cardiac events in all the multivariate models performed. Dark-Paps improved prognostic estimation when added to NSVT (p = 0.0006), to LGE (p = 0.005) and to a model including NSVT+LGE (p = 0.014). Dark-Paps allowed a significant net reclassification when added to NSVT (NRI 0.30, p =0.03), to LGE (NRI 0.25, p =0.04), and to NSVT + LGE (NRI 0.32, p =0.02). Conclusions Dark-Paps sign could be considered a novel imaging prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction.

Is catheter-tissue contact force value important for ablation of ventricular arrhythmias originating from the left ventricular papillary muscles?

Good catheter-tissue contact is mandatory to create effective ablation lesions. The minimal contact force value for ablation of arrhythmias originating from the left ventricle is 8.0-10.0 grams but is not known for arrhythmias arising from papillary muscles. To analyze contact force values during successful ablation procedures of arrhythmias originating from the left ventricular papillary muscles. 24 consecutive patients (mean age 57.9 ± 11.9 years, 16 males) underwent ablation of premature ventricular complexes originating from left ventricular papillary muscles with the use of CARTO electro-anatomical system and intracardiac echocardiography. Acute complete abolition of ventricular ectopy was obtained in 23 (96%) patients. The fluoroscopy time was 3.9 ± 3.5 min and procedure duration - 114.8 ± 37.9 min. The mean contact force during successful ablations was 3.0 ± 1.1 grams and 3.18 ± 1.8 grams for antero-lateral and postero-medial papillary muscle, respectively (NS). The mean contact force during a single unsuccessful ablation was 3.0 grams. At control Holter ECG, the mean Ectopy Burden was Reduced in the Antero-Lateral Papillary Muscle Group from 18.0% ± 7.9% to 2.6% ± 2.9% (p = 0.005415) and in the Postero-Medial Papillary Muscle Group - from 34.8% ± 13.7%-1.7% ± 1.3% (p = 0.012694). During Median 27 (IQR: 17-34) Months of Follow-up There one Recurrence of Arrhythmia. The values of contact force for successful ablation of ventricular ectopy originating from the left ventricular papillary muscles may be much lower than those for ablation of other foci which questions the role of contact force measurement when ablating these arrhythmias.

Combination of Intracardiac Echocardiography and Contact Force Sensing for Left Ventricular Papillary Muscle Arrhythmias.

The catheter ablation of ventricular arrhythmias (VAs) arising from the left ventricular (LV) papillary muscles (PMs) is challenging. This study sought to address whether the combination of intracardiac echocardiography (ICE) and contact force sensing (CFS) can improve the acute and long-term ablation outcomes of left ventricular papillary muscle arrhythmias. From May 2015 to August 2022, a total of thirty-three patients underwent catheter ablation for LV PM arrhythmias: VAs were located in anterolateral PMs in 11 and posteromedial PMs in 22. A combination of intracardiac echocardiography (ICE) and contact force sensing (CFS) was used in 21 of the 33 procedures. A mean of 6.93 ± 4.91 for lesions was used per patient, comparable between the CFS/ICE and no ICE/CFS (4.90 ± 2.23 vs. 10.17 ± 5.89; p = 0.011). The mean CF achieved in the ICE/CFS group was 7.52 ± 3.31 g. Less X-ray time was used in the combination group (CFS/ICE: 165.67 ± 47.80 S vs. no ICE/CFS: 365.00 ± 183.73 S; p < 0.001). An acute success rate of 100% was achieved for the ICE/CFS group (n = 22) and 66.67% for the no ICE/CFS group (n = 8). VA recurrence at the 11.21 ± 7.21-month follow-up was 14.2% for the ICE/CFS group and 50% for the no ICE/CFS group (p = 0.04). No severe complications occurred in all patients. The combination of intracardiac echocardiography (ICE) and contact force sensing (CFS) could provide precise geometries of cardiac endocavitary structures and accurate contact information for the catheter during ablation, which improved acute and long-term ablation outcomes. The routine adoption of this strategy should be considered to improve the outcomes of LV PM VA ablation.

A rapid wide complex tachycardia

A rapid wide complex tachycardia

Investigating the sarcolemma-sarcomere connection and force transmission in the heart.

External mechanical signals are communicated through cardiac muscle cells by converting them to internal biochemical signals during mechanotransduction. In the heart, altered transmission of these signals can affect myocardial structure and function. This study examines the impact of sarcospan deletion, a sarcolemma protein, on cardiac muscle mechanics. Sarcospan is an integral member of the dystrophin-glycoprotein complex (DGC) and we are interested in investigating how it influences sarcomere contractile function. Measurements of cardiac contractile parameters were conducted using permeabilized left ventricular papillary muscle bundles obtained from wild-type and SSPN-deficient (SSPN-/-) mouse hearts. Myofilament Ca2+-sensitivity and cooperativity of thin filament activation was similar between WT and SSPN-/- cardiac muscle preparations. However, SSPN-/- muscle bundles exhibited a significantly faster rate of tension redevelopment (kTR) at submaximal activation conditions (pCa 5.8) but no significant changes in maximal kTR (recorded at maximal Ca2+ activation, pCa 4.5). Maximal steady-state isometric force and sinusoidal stiffness were proportionally increased in SSPN-/- cardiac muscle preparations during Ca2+ activation. These intriguing observations suggest that SSPN may play an inherent role in balancing pathways involved in force transmission and its deletion may cause compensatory remodeling of sarcomeric proteins (e.g. isoform switching or protein modification) changing mechanical properties of cardiac muscle. Mouse hearts lacking SSPN-/- exhibit increased sarcolemmal expression of integrin-linked kinase (ILK) and vinculin. ILK is an important biomechanical sensor shown to regulate cardiac contractility and ventricular hypertrophy whereas increasing vinculin expression has been shown to improve heart function and impact myofilament organization. Further examination of the WT and SSPN-/- myofibrils will allow us to assess sarcomere protein alterations that contribute to increased force at submax and max levels of Ca2+ activation. Therefore, the concentric enlargement observed in SSPN-/- mouse hearts could be explained by remodeling of the sarcomere itself.

Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion

BackgroundType 2 Diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and associated with poor outcome after myocardial infarction (MI). In T2DM, cardiac metabolic flexibility, i.e. the switch between carbohydrates and lipids as energy source, is disturbed. The RabGTPase-activating protein TBC1D4 represents a crucial regulator of insulin-stimulated glucose uptake in skeletal muscle by controlling glucose transporter GLUT4 translocation. A human loss-of-function mutation in TBC1D4 is associated with impaired glycemic control and elevated T2DM risk. The study’s aim was to investigate TBC1D4 function in cardiac substrate metabolism and adaptation to MI.MethodsCardiac glucose metabolism of male Tbc1d4-deficient (D4KO) and wild type (WT) mice was characterized using in vivo [18F]-FDG PET imaging after glucose injection and ex vivo basal/insulin-stimulated [3H]-2-deoxyglucose uptake in left ventricular (LV) papillary muscle. Mice were subjected to cardiac ischemia/reperfusion (I/R). Heart structure and function were analyzed until 3 weeks post-MI using echocardiography, morphometric and ultrastructural analysis of heart sections, complemented by whole heart transcriptome and protein measurements.ResultsTbc1d4-knockout abolished insulin-stimulated glucose uptake in ex vivo LV papillary muscle and in vivo cardiac glucose uptake after glucose injection, accompanied by a marked reduction of GLUT4. Basal cardiac glucose uptake and GLUT1 abundance were not changed compared to WT controls. D4KO mice showed mild impairments in glycemia but normal cardiac function. However, after I/R D4KO mice showed progressively increased LV endsystolic volume and substantially increased infarction area compared to WT controls. Cardiac transcriptome analysis revealed upregulation of the unfolded protein response via ATF4/eIF2α in D4KO mice at baseline. Transmission electron microscopy revealed largely increased extracellular matrix (ECM) area, in line with decreased cardiac expression of matrix metalloproteinases of D4KO mice.ConclusionsTBC1D4 is essential for insulin-stimulated cardiac glucose uptake and metabolic flexibility. Tbc1d4-deficiency results in elevated cardiac endoplasmic reticulum (ER)-stress response, increased deposition of ECM and aggravated cardiac damage following MI. Hence, impaired TBC1D4 signaling contributes to poor outcome after MI.

Idiopathic Ventricular Tachycardia.

Idiopathic ventricular tachycardia (VT) is an important cause of morbidity and less commonly, mortality in patients with structurally normal hearts. Appropriate diagnosis and management are predicated on an understanding of the mechanism, relevant cardiac anatomy, and associated ECG signatures. Catheter ablation is a viable strategy to adequately treat and potentially provide a cure in patients that are intolerant to medications or when these are ineffective. In this review, we discuss special approaches and considerations for effective and safe ablation of VT arising from the right ventricular outflow tract, left ventricular outflow tract, left ventricular fascicles, papillary muscles, and moderator band.

Dark papillary muscles sign: a novel prognostic marker for cardiac magnetic resonance

ObjectivesThe prognostic role of left ventricular (LV) papillary muscle abnormalities in patients with preserved LV systolic ejection fraction (LVEF) is unknown. We sought to evaluate the prognosis role of LV papillary muscle abnormalities by CMR in patients with ventricular arrhythmias, preserved LVEF with no cardiac disease.MethodsA total of 391 patients with > 500/24 h premature ventricular complexes and/or with non-sustained ventricular tachycardia (NSVT), preserved LVEF, and no cardiac disease were enrolled. Different features of LV papillary muscles were considered: supernumerary muscles, papillary thickness, the attachment, late gadolinium enhancement (LGE). Dark-Paps was defined as end-systolic signal hypointensity of both papillary muscles in early post-contrast cine CMR images. Mitral valve prolapse, mitral annular disjunction (MAD), and myocardial LGE were considered.ResultsDark-Paps was found in 79 (20%) patients and was more frequent in females. It was associated with higher prevalence of mitral valve prolapse and MAD. During a median follow-up of 2534 days, 22 hard cardiac events occurred. At Kaplan-Meier curve analysis, patients with Dark-Paps were at higher risk of events than those without (p < 0.0001). Dark-Paps was significantly associated with hard cardiac events in all the multivariate models. Dark-Paps improved prognostic estimation when added to NSVT (p = 0.0006), to LGE (p = 0.005) and to a model including NSVT+LGE (p = 0.014). Dark-Paps allowed a significant net reclassification when added to NSVT (NRI 0.30, p = 0.03), to LGE (NRI 0.25, p = 0.04), and to NSVT + LGE (NRI 0.32, p = 0.02).ConclusionsIn LV papillary muscles, Dark-Paps is a novel prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction.Key Points• Papillary muscle abnormalities are seen in patients with ventricular arrhythmias and preserved left ventricular ejection fraction.• Early post-contrast hypointensity of papillary muscles in end-systolic cine images (Dark-Paps) is a novel prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction.• Dark-Paps had an additive prognostic role over late gadolinium enhancement and non-sustained ventricular tachycardia.

Myricetin May Improve Cardiac Dysfunction Possibly Through Regulating Blood Pressure and Cellular Stress Molecules in High-Fructose-Fed Rats.

The aim of this study was to examine the effect of myricetin on cardiac dysfunction caused by high fructose intake. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Myricetin was administered by oral gavage for the last 6 weeks. Systolic blood pressure was measured by tail-cuff method. The effects of isoprenaline, phenylephrine, and acetylcholine on cardiac contractility and rhythmicity were recorded in the isolated right atrium and left ventricular papillary muscles. In addition to biochemical measurements, the cardiac expressions of cellular stress-related proteins were determined by western blotting. Myricetin improved systolic blood pressure but did not affect body weight, plasma glucose, and triglyceride levels in fructose-fed rats. The impairment of isoprenaline- and phenylephrine-mediated increases in atrial contraction and sinus rate in fructose-fed rats was restored by myricetin treatment. Isoprenaline, phenylephrine, and acetylcholine-mediated papillary muscle contractions were not changed by fructose or myricetin administration. The expression of the mitochondrial fission marker dynamin-related protein 1 and the mitophagic marker PTEN-induced kinase 1 (PINK1) was enhanced in the fructose-fed rat, and myricetin treatment markedly attenuated PINK1 expression. High-fructose intake augmented phosphorylation of the proinflammatory molecule Nuclear factor kappa B (NF-κB) and the stress-regulated kinase JNK1, but myricetin only reduced NF-κB expression. Moreover, myricetin diminished the elevation in the expression of the pro-apoptotic Bax. Our results imply that myricetin has a protective role in cardiac irregularities induced by a high-fructose diet through reducing systolic blood pressure, improving cardiac adrenergic responses, suppressing PINK1, NF-κB, and Bax expression, and thus reflecting a potential therapeutic value.

Calcified False Tendon Linked to Sudden Cardiac Death in a Young Adult: An Autopsy-based Case Report

Left Ventricular False Tendons (LVFTs) are cord-like structures that traverse the cavity of the left ventricle, connecting the left ventricular free wall or papillary muscle and the ventricular septum without attachment to the mitral valve leaflets. They are incidentally found in autopsy heart specimens. False tendons are generally benign anatomic variants and can be associated with functional murmurs and electrocardiographic abnormalities. False tendons can also be a cause of ventricular arrhythmias. Two-dimensional echocardiography serves as a useful imaging modality in detecting false tendons. They should be differentiated from other entities such as thickened ventricular trabeculations, an accessory anterior mitral leaflet, thrombus, vegetation, and ventricular masses or tumours. Most LVFTs are transverse and are located in the apex. They are found to arise from the inner trabeculated layer of the myocardium. The exact prevalence of LVFTs remains unclear. Present report is a case of postmortem findings in the heart of a 34-year-old male who experienced a sudden collapse while walking after lunch. On gross examination, the left ventricular wall and the lower part of the interventricular septum showed focal grey-white areas. A well-defined, grey-white, hard polypoidal lesion was noted in the left ventricle near the apex, attached to the papillary muscles. The left anterior descending artery showed early atherosclerotic changes. LVFT was diagnosed, which could have been the reason for the arrhythmia. Hence, the evaluation of cardiac murmurs and arrhythmias by two-dimensional echocardiography and cardiac Magnetic Resonance Imaging (MRI) serves as helpful parameters in detecting LVFTs.

Cardiac Rhabdomyoma in Four Göttingen Minipigs.

Göttingen minipigs are increasingly used as an alternative large animal model in nonclinical toxicology studies, and proliferative lesions in this species are rare. Here, we report four cases of cardiac rhabdomyoma in Göttingen minipigs, an incidental and benign mass in the heart. Three cases lacked gross observations and had a microscopic nodule in either the left ventricle or interventricular septum. The last case had a large, firm, raised nodule on a left ventricular papillary muscle noted at necropsy, with additional microscopic intramural masses in the left ventricular wall. In all cases, microscopic evaluation revealed well-circumscribed, expansile nodules composed of bundles of large, highly vacuolated, ovoid to polygonal cells with variable cytoplasmic processes radiating from a centrally located nucleus. Cells displayed patchy accumulation of intracytoplasmic, PAS-positive material and haphazardly arranged cytoplasmic cross-striations. There was no evidence of cardiac insufficiency or other data to suggest the masses were clinically meaningful. Cardiac rhabdomyomas have been reported in meat-hybrid swine, with a breed predisposition in red wattle. This lesion is well established in guinea pigs, but documentation in other laboratory species used in toxicologic studies is limited to two beagle dogs. To our knowledge, this is the first report of spontaneous cardiac rhabdomyoma in Göttingen minipigs.

Impact of Left Ventricular Papillary Muscle Ventricular Arrhythmia Ablation on Mitral Valve Function.

Although efficacious, catheter ablation (CA) of ventricular arrhythmias (VAs) originating from left ventricular (LV) papillary muscles (PAPs) has the potential to affect mitral valve (MV) function. The aim of this study was to determine whether lesions delivered during CA of VAs from LV PAPs affected MV function. Consecutive patients undergoing CA of LV PAP VAs from January 2015 to December 2020 in whom both preprocedural and postprocedural transthoracic echocardiography was performed were included. Radiofrequency ablation was performed with an irrigated-tip catheter with or without contact force sensing and intracardiac echocardiographic guidance. The PAPs were delineated into segments: tip, body, and base. Pre- and post-CA transthoracic echocardiograms were reviewed to assess MV regurgitation, which was graded 0 (none), 1 (mild), 2 (moderate), or 3 (severe). A change of≥2 grades from baseline was considered significant. A total of 103 patients (mean age 63 ± 15 years, 78% men) were included. VAs were ablated from the anterolateral PAP in 35% (n=36), posteromedial PAP in 55% (n=57), and both PAPs in 10% (n=10). Lesion distribution was as follows: PAP tip in 52 (50%), PAP base in 34 (33%), PAP body in 13 (13%), and entire PAP in 4 (4%). The mean number of lesions delivered was 16 ± 13 (median 14). Of 103 patients, 102 (99%) showed no change in MV function. Using intracardiac echocardiographic guidance, lesions can be safely delivered on various aspects of this structure without adverse impact on MV function.

Influence of long-term sodium-glucose cotransporter 2 inhibition on cardiac remodeling in rats with type 1 diabetes mellitus

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. However, as most clinical trials were performed in type 2 DM, the effects of SGLT2 inhibitors in patients with type 1 DM still need further clarification. In this study, we evaluated the effects of long-term treatment with the SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, and energy metabolism in rats with type 1 DM. Methods Male Wistar rats were divided into three groups: control (C, n=15); DM (n=15); and DM treated with dapagliflozin (DM+DAPA, n=15) for 30 weeks. DM was induced by streptozotocin; DAPA was added to the rat chow (5 mg/kg/day). Cardiac performance was evaluated by echocardiogram and myocardial function in isolated left ventricular (LV) papillary muscle preparations. Myocardial energy metabolism enzyme activities were evaluated by spectrophotometry. Statistical analyzes: ANOVA and Tukey or Kruskal-Wallis and Dunn. Results DM+DAPA had lower glycemia than DM [C 112 (108–116); DM 531 (522–535)*; DM+DAPA 267 (179–339) mg/dL; p&amp;lt;0.05 vs C and DM+DAPA]. Echocardiogram showed that DM and DM+DAPA had left atrium and left ventricle dilatation with systolic and diastolic dysfunction; in DM+DAPA, the changes were attenuated in relation to DM. Developed tension and +dT/dt were higher in DM+DAPA than DM in basal condition. After inotropic stimulation with post-pause contraction, extracellular calcium concentration elevation, and isoproterenol addition to the nutrient solution, +dT/dt and –dT/dt were higher in DM+DAPA than DM. Hexokinase, phosphofructokinase, and pyruvate kinase activity was lower in DM than the C. Phosphofructokinase and pyruvate kinase activity was higher in DM+DAPA than DM. Conclusion Long-term dapagliflozin treatment attenuates cardiac remodeling and myocardial dysfunction and preserves hexokinase, phosphofructokinase and pyruvate kinase activity in rats with type 1 diabetes mellitus. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): CNPq - National Council for Scientific and Technological Developmentdoctor

Functional comparison of phosphomimetic S15D and T160D mutants of myosin regulatory light chain exchanged in cardiac muscle preparations of HCM and WT mice.

In this study, we investigated the rescue potential of two phosphomimetic mutants of the myosin regulatory light chain (RLC, MYL2 gene), S15D, and T160D RLCs. S15D-RLC mimics phosphorylation of the established serine-15 site of the human cardiac RLC. T160D-RLC mimics the phosphorylation of threonine-160, identified by computational analysis as a high-score phosphorylation site of myosin RLC. Cardiac myosin and left ventricular papillary muscle (LVPM) fibers were isolated from a previously generated model of hypertrophic cardiomyopathy (HCM), Tg-R58Q, and Tg-wild-type (WT) mice. Muscle specimens were first depleted of endogenous RLC and then reconstituted with recombinant human cardiac S15D and T160D phosphomimetic RLCs. Preparations reconstituted with recombinant human cardiac WT-RLC and R58Q-RLC served as controls. Mouse myosins were then tested for the actin-activated myosin ATPase activity and LVPM fibers for the steady-state force development and Ca2+-sensitivity of force. The data showed that S15D-RLC significantly increased myosin ATPase activity compared with T160D-RLC or WT-RLC reconstituted preparations. The two S15D and T160D phosphomimetic RLCs were able to rescue Vmax of Tg-R58Q myosin reconstituted with recombinant R58Q-RLC, but the effect of S15D-RLC was more pronounced than T160D-RLC. Low tension observed for R58Q-RLC reconstituted LVPM from Tg-R58Q mice was equally rescued by both phosphomimetic RLCs. In the HCM Tg-R58Q myocardium, the S15D-RLC caused a shift from the super-relaxed (SRX) state to the disordered relaxed (DRX) state, and the number of heads readily available to interact with actin and produce force was increased. At the same time, T160D-RLC stabilized the SRX state at a level similar to R58Q-RLC reconstituted fibers. We report here on the functional superiority of the established S15 phospho-site of the human cardiac RLC vs. C-terminus T160-RLC, with S15D-RLC showing therapeutic potential in mitigating a non-canonical HCM behavior underlined by hypocontractile behavior of Tg-R58Q myocardium.