Left Ventricular Apex Research Articles

Exploring the effects of mavacamten through hemodynamic force analysis in patients with obstructive hypertrophic cardiomyopathy

Abstract Introduction Mavacamten is a first-in-class allosteric myosin inhibitor effective in relieving left ventricular (LV) outflow tract obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). To date, however, its effect on cardiac mechanics is still unclear. Hemodynamic force (HDF) analysis represents the fluid dynamics correlate of deformation imaging, showing a greater sensitivity in detecting early mechanical abnormalities or response to treatment [1]. Purpose To explore the in vivo effect of mavacamten on cardiac mechanics in patients with HCM after a 3 year-treatment, using HDF analysis. Methods LV HDF analysis was performed in 6 patients with oHCM (representing a cohort of the MAVA-LTE study) at baseline and after 3 years of treatment. Apical 4-, 2-, and 3-chamber echocardiographic views were analysed using a dedicated and sofisticated software. Base-apex forces (where positive deflections represent a force directed from the apex to the base of LV, whilst negative ones are directed toward the LV apex) were assessed in terms of timing indexed to cardiac cycle duration. HDF curves from the 6 patients treated with macavamten were compared to those obtained from oHCM patients (n=20), non-obstructive HCM (noHCM) patients (n=20), and healthy controls (n=22). Results Figure 1 shows a different pattern of transition between diastole and systole in HCM patients compared to controls. Specifically, HCM patients exhibited an earlier onset of the systolic phase, expressed as a fusion of late diastolic deceleration and systolic thrust. This was numerically represented as a decrease in diastolic-systolic transition time, which is 0.22 [0.20-0.24] for oHCM, 0.23 [0.21-0.25] for noHCM and 0.26 [0.26-0.30] for controls (p ≤0.001 for control vs oHCM, p ≤0.01 for control vs noHCM). Additionally, HCM patients showed an increased rate of force generation. The time to systolic peak (i.e., time interval from the onset of systole to the maximum force) was reduced in HCM patients compared to controls, and was shorter in oHCM than in noHCM patients (0.13 [0.11-0.15] vs 0.16 [0.14-0.17], p ≤0.01), thus reflecting an increased clinotropism in HCM. After 3 years of mavacamten treatment, the diastolic-systolic transition time and the time to systolic peak returned to a level similar to that of healthy controls (0.30 [0.27-0.30] in mavacamten group vs 0.26 [0.26-0.30], p >0.05, and 0.21 [0.20-0.22] vs 0.19[0.17-0.20], p=0.04, respectively) (Figure 2). Conclusion HDF analysis reveals that mavacamten affects the duration of transition from diastole to systole and prolongs time from the onset to the peak in systole. These findings may explain the removal of the mechanical coupling substrate responsible for the systolic anterior movement of mitralic leaflets and the subsequent resolution of LV outflow tract obstruction by mavacamten.Distribution of time parameters

Prevalence and clinical significance of left ventricular thrombus discovered by pathological examination in explanted hearts of patients with end-stage cardiomyopathy

Abstract Objective We sought to determine the prevalence of anatomic LV thrombus detected by pathological examination of explanted hearts in patients with end-stage cardiomyopathy (CM) who have undergone heart transplantation, and to examine the relationship between anatomic LV thrombus missed by cardiac imaging and thromboembolic events. Methods and results A total of consecutive 148 explanted hearts from patients (44 years; 80% were men) undergoing heart transplantation were examined. The most common etiology of end-stage heart failure was dilated CM (53%). Of 148 explanted hearts, LV thrombus was present in 19 patients/hearts (13%). Excluding patients with ischemic CM (n=7), LV thrombus was present in 8 DCMs (9%), 1 genetic associated with LV noncompaction (100%), 2 hypertrophic CM (25%), and 1 arrhythmogenic CM (14%). None of patients with cardiac sarcoidosis (n=5) had LV thrombus. Of these patients, 11 (58%) received anticoagulants with favorable numbers of time in therapeutic range. No patient in the cohort had history of thromboembolic event before heart transplantation. Only 11 patients (26 %) with pathological evidence of LV thrombus had LV thrombus detected by previous echocardiograms (median time difference from echocardiogram to heart transplantation = 170 days). Six of 19 patients with anatomic LV thrombus had undergone cardiac MRI; LV thrombus had been detected in 2 patients (33%). The most common site of missed LV thrombus was LV cavity (where thrombi did not attach to any particular LV endocardial surface) followed by LV apex (Figure). Conclusion The prevalence of LV thrombus found by pathological examination in end-stage heart diseases was 13 % despite anticoagulation in most patients. However, the presence of these thrombi did not cause any serious thromboembolic events. Anatomic LV thrombi were missed by echocardiography/cardiac MRI in approximately 70% of patients. Genetic associated LV noncompaction and HCM were the most 2 prevalent CMs with anatomic thrombi, while none of patients with cardiac sarcoidosis had evidence of LV thrombus. Further study in thromboembolic milieu involving endocardial surface in specific type of CM may be needed.

Non-invasive assessment of left ventricular hemodynamic forces in hypertrophic cardiomyopathy

Abstract Background Hemodynamic force (HDF) analysis allows non-invasive measurement of intraventricular pressure gradients, portraying cyclic spatial-temporal interaction between blood and tissues. Impaired HDFs have been implicated in early detecting of adverse cardiac remodelling and treatment response in various cardiovascular disorders, providing insights into cardiac physiology not offered by traditional cardiovascular imaging (1). Mainly explored in heart failure, HDF analysis has not been previously applied to hypertrophic cardiomyopathy (HCM). Purpose To investigate differences in systo-diastolic function in HCM patients compared to healthy controls using HDF analysis. Methods Forty patients with HCM diagnosis (20 obstructive and 20 non-obstructive) were retrospectively evaluated in comparison with 22 healthy controls. Left ventricular (LV) HDFs were derived from routine transthoracic apical 4-, 2- and 3-chamber views using a dedicated software. Apical-basal HDF curves were generated, where positive deflections represent forces directed from the LV apex to the base, whilst negative ones are directed toward the apex. Amplitude and timing parameters were derived, the latter indexed to total cardiac cycle duration. Results Table 1 shows the demographic, clinical and echocardiographic characteristics of HCM compared to controls. Patients with HCM were older, had a slower heart rate due to treatment with beta-blockers, and showed hypercontractility, as expressed by higher LV ejection fraction. Compared to controls, HCM patients showed reduced LV longitudinal force, i.e. the force during the whole cardiac cycle (4.17% [2.36-5.52] vs. 6.01% [4.73-7.78], p=0.002), shorter time interval to systolic peak (0.15 [0.12-0.16] vs. 0.19 [0.17-0.20], p <0.001), and shorter duration of LV impulse (0.29 [0.27-0.32] vs. 0.34 [0.32-0.37], p <0.001) (Figure 1). However, no differences in terms of systolic force peak (p=0.283) or LV impulse intensity (p=0.689) were detected. During the transition between systole and diastole, LV suction (i.e. the interval including late systolic deceleration and early diastolic suction) was significantly longer (0.26 [0.22-0.29] vs. 0.23 [0.21-0.25], p=0.023) but less pronounced (6.30% [4.56-8.44] vs. 8.72% [6.71-12.59], p=0.005), likely reflecting a relaxation impairment from the very beginning of diastole. Such impairment was maintained during early diastolic filling, where the amplitude of the positive deceleration flow force was severely reduced in HCM compared to controls (2.98% [1.98-4.58] vs. 7.11% [4.55-8.72], p <0.001). Conclusions HDF analysis in HCM patients revealed unique systolic and diastolic changes reflecting faster LV contraction during systole and slower and weaker LV forces during diastole. This analysis deepens our understanding of HCM mechanic abnormalities and may help assess response to innovative treatment options.

Impella malrotation affects left ventricle unloading in cardiogenic shock patients.

Impella malrotation-inlet orientation away from the left ventricular (LV) apex with normal console waveforms and proper device depth-is commonly observed and possibly associated worse haemodynamics. This study aimed to characterize the haemodynamic consequences of Impella malrotation in cardiogenic shock (CS) patients. We included 100 CS patients (60±12years; 79.0% males) with available echocardiography during Impella support and pulmonary artery catheter assessment before and during (at 48h) Impella support. Impella malrotation was identified in 36%. At 48h, malrotation patients had higher pulmonary artery wedge pressure (PAWP, 16.0±8.2 vs. 13.0±4.6mmHg; P=0.033), higher systolic pulmonary artery pressure (PAP, 35.0±11.3 vs. 29.5±9.0mmHg; P=0.015), higher diastolic-PAP (19.3±8.1 vs. 15.1±6.1mmHg; P=0.007), higher mean-PAP (25.7±9.1 vs. 20.8±6.8mmHg; P=0.005), higher right atrial pressure (10.3±4.8 vs. 7.7±4.3mmHg; P=0.009), higher pulmonary vascular resistance index (4.78±2.75 vs. 3.49±1.94 WUm2; P=0.020) and higher pulmonary artery elastance (0.91±0.60 vs. 0.67±0.40mmHg/mL; P=0.045). Serum lactate at 48h was higher in malrotation patients (6.63±6.25 vs. 3.60±4.21mmol/L; P=0.004). Malrotation patients presented larger LVEDD during support (52±10 vs. 46±11mm; P=0.006), higher rates of aortic regurgitation (AR, 86 vs. 56%; P=0.004) and higher increase in AR severity (+0.94±0.92 vs. +0.46±0.95; P=0.016). No significant differences were found in major adverse outcomes. In CS patients, Impella malrotation is associated with suboptimal unloading of the LV, worse pulmonary haemodynamics and worse indexes of right ventricular afterload.

Severe stress cardiomyopathy following spinal corrective surgery for scoliosis complicated with pectus excavatum: a case report

BackgroundStress cardiomyopathy (SCM) is an acute heart failure syndrome characterized by transient, usually reversible left ventricular systolic dysfunction with normal or enhanced basal compensatory wall motion abnormalities involving the left ventricular anterior septum and apex, resulting in a “ballooning” appearance. However, it has rarely been reported in patients undergoing spinal surgery.Case presentationWe report a case of severe stress cardiomyopathy in a scoliosis patient with pectus excavatum who underwent spinal corrective surgery. During the wake-up period, circulatory collapse occurred. After multidisciplinary consultation, the patient was diagnosed with stress cardiomyopathy. At last, she had a good prognosis after a series of treatments including ECMO.ConclusionStress cardiomyopathy is a reversible but uncommon condition. It can cause death if it is not diagnosed in time. Consequently, this report should improve the awareness of orthopedists and anesthesiologists for timely identification and management. For patients with potential risk factors, timely preoperative intervention should be performed to reduce the occurrence of stress cardiomyopathy.

Takotsubo syndrome with transient obstruction of the left ventricle outflow tract: A case report

BACKGROUND: Modern data have expanded our understanding of the pathogenetic mechanisms and clinical and laboratory findings in a patient with Takotsubo syndrome (TS). Nonetheless, its timely diagnosis and treatment remain challenging. All patients are initially treated according to the acute coronary syndrome protocol, with a "working" diagnosis of myocardial infarction without an obstructive lesion in the coronary arteries. However, the treatment of in-hospital complications of TS has its limitations and specific features. CLINICAL CASE DESCRIPTION: Herein, we have reported a case of TS that presented with the classic apical ballooning of the left ventricular apex, which had developed without an obvious stress factor, which is quite rare. The disease was complicated by the development of cardiogenic shock (CGS) and transient obstruction of the left ventricular outflow tract (LVOTO), which reportedly occurs in about 25% of the patients. CGS in patients with TS is a life-threatening complication and a challenging therapeutic problem, especially when it is also associated with a dynamic LVOTO. In such conditions, the only therapeutic option is mechanical circulatory support. However, in our patient, low doses of dobutamine were used to stabilize the patient’s hemodynamics. This treated produced a good therapeutic effect. CONCLUSION: Our case report findings emphasize the need for further research into the mechanisms of LVOTO development in TS, as well as the development of standardized approaches for the treatment of such patients in the acute phase of the disease.

Clinical Implications of Left Ventricular Apex Mechanics in Patients With Apical Hypertrophic Cardiomyopathy

Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathologic hypertrophy mainly at the left ventricular (LV) apex. Although previous studies have indicated apical dysfunction in ApHCM, how apical mechanics change during disease progression has not been thoroughly examined. The aims of this study were to characterize the mechanics of the LV apex in patients with ApHCM at different disease stages and to explore the clinical significance of these alterations. One hundred four patients with ApHCM were divided into three subtypes on the basis of LV apical maximum wall thickness (AMWT) and extent of hypertrophy: relative type (isolated apical hypertrophy with AMWT<15mm), pure type (isolated apical hypertrophy with AMWT≥15mm), and mixed type (both apical and midventricular hypertrophy with AMWT≥15mm). Two-dimensional speckle-tracking echocardiography was used to analyze LV segmental strain, global strain, and twist. Comparisons of these parameters were performed among ApHCM subtypes and 30 healthy control subjects. Logistic regression and Cox proportional-hazards regression analyses were used to explore associations between myocardial mechanics and clinical indicators. A composite outcome of new-onset atrial fibrillation, heart failure hospitalization, myectomy, and all-cause mortality was assessed. Even in relative ApHCM patients, apical longitudinal strain (LS), circumferential strain, and radial strain (RS) were significantly impaired compared with control subjects (LS: -14.6±4.1% vs -20.0±1.7% [P=.001]; circumferential strain: -19.6±2.5% vs -25.6±3.7% [P=.002]; RS: 26.6±7.4% vs 35.6± 11.1% [P=.026]), while apical rotation and LV twist remained unchanged. In patients with greater apical hypertrophy (mixed and pure patients), apical LS and RS were more abnormal. Moreover, apical rotation showed significant reductions compared with relative-type patients. After adjusting for clinical and myocardial mechanical parameters, apical rotation was independently associated with New York Heart Association functional class≥II (odds ratio, 0.81; 95% CI, 0.66-0.99; P=.036) and the composite outcome (hazard ratio, 0.82; 95% CI, 0.73-0.91; P=.001). Relative ApHCM demonstrates apical dysfunction but sparing of apical rotation, which was abnormal in more extensive phenotypes. LV apex mechanics were closely related to clinical patterns, with apical rotation correlated with both New York Heart Association functional class≥II and clinical events.

Inversion of Left Ventricular Axial Shortening: In Silico Proof of Concept for Treatment of HFpEF.

Left ventricular (LV) longitudinal function is mechanically coupled to the elasticity of the ascending aorta (AA). The pathophysiologic link between a stiff AA and reduced longitudinal strain and the subsequent deterioration in longitudinal LV systolic function is likely relevant in heart failure with preserved ejection fraction (HFpEF). The proposed therapeutic effect of freeing the LV apex and allowing for LV inverse longitudinal shortening was studied in silico utilizing the Living Left Heart Human Model (Dassault Systémes Simulia Corporation). LV function was evaluated in a model with (A) an elastic AA, (B) a stiff AA, and (C) a stiff AA with a free LV apex. The cardiac model simulation demonstrated that freeing the apex caused inverse LV longitudinal shortening that could abolish the deleterious mechanical effect of a stiff AA on LV function. A stiff AA and impairment of the LV longitudinal strain are common in patients with HFpEF. The hypothesis-generating model strongly suggests that freeing the apex and inverse longitudinal shortening may improve LV function in HFpEF patients with a stiff AA.

Tudor-SN promotes cardiomyocyte proliferation and neonatal heart regeneration through regulating the phosphorylation of YAP

BackgroundThe neonatal mammalian heart exhibits considerable regenerative potential following injury through cardiomyocyte proliferation, whereas mature cardiomyocytes withdraw from the cell cycle and lose regenerative capacities. Therefore, investigating the mechanisms underlying neonatal cardiomyocyte proliferation and regeneration is crucial for unlocking the regenerative potential of adult mammalian heart to repair damage and restore contractile function following myocardial injury.MethodsThe Tudor staphylococcal nuclease (Tudor-SN) transgenic (TG) or cardiomyocyte-specific knockout mice (Myh6-Tudor-SN −/−) were generated to investigate the role of Tudor-SN in cardiomyocyte proliferation and heart regeneration following apical resection (AR) surgery. Primary cardiomyocytes isolated from neonatal mice were used to assess the influence of Tudor-SN on cardiomyocyte proliferation in vitro. Affinity purification and mass spectrometry were employed to elucidate the underlying mechanism. H9c2 cells and mouse myocardia with either overexpression or knockout of Tudor-SN were utilized to assess its impact on the phosphorylation of Yes-associated protein (YAP), both in vitro and in vivo.ResultsWe previously identified Tudor-SN as a cell cycle regulator that is highly expressed in neonatal mice myocardia but downregulated in adults. Our present study demonstrates that sustained expression of Tudor-SN promotes and prolongs the proliferation of neonatal cardiomyocytes, improves cardiac function, and enhances the ability to repair the left ventricular apex resection in neonatal mice. Consistently, cardiomyocyte-specific knockout of Tudor-SN impairs cardiac function and retards recovery after injury. Tudor-SN associates with YAP, which plays important roles in heart development and regeneration, inhibiting phosphorylation at Ser 127 and Ser 397 residues by preventing the association between Large Tumor Suppressor 1 (LATS1) and YAP, correspondingly maintaining stability and promoting nuclear translocation of YAP to enhance the proliferation-related genes transcription.ConclusionTudor-SN regulates the phosphorylation of YAP, consequently enhancing and prolonging neonatal cardiomyocyte proliferation under physiological conditions and promoting neonatal heart regeneration after injury.Graphical

Left ventricular apical hydatid cyst - A rare case report

ABSTRACT Cardiac hydatid cyst is an extremely rare manifestation of cystic echinoccococis, but without prompt diagnosis and management, it can be fatal. Despite the absence of standardized guidelines, an early, complete surgical removal in conjunction with anthelmintic therapy plays a central role and is associated with an excellent prognosis. We report an indigenous case of left ventricular apical hydatid cyst in a 75 - year - old female who presented with atypical symptoms including abnormal fatigue and increasing exercise intolerance. Although serological tests were negative, imaging modalities revealed a 36 x 30 mm oval structure in the left ventricular apex, suggesting a type I hydatid cyst. A single encapsulated cyst was surgically removed through a median sternotomy under cardiopulmonary bypass. Histopathological analysis confirmed a hydatid cyst, and Echinococcus ortleppi was identified. The patient was discharged without incident and was prescribed 3 cycles of Albedazole.

Apical hypertrophic cardiomyopathy in a Caucasian male: A case report

Apical hypertrophic cardiomyopathy (ApHCM) is relatively uncommon variant of hypertrophic cardiomyopathy which typically influences the left ventricular apex. We report a case of a 64-year-old Caucasian male who presented to the ER with pain in his chest (angina) and diaphoresis, diagnosis of ApHCM was reached. The variable presentation, clinical course of the disease and limited literature among Caucasian population creates a challenge in detecting it and results in delayed or missed diagnosis, however by spotting its characteristic features on electrocardiography (the “giant” negative precordial T‐waves) and the “ace of spades” configuration on echocardiogram as well as using cardiac catheterization and cardiac MRI, diagnosis can be confirmed. This particular case will underscore the infrequent occurrence of ApHCM in Caucasians, along with the its complex diagnostic and presentation characteristics it produces.

Arrhythmogenic right ventricular cardiomyopathy with sustained ventricular tachycardia: a case report

IntroductionArrhythmogenic right ventricular cardiomyopathy (ARVC) is an infrequent hereditary disorder distinguished by fibrofatty replacement of the myocardium in the right ventricular, which predisposes individuals to life-threatening arrhythmias. This case delineates an ARVC patient who suffered recurrent bouts of sustained ventricular tachycardia (VT). In this case, we mainly discuss the application of myocardial contrast echocardiography (MCE) in displaying myocardial fibrosis in patients with ARVC.Case presentationA 43-year-old male experienced three episodes of unexplained VT over an eight-year period, accompanied by symptoms of chest discomfort, palpitations and dizziness. Coronary angiography revealed no significant coronary stenosis. The electrocardiogram (ECG) results indicated characteristic epsilon waves in right precordial leads, and subsequent echocardiography identified right ventricular enlargement and right ventricular systolic dysfunction. MCE further disclosed regional myocardial ischemia at the epicardium of the left ventricular apex. Ultimately, cardiovascular magnetic resonance imaging (CMR) corroborated the ARVC diagnosis, highlighting linear intensification in the right ventricle during the delayed enhancement.ConclusionPrompt identification of ARVC is crucial for timely intervention and management. MCE may offer an effective and valuable technique for the detection of myocardial involvement in ARVC patient.

HCN2-based biological pacing in a modified rat AV-block model

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Eurostars - Heartpace 114245 Background Electronic pacemakers have several important shortcomings which are difficult to overcome due to their hardware-based design. Gene therapy-based biological pacemakers may provide a different platform which can overcome these limitations. Such biological pacemaker strategies center around overexpression of the pacemaker ion channel HCN2, either alone or with other transgenes to potentiate pacemaker performance, such as the skeletal muscle sodium channel SkM1. In order to develop clinically applicable pacemaker gene therapies further engineering is needed, which would benefit from a reliable small animal model. At present it is unknown if the rat AV block model can be used to evaluate ion channel-based biological pacing. Aim In the present study, we aim to validate a modified rat AV-block model for the evaluation of HCN2 and SKM1-based biological pacing. Methods AV-block was generated in female rats by epicardially applied needle ablation of the AV-nodal region, as previously described (N.K. ). Complete AV-block was confirmed 7 days post-ablation by loss of P-wave and QRS-complex association on the body surface ECG. Seven days post-ablation, 3 groups of animals were injected into the left ventricular apex with Ad5-TNNT2-HCN2, Ad5-TNNT2-SkM1 or saline (control). 14 days post-ablation, ECG analysis was performed during anesthesia under baseline and after i.v. administration of isoprenaline. Upon completion of functional testing, tissue samples were harvested followed by gene expression analysis using qPCR. Results Injection of Ad5-TNNT2-HCN2, Ad5-TNNT2-SkM1 or saline did not result in ectopic activation patterns in baseline conditions 7 days after injection. Administration of isoprenaline results in reversal of the QRS complexes 90% of total measurement time in Ad5-TNNT2-HCN2 injected animals. Saline and Ad5-TNNT2-SkM1 showed no change in activation pattern upon isoprenaline administration. Gene expression analysis revealed expression of HCN2 in the injection site following Ad5-TNNT2-HCN2 injection, with minimal spread to non-target regions. However, this analysis also showed Ad5-TNNT2-SkM1 did not express well in this context. Conclusion Our modified rat AV-block model, when administered with isoprenaline, recapitulated expected biological pacemaker activity of HCN2 gene delivery. However, lack of effective expression of SkM1 renders direct comparison of these relevant transgenes difficult. Nevertheless, we expect this rat AV-block model can provide a valuable tool for the evaluation of novel ion channel-based biological pacemaker strategies.

The bail out option; using endocardial pacing and defibrillation leads epicardially

Abstract Introduction Although transvenous implantation of cardiac pacemakers and defibrillators is technically feasible and less invasive than surgical placement of epicardial leads, certain patients including pediatric patients and patients with complex congenital heart disease will require epicardial pacing and most of them will need pacing throughout their whole life. There are specific leads for epicardial pacing which were developed over time to the currently used bipolar steroid-eluting epicardial leads which may be rarely nationally unavailable. In addition, there are no available dedicated epicardial shock leads (1,2). There is no enough data on the techniques, feasibility, and efficacy of using endocardial leads, including shock leads for epicardial pacing/ defibrillation (3). Purpose We aim to describe our center’s experience in implanting endocardial leads for epicardial pacing or defibrillation and to assess its feasibility &amp; durability. Methods Due to periods of national unavailability of epicardial permanent pacing leads and worldwide unavailability of dedicated epicardial shock leads, a limited cohort of patients requiring urgent epicardial pacing/ ICDs were offered pacing through epicardially implanted endocardial leads. The lead screw is advanced into myocardium, then a purse-string suture is placed around and tied to the lead for fixation. Ventricular pacing lead is fixed to LV apex, while atrial lead is fixed to RA free wall. Shock coils are fixed to LV and RA free walls (Fig. 1). We retrospectively revised our records for these patients &amp; analyzed their clinical data, follow up programming parameters including sensing, pacing thresholds and impedances. Results In the last 8 years, surgeons implanted 9 endocardial leads epicardially. Two were pacing leads implanted for ventricular and atrial pacing in two different pediatric patients, and 7 were shock leads in patients with life threatening VTs despite medical treatment. The patients with ICDs were as follows: one was an adult patient with a Glenn shunt. The other 6 patients were pediatrics with low body weight; 4 of them had long QT syndrome and two had idiopathic VF. The mean follow-up periods were 38 months. Throughout the visits, the pacing thresholds, sensing functions, lead and shock impedances were stable in all patients (Table 1). Two of the patients with epicardial ICDs received appropriate shocks. None received inappropriate shocks. So far, only one patient required battery replacement. Conclusion In view of our findings, using endocardial leads as a bail out alternative to epicardial leads for pacing or defibrillation appears to be safe and effective. This finding is essentially important regarding the shock leads as there are no dedicated epicardial defibrillation leads. It should be noted that these results depend largely on the surgeon’s experience and on achieving acceptable pacing parameters and defibrillation thresholds intraoperatively.Table 1Figure 1

Ischaemic strokes and myocardial infarctions in a young male cannabis user

Ischaemic cerebral infarctions are seen in young people but, under the age of 30, multiple bilateral infarcts are uncommon; genetic pre-disposition and co-morbidities often underlie them. There is growing awareness of the potential impact of modifiable risk factors, such as cannabis, for those experiencing stroke and other cardiovascular events. A case of a 29-year-old man is de­scribed who presented with sudden onset occipital headache and right eye vision loss. Computerised axial tomographic scanning (CT) of the brain dem­onstrated multifocal bilateral areas of low attenuation. A brain magnetic reso­nance imaging (MRI), confirmed bilateral acute cerebral infarctions. In view of a significant elevation in troponin levels at a previous admission, cardiac via­bility magnetic resonance imaging (cvMRI) was carried out and demonstrated acute infarction affecting the left ventricular apex and multiple smaller infarcts elsewhere within the myocardium. On this occasion he did not complain of chest pain. The electrocardiogram (ECG) showed ischaemic changes. The patient denied a family history of ischaemic heart disease, diabetes mellitus, hypertension and hypercholesterolaemia, but admitted to daily use of can­nabis and cigarette smoking. We considered the regular use of cannabis as a possible aetiology in the development of multi-territory cerebral and myocar­dial infarcts, previous myopericarditis and left ventricular dysfunction

GUIDEWIRE SHAPE MODIFICATION: A SIMPLE TECHNIQUE TO PREVENT CONDUCTION SYSTEM INJURIES DURING TRANSCATHETER VALVE IMPLANTATION

Abstract Background Atrioventricular (AV) conduction abnormalities remain one of the important unsolved issues with transcatheter aortic valve implantation (TAVI). To minimize trauma on the conduction fibers, we introduced a simple technique involving the bending of the stiff guidewire wire at the level of the arch to prevent and minimize contact with the interventricular septum. Aim To report the technique for shape manipulation of the stiff guidewire during TAVI and to evaluate its safety and effectiveness in reducing the need for permanent pace–make implantation after TAVI. Methods and Results Before insertion into the left ventricle the TAVI stiff wire was bended by hand to obtain a ³180° degree curve 15–20cm from its tip. Distance between stiff wire and septum was assessed in cranial–lao cusp overlap projection. Among 26 consecutive patients who underwent TAVI with a bended stiff wire, 13(50%) presented preoperative factors of increased risk for need of PM implantation after TAVI due to LVOT calcification (10, 38.5%), bicuspid aortic valve with raphe opposite to the septum (2, 7.7%) and baseline RBBB (2, 7.7%). Wire was observed to be distant from the septum &amp;gt;5mm in 22/26 (85%) cases. Median distance from septum was 9.0 [6.0, 12.0] mm. Pre–dilatation was required in 20 patients (77%). Balloon was observed to inflate distant from septum in 18 (90%) of them. Self–expandable valves were most frequently employed (n = 21, 81%).No patient required new PM implantation after TAVI. The two patients with baseline RBBB developed transient complete AVB, which recovered before discharge.No major complication (vascular, ventricular perforation, annular rupture, device embolization) was observed. Conclusions In this early preliminary experience stiff wire bending was able not only to keep far from the septum the wire in the majority of patients, without any complication, but also to provide wire stability and prevented inadvertent pressure of the wire over the left ventricular apex. No patient required PM implantation after TAVI. While wire bending seems promising in minimizing trauma on the conduction system, this study is to be considered hypothesis generating and more data are needed to confirm its findings.

A LABILE EQUILIBRIUM: THE CONTROVERSIAL ROLE OF BETA–BLOCKERS IN A CASE OF MID–VENTRICULAR TAKOTSUBO SYNDROME

Abstract Case Report Takotsubo syndrome (TTS) is a non–ischemic heart disease mimicking acute coronary syndrome. The mid–ventricular variant is almost rare (15% of TTS cases). A 62 years old woman was referred to our hospital for oppressive chest pain radiating to the jaw lasting at least 30 minutes after an attempted strangulation by a family member. She denied any conventional cardiovascular risk factor; she was taking beta–blockers (BB) to reduce symptomatic and idiopathic premature ventricular complexes (PVCs) burden. On arrival, the patient was hemodynamically stable, reporting only swallowing difficulties. Physical examination revealed neck bruising and irregular pulse. The initial ECG showed sinus rhythm with a heart rate of 62 bpm, PVCs and a biphasic T wave in lead aVL. Hs–cTnI first dosage was 145 pg/mL. Transthoracic echocardiography (TTE) found moderate left ventricular (LV) dysfunction and severe hypokinesis of mid septal and mid inferior segments. Coronary angiography revealed normal coronary arteries. Left ventriculogram showed hypokinesis of the midventricular section with a hyperdynamic base and apex suggestive of mid–ventricular variant of TTS. After a few hours, she experienced a lipothymic episode and telemetry showed marked sinus bradycardia followed by multiple sinus pauses. A TTE was immediately performed, demonstrating a worsening LV ejection fraction with new development of severe symmetrical akinesia of the LV apex. Successively, psychotherapy was started. Wall motion abnormalities and LV systolic function completely recovered over a few days. At present the patient is in good health status. Discussion domestic violence against women is prevalent, but it is often omitted as a potential stress trigger that affects their hearts. In Italy, it’s reported that 32% of women had experienced physical violence. Strangulation is very uncommon as cause of TTS and psychotherapy may prevent recurrences and recover in a shorter time. Bradycardia due to atrioventricular block and asystole has been described in the acute phase of TTS and it is often attributed to BB therapy. Although BB have been proposed to add further benefit of blunting the effect of catecholamine excess, their use should be used cautiously in the acute phase of TTS. Moreover, beta–adrenoceptor hypersensitivity may generate a parasympathetic drive when on BB infusion, provoking a worsening LV dysfunction and a transient sick sinus syndrome as we described.

Cardiac Left Ventricular miRNA-26a Is Downregulated in Ovariectomized Mice, Upregulated upon 17-Beta Estradiol Replacement, and Inversely Correlated with Collagen Type 1 Gene Expression.

Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood. Data in humans is confounded by age and co-morbidities. We investigated the effects of ovariectomy and estrogen replacement on the left ventricular (LV) gene expression of pro-inflammatory and pro-fibrotic factors involved in HFpEF and putative regulating miRNAs. Nine-week-old C57BL/6 female mice were subjected to ovariectomy (OVX) or SHAM operation. OVX and SHAM groups were sacrificed 1-, 6-, and 12-weeks post-surgery (T1/SHAM; T1/OVX; T6/SHAM; T6/OVX, T12/SHAM). 17β-estradiol (E2) or vehicle (VEH) was then administered to the OVX groups for 6 weeks (T12/OVX/E2; T12/OVX/VEH). Another SHAM group was sacrificed 12-weeks post-surgery. RNA and miRNAs were extracted from the LV apex. An early 3-fold increase in the gene expression of IL-1α, IL-6, Mmp9, Mmp12, Col1α1, and Col3α1 was observed one-week post-surgery in T1/OVX vs. T1/SHAM, but not at later time points. miRNA-26a was lower in T1/OVX vs. T1/SHAM and was inversely correlated with Col1α1 and Col3α1 expression 1-week post-surgery (r = -0.79 p < 0.001; r = -0.6 p = 0.007). miRNAs-26a, 29b, and 133a were significantly higher, while Col1α1, Col3α1, IL-1α, IL-6, Tnfα, Mmp12, and FasL gene expression was significantly lower in E2- compared to vehicle-treated OVX mice. miRNA-26a was inversely correlated with Col3α1 in T12/OVX/ E2 (r = -0.56 p = 0.02). OVX triggered an early increase in the gene expression of pro-inflammatory and pro-fibrotic factors, highlighting the importance of the early phase post-cessation of ovarian function. E2 replacement therapy, even if it was not immediately initiated after OVX, reversed these unfavorable changes and upregulated cardiac miRNA-26a, previously unknown to be affected by menopausal status.

Echocardiographic detection of mesocardia, situs solitus associated with multiple congenital heart defects in a neonate: Rare case report

Mesocardia is a condition in which the heart is longitudinally oriented along its long axis in the midline. Cardiac position refers to the anatomical position of the left ventricular apex in the thorax. The heart has three positions: dextrocardia or right-sided heart, levocardia or left-sided heart, mesocardia or midline heart. Mesocardia is extremely rare. It represents only 0.2% of cardiac anomalies. Mesocardia is usually associated with cardiac structural abnormalities, heterotaxy syndrome, chromosomal disorders and genetic syndromes. Occasionally, it is an isolated finding. We are presenting an interesting case report of severely symptomatic neonate afflicted with mesocardia, situs solitus, moderate sized atrial septal defect (ASD) and large ventricular septal defect (VSD).

Comparison of electrographic changes, clinical features and outcomes in different variants of Takotsubo syndrome

BackgroundDysfunction of the left ventricular (LV) apex (apical variant) is the most common form in Takotsubo syndrome (TS). Several less common non-apical variants have been described – mid-ventricular, basal and focal. We hypothesised that the clinical presentation, and electrocardiographic (ECG) findings may vary between apical and non-apical TS. MethodsWe prospectively identified 194 consecutive patients with TS presenting to Middlemore Hospital, Auckland and obtained clinical, echocardiography, coronary angiography, and long-term follow-up data. ECGs at admission and Day 1 were compared. ResultsOf 194 patients with TS, 168 (86.6%) had apical TS, and 26 (13.4%) non-apical TS (11 mid-ventricular TS, 5 basal TS, 10 focal TS). Apical TS patients had more significant LV systolic impairment (p = 0.001) and longer length of stay (p = 0.001). The extent of T-wave inversion (TWI) was similar for both groups on admission (p = 0.88). By Day 1 the extent of TWI was greater in apical TS group (median number of leads 5 vs. 1, p = 0.02). The change in QTc interval between admission and Day 1 was greater in apical TS group (29.7 ms vs. 2.77 ms, p < 0.001). Composite in-hospital complication rate was similar for both groups (13.7% vs. 15.4%, p = 0.77). ConclusionsCompared with non-apical variants, apical TS patients develop more extensive TWI and greater QT prolongation on ECG, and more significant LV systolic impairment, but in-hospital complications were similar. Clinicians should be aware that there is a sub-group of TS patients who have non-apical regional wall motion abnormalities and who don't develop ECG changes typical of the more common apical variant.