Functional Recovery Of Left Ventricle Research Articles

Clinical predictors of late left ventricle recovery in tako-tsubo syndrome

Abstract Funding Acknowledgements None. Introduction Tako-Tsubo syndrome (TTS) or stress cardiomyopathy is characterized by transient dysfunction of the left ventricle (LV) and a clinical presentation that can mimic an acute coronary syndrome. Recovery from contraction abnormalities may occur hours to weeks after the acute event. Although traditionally considered a disease with a favorable prognosis, it has been observed to have a complication rate during hospitalization similar to acute myocardial infarction and a significant mortality rate during follow-up (greater than 5% per patient-year). The recovery time of LV function has demonstrated important prognostic value. Purpose The aim of this work was to determine the clinical predictors of late left ventricular recovery in TTS. Methods Data from the multicenter national registry on Takotsubo Syndrome (RETAKO) were utilized. Clinical, laboratory, echocardiographic, and other imaging test characteristics, as well as events during hospitalization and follow-up, were collected. Recovery within the first days after the acute event was considered early recovery. Patients who died within the first 10 days after the acute event were excluded. Results A total of 1,463 patients were analyzed, of whom 373 (25.5%) had late recovery. The mean age was 71 years, and 86.6% were women. In the late recovery group, factors more common were age over 75 years, male gender, neurological disease, lung disease, peripheral arterial disease, active cancer, physical trigger, initial presentation as dyspnea or syncope, presence of shock, greater left ventricular dysfunction at diagnosis, and higher levels of proBNP. In multivariate analysis, the presence of neurological disease, active cancer, shock during hospitalization, lower initial LV ejection fraction, and physical trigger were associated with late recovery. Conclusions Patients with TTS showing late recovery of LV function have different clinical characteristics and disease presentation compared to those with early recovery. Late recovery was associated with the presence of neurological disease or active cancer, shock during hospitalization, lower initial LV ejection fraction, and physical trigger.

Electroacupuncture preconditioning protects against myocardial ischemia-reperfusion injury by modulating dynamic inflammatory response

BackgroundThe protective effects of electroacupuncture (EA) preconditioning against myocardial ischemia-reperfusion injury (MIRI) have been reported. However, the underlying mechanism remains unclear. Recent research has indicated that the dynamic inflammatory response following MIRI plays an essential role in the progression of myocardial injury. This study aimed to investigate the myocardial protective effects of EA preconditioning on MIRI in rats and to explore the relevant mechanism from the perspective of dynamic inflammatory response. MethodsA MIRI model was employed, and the rats were subjected to EA on Neiguan for four days prior to modeling. The myocardial protective effect of EA preconditioning was evaluated by echocardiography, Evans blue and triphenyltetrazolium chloride staining. Real-time polymerase chain reaction, Western blot, hematoxylin & eosin staining, and immunohistochemistry were utilized to detect the content of mitochondrial DNA, NOD receptor family protein 3 (NLRP3) inflammasome activation, neutrophil recruitment and macrophage infiltration in blood samples and myocardium below the ligation. ResultsWe found that EA preconditioning could accelerate the recovery of left ventricle function after MIRI and reduce the myocardial infarction area, thereby protecting the myocardium against MIRI. Furthermore, EA preconditioning was observed to ameliorate mitochondrial impairment, reduce the level of plasma mitochondrial DNA, modulate NLRP3 inflammasome activation, attenuate neutrophil infiltration, and promote the polarization of M1 macrophages towards M2 macrophages in the myocardium after MIRI. ConclusionEA preconditioning could reduce plasma mtDNA, suppress overactivation of the NLRP3 inflammasome, facilitate the transition from the acute pro-inflammatory phase to the anti-inflammatory reparative phase after MIRI, and ultimately confer cardioprotective benefits.

Impact of Impella protected-percutaneous coronary intervention on left ventricle function recovery of patients with extensive coronary disease and poor left ventricular function

BackgroundThe use of Impella support is increasingly adopted to “protect” patients with severe coronary artery disease (CAD) and left ventricle (LV) dysfunction undergoing percutaneous coronary intervention (PCI). AimsTo evaluate the impact of Impella-protected (Abiomed, Danvers, Massachusetts, USA) PCIs on myocardial function recovery. MethodsPatients with significant LV dysfunction undergoing multi-vessel PCIs with pre-intervention Impella implantation were evaluated by echocardiography before PCI and at median follow up of 6 months: global and segmental LV contractile function were assessed by LV ejection fraction (LVEF) and wall motion score index (WMSI), respectively. Extent of revascularization was graded using the British Cardiovascular Intervention Society Jeopardy score (BCIS-JS). Study endpoints were LVEF and WMSI improvement, and its correlation with revascularization. ResultsA total of 48 high surgical risk (mean EuroSCORE II 8) patients with median LVEF value of 30%, extensive wall motion abnormalities (median WMSI 2.16), and severe multi-vessel CAD (mean SYNTAX score 35) were included. PCIs brought a significant reduction of ischemic myocardium burden with BCIS-JS decrease from mean value of 12 to 4 (p < 0.001). At follow-up, WMSI reduced from 2.2 to 2.0 (p = 0.004) and LVEF increased from 30% to 35% (p = 0.016). WMSI improvement was proportional to the baseline impairment (R − 0.50, p < 0.001), and confined to revascularized segments (from 2.1 to 1.9, p < 0.001). ConclusionsIn patients with extensive CAD and severe LV dysfunction, multi-vessel Impella-protected PCI was associated to an appreciable contractile recovery, mainly determined by regional wall motion improvement in revascularized segments.

An Increase in Plasma MicroRNA-143 Levels in the Acute Phase Is Positively Correlated With Recovery of Cardiac Function in the Chronic Phase in Patients With Acute Myocardial Infarction.

MicroRNA (miR)-143 and miR-145 are non-coding RNAs present in smooth muscle cells and the heart. However, their behavior and physiological role in patients with acute myocardial infarction (AMI) have not been clarified.Methods and Results: Plasma miR-143 and miR-145 concentrations were measured on Day 0 (on admission) and on Day 7 in AMI patients who could be followed up for 6 months (n=25). The control group consisted of subjects without significant coronary stenosis (n=20). Blood samples were collected from the antecubital vein, and plasma miR-143 and miR-145 concentrations were measured by quantitative reverse transcription-polymerase chain reaction. In AMI patients (n=25), left ventricular ejection fraction (LVEF) was measured by echocardiography in the acute and chronic (6 months) phases. On Day 7, plasma miR-143 and miR-145 concentrations were significantly higher in AMI patients than in the control group and on Day 0 in AMI patients. Plasma miR-143 and miR-145 concentrations increased significantly from Day 0 to Day 7. The increase in plasma miR-143 concentrations (∆miR-143) in the acute phase was positively correlated with the increase in LVEF in the chronic phase. Among many factors, only ∆miR-143 was favorably correlated with left ventricle (LV) functional recovery in the chronic phase. An increase in plasma miR-143 concentrations in the acute phase may be a biomarker predicting recovery of LV function in the chronic phase in AMI patients.

Cardiomyocyte tetrahydrobiopterin synthesis regulates fatty acid metabolism and susceptibility to ischaemia-reperfusion injury.

What is the central question of this study? What are the physiological roles of cardiomyocyte-derived tetrahydrobiopterin (BH4) in cardiac metabolism and stress response? What is the main finding and its importance? Cardiomyocyte BH4 has a physiological role in cardiac metabolism. There was a shift of substrate preference from fatty acid to glucose in hearts with targeted deletion of BH4 synthesis. The changes in fatty-acid metabolic profile were associated with a protective effect in response to ischaemia-reperfusion (IR) injury, and reduced infarct size. Manipulating fatty acid metabolism via BH4 availability could play a therapeutic role in limiting IR injury. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthases in which its production of NO is crucial for cardiac function. However, non-canonical roles of BH4 have been discovered recently and the cell-specific role of cardiomyocyte BH4 in cardiac function and metabolism remains to be elucidated. Therefore, we developed a novel mouse model of cardiomyocyte BH4 deficiency, by cardiomyocyte-specific deletion of Gch1, which encodes guanosine triphosphate cyclohydrolase I, a required enzyme for de novo BH4 synthesis. Cardiomyocyte (cm)Gch1 mRNA expression and BH4 levels from cmGch1 KO mice were significantly reduced compared to Gch1flox/flox (WT) littermates. Transcriptomic analyses and protein assays revealed downregulation of genes involved in fatty acid oxidation in cmGch1 KO hearts compared with WT, accompanied by increased triacylglycerol concentration within the myocardium. Deletion of cardiomyocyte BH4 did not alter basal cardiac function. However, the recovery of left ventricle function was improved in cmGch1 KO hearts when subjected to ex vivo ischaemia-reperfusion (IR) injury, with reduced infarct size compared to WT hearts. Metabolomic analyses of cardiac tissue after IR revealed that long-chain fatty acids were increased in cmGch1 KO hearts compared to WT, whereas at 5min reperfusion (post-35min ischaemia) fatty acid metabolite levels were higher in WT compared to cmGch1 KO hearts. These results indicate a new role for BH4 in cardiomyocyte fatty acid metabolism, such that reduction of cardiomyocyte BH4 confers a protective effect in response to cardiac IR injury. Manipulating cardiac metabolism via BH4 could play a therapeutic role in limiting IR injury.

Left ventricular dysfunction in the immediate post-natal period.

Our objective was to examine the clinical presentation, echocardiographic findings, and outcomes of newborns presenting with left ventricle (LV) dysfunction in the first 48 hours of life without perinatal asphyxia or structural heart disease. We hypothesize that LV dysfunction may occur due to maladaptation to extrauterine life. This is a retrospective cohort analysis including infants born in a quaternary perinatal centre. Late preterm and term neonates who were diagnosed with left ventricular dysfunction at less than 48 hours of life were identified using an echocardiography clinical laboratory's database and extracorporeal life support database. LV dysfunction was defined as m-mode fractional shortening (FS) <28% or ejection fraction (EF) <50% on echocardiography or reduced function reported by a cardiologist. Data extracted included patient & maternal demographics, echocardiogram parameters, clinical status, and medications. The primary outcome measure was time to recovery of LV function based on echocardiography. Of the 69 patients identified, 19 patients were included in the final analysis. The mean gestational age was 38 weeks. Thirteen (68%) infants did not have an underlying cause identified despite extensive work-up. Four (21%) infants had exposure to maternal illicit drug use during pregnancy. Three infants died, and all infants without identifiable etiologies had recovery of LV function within 14 days of life. LV dysfunction can occur during the abrupt transition from fetal to neonatal circulation and can be associated with maternal illicit drug use.

An Uncommon Case of Ischemic Heart Disease

<h3>Introduction</h3> Diminutive coronary artery syndrome (DCAS) is rare anomaly, defined as a small luminal diameter of >1 of the major coronary vessels. <h3>Case Report</h3> A previously healthy 5 month old infant presented with acute onset dyspnea. Laboratory and radiographic analysis suggested heart failure and end-organ hypoperfusion. A transthoracic echocardiogram demonstrated a dilated (LVDd z score + 6), and hyper-trabeculated left ventricle (LV) (fig 1) with depressed systolic function (ejection fraction 20-25%). The aortic valve (AV) was bicuspid with normal sized annulus, and without any gradient. Interrogation of the coronary arteries revealed normal origins with hypoplasia of the left main ostium, a short left main segment (fig 2), and turbulence by color doppler. CT angiography revealed near atresia of the left coronary artery (LCA) ostium and the main segment measured <1 mm. Cardiac catheterization confirmed findings and revealed stasis of contrast in the LCA. Patch augmentation of the LCA was performed with ECMO support, and required conversion to Berlin Heart Left Ventricular Assist Device (LVAD). While on LVAD support, recovery of LV function was noted, allowing LVAD explantation and unroofing of the myocardial bridge along the mid- and proximal left anterior descending artery. The patient remains supported on an oral heart failure regimen. <h3>Summary</h3> To our knowledge, our patient is the first reported infant with DCAS presenting with decompensated heart failure, associated with LV non compaction and bicuspid AV. We suggest that DCAS should be evaluated in infants with unexplained cardiomyopathy, as ventricular dysfunction in our patient was likely driven by coronary artery insufficiency.

Premature ventricular complex site of origin and ablation outcomes in patients with diabetes mellitus.

Premature ventricular complexes (PVCs) are frequent in patients with diabetes mellitus (DM). Still, the PVCs characteristics as well as the outcomes after catheter ablation in this population remain unknown. Aim of the study was to describe principal features of PVCs ablated in a wide DM-patients cohort and report postablation clinical outcomes in the follow-up of patients with DM and left ventricular dysfunction. From April 2012 to April 2020 data of 544 patients (315 [58%] men, 55±16 y), consecutive patients submitted for PVC ablation, were prospectively collected. Patients with left ventricle (LV) systolic disfunction (LVEF<50%) were included in a prospective protocol and followed at 6 and 12 months, and annually thereafter. Baseline characteristic as well ablation outcomes were analyzed based on the presence of DM. Sixty (11%) patients had DM. Patients with DM more frequently had a PVC's site of origin (SOO) in the LV (45 [75%] vs. 229 [48%], P<0.001). The most frequent PVC's SOO in DM patients was the LV outflow tract (OT) (35 [58%] patients: 12 aortic cusps; 12 LV summit; 11 in the myocardium immediately inferior to the valvular plane). Fifty-five (92%) patients with DM had an acute successful ablation, without differences compared with patients without DM (55 [92%] vs. 437 [90%], P=0.9). Twenty-tree (38%) DM-patients had LV dysfunction at the ablation time. In these patients, mean PVC burden decreased from 26±11% at baseline to 4±5% (P<0.001); LVEF increased from 36±8% to 42±11% (P<0.01) and NYHA class improved from 2.2±0.6 to 1.8+0.5 (P<0.01), after a mean follow-up of 37±14 months. Patients with DM frequently have PVC with a LV-SOO, being the LVOT the most frequent SOO in this population. Among DM patients with LV dysfunction, ablation persistently and significantly reduce the PVC burden improving functional status. Patients with DM have lower benefit in terms of LV function recovery after ablation compared with non-diabetic patients.

A comparison of rate control and rhythm control in tachycardia induced cardiomyopathy patients with persistent atrial flutter

Abstract Background/Introduction Tachycardia induced cardiomyopathy (TIC) is a potentially reversible dysfunction of the left ventricle (LV) caused by tachyarrhythmias. Early recognition of TIC and treatment of the culprit arrhythmia using pharmacological therapy or catheter ablation results in the recovery of LV function. For atrial flutter (AFL)-induced TIC, rhythm control strategy, such as catheter ablation has been recommended. On the other hand, the efficacy of rate control strategy has remained unclear due to the difficulty of control with arrhythmic medications. However, not all patients can take rhythm control treatments due to their backgrounds. Purpose The aim of this cohort study was to establish whether rate control strategy using β-blocker is as effective as invasive rhythm control strategy for the recovery of LV function in patients with TIC due to AFL. Methods We prospectively assessed 47 symptomatic non-ischaemic heart failure (HF) patients with left ventricular ejection fraction (LVEF) below 50% and suspected TIC induced by persistent AFL. Patients were divided into rhythm control strategy group (n=22, treatment: catheter ablation, electrical cardioversion) and rate control strategy group (n=25, treatment: bisoprolol). As a sub-group study, the rate control strategy group was divided into the strict rate control group (n=12, average heart rate below 80 bpm) and lenient rate control group (n=13, average heart rate below 110 bpm). The primary outcome was the recovery of LV function, defined as an increase of LVEF over 20% or to a value of 55% or greater after 6 months. Results There were no significant differences in baseline AFL heart rate, New York Heart Association class, LVEF, estimated glomerular filtration rate, and brain natriuretic peptide between the two groups. A greater proportion of patients who showed the recovery of LVEF after 6 months belonged to the rhythm control strategy group (90.9% vs. 52.0%, p=0.004). The cumulative incidence of HF re-hospitalization was significantly higher in the rate control strategy group than in the rhythm control strategy group (hazard ratio: 4.90, 95% CI: 1.06–22.69). As a result of sub-group study, LVEF recovery was greater in the strict rate control group compared to the lenient rate control group (75.0% vs. 30.8%, p=0.027) Conclusion Rate control strategy was significantly inferior to rhythm control strategy for the recovery of LVEF in TIC patients with persistent AFL. Rhythm control should be the first choice in the management of TIC with AFL, and strict rate control should be an alternative if rhythm control is not available. Primary outcomes Funding Acknowledgement Type of funding source: None

Reversible LV Dysfunction After TAVR

Aortic stenosis (AS) is characterized by gradual thickening, fibrosis, and calcification leading to reduced opening of aortic valve leaflets. Aortic valve narrowing increases the afterload on left ventricle (LV), which consequently leads to hypertrophy and myocardial fibrosis which over a period of time leads to diastolic dysfunction. LV diastolic dysfunction is an independent predictor of heart failure rehospitalization and mortality in post-aortic valve replacement patients. Chronic pressure overload leads to development of systolic dysfunction due to afterload mismatch. Patients with severe symptomatic AS and depressed LV function without significant myocardial scarring will derive maximum benefit after percutaneous valve replacement and thus show immediate improvement after reduction of LV afterload. We report two such cases which had good LV function recovery immediately after transcatheter aortic valve replacement (TAVR).

Left Ventricle Function Recovery After Revascularisation in Patients With Acute Myocardial Infarction (Single Vessel Disease): Comparison of 2D Strain Imaging With Standard Echocardiography

Left Ventricle Function Recovery After Revascularisation in Patients With Acute Myocardial Infarction (Single Vessel Disease): Comparison of 2D Strain Imaging With Standard Echocardiography

Atrial Fibrillation-Mediated Cardiomyopathy.

AF-mediated cardiomyopathy (AMC) is an important reversible cause of heart failure that is likely underdiagnosed in today's clinical practice. AMC describes AF either as the sole cause for ventricular dysfunction or exacerbating ventricular dysfunction in patients with existing cardiomyopathy or heart failure. Studies suggest that irreversible ventricular and atrial remodeling can occur in AMC, making timely diagnosis and intervention critical to optimize clinical outcome. Clinical correlation between AF onset/burden and progression of cardiomyopathy/heart failure symptoms provides strong evidence for the diagnosis of AMC. Cardiac MRI, continuous cardiac monitoring, and biomarkers are important diagnostic tools. From the therapeutic standpoint, early data suggest that AF ablation may improve long-term outcomes in AMC patients compared with medical rate and rhythm control. Patients with more AF burden and less severe underlying structural heart disease are more likely to experience left ventricle function recovery with successful AF ablation. Despite recent advances, significant knowledge gaps exist in our understanding of the epidemiology, mechanisms, diagnosis, management strategies, and prognosis of AMC.

THIS TOO SHALL PASS (UNTIL IT DOESN'T): A RARE CASE OF TAKOTSUBO CARDIOMYOPATHY WITH PERSISTENT LEFT VENTRICULAR DYSFUNCTION

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Takotsubo cardiomyopathy (TCM) is characterized by acute regional dysfunction of the left ventricle (LV) triggered by emotional or physical stress. There is an absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture. TCM is usually reversible within a few weeks to months. Here, we present a rare case of TCM in which 6 months post inciting event there was not only a lack in recovery of LV function, but also new onset ventricular arrhythmias requiring AICD placement. CASE PRESENTATION: A 72-year-old male with a past medical history of hypertension, hyperlipidemia, and diabetes, presented with substernal chest pain for the last 10 days. The patient also reported increased work-related stress recently. EKG showed diffuse ST segment elevations and T wave inversions. Transthoracic echocardiogram (TTE) demonstrated a severely hypokinetic LV apical segment with a left ventricular ejection fraction (LVEF) of 45%. There was no significant atherosclerotic occlusion on coronary angiography. On follow up visit 4 months later, EKG showed persistent diffuse Q waves in anteroseptal and inferior leads with resolution of T wave inversions. The patient also developed new-onset paroxysmal atrial fibrillation. 6 months later, the patient presented with a complaint of palpitations, dizziness, and lethargy. TTE at that time showed persistent diminished LVEF to 45% with continued LV apical hypokinesis. The patient underwent an electrophysiology study that showed new-onset inducible ventricular tachycardia and lengthy sinus nodal reentrant tachycardia. He underwent successful left subclavian dual-lead AICD placement, with resolution of symptoms. DISCUSSION: TCM is generally characterized as transient LV dysfunction secondary to a stressor, with regression of wall motion abnormalities and gradual restoration of LVEF until complete recovery is achieved. Here, we describe a unique case, in which more than 6 months after the inciting event, LV function was still impaired. In approximately 20% of cases of TCM, complications may occur, including cardiogenic shock, heart failure, rhythm disorders, LV thrombus formation, free wall rupture, and death. There have been very few cases, as in this case, in which not only did LV function not recover but rhythm disorders developed months after the inciting event. Differences in the evolution of TCM may be attributed to the different pathophysiological mechanisms that have been cited to contribute to the disorder – namely, catecholamine-induced myocardial stunning, transient epicardial vasospasm, coronary microvascular dysfunction, and transient LV obstructions. CONCLUSIONS: TCM is often characterized as transient LV dysfunction. This case demonstrated the need for close monitoring post inciting event, as there is a possibility for persistent LVEF depression, as well as further complications that could significantly increase mortality. Reference #1: Virani, S. S., Khan, A. N., Mendoza, C. E., Ferreira, A. C., & de Marchena, E. (2007). Takotsubo cardiomyopathy, or broken-heart syndrome. Texas Heart Institute journal, 34(1), 76-9. Reference #2: Zalewska-Adamiec, M., Bachorzewska-Gajewska, H., Tomaszuk-Kazberuk, A., Nowak, K., Drozdowski, P., Bychowski, J., Krynicki, R., Musial, W. J., … Dobrzycki, S. (2016). Takotsubo cardiomyopathy: serious early complications and two-year mortality - a 101 case study. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 24(9), 511-9. DISCLOSURES: no disclosure on file for Rakesh Gupta; No relevant relationships by Christina Jee Ah Rhee, source=Web Response No relevant relationships by Sharmila Sarkar, source=Web Response

Long-term exposure to high altitude hypoxia during pregnancy increases fetal heart susceptibility to ischemia/reperfusion injury and cardiac dysfunction

BackgroundHigh altitude hypoxia (HAH) exposure affects fetal development. However, the fetal cardiovascular responses to the HAH are not well understood. We have tested the hypothesis that long-term HAH exposure alters the hypoxia/ischemia-sensitive gene expressions, leading to an increase in fetal heart susceptibility to ischemia/reperfusion (I/R) injury and cardiac dysfunction. MethodsTime-dated pregnant sheep were exposed to high-altitude (3820 m) or were maintained at sea level (~300 m) for 110 days. Fetal hearts were isolated from the near-term ewes and subjected to I/R in a Langendorff preparation. ResultsHAH decreased the fetal body and heart weights in the female but not male fetuses. HAH had no effect on the left ventricle (LV) function at baseline, but increased the LV infarct size and attenuated the post-ischemic recovery of LV function in both male and female fetuses, as compared with the normoxic groups. HAH increased the protein levels of hypoxia-inducible factor (HIF)-1α and DNA methyltransferases type 3b (DNMT3b), but attenuated protein kinase C epsilon (PKCε) levels in the fetal hearts. AHA induced a 4.3 fold increase of miR-210 in the males and a 2.9 fold increase in female hearts. In addition, HAH had no effect on mTOR protein and phosphorylation levels but increased the autophagy biomarker, LC3B-II protein levels and LC3B-II/LC3B-I ratio in the fetal hearts. ConclusionThe results suggest that gestational HAH exposure induces in utero programming of the hypoxia/ischemia-sensitive gene expression pattern in the developing heart and increases cardiac susceptibility to I/R injury.

Left ventricular function after takotsubo is not fully recovered in long-term follow-up: A speckle tracking echocardiography study.

Complete improvement of left ventricle (LV) systolic function is an essential feature of takotsubo cardiomyopathy (TTC). It is suggested that 2-dimensional speckle tracking echocardiography (2D STE) can evaluate LV dysfunction more accurately than conventional echocardiography. Thus, the purpose of this research was to assertain whether LV function recovery is complete after the acute phase of TTC using 2D STE commencing 6 to 9 months after discharge. Thirty patients (29 females, 67 ± 11 years) with an apical ballooning TTC pattern 225.5 ± 27.4 days after their index event were enrolled. The control group consisted of 20 (19 females, 64 ± 9 years) age- and sex-matched volunteers without structural heart disease. Classic echocardiographic parameters, longitudinal strain and LV twist parameters were assessed and compared between the groups. There were no differences in traditional LV systolic, diastolic parameters and in global peak longitudinal strain. In comparison to controls, patients with TTC had lower mean apical rotation (14.4° ± 6.5° vs. 18.3° ± 6.7°; p = 0.048), slower mean peak early diastolic apical rotation rate (-85.1-°/s ± 40.9-°/s vs -119.4-°/s ± 41.9-°/s; p = 0.006) and higher pre-stretch index in the apex (2.16, IQR 0.33-5.50 vs. 0.00, IQR 0.00-2.95, p = 0.008). The improvement of LV function in patients with TTC as assessed by 2D STE may not always be complete. Some residual abnormalities in LV apex function were observed in long-term recovery following TTC episodes.

Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion.

Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.Am J Physiol Heart Circ Physiol 308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM-Sirt1(-/-)) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1(-/-)mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1(-/-)mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fed C3(-/-)mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting that cardiac Sirt1 regulates the local complement system during CR.

Diastolic Dyssynchrony in Acute ST Segment Elevation Myocardial Infarction and Relationship with Functional Recovery of Left Ventricle.

BackgroundIncidence of diastolic dyssynchrony (DD) and its impact on functional recovery of left ventricle (LV) after ST segment elevation myocardial infarction (STEMI) is not known.MethodsConsecutive patients with STEMI who underwent successful revascularization were prospectively enrolled. Echocardiography with tissue Doppler imaging was performed within 48 hours of admission and at 6 months. LV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), ejection fraction (EF), and left atrial volume index (LAVI) were calculated. Diastolic delay was calculated from onset of QRS complex to peak of E wave in tissue Doppler image and presented as maximal temporal difference between peak early diastolic velocity of 6 basal segments of LV (TeDiff). Study patients were compared with demographically matched control group.ResultsForty eight consecutive patients (55 ± 10 years, 88% male) and 24 controls (56 ± 6 years, 88% male) were included. TeDiff was higher in STEMI than in controls (35.9 ± 19.9 ms vs. 26.3 ± 6.8 ms, p = 0.025). Presence of DD was higher in STEMI than controls (58% vs. 33%, p = 0.046) according to calculated cut-off value (≥ 29 ms). There was no correlation between TeDiff and change in EDVI, ESVI, and LAVI at 6 months, however TeDiff and change in EF at 6 months was positively correlated (r = 0.328, p = 0.023). Patients with baseline DD experienced remodeling less frequently compared to patients without baseline DD (11% vs. 38%, p = 0.040) during follow-up.ConclusionSTEMI disrupts diastolic synchronicity of LV. However, DD during acute phase of STEMI is associated with better recovery of LV thereafter. This suggests that DD is associated with peri-infarct stunned myocardium that is salvaged with primary intervention as well as infarct size.

Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism

The alpha2-adrenergic receptor agonist Dexmedetomidine (Dex) is a sedative medication used by anesthesiologists. Dex protects the heart against ischemia-reperfusion (IR) and can also act as a preconditioning mimetic. The mechanisms involved in Dex-dependent cardiac preconditioning, and whether this action occurs directly or indirectly on cardiomyocytes, still remain unclear. The endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway and endothelial cells are known to play key roles in cardioprotection against IR injury. Therefore, the aims of this work were to evaluate whether the eNOS/NO pathway mediates the pharmacological cardiac effect of Dex, and whether endothelial cells are required in this cardioprotective action. Isolated adult rat hearts were treated with Dex (10nM) for 25min and the dimerization of eNOS and production of NO were measured. Hearts were then subjected to global IR (30/120min) and the role of the eNOS/NO pathway was evaluated. Dex promoted the activation of eNOS and production of NO. Dex reduced the infarct size and improved the left ventricle function recovery, but this effect was reversed when Dex was co-administered with inhibitors of the eNOS/NO/PKG pathway. In addition, Dex was unable to reduce cell death in isolated adult rat cardiomyocytes subjected to simulated IR. Cardiomyocyte death was attenuated by co-culturing them with endothelial cells pre-treated with Dex. In summary, our results show that Dex triggers cardiac protection by activating the eNOS/NO signaling pathway. This pharmacological effect of Dex requires its interaction with the endothelium.

AT1 and Aldosterone Receptors Blockade Prevents the Chronic Effect of Nandrolone on the Exercise-Induced Cardioprotection in Perfused rat Heart Subjected to Ischemia and Reperfusion

Myocardial tolerance to ischaemia/reperfusion (I/R) injury is improved by exercise training, but this cardioprotection is impaired by the chronic use of anabolic androgenic steroids (AAS). The present study evaluated whether blockade of angiotensin II receptor (AT1-R) with losartan and aldosterone receptor (mineralocorticoid receptor, MR) with spironolactone could prevent the deleterious effect of AAS on the exercise-induced cardioprotection. Male Wistar rats were exercised and treated with either vehicle, nandrolone decanoate (10mg/kg/week i.m.) or the same dose of nandrolone plus losartan or spironolactone (20mg/kg/day orally) for 8weeks. Langendorff-perfused hearts were subjected to I/R and evaluated for the postischaemic recovery of left ventricle (LV) function and infarct size. mRNA and protein expression of angiotensin II type 1 receptor (AT1-R), mineralocorticoid receptor (MR), and KATP channels were determined by reverse-transcriptase polymerase chain reaction and Western blotting. Postischaemic recovery of LV function was better and infarct size was smaller in the exercised rat hearts than in the sedentary rat hearts. Nandrolone impaired the exercise-induced cardioprotection, but this effect was prevented by losartan (AT1-R antagonist) and spironolactone (MR antagonist) treatments. Myocardial AT1-R and MR expression levels were increased, and the expression of the KATP channel subunits SUR2a and Kir6.1 was decreased and Kir6.2 increased in the nandrolone-treated rat hearts. The nandrolone-induced changes of AT1-R, MR, and KATP subunits expression was normalized by the losartan and spironolactone treatments. The chronic nandrolone treatment impairs the exercise-induced cardioprotection against ischaemia/reperfusion injury by activating the cardiac renin-angiotensin-aldosterone system and downregulating KATP channel expression.

Lack of Microsomal Prostaglandin E 2 Synthase-1 in Bone Marrow–Derived Myeloid Cells Impairs Left Ventricular Function and Increases Mortality After Acute Myocardial Infarction

Microsomal prostaglandin E(2) synthase-1 (mPGES-1), encoded by the Ptges gene, catalyzes prostaglandin E(2) biosynthesis and is expressed by leukocytes, cardiac myocytes, and cardiac fibroblasts. Ptges(-/-) mice develop more left ventricle (LV) dilation, worse LV contractile function, and higher LV end-diastolic pressure than Ptges(+/+) mice after myocardial infarction. In this study, we define the role of mPGES-1 in bone marrow-derived leukocytes in the recovery of LV function after coronary ligation. Cardiac structure and function in Ptges(+/+) mice with Ptges(+/+) bone marrow (BM(+/+)) and Ptges(+/+) mice with Ptges(-/-) BM (BM(-/-)) were assessed by morphometric analysis, echocardiography, and invasive hemodynamics before and 7 and 28 days after myocardial infarction. Prostaglandin levels and prostaglandin biosynthetic enzyme gene expression were measured by liquid chromatography-tandem mass spectrometry and real-time polymerase chain reaction, immunoblotting, immunohistochemistry, and immunofluorescence microscopy, respectively. After myocardial infarction, BM(-/-) mice had more LV dilation, worse LV systolic and diastolic function, higher LV end-diastolic pressure, more cardiomyocyte hypertrophy, and higher mortality but similar infarct size and pulmonary edema compared with BM(+/+) mice. BM(-/-) mice also had higher levels of COX-1 protein and more leukocytes in the infarct, but not the viable LV, than BM(+/+) mice. Levels of prostaglandin E(2) were higher in the infarct and viable myocardium of BM(-/-) mice than in BM(+/+) mice. Lack of mPGES-1 in bone marrow-derived leukocytes negatively regulates COX-1 expression, prostaglandin E(2) biosynthesis, and inflammation in the infarct and leads to impaired LV function, adverse LV remodeling, and decreased survival after acute myocardial infarction.