Association of Interstage Monitoring Era and Likelihood of Hemodynamic Compromise at Intervention for Recoarctation Following the Norwood Operation.

Background Intensive monitoring has been associated with a lower death rate between the Norwood operation and superior cavopulmonary connection, possibly due to early identification and effective treatment of residual anatomic lesions like recoarctation before lasting harm occurs. Methods and Results Neonates undergoing a Norwood operation and receiving interstage care at a single center between January 1, 2005, and September 18, 2020, were studied. In those with recoarctation, we evaluated association of era ([1] preinterstage monitoring, [2] a transitional phase, [3] current era) and likelihood of hemodynamic compromise (progression to moderate or greater ventricular dysfunction/atrioventricular valve regurgitation, initiation/escalation of vasoactive/respiratory support, cardiac arrest preceding catheterization, or interstage death with recoarctation on autopsy). We also analyzed whether era was associated with technical success of transcatheter recoarctation interventions, major adverse events, and transplant-free survival. A total of 483 subjects were studied, with 22% (n=106) treated for recoarctation during the interstage period. Number of catheterizations per Norwood increased (P=0.005) over the interstage eras, with no significant change in the proportion of subjects with recoarctation (P=0.36). In parallel, there was a lower likelihood of hemodynamic compromise in subjects with recoarctation that was not statistically significant (P=0.06), with a significant difference in the proportion with ventricular dysfunction at intervention (P=0.002). Rates of technical success, procedural major adverse events, and transplant-free survival did not differ (P>0.05). Conclusions Periods with interstage monitoring were associated with increased referral for catheterization but also reduced likelihood of ventricular dysfunction (and a suggestion of lower likelihood of hemodynamic compromise) in subjects with recoarctation. Further study is needed to guide optimal interstage care of this vulnerable population.

Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunction and AV block.

BACKGROUND: It is unknown whether His-Purkinje conduction system pacing (HPCSP), as either His bundle or left bundle branch pacing, could be an alternative to cardiac resynchronization therapy (BiVCRT) for patients with left ventricular dysfunction needing ventricular pacing due to atrioventricular block. The aim of the study is to compare the echocardiographic response and clinical improvement between HPCSP and BiVCRT. METHODS: Consecutive patients who successfully received HPCSP were compared with a historical cohort of BiVCRT patients. Patients were 1:1 matched by age, LVEF, atrial fibrillation, renal function and cardiomyopathy type. Responders were defined as patients who survived, did not require heart transplantation and increased LVEF ≥5 points at 6-month follow-up. RESULTS: HPCSP was successfully achieved in 92.5% (25/27) of patients. During follow-up, 8% (2/25) of HPCSP patients died and 4% (1/25) received a heart transplant, whereas 4% (1/25) of those in the BiVCRT cohort died. LVEF improvement was 10% ± 8% HPCSP versus 7% ± 5% BiVCRT (p = .24), and the percentage of responders was 76% (19/25) HPCSP versus 64% (16/25) BiVCRT (p = .33). Among survivors, the percentage of patients who improved from baseline II-IV mitral regurgitation (MR) to 0-I MR was 9/11 (82%) versus 2/8 (25%) (p = .02). Compared to those with BiVCRT, patients with HPCSP achieved better NYHA improvement: 1 point versus 0.5 (OR 0.34; p = .02). CONCLUSION: HPCSP in patients with LVEF ≤45% and atrioventricular block improved the LVEF and induced a response similar to that of BiVCRT. HPCSP significantly improved MR and NYHA functional class. HPCSP may be an alternative to BiVCRT in these patients. (Figure 1. Central Illustration). [Figure: see text].

Ventricular Dysfunction in Obese and Nonobese Rats with Metabolic Syndrome.

Obesity and dyslipidemias are both signs of metabolic syndrome, usually associated with ventricular arrhythmias. Here, we tried to identify cardiac electrical alteration and biomarkers in nonobese rats with metabolic syndrome (MetS), and these findings might lead to more lethal arrhythmias than obese animals. The MetS model was developed in Wistar rats with high-sucrose diet (20%), and after twenty-eight weeks were obtained two subgroups: obese (OMetS) and nonobese (NOMetS). The electrocardiogram was used to measure the ventricular arrhythmias and changes in the heart rate variability. Also, we measured ventricular hypertrophy and its relationship with electrical activity alterations of both ventricles, using micro-electrode and voltage clamp techniques. Also, we observed alterations in the contraction force of ventricles where a transducer was used to record mechanical and electrical papillary muscle, simultaneously. Despite both subgroups presenting long QT syndrome (0.66 ± 0.05 and 0.66 ± 0.07 ms with respect to the control 0.55 ± 0.1 ms), the changes in the heart rate variability were present only in OMetS, while the NOMetS subgroup presented changes in QT interval variability (NOMetS SD = 1.8, SD2 = 2.8; SD1/SD2 = 0.75). Also, the NOMetS revealed tachycardia (10%; p < 0.05) with changes in action potential duration (63% in the right papillary and 50% in the left papillary) in the ventricular papillary which are correlated with certain alterations in the potassium currents and the force of contraction. The OMetS showed an increase in action potential duration and the force of contraction in both ventricles, which are explained as bradycardia. Our results revealed lethal arrhythmias in both MetS subgroups, irrespectively of the presence of obesity. Consequently, the NOMetS showed mechanical-electrical alterations regarding ventricle hypertrophy that should be at the NOMetS, leading to an increase of CV mortality.

Omecamtiv mecarbil treatment improves post-resuscitation cardiac function and neurological outcome in a rat model.

BACKGROUND: Myocardial dysfunction is a major cause of poor outcomes in the post-cardiac arrest period. Omecamtiv mecarbil (OM) is a selective small molecule activator of cardiac myosin that prolongs myocardial systole and increases stroke volume without apparent effects on myocardial oxygen demand. OM administration is safe and improves cardiac function in patients with acute heart failure. Whether OM improves post-resuscitation myocardial dysfunction remains unclear. This study investigated the effect of OM treatment on post-resuscitation myocardial dysfunction and outcomes. METHODS AND RESULTS: Adult male rats were resuscitated after 9.5 min of asphyxia-induced cardiac arrest. OM and normal saline was continuously intravenously infused after return of spontaneous circulation (ROSC) at 0.25 mg/kg/h for 4 h in the experimental group and control group, respectively (n = 20 in each group). Hemodynamic parameters were measured hourly and monitored for 4 h after cardiac arrest. Recovery of neurological function was evaluated by neurological functioning scores (0-12; favorable: 11-12) for rats 72 h after cardiac arrest. OM treatment prolonged left ventricular ejection time and improved post-resuscitation cardiac output. Post-resuscitation heart rate and left ventricular systolic function (dp/dt40) were not different between groups. Kaplan-Meier analysis showed non-statistically higher 72-h survival in the OM group (72.2% [13/18] and 58.8% [10/17], p = 0.386). The OM group had a higher chance of having favorable neurological outcomes in surviving rats 72 h after cardiac arrest (84.6% [11/13] vs. 40% [4/10], p = 0.026). The percentage of damaged neurons was lower in the OM group in a histology study at 72 h after cardiac arrest (55.5±2.3% vs. 76.2±10.2%, p = 0.004). CONCLUSIONS: OM treatment improved post-resuscitation myocardial dysfunction and neurological outcome in an animal model. These findings support further pre-clinical studies to improve outcomes in post-cardiac arrest care.

Value of point-of-care neutrophil gelatinase associated lipocalin in early diagnosis of acute kidney injury in patients with left ventricular systolic dysfunction after coronary angiography.

BACKGROUND: Increased neutrophil gelatinase-associated lipocalin (NGAL) levels are associated with toxic or ischemic renal injury. OBJECTIVE: This study aimed to assess the usefulness of serial NGAL measurements with a point-of-care assay in patients with left ventricular systolic dysfunction (LVSD) for earlier detection of contrast-induced nephropathy (CIN). MATERIALS AND METHODS: A total of 84 patients with LVSD patients referred for coronary angiography were consecutively enrolled in the study. The study population was divided into two groups as the CIN and the non-CIN groups according to the CIN's determination. The serum creatinine levels were calculated 24 h before the procedure and at the 48th and 72nd h after the cardiac catheterization. The plasma NGAL concentration was measured before and at 4 and 24 h after the cardiac catheterization. RESULTS: Baseline and serial NGAL levels were significantly higher in patients with CIN compared to the patients without CIN. NGAL 24th h levels after the index procedure were found to be an independent and significant predictor of CIN in multivariate analysis. CONCLUSIONS: Serial point-of-care NGAL measurements might help earlier detection of CIN in patients with heart failure after coronary angiography.

Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy.

There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

Association of Major Adverse Cardiovascular Events in Patients With Stroke and Cardiac Wall Motion Abnormalities.

Background The association of cardiac wall motion abnormalities (CWMAs) in patients with stroke who have major adverse cardiovascular events (MACE) remains unclear. The purpose of this study was to estimate the 50-month risk of MACE, including stroke recurrence, acute coronary events, and vascular death in patients with stroke who have CWMAs. Methods and Results We performed a retrospective analysis of prospectively collected acute stroke data (acute stroke and transient ischemic attack) over 50 months by electronic medical records. Data included demographic and clinical information, vascular imaging, and echocardiography data including CWMAs and MACE. Of a total of 2653 patients with acute stroke/transient ischemic attack, CWMA was observed in 355 (13.4%). In patients with CWMAs, the embolic stroke of undetermined source (50.7%) was the most frequent index stroke subtype and stroke recurrences (P=0.001). In multivariate Cox regression after adjustment for demographics, traditional risk, and confounding factors, CWMA was independently associated with a higher risk of MACE (adjusted hazard ratio [HR], 1.74; 95% CI, 1.37-2.21 [P=0.001]). Similarly, CWMA independently conferred an increased risk for ischemic stroke recurrence (adjusted HR, 1.50; 95% CI, 1.01-2.17 [P=0.04]), risk of acute coronary events (aHR, 2.50; 95% CI, 1.83-3.40 [P=0.001]) and vascular death (adjusted HR, 1.57; 95% CI, 1.04-2.40 [P=0.03]), in comparison to the patients with stroke without CWMA. Conclusions In a multiethnic cohort of ischemic stroke with CWMA, CWMA was associated with 1.7-fold higher risks of MACE independent of established risk factors. Embolic stroke of undetermined source was the most common stroke association with CWMA. Patients with stroke should be screened for CWMA to identify those at higher risk of MACE.

Left and right ventricular dysfunction in patients with COVID-19-associated myocardial injury.

PURPOSE: SARS-COV-2 infection can develop into a multi-organ disease. Although pathophysiological mechanisms of COVID-19-associated myocardial injury have been studied throughout the pandemic course in 2019, its morphological characterisation is still unclear. With this study, we aimed to characterise echocardiographic patterns of ventricular function in patients with COVID-19-associated myocardial injury. METHODS: We prospectively assessed 32 patients hospitalised with COVID-19 and presence or absence of elevated high sensitive troponin T (hsTNT+ vs. hsTNT-) by comprehensive three-dimensional (3D) and strain echocardiography. RESULTS: A minority (34.3%) of patients had normal ventricular function, whereas 65.7% had left and/or right ventricular dysfunction defined by impaired left and/or right ventricular ejection fraction and strain measurements. Concomitant biventricular dysfunction was common in hsTNT+ patients. We observed impaired left ventricular (LV) global longitudinal strain (GLS) in patients with myocardial injury (-13.9% vs. -17.7% for hsTNT+ vs. hsTNT-, p = 0.005) but preserved LV ejection fraction (52% vs. 59%, p = 0.074). Further, in these patients, right ventricular (RV) systolic function was impaired with lower RV ejection fraction (40% vs. 49%, p = 0.001) and reduced RV free wall strain (-18.5% vs. -28.3%, p = 0.003). Myocardial dysfunction partially recovered in hsTNT + patients after 52 days of follow-up. In particular, LV-GLS and RV-FWS significantly improved from baseline to follow-up (LV-GLS: -13.9% to -16.5%, p = 0.013; RV-FWS: -18.5% to -22.3%, p = 0.037). CONCLUSION: In patients with COVID-19-associated myocardial injury, comprehensive 3D and strain echocardiography revealed LV dysfunction by GLS and RV dysfunction, which partially resolved at 2-month follow-up. TRIAL REGISTRATION: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

Trauma, a Matter of the Heart-Molecular Mechanism of Post-Traumatic Cardiac Dysfunction.

Trauma remains a leading global cause of mortality, particularly in the young population. In the United States, approximately 30,000 patients with blunt cardiac trauma were recorded annually. Cardiac damage is a predictor for poor outcome after multiple trauma, with a poor prognosis and prolonged in-hospitalization. Systemic elevation of cardiac troponins was correlated with survival, injury severity score, and catecholamine consumption of patients after multiple trauma. The clinical features of the so-called "commotio cordis" are dysrhythmias, including ventricular fibrillation and sudden cardiac arrest as well as wall motion disorders. In trauma patients with inappropriate hypotension and inadequate response to fluid resuscitation, cardiac injury should be considered. Therefore, a combination of echocardiography (ECG) measurements, echocardiography, and systemic appearance of cardiomyocyte damage markers such as troponin appears to be an appropriate diagnostic approach to detect cardiac dysfunction after trauma. However, the mechanisms of post-traumatic cardiac dysfunction are still actively being investigated. This review aims to discuss cardiac damage following trauma, focusing on mechanisms of post-traumatic cardiac dysfunction associated with inflammation and complement activation. Herein, a causal relationship of cardiac dysfunction to traumatic brain injury, blunt chest trauma, multiple trauma, burn injury, psychosocial stress, fracture, and hemorrhagic shock are illustrated and therapeutic options are discussed.

Longitudinal diastolic strain slope as an early sign for systolic dysfunction among patients with active cancer.

BACKGROUND: Diastolic dysfunction is a common finding in patients receiving cancer therapy. This study evaluated the correlation of diastolic strain slope (Dss) with routine echocardiography diastolic parameters and its role in early detection of systolic dysfunction and cardiovascular (CV) mortality within this population. METHODS: Data were collected from the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling adult patient receiving cancer therapy. All patients performed at least three echocardiography exams (T1, T2, T3), including left ventricle Global Longitudinal Strain (LV GLS) and Dss. Systolic dysfunction was determined by either LV GLS relative reduction of ≥ 15% or LV ejection fraction reduction > 10% to < 53%. Dss was assessed as the early lengthening rate, measured by the diastolic slope (delta%/sec). RESULTS: Among 144 patients, 114 (79.2%) were female with a mean age of 57.31 ± 14.3 years. Dss was significantly correlated with e' average. Mid segment Dss change between T1 and T2 showed significant association to systolic dysfunction development (Odds Ratio (OR) = 1.04 [1.01,1.06]. p = 0.036). In multivariate prediction, Dss increase was a significant predictor for the development of systolic dysfunction (OR = 1.06 [1.03,1.1], P < 0.001).An 8% increase in Dss between T1 and T2 was associated with a trend in increased CV mortality (HR = 3.4 [0.77,15.4], p = 0.085). CONCLUSIONS: This study is the first to use the novel measurement of Dss in patients treated with cancer therapies and to show significant correlation between routine diastolic dysfunction parameters and Dss. Changes in the mid segment were found to have significant independent early predictive value for systolic dysfunction development in univariate and multivariate analyses.

Early detection of ventricular dysfunction in juvenile systemic sclerosis by speckle tracking echocardiography.

OBJECTIVE: Cardiac involvement is the most important cause of mortality in juvenile systemic sclerosis (JSSc). Recent reports in adult patients underline that traditional techniques of imaging are inadequate to assess the subclinical cardiac involvement, while speckle tracking echocardiography (STE) is able to identify ventricular dysfunctions in the early stages. The aim of our study was to assess the role of STE in JSSc. METHODS: Demographic, clinical and laboratory data were collected from patients with JSSc. Cardiac investigations performed at baseline (T0) and 18 (T18) and 36 months (T36) follow-up included electrocardiography, conventional echocardiography with measurement of the ejection fraction (EF) and STE with assessment of left and right ventricular global longitudinal strain (LV-GLS and RV-GLS). Cardiac parameters have been compared with demographic characteristics and disease severity, assessed by the Juvenile Systemic Sclerosis Severity Score (J4S). RESULTS: A total of 18 patients, 12 (67%) females, entered the study. At T0, electrocardiography was abnormal in three patients, EF was reduced in one, LV-GLS was abnormal in three (16.7%) and RV-GLS was abnormal in five (27.8%). At T18, EF remained stable while at T36 the result decreased in seven of nine patients. At the same time, LV-GLS also worsened (from -21.6% to -18.2%, P = 0.01). LV-GLS and RV-GLS at baseline showed a significant correlation with J4S (P = 0.012 and P = 0.02, respectively). CONCLUSION: STE is more sensitive than standard echocardiography to identify cardiac involvement in JSSc. Over time, we observed a gradual worsening of LV-GLS, a sign of left ventricular dysfunction, that anticipated by several months the decrease of EF.

Cardiomyocyte Oga haploinsufficiency increases O-GlcNAcylation but hastens ventricular dysfunction following myocardial infarction.

RATIONALE: The beta-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to proteins is a pro-adaptive response to cellular insults. To this end, increased protein O-GlcNAcylation improves short-term survival of cardiomyocytes subjected to acute injury. This observation has been repeated by multiple groups and in multiple models; however, whether increased protein O-GlcNAcylation plays a beneficial role in more chronic settings remains an open question. OBJECTIVE: Here, we queried whether increasing levels of cardiac protein O-GlcNAcylation would be beneficial during infarct-induced heart failure. METHODS AND RESULTS: To achieve increased protein O-GlcNAcylation, we targeted Oga, the gene responsible for removing O-GlcNAc from proteins. Here, we generated mice with cardiomyocyte-restricted, tamoxifen-inducible haploinsufficient Oga gene. In the absence of infarction, we observed a slight reduction in ejection fraction in Oga deficient mice. Overall, Oga reduction had no major impact on ventricular function. In additional cohorts, mice of both sexes and both genotypes were subjected to infarct-induced heart failure and followed for up to four weeks, during which time cardiac function was assessed via echocardiography. Contrary to our prediction, the Oga deficient mice exhibited exacerbated-not improved-cardiac function at one week following infarction. When the observation was extended to 4 wk post-MI, this acute exacerbation was lost. CONCLUSIONS: The present findings, coupled with our previous work, suggest that altering the ability of cardiomyocytes to either add or remove O-GlcNAc modifications to proteins exacerbates early infarct-induced heart failure. We speculate that more nuanced approaches to regulating O-GlcNAcylation are needed to understand its role-and, in particular, the possibility of cycling, in the pathophysiology of the failing heart.

Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats.

Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX™ staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a "frail" myocardial tissue unable to adapt itself to stress.

Mechanistic validation of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging Guidelines for the assessment of diastolic dysfunction in heart failure with reduced ejection fraction.

BACKGROUND: The American Society for Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) 2016 guidelines for assessment of diastolic dysfunction (DD) are based primarily on the effects of diastolic dysfunction on left ventricular filling hemodynamics. However, these measures do not provide quantifiable mechanistic information about diastolic function. The Parameterized Diastolic Filling (PDF) formalism is a validated theoretical framework that describes DD in terms of the physical properties of left ventricular filling. AIMS: We hypothesized that PDF analysis can provide mechanistic insight into the mechanical properties governing higher grade DD. METHODS: Patients referred for echocardiography showing reduced left ventricular ejection fraction (< 45%) were prospectively classified into DD grade according to 2016 ASE/EACVI guidelines. Serial E-waves acquired during free breathing using pulsed wave Doppler of transmitral blood flow were analyzed using the PDF formalism. RESULTS: Higher DD grade (grade 2 or 3, n = 20 vs grade 1, n = 30) was associated with increased chamber stiffness (261 ± 71 vs 169 ± 61 g/s2, p < 0.001), increased filling energy (2.0 ± 0.9 vs 1.0 ± 0.5 mJ, p < 0.001) and greater peak forces resisting filling (median [interquartile range], 18 [15-24] vs 11 [8-14] mN, p < 0.001). DD grade was unrelated to chamber viscoelasticity (21 ± 4 vs 20 ± 6 g/s, p = 0.32). Stiffness was inversely correlated with ejection fraction (r = - 0.39, p = 0.005). CONCLUSIONS: Higher grade DD was associated with changes in the mechanical properties that determine the physics of poorer left ventricular filling. These findings provide mechanistic insight into, and independent validation of the appropriateness of the 2016 guidelines for assessment of DD.

Headache and Left Ventricular Efficiency After Transcatheter Closure of Atrial Septal Defect.

OBJECTIVE/BACKGROUND: This study aimed to clarify the relationship between migraine-like headache and ventriculo-arterial coupling after transcatheter closure of the atrial septal defect in children. We hypothesized that migraine headache after defect closure would be related to an abnormal hemodynamic response against an increased left ventricular filling. DESIGN: A retrospective cohort study. METHODS: We calculated the end-ventricular systolic elastance (Ees), effective arterial elastance (Ea), and ventricular energy efficiency approximated based on echocardiography before and after defect closure, and compared these parameters between the subjects with and without headache after defect closure. RESULTS: A total of 167 subjects were studied. Age at the procedure, defect diameter, and pulmonary to systemic blood flow ratio were 11 (9-17) years, 12.8 (9.2-16.0) mm, and 1.8 (1.6-2.3), respectively. We identified 47 (28%) subjects with migraine headache after defect closure. Although there was no significant difference in the Ees, Ea, and ventricular energy efficiency before defect closure between the groups, the Ees (4.0 [3.4-4.9] vs 4.8 [3.7-6.1], P = .014) and ventricular energy efficiency (0.79 [0.76-0.82] vs 0.83 [0.79-0.85], P = .001) after defect closure in subjects with headache were significantly lower than those in subjects without headache. Migraine headache after defect closure was significantly associated with age (odds ratio: 0.97, 95% confidential interval: 0.94-1.00, P = .036) and a decrease in the ventricular energy efficiency after defect closure (odds ratio: 6.42, 95% confidential interval: 2.76-14.90, P < .001). CONCLUSION: A loss of ventricular energy efficiency was common in pediatric subjects with migraine-like headache after transcatheter closure of the atrial septal defect, which suggested that the left ventricular function maladaptation was related to headache development after defect closure. We advocate that an impaired ventriculo-arterial coupling may be one of the mechanisms for developing attacks in not only this population but also in other patients with migraine.

Impact of delayed ventricular wall area ratio on pathophysiology of mechanical dyssynchrony: implication from single-ventricle physiology and 0D modeling.

Electrical disparity can induce inefficient cardiac performance, representing an uncoordinated wall motion at an earlier activated ventricular wall: an early shortening followed by a systolic rebound stretch. Although regional contractility and distensibility modulate this pathological motion, the effect of a morphological factor has not been emphasized. Our strain analysis in 62 patients with single ventricle revealed that those with an activation delay in 60-70% of ventricular wall area suffered from cardiac dysfunction and mechanical discoordination along with prolonged QRS duration. A computational simulation with a two-compartment ventricular model also suggested that the ventricle with an activation delay in 70% of the total volume was most vulnerable to a large activation delay, accompanied by an uncoordinated motion at an earlier activated wall. Taken together, the ratio of the delayed ventricular wall has a significant impact on the pathophysiology due to an activation delay, potentially highlighting an indicator of cardiac dysfunction.

Subtle cardiac dysfunction in nephropathic cystinosis: insight from tissue Doppler imaging and 2D speckle tracking echocardiography.

BACKGROUND: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder that initially affects the kidney progressing to multi-organ failure due to accumulation of cystine in all tissue compartments. OBJECTIVE: The main objective of this study is the evaluation of cardiac function in cystinosis patients using non-conventional echocardiographic modalities like pulsed wave tissue Doppler imaging (PW-TDI) and 2D speckle tracking echocardiography (2D-STE). METHODS: This is a case control study conducted on fifteen patients with cystinosis and 15 normal controls. Echocardiography was done for all participants and PW-TDI was performed for measurement of S', E', A' velocities and myocardial performance index (MPI) at basal parts of septal, left ventricle (LV), and right ventricle (RV) free walls. 2D-STE was done for evaluation of global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) of LV. Mitral E and A velocities and tricuspid annular plane systolic excursion (TAPSE) were also measured. RESULTS: The GLS, GRS, and S' velocity at basal septum and LV lateral wall were significantly lower in patients denoting LV systolic dysfunction (p = 0.005, p < 0.0001, p = 0.001, p = 0.006, respectively), while E/E' were significantly higher in patients group denoting LV diastolic dysfunction (p < 0.001). For RV function, TAPSE, S', and E' velocity were significantly lower in patients group (p 0.013, p < 0.01, p = 0.05, respectively) indicating RV systolic and diastolic dysfunction. The TDI-derived MPI for both LV and RV were significantly higher in patients group (p < 0.0001, p < 0.01, respectively) indicating both ventricular systolic and diastolic dysfunction. For prediction of cardiac dysfunction among patients, the receiver operating characteristic (ROC) curve showed that GRS ≤ 29% had sensitivity 93.3% and specificity 100%, GLS > - 20.1% had sensitivity 66.7% and specificity 93.3%, LV-E/E' >7.87 had sensitivity 73.3% and specificity 93.3%, and MPI-LV > 0.36 had sensitivity 100% and specificity 93.3% while MPI-RV > 0.29 had sensitivity 80% and specificity 93.3% and TAPSE ≤ 19 mm had sensitivity 80% and specificity 73.3%. CONCLUSIONS: Patients with cystinosis have significant both left and right ventricular dysfunction, which can be better evaluated using the non-conventional echocardiographic modalities like TDI and 2D-STE for early detection of subtle cardiac dysfunction.