Cardiac Syndrome Research Articles

Genetically Regulated Gene Expression in the Brain Associated With Chronic Pain: Relationships With Clinical Traits and Potential for Drug Repurposing

BackgroundChronic pain is a common, poorly understood condition. Genetic studies including genome-wide association studies have identified many relevant variants, which have yet to be translated into full understanding of chronic pain. Transcriptome-wide association studies using transcriptomic imputation methods such as S-PrediXcan can help bridge this genotype-phenotype gap. MethodsWe carried out transcriptomic imputation using S-PrediXcan to identify genetically regulated gene expression associated with multisite chronic pain in 13 brain tissues and whole blood. Then, we imputed genetically regulated gene expression for over 31,000 Mount Sinai BioMe participants and performed a phenome-wide association study to investigate clinical relationships in chronic pain–associated gene expression changes. ResultsWe identified 95 experiment-wide significant gene-tissue associations (p < 7.97 × 10−7), including 36 unique genes and an additional 134 gene-tissue associations reaching within-tissue significance, including 53 additional unique genes. Of the 89 unique genes in total, 59 were novel for multisite chronic pain and 18 are established drug targets. Chronic pain genetically regulated gene expression for 10 unique genes was significantly associated with cardiac dysrhythmia, metabolic syndrome, disc disorders/dorsopathies, joint/ligament sprain, anemias, and neurologic disorder phecodes. Phenome-wide association study analyses adjusting for mean pain score showed that associations were not driven by mean pain score. ConclusionsWe carried out the largest transcriptomic imputation study of any chronic pain trait to date. Results highlight potential causal genes in chronic pain development and tissue and direction of effect. Several gene results were also drug targets. Phenome-wide association study results showed significant associations for phecodes including cardiac dysrhythmia and metabolic syndrome, thereby indicating potential shared mechanisms.

Takotsubo Cardiomyopathy: Broken Heart Syndrome in A Tertiary Teaching &amp; Referral Hospital in East Africa: Case Report &amp; Literature Review

Purpose: Takotsubo cardiomyopathy (TC), also known as broken heart syndrome, refers to an abrupt and short-lived cardiac syndrome that encompasses dramatic left ventricular apical akinesia. besides mirroring acute coronary syndrome. Patients with Takotsubo cardiomyopathy (broken heart syndrome) usually present with symptoms that are similar to acute coronary syndrome. The patient commonly presents with chest pain, dyspnea, palpitation, nausea and vomiting, syncope as well as cardiogenic shock. However, Takotsubo cardiomyopathy usually occurs in association with a preceding physical or emotional stressful event.&#x0D; Methodology: A 25-year-old black female presented to the largest teaching &amp; referral hospital in Kenya with chest pain, dyspnea, palpitations, nausea and vomiting. The patient was received in the emergency room where she was stabilized, a battery of investigations ordered and a diagnosis of TC was made after reviewing the results. She was managed as an inpatient on appropriate medication&#x0D; Findings: Patient generally responded positively to the treatment and tolerated well the surgical procedures. Follow up echocardiograms performed weekly revealed progressive reduction in size of the thrombus, which had completely resolved at 4 weeks. There was no more thrombi formation after thromboembolectomy of the left femoral artery.&#x0D; Recommendations: TC is a rescindable type of cardiomyopathy that is associated with good prognosis and an exceptional morphological characteristic of the left ventricle, that is defined by apical inflating appearance that has been recognized for nearly a quarter a century. We also recommend that patients with identified LV thrombus ought to be anticoagulated till LV function normalizes in addition to the thrombus no longer being present on echocardiogram.

Effects of remote ischemic preconditioning on coronary blood flow and microcirculation

This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative flow ratio (QFR) and index of microcirculatory resistance (IMR). We randomly divided 129 patients undergoing coronary angiography (CAG) into RIPC and control groups. Following the first CAG, we randomly divided the patients further into the unilateral upper limb and lower limb groups for four cycles of ischemia/reperfusion circulation; subsequently, we performed the second CAG. During each CAG, contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and IMR (in patients with cardiac syndrome X) were calculated and compared. We measured 253 coronary arteries in 129 patients. Compared to the control group, the average cQFR of the RIPC group increased significantly after RIPC. Additionally, 23 patients with cardiac syndrome X (IMR > 30) were included in this study. Compared to the control group, IMR and the difference between cQFR and fQFR (cQFR-fQFR) both decreased significantly after receiving RIPC. The application of RIPC can increase coronary blood flow and improve coronary microcirculation function.

The Importance of Left Ventricular Outflow Tract and Mid-Ventricular Gradients in Stress Echocardiography: A Narrative Review.

This review aims to serve as a guide for clinical practice and to appraise the current knowledge on exercise stress echocardiography in the evaluation of intraventricular obstruction in HCM, in patients with cardiac syndrome X, in athletes with symptoms related to exercise, and in patients with normal left ventricular systolic function and exercise-related unexplained tiredness. The appearance of intraventricular obstruction while exercising is considered rare, and it usually occurs in patients with hypertrophy of the left ventricle. The occurrence of intraventricular obstruction when exercising has been evidenced in patients with hypertrophic cardiomyopathy, athletes, patients with cardiac syndrome X, patients with syncope or dizziness related to exercise, and patients with dyspnea and preserved ejection fraction. The clinical significance of this observation and the exercise modality that is most likely to trigger intraventricular obstruction remains unknown. Supine exercise and lying supine after exercise are less technically demanding, but they are also less physiologically demanding than upright exercise. Importantly, in everyday life, human beings generally do not become supine after exercise, as takes place in post-exercise treadmill stress echocardiograms in most echocardiography labs. The presence of induced intraventricular obstruction might be considered when patients have exercise-related symptoms that are not understood, and to assess prognosis in hypertrophic cardiomyopathy.

Takotsubo cardiomyopathy prevalence and associated factors in patients presenting with a clinical picture of acute myocardial infarction in Palestine

BackgroundTakotsubo cardiomyopathy (TC) is a transient cardiac syndrome that manifests with symptoms resembling acute myocardial infarction (MI). It is characterized by temporary wall-motion abnormalities predominantly affecting the apical and mid-portions of the left ventricle, despite the absence of significant obstructive coronary disease. TC poses diagnostic challenges due to its resemblance to ST-segment elevation myocardial infarction.Our study aimed to determine the prevalence of TC and identify the factors associated with its occurrence in patients presenting with acute MI in Palestine.ResultsA retrospective analysis was conducted on a cohort of patients diagnosed with TC at Al-Makassed hospital. Women accounted for 90.7% of TC cases (95% CI 88.2–93.2%). The mean age of affected individuals ranged from 62 to 76 years. The most common presenting symptoms were chest pain (83.4%, 95% CI 80.0–86.7%) and dyspnea (20.4%, 95% CI 16.3–24.5%), often following an emotionally or physically stressful event. Electrocardiography (ECG) on admission indicated ST-segment elevations in 71.1% of cases (95% CI 67.2–75.1%), accompanied by mild elevations of Troponins in 85.0% of cases (95% CI 80.8–89.1%). Despite the initial severity, left ventricular ejection fraction (LVEF) improved from 20–49.9 to 59–76% within a mean time of 7–37 days. The in-hospital mortality rate was 1.7% (95% CI 0.5–2.8%), with complete recovery observed in 95.9% of cases (95% CI 93.8–98.1%) and rare recurrence. The underlying etiology is believed to involve exaggerated sympathetic stimulation.ConclusionsTC should be considered as a significant differential diagnosis in acute coronary syndrome (ACS) cases, particularly among postmenopausal women with a preceding stressful event. Our study provides insights into the prevalence and characteristics of TC in the Palestinian population. While stress has been recognized as a potential trigger for TC, further research is needed to explore if there are specific associations between occupation and other unique stressors in the Palestinian context and the prevalence of TC. The study’s results can raise awareness among healthcare professionals in Palestine about the prevalence and characteristics of TC in their patient population.

Integrated Approach Including Docking, MD Simulations, and Network Analysis Highlights the Action Mechanism of the Cardiac hERG Activator RPR260243.

hERG is a voltage-gated potassium channel involved in the heart contraction whose defections are associated with the cardiac arrhythmia Long QT Syndrome type 2. The activator RPR260243 (RPR) represents a possible candidate to pharmacologically treat LQTS2 because it enhances the opening of the channel. However, the molecular detail of its action mechanism remains quite elusive. Here, we address the problem using a combination of docking, molecular dynamics simulations, and network analysis. We show that the drug preferably binds at the interface between the voltage sensor and the pore, enhancing the canonical activation path and determining a whole-structure rearrangement of the channel that slightly impairs inactivation.

Characteristics of heart failure in the Amsterdam metropolitan area (AMSTERDAM-HF): Data from a dynamic general practice cohort (2011−2021)

BackgroundHeart failure (HF) is a common cardiac syndrome with a high disease burden and poor prognosis in our aging populations. Understanding the characteristics of patients with newly diagnosed HF is essential for improving care and outcomes. The AMSTERDAM-HF study is aimed to examine the population characteristics of patients with incident HF. MethodsWe performed a retrospective dynamic cohort study in the Amsterdam general practice network consisting of 904,557 individuals. Incidence HF rates, geographical demographics, patient characteristics, risk factors, symptoms prior to HF diagnosis, and prognosis were reported. ResultsThe study identified 10,067 new cases of HF over 6,816,099 person-years. The median age of patients was 77 years (25th–75th percentile: 66–85), and 48% were male. The incidence rate of HF was 213.44 per 100,000 patient-years, and was higher in male versus female patients (incidence rate ratio: 1.08, 95%-CI:1.04–1.13). Hypertension (men 46.3% and women 55.8%), coronary artery disease (men 36% and women 25%) and diabetes mellitus (men 30.5% and women 26.8%) were the most common risk factors. Dyspnoea and oedema were key reported symptoms prior to HF diagnosis. Survival rates at 10-year follow-up were poor, particularly in men (36.4%) compared to women (39.7%). Incidence rates, comorbidity burden and prognosis were worse in city districts with high ethnic diversity and low socio-economic position. ConclusionOur study provides insights into incident HF in a contemporary Western European, multi-ethnic, urban population. It highlights notable sex, age, and geographical differences in incidence rates, risk factors, symptoms and prognosis.

Structure-function relationship of new peptides activating human Nav1.1

Nav1.1 is an important pharmacological target as this voltage-gated sodium channel is involved in neurological and cardiac syndromes. Channel activators are actively sought to try to compensate for haploinsufficiency in several of these pathologies. Herein we used a natural source of new peptide compounds active on ion channels and screened for drugs capable to inhibit channel inactivation as a way to compensate for decreased channel function. We discovered that JzTx-34 is highly active on Nav1.1 and subsequently performed a full structure-activity relationship investigation to identify its pharmacophore. These experiments will help interpret the mechanism of action of this and formerly identified peptides as well as the future identification of new peptides. We also reveal structural determinants that make natural ICK peptides active against Nav1.1 challenging to synthesize. Altogether, the knowledge gained by this study will help facilitate the discovery and development of new compounds active on this critical ion channel target.

Long QT syndrome-associated calmodulin variants disrupt the activity of the slowly activating delayed rectifier potassium channel.

Calmodulin (CaM) is a highly conserved mediator of calcium (Ca2+ )-dependent signalling and modulates various cardiac ion channels. Genotyping has revealed several CaM mutations associated with long QT syndrome (LQTS). LQTS patients display prolonged ventricular recovery times (QT interval), increasing their risk of incurring life-threatening arrhythmic events. Loss-of-function mutations to Kv7.1 (which drives the slow delayed rectifier potassium current, IKs, a key ventricular repolarising current) are the largest contributor to congenital LQTS (>50% of cases). CaM modulates Kv7.1 to produce a Ca2+ -sensitive IKs, but little is known about the consequences of LQTS-associated CaM mutations on Kv7.1 function. Here, we present novel data characterising the biophysical and modulatory properties of three LQTS-associated CaM variants (D95V, N97I and D131H). We showed that mutations induced structural alterations in CaM and reduced affinity for Kv7.1, when compared with wild-type (WT). Using HEK293T cells expressing Kv7.1 channel subunits (KCNQ1/KCNE1) and patch-clamp electrophysiology, we demonstrated that LQTS-associated CaM variants reduced current density at systolic Ca2+ concentrations (1μm), revealing a direct QT-prolonging modulatory effect. Our data highlight for the first time that LQTS-associated perturbations to CaM's structure impede complex formation with Kv7.1 and subsequently result in reduced IKs. This provides a novel mechanistic insight into how the perturbed structure-function relationship of CaM variants contributes to the LQTS phenotype. KEY POINTS: Calmodulin (CaM) is a ubiquitous, highly conserved calcium (Ca2+ ) sensor playing a key role in cardiac muscle contraction. Genotyping has revealed several CaM mutations associated with long QT syndrome (LQTS), a life-threatening cardiac arrhythmia syndrome. LQTS-associated CaM variants (D95V, N97I and D131H) induced structural alterations, altered binding to Kv7.1 and reduced IKs. Our data provide a novel mechanistic insight into how the perturbed structure-function relationship of CaM variants contributes to the LQTS phenotype.

Development of a person-centred digital platform for the long-term support of people living with an adult-onset genetic disease predisposition: a mixed-methods study protocol

IntroductionIndividuals at an inherited high-risk of developing adult-onset disease, such as breast cancer, are rare in the population. These individuals require lifelong clinical, psychological and reproductive assistance. After a positive...

#2567 ASSOCIATION OF IMBALANCE OF MYOCARDIAL OXYGEN SUPPLY/DEMAND WITH MYOCARDIAL INJURY IN END STAGE KIDNEY DISEASE PATIENTS

Abstract Background and Aims It is well known that oxygen transport ability is impaired in patients with anemia, low hemoglobin (Hb) level, whereas the double product (DP, bpm*mmHg), consisting of the systolic blood pressure (SBP) multiplied by the heart rate (HR), is an index of myocardial oxygen consumption. The combination of these two markers could be a potential marker for balance of myocardial oxygen supply and demand. Therefore, we hypothesized that the balance of these two markers may lead to myocardial damage in end-stage kidney disease (ESKD) patients who is susceptible to vulnerable heart in oxygen balance. The purpose of this study is to examine the association of balance of DP and Hb with myocardial injury in ESKD patients. Method A single-center, cross-sectional study has conducted. From December 2010 to November 2021, 327 consecutive ESKD patients started maintenance hemodialysis (HD). Among them, 44 patients met the exclusion criteria as follows: (1) missing data of cardiac troponin T (cTnT); (2) complicating acute cardiac syndrome; (3) death during hospitalization for HD initiation, a total of 283 ESKD patients were enrolled into the study finally. The patients were divided four groups according to the high or low of Hb level of 9 g/dL and DP 12500, a median of our patients, and named low-DP/high-Hb; G1, low-DP/low-Hb; G2, high-DP/high-Hb; G3, and high-DP/low-Hb; G4. The patients with G1 group were defined as a well oxygen balanced group, whereas those with G4 was defined as an imbalance of oxygen supply and demand group. Based on the results of previous study, cTnT cut off for myocardial injury was serum cTnT ≧0.15 ng/mL. Odds ratio (OR) for myocardial injury was calculated in each group compared with well oxygen balanced group by logistic regression analysis. Results Median age was 72 years, 71% of them were male, 52.6% had diabetes. Mean Hb level was 9.09 ± 1.61, and median DP was 12144 (25% tile 10540, 75% tile 14688). Median cTnT was 0.083 (25% tile 0.057 and 75% tile 0.13), and 20.4% of patients were defined as suffering from myocardial injury latently. In the adjusted model, the odds for myocardial injury was significantly increasing in high-DP compared with low-DP (OR: 1.87, p = 0.049), while low-Hb did not show significant increment of odds for myocardial injury compared with high-Hb. As shown in the Table 1, compared to well-balanced group (G1), OR increased by exposing only high-DP (G3), however it was not statistically significant (OR 1.20, p = 0.68). Interestingly, by exposing with high-DP with low-Hb simultaneously (G4), synergistic increased OR was found compared with well-balanced (G1) group (OR 3.07, 95%CI 1.24-7.62, p = 0.015). Furthermore, these associations were enhanced and weakened if Hb cut-off level became to be lower (Hb 8 g/dL) and higher (Hb 10 g/dL), as shown in Tables 2, 3. Conclusion Imbalance of oxygen supply (Hb) and demand (DP) was associated with myocardial injury in incident HD patients. Appropriate control of anemia, SBP and HR may have possibility to prevent myocardial injury. Especially we need to pay attention more to the Hb level if BP and HR control is insufficient. Tables 1, 2, 3. Odds ratio for cTnT≧0.15 in four groups divided by DP and Hb (adjusted for age, male, CRP, albumin, diabetes mellitus).

HEART Score Recalibration Using Higher Sensitivity Troponin T

We examined the diagnostic performance of a recalibrated History, Electrocardiogram, Age, Risk factors, Troponin (HEART), and Thrombolysis in Myocardial Infarction (TIMI) score in patients with suspected acute cardiac syndrome (ACS). Recalibration of troponin thresholds was performed, including shifting from the 99th percentile to the limit of detection (LOD) or to the limit of quantification (LOQ) We compared the discharge potential and safety of the recalibrated composite scores using a single presentation high-sensitivity cardiac troponin (hs-cTn) T to the conventional scores and with a LOD/LOQ troponin strategy alone. We undertook a 2-center prospective cohort study in the United Kingdom (UK) (2018) (Clinicaltrials.gov NCT03619733) to specifically assess recalibrated risk scores (shifting the troponin subset scoring from 99th percentile to LOD [UK]) and combined the results of this with secondary analyses of 2 prospective cohort studies in the UK (2011) and the United States (2018, using LOQ rather than LOD). The primary outcome was major adverse cardiovascular events (MACE), defined as adjudicated type 1 myocardial infarction (MI), urgent coronary revascularization, and all-cause death, at 30 days. We evaluated the original scores using hs-cTn below the 99th percentile and recalibrated scores using hs-cTn <LOD/LOQ and compared these composite scores with a single hs-cTnT less than LOD/LOQ combined with a nonischemic ECG. For each discharge strategy, an assessment of clinical effectiveness was also made, defined as the proportion of patients eligible for discharge from the emergency department without the need for further inpatient testing. We studied 3,752 patients (3,003 in the UK and 749 in the United States). Median age was 58 years, and 48% were female. At 30 days, 330/3,752 (8.8%) experienced MACE. The sensitivities of the original HEART less or equal to 3 and recalibrated HEART less or equal to 3 scores for rule-out were 96.1% (95% confidence interval [CI], 93.4 to 97.9) and 98.6% (95% CI, 96.5 to 99.5) respectively; the original TIMI less or equal to 1 and recalibrated TIMI less or equal to 1 scores' sensitivities were 79.7% (95% CI, 74.9 to 83.9) and 96.1% (95% CI, 93.4 to 97.9) respectively; and nonischemic ECG with hs-cTn T below the 99th percentile and hs-cTn T less than LOD/LOQ was 79.7% (95%CI, 0.749 to 0.839) and 99.1% (95% CI, 0.974 to 0.998), respectively. Recalibrated HEART less or equal to 3 was projected to discharge 14% more patients than hs-cTn T less than LOD/LOQ. The improved sensitivity ofrule-out for recalibrated HEART less than or equal to 3 came at the cost of reduced specificity (50.8% versus 53.8% for recalibrated HEART and conventional HEART respectively). This study indicates that recalibrated HEART score of less or equal to 3 is a feasible and safe early discharge strategy using a single presentation hs-cTnT. This finding should be further tested using competitor hs-cTn assays in independent prospective cohorts before implementation.

Factors influencing heart failure in adult patients

The work presented allows the analysis and determination of the main factors that affect heart failure. Considering that this disease is a syndrome that is increasing and increasingly affects younger people, while, in older patients, it can cause mortality. For the study, a deductive–analytical method was used, establishing as binding factors functional class III according to the NYHA scale, which is Diabetes Mellitus as comorbidity, dyslipidemia, deterioration of glomerular filtration rate, and arrhythmias. In addition, fewer patients with readmissions and decreased ejection fraction were found. Finally, it is possible to affirm that cardiac syndrome increasingly affects people’s health without age discrimination, which makes it necessary to promote a healthy lifestyle and periodic reviews in work environments.

Post-cardiac injury syndrome occurred two months after permanent dual-chamber pacemaker implantation

BackgroundPost cardiac injury syndrome (PCIS) is characterized by the development of pericarditis with or without pericardial effusion due to a recent cardiac injury. The relatively low incidence makes diagnosis of PCIS after implantation of a pacemaker easily be overlooked or underestimated. This report describes one typical case of PCIS.Case presentationWe present a case report of a 94-year-old male with a history of sick sinus syndrome managed with a dual-chamber pacemaker who presented with PCIS after two months of pacemaker implantation. He gradually developed chest discomfort, weakness, tachycardia and paroxysmal nocturnal dyspnea and cardiac tamponade after two months of pacemaker. Post-cardiac injury syndrome related to dual-chamber pacemaker implantation was considered based on exclusion of other possible causes of pericarditis. His therapy was drainage of pericardial fluid and managed with a combination of colchicine and support therapy. He was placed on long-term colchicine therapy to prevent any recurrences.ConclusionThis case illustrated that PCIS can occur after minor myocardial injury, and that the possibility of PCIS should be considered if there is a history of possible cardiac insult.

C70 WEARABLE CARDIOVERTER DEFIBRILLATOR IN LONG QT SYNDROME DURING PREGNANCY: TIME TO USE THE SHIELD

Abstract Introduction Long QT Syndrome (LQTS) is a rare cardiac channelopathy characterized by a high risk of lethal arrhythmias. Pregnancy and post–partum period may induce an increased vulnerability, so an appropriate prevention is needed. Case presentation A 31–year–old primigravid woman at 36 weeks of pregnancy was referred to our Cardiomyopathy Unit located in a tertiary centre for LQTS screening. The patient had a family history of LQTS (mother and brother) and Brugada syndrome (cousin). The 12–lead ECG (Figure 1) showed a long QT interval (QT corrected: 508 msec), while the transthoracic echocardiogram was unremarkable. The genetic test performed is still ongoing. The patient reported sporadic episodes of palpitations at rest and the following 24–hour ambulatory ECG revealed a very high burden of polymorphic ventricular arrhythmias, with about sixteen thousand premature ventricular complexes and a non–sustained ventricular tachycardia. Therefore, due to the patient’s high–risk for life–threatening arrhythmic events, metoprolol 25 mg o.d. was initiated and a wearable cardioverter defibrillator (WCD) with remote monitoring was provided during pregnancy and labour. After 3 weeks a caesarean delivery in epidural analgesia was performed and managed by a pregnancy heart team including a cardiologist, gynaecologist, obstetrician, and anaesthetist in close cardiac monitoring. No maternal or infant complications occurred, without arrhythmic episodes detected by the device. The WCD will be maintained also in the post–partum period with a narrow follow–up of the patient. Discussion In pregnant high–risk LQTS patients, beta–blockers are the first line therapeutic option, but they do not able to interrupt lethal arrythmias in out–of–hospital setting. The implantable cardiac defibrillator is not the best choice, due to the concerns about radiation exposure and anaesthesia during pregnancy. Moreover, lead–associated thrombosis and infections during pregnancy were reported in literature. The WCD is the ideal option in these cases. It is an external device suited for transient higher arrhythmic risk periods. Moreover, it allows a remote monitoring of arrhythmic burden (figure 2) which may help clinicians in guiding the follow–up and the therapeutic management of the patient. One drawback is the need of continuous patient’s compliance. Finally, a pregnancy heart team is mandatory in presence of these rare cardiac syndromes.

Evaluating the pure effect of weight on cardiac function in patients with cardiac syndrome X.

Obese patients have more coronary artery disease (CAD) risk factors that may affect myocardial function. We aimed to assess the ability of echocardiography-derived conventional parameters, left atrial strain, and global longitudinal strain to detect early diastolic and systolic dysfunction in obese individuals with almost no CAD risk factors. We studied 100 participants with structurally normal hearts, ejection fractions above 50%, almost normal coronary arteries in coronary angiogram (syndrome X), and no cardiovascular risk factor except dyslipidemia. Participants were classified as normal-weight (BMI<25.0kg/m2 , n=28) and high-weight (BMI≥25.0kg/m2 , n=72). Conventional echocardiographic parameters and two-dimensional speckle tracking (2DSTE) were used to measure peak LA strain and global longitudinal strain to evaluate diastolic and systolic function, respectively. There was no significant difference in the standard and conventional echocardiographic parameters between the two groups. 2DSTE echocardiographic parameters of the longitudinal deformation of the LV myocardium were not significantly different within the two groups. However, there were significant differences between the subjects with normal-weight and high-weight in terms of LA strain (34.51±8.98% vs. 39.06±8.62%, p=.021). The normal-weight group had lower LA strain, in compression with the high-weight group. All echocardiographic parameters were in the normal range. In the present study we demonstrated that global longitudinal subendocardial deformations, for the evaluation of systolic function, and conventional echocardiographic parameters, for the evaluation of diastolic function, were not significantly different between normal- and high-weight groups. Although LA strain was higher among overweight patients, it was not above the normal range of diastolic dysfunction.

Successful catheter ablation of the accessory pathway in an unusual location in a 13-year-old girl with a coronary sinus diverticulum and Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White syndrome is a congenital cardiac pre-excitation syndrome that is effectively treated by ablating the accessory pathway. However, accessory pathways located in the posteroseptal region can sometimes be challenging. In this paper, we present the successful ablation of the epicardial posteroseptal accessory pathway through the middle cardiac vein in a 13-year-old girl with a coronary sinus diverticulum and Wolff-Parkinson-White syndrome, after unsuccessful ablation attempts at different locations. If the ablation procedure fails, the possibility of the posteroseptal pathway should be kept in mind, and coronary sinus angiography should be performed. In cases with a coronary sinus diverticulum where ablation is not successful, other coronary sinus structures, for example, the middle cardiac vein should be considered as potential accessory pathways.

Cardiac Autonomic Regulation and Metabolic Syndrome: Clinical Use of A Unitary Autonomic Nervous System Index

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Non-invasive Evaluation of Coronary Flow Reserve in Cardiac Syndrome X Patients.

Non-invasive Evaluation of Coronary Flow Reserve in Cardiac Syndrome X Patients.

A Cross-Sectional Study of the Neuropsychiatric Phenotype of CACNA1C-Related Disorder (P11-9.004)

<h3>Objective:</h3> To investigate the full neurologic, psychiatric, and developmental phenotypic spectrum of individuals with <i>CACNA1C</i>-related disorder. <h3>Background:</h3> <i>CACNA1C</i> encodes the voltage gated L-type Ca_V1.2 calcium channel. A specific gain of function pathogenic variant in <i>CACNA1C</i> causes Timothy syndrome type 1 (TS1) with multi-system involvement including cardiac long QT syndrome, syndactyly, and neuropsychiatric symptoms. We found that the TS1 variant alters neuronal activity-dependent signaling and interneuron migration. The broader spectrum of <i>CACNA1C</i>-related disorder (CRD) includes isolated cardiac disease, isolated neurologic deficits, and TS, but it is unknown how the clinical presentation of CRD variants other than TS relate to neural defects. We surveyed individuals with CRD to define the neuropsychiatric and developmental phenotype to guide future research into the role of calcium channels in neural development. <h3>Design/Methods:</h3> Caregivers of and individuals with CRD completed an online survey of pre- and perinatal events, cardiac events, developmental milestones, neuropsychiatric symptoms, and neuropsychiatric diagnoses. Multiple Mann-Whitney tests were used for comparison of categorical values and Fisher’s exact test for comparison of categorical variables between participants with and without LQTS. <h3>Results:</h3> Twenty-four participants with germline <i>CACNA1C</i> variants completed the survey. The most common neuropsychiatric symptoms and/or diagnoses were developmental delay in 92%, incoordination in 71%, hypotonia in 67%, autism spectrum disorder in 50% (autistic features in 92%), seizures in 37.5%, and attention deficit hyperactivity disorder in 21% of participants. There were no significant differences in symptoms between participants with and without LQTS. <h3>Conclusions:</h3> In our CRD cohort there was an increased prevalence of multiple neuropsychiatric symptoms compared with the general population. These findings indicate the key role of Ca_V1.2 in brain development and the clinical importance of screening and treating neuropsychiatric symptoms in all individuals with CRD. Future directions include deep phenotyping of neuropsychiatric symptoms and efforts to relate these symptoms to specific cellular defects. <b>Disclosure:</b> Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tome. Mrs. Timothy has nothing to disclose. Dr. Underwood has received personal compensation for serving as an employee of Akrivia Health. Dr. Underwood has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for HM Courts and Tribunal Service. The institution of Dr. Underwood has received research support from the Wellcome Trust. Prof. Hall has stock in meomics. The institution of Prof. Hall has received research support from takeda. Dr. Bernstein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CHANGE HEALTHCARE. The institution of Dr. Bernstein has received research support from NIH. Prof. Pasca has received intellectual property interests from a discovery or technology relating to health care.