History Of Dilated Cardiomyopathy Research Articles

Pulsed field ablation-based superior vena cava isolation in the presence of defibrillator leads

Abstract Introduction Only a minority of operators in the MANIFEST-PF multinational survey performed superior vena cava isolation by means of pulsed field ablation (PFA). This is the first report of off-label PFA-mediated superior vena cava isolation in the presence of defibrillator leads. Purpose Aim of this study was to evaluate the effect of PFA applications in the superior vena cava in the terms of alterations in pacing, sensing, or impedance parameters, inappropriate anti-tachycardia pacing, ICD shock and leads dislodgment. Methods Five patients with a history of dilated cardiomyopathy, dual chamber defibrillator implantation, and worsening heart failure because of persistent atrial fibrillation (AF) underwent catheter ablation of AF. Three of the patients had dual coil defibrillator leads. PFA was selected for the index procedure in these decompensated heart failure patients with enlarged atria focusing beyond pulmonary vein isolation in posterior wall and roof ablation as well as in superior vena cava isolation. Results Basket configuration and two sets of two lesions at the trunk of the vessel (with rotation between each pair) were used for superior vena cava isolation in the presence of atrial and defibrillator leads, without any impact on device and leads measurements or sinus node function. All patients were in AF and cardioverted into sinus rhythm post- superior vena cava isolation. They remained at sinus rhythm at regular 3-month follow-up while device interrogation revealed intact sinus node function. Conclusion PFA applications in the superior vena cava of AF patients with implanted defibrillators confirmed that it is a safe and feasible method regardless of energy application adjacent to the leads.

Management of incessant ventricular arrhythmias in a patient with left ventricular assist device: a case report

BackgroundThe implantation of left ventricular assist devices (LVADs) as a bridge to transplantation or as destination therapy in end-stage heart failure patients is frequently complicated by the emergence of ventricular arrhythmias (VAs). These arrhythmias have been implicated in precipitating deleterious clinical outcomes, increased mortality rates and augmented healthcare expenditures.Case PresentationWe present a challenging case of a 49-year-old male with a history of dilated cardiomyopathy who received an LVAD. Post-implantation, the patient suffered from intractable VAs, leading to multiple rehospitalizations and hemodynamic deterioration. Despite exhaustive medical management and electrical cardioversion attempts, the patient’s VAs persisted, ultimately necessitating prioritization for cardiac transplantation.DiscussionThis case highlights the challenges in managing VAs in LVAD patients and the importance of multidisciplinary collaboration. While pharmacological intervention is the initial strategy, catheter ablation may be considered in selected cases when medication is insufficient. In instances of intractable VAs, expeditious listing for heart transplantation as a high-priority candidate is advisable when feasible.

Superior vena cava isolation with pulsed field ablation in the presence of defibrillator leads.

Two patients with a history of dilated cardiomyopathy, dual chamber defibrillator implantation, and worsening heart failure because of persistent atrial fibrillation (AF) underwent catheter ablation of AF. Pulsed field ablation (PFA) was selected for the index procedure in these decompensated heart failure patients with enlarged atria.1 The 12-Fr over-the-wire pentaspline PFA catheter (Farawave) was advanced through a 13-Fr steerable sheath (Faradrive) to the ostium of each PV, and a total of eight PFA lesions were applied per vein. Phrenic nerve function was evaluated by direct phrenic capture and by observing diaphragmatic motion during inspiration. For posterior wall ablation, the catheter was placed into a flower configuration and positioned along the posterior left atrium to deliver overlapping sets of pulses at each location. As per institution protocol, superior vena cava (SVC), as a potential nonpulmonary trigger for AF, is isolated when active despite a risk of sinus node injury.2 Basket configuration (Figure 1) and two sets of two lesions at the trunk of the vessel (with rotation between each pair) were used for SVC isolation in the presence of atrial and defibrillator leads, without any impact on device and leads measurements or sinus node function (Figure 2). We observed incidence of phrenic capture during PFA, and no evidence of phrenic injury was detected after the procedure. Both patients were in AF and cardioverted into sinus rhythm post-SVC isolation. They remained at sinus rhythm at regular 3-month follow-up while device interrogation revealed intact sinus node function. Only 4.2% of operators in the MANIFEST-PF multinational survey (including 1758 consecutive unselected AF patients) performed SVC isolation by mean of PFA occasionally.3 This is the first report of off-label pulsed field ablation-mediated SVC isolation without device or lead malfunction. Human studies evaluating cardiac implantable electrical devices during ablation procedure remain limited. A recent study by a high-volume center indicated that PFA is a safe and feasible method in patients with devices in the terms of alterations in pacing, sensing, or impedance parameters, inappropriate anti-tachycardia pacing, and ICD shock and leads dislodgment.4 Indeed, our pilot procedures with PFA applications in the SVC of AF patients with implanted devices confirmed the previous results without apparent additional risk because of energy application adjacent to the electrodes. None declared. None. The authors declare no conflict of interests for this article. Approval of the research protocol: N/A. Informed Consent: Ν/Α. Registry and the Registration No. of the study/trial: N/A. Animal Studies: N/A. Data are available in the article.

Wide QRS Complexes Following Ablation for Reentrant Tachycardia

Scenario: A 25-year-old man was referred from a cardiology clinic for an acute exacerbation of supraventricular tachycardia (SVT) during an exercise stress echocardiogram. He has a history of dilated cardiomyopathy (50% left ventricular ejection fraction [LVEF]), wall motion abnormalities, and long QT syndrome. In the clinic before admission, an SVT event was captured during an electrocardiogram (ECG) recording and resolved with a carotid sinus massage. The patient was fully conscious during the event. A few days later, he underwent an electrophysiology (EP) study with radio frequency ablation for atrioventricular reentrant tachycardia (AVRT). He was transferred to the cardiac step-down unit after the EP procedure, and his blood pressure was 94/56 mm Hg, heart rate 87/min, respiratory rate 21/min (regular), oxygen saturation 94% via room air, and body temperature 37 °C (99 °F). The 12-lead ECG below was taken 6 hours after admission to the unit.Normal sinus rhythm, frequent premature ventricular complexes (PVCs) in a quadrigeminy pattern, prolonged QTc interval.Generally, wide QRS complexes (>120 milliseconds) represent electrical activity that originates from the ventricles. Exceptions are aberrantly conducted supraventricular beats, preexcitation associated with an accessory pathway, bundle branch block, and electrolyte imbalance. Given the AVRT diagnosis with recent ablation treatment, these PVCs may be mistaken for preexcitations associated with an accessory pathway, especially as the PVC QRSs appear slurred (ie, “pseudo” delta wave), a characteristic associated with an accessory pathway. However, some features support PVC as the cause. First, the wide QRS complexes are premature, albeit only slightly at first glance. However, if calipers are used, or even on careful visual inspection, one can appreciate that these beats are indeed premature. In this case, the P waves fall just before the PVC but should not be confused with a delta wave. Furthermore, there is a complete compensatory pause after the PVCs because the timing of the sinus node is not interrupted. In contrast, a supraventricular beat (eg, aberrancy, premature atrial complex) would typically have a P wave before the QRS complex, and one would see an incomplete pause because these beats usually enter the sinus node and reset its timing.PVCs can be monomorphic, as in this case, or polymorphic (multiple QRS morphologies). Interestingly, the morphology of the PVC can be used to determine the ventricle of origin (ie, left or right) by examining lead V1. In this example, the morphology resembles a left bundle branch block (ie, negative wide QRS complex). This pattern indicates that the ectopic impulse is moving away from lead V1 and travels toward the left ventricle (ie, deep S wave). The QRS complex is wide because the ventricular impulse travels slowly from the right ventricle, outside the normal conduction system, to the left ventricle, slowing depolarization.Premature beats, including PVCs, can trigger reentrant tachyarrhythmias when an accessory pathway is present. Although PVCs were not documented as the source of the AVRT events in this patient, they are a likely source. This patient’s history of cardiomyopathy may be contributing to the occurrence of PVCs, which may also need to be treated with ablation. Considering that this patient has a prolonged QTc and other significant risk factors (postablation, AVRT, cardiomyopathy, and reduced EF), medications that prolong the QT/QTc should be closely reviewed and adjusted if necessary to prevent torsades de pointes. This patient was discharged home and was followed up by outpatient cardiology.

Peak oxygen consumption is associated with the inotropic reserve in patients with heart failure with reduced ejection fraction undergoing cardiopulmonary testing

Abstract Background The role of cardiopulmonary exercise testing (CPET) in the prognostic evaluation of heart failure with reduced ejection fraction (HFrEF) is powerful and well-established. Nevertheless, the value of CPET in predicting left ventricular inotropic reserve in HFrEF remains unknown. Purpose The investigation of possible associations between CPET variables and left ventricular contractile reserve in patients with HFrEF. Methods Consecutive patients aged ≥18 years old with a diagnosis of heart failure and a left ventricular ejection fraction ≤40%, as assessed by echocardiography, were prospectively enrolled. Demographic and clinical data were recorded. All subject underwent CPET with either a Bruce or a modified Bruce protocol. Peak oxygen consumption (VO2), carbondioxide production (VCO2), minute ventilation to carbon dioxide production (VE/VCO2) slope, minute ventilation (VE), and VO2/heart rate (HR) values were calculated, while hemodynamic parameters during the test were also measured. Results In total, 191 patients with HFrEF were included in the analysis. The mean age was 58.8±11.8 years and 30 (15.7%) patients were women. Ischemic heart disease was the etiology of HFrEF in 101 (52.9%) patients, whereas 90 (47.1%) patients had a history of dilated cardiomyopathy. The mean exercise time was 7.6±.3 minutes. Mean peak VO2 and VE/VCO2 slope values were calculated at 19.1±6.1 ml kg–1 min–1 and 43.7±10.1, respectively. According to peak VO2 values, 70 patients (37.2%) were in Weber class A, 57 (29.8%) in class B, 48 (25.1%) in class C and 15 (7.9%) in class D. In univariate analysis, the change between rest and peak systolic blood pressure (ΔSBP), which is considered to reflect the left ventricular inotropic reserve, was positively correlated to the peak VO2 (p<0.001), the total pulmonary ventilation (VE) (p<0.001) and the peak heart rate during exercise (p=0.02). In multivariable analysis, peak VO2 was independently, linearly associated with the ΔSBP during CPET (Figure 1) (β=0.661, p=0.022). In Roc analysis, it was found that a cut-off value for peak VO2 of 16 ml kg–1 min–1 exhibits 64% sensitivity and 60% specificity in predicting a ΔSBP>40mmHg during exercise (area under the curve: 0.657, p<0.001 – Figure 2). Conclusion The peak oxygen consumption during cardiopulmonary testing represents an acceptable predictor of inotropic reserve in patients with HFrEF. Funding Acknowledgement Type of funding sources: None.

Familial Dilated Cardiomyopathy and Sudden Cardiac Arrest: New Association with a SCN5A Mutation.

Dilated cardiomyopathy (DCM) has significant morbidity and mortality. Familial transmission is reported in 20–35% of cases, highlighting the role of genetics in this disorder. We present an interesting family in which the index case is a 64-year-old woman who survived a sudden cardiac arrest. She presented left ventricular dilatation and dysfunction, which indicated the presence of DCM, as well as a history of DCM and sudden arrest in her family (mother and sister). Genetic testing identified a heterozygous mutation c.74A > G missense change that causes an amino acid, p.Glu25Gly, change in the N-terminal domain of the SCN5A protein. After performing an exhaustive family medical history, we found that this previously not described mutation segregated within the family. All relatives with the DCM phenotype were carriers, whereas none of the noncarriers showed signs of heart disease, so this mutation is the most likely cause of the disease. This is the first time that a variant in the N-terminal domain of SCN5A has been associated with DCM.

ECG wearable rhythm monitoring in covid-19 patients

Funding AcknowledgementsType of funding sources: None.BackgroundWearable monitors and external smart-phone enabled devices represent the new era in remote patient management during covid-19 pandemy. There is growing evidence showing that arrhythmias are one of the major complications of SARS-CoV-2 infection especially in high risk group of patients. MethodsWe enrolled 34consecutive patients with confirmed diagnosis of SARS-CoV-2 (mean age62.45 ± 5.25years, 16male). Remote wireless rhythm monitoring was performed using portative ECG sensor.Average follow-up period was 21 days during in-hospital stage and 2 months after discharge.ResultsAmong hospitalized patients with verified SARS-CoV-2 some presented different arrhytmias before admission (9 patients had atrial fibrillation and 11 patients had history of ventricular extrasystoles and non-sustained ventricular tachycardia). One patient underwent cardiac transplantation 1.5 years ago (female 38 years old with a history of dilated cardiomyopathy) and one patient had implanted CRTD device as primary prevention (male 54 years old with a history of myocardial infarction and low LVEF 28%). Other 12 patients did not experience any cardiac arrhythmias before admission. During monitoring period one patient demonstrated asymptomatic pauses longer than 6 seconds (Figure 1) revealed by portative device. After 2 months of follow up he continued to have hemodinamycally significant rhythm pauses and underwent pacemaker implantation. One patient had spontaneus AF conversion into sinus rhythm (Figure 2) also confirmed by wireless monitoring. Other patients did not demonstrate clinically significant arrhythmias. The duration of QT interval was also monitored during in-hospital period in all patients, average score was 451 ± 12 msec.ConclusionsUsing of wearable electronic devices may contribute to better monitoring of the state of patients and control of symptoms. Figure. Hemodynamically significant rhythm pause

COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

Abstract 251: Modeling LMNA Associated Cardiomyopathy Using Patient-Specific Human Induced Pluripotent Stem Cells

Mutations in LMNA are the most prevalent cause of dilated cardiomyopathy (DCM), accounting for up to 5-10% all the familial DCM. LMNA encodes the lamin A/C proteins which form filamentous structures that underline nuclear envelop. Sudden cardiac death and arrhythmia are common in patients with LMNA mutations. Despite recent advancement in the field, still the exact mechanism that link the mutation in LMNA to the formation of DCM and arrythmia is still largely unknown. In this study, we have generated an in vitro model of LMNA associated DCM using patient specific human induced pluripotent stem cells (hiPSCs). A family with pathogenic deletion in LMNA gene (c. 1142-1157 + 1del17) and history of DCM were selected. hiPSCs were generated from 4 affected individuals in the family and 5 healthy individuals. hiPSCs were then directly differentiated into cardiomyocytes and assessed at day 30 post differentiation. Cardiomyocytes derived from LMNA variant patients showed significantly higher level of nuclear deformation compared to control group. Moreover, after 2 days of mechanical stress cardiomyocytes derived from LMNA variant patients showed significantly higher level of nuclear dysmorphism while the control group were not affected. Field potential analysis of cardiomyocytes derived from LMNA patients compared to controls using multielectrode array revealed significantly higher beat rate irregularity in LMNA variant group which was consistent with the clinical symptoms of the patients. Furthermore, calcium transient of the cardiomyocytes derived from LMNA variant patients were significantly different from control group. Finally, patch clamp analysis also proved our previous findings and showed electrophysiological abnormalities in patients’ cells. In summary our finding thus far shows significant electrophysiological differences between cardiomyocytes derived from LMNA variant patients and control group which could help to unravel the cellular mechanism underlying formation of arrhythmia in LMNA variant patients.

Genetic Testing Outcomes in Pediatric Dilated Cardiomyopathy

Purpose Dilated cardiomyopathy (DCM) is characterized by ventricular dilation and systolic dysfunction, with 25-50% familial inheritance and up to 40% transplant rate within 5 years of diagnosis. Genotype-phenotype correlation for pediatric DCM is poorly described. The objective was to identify genetic characteristics associated with earlier onset or severe phenotype. Methods Retrospective chart review of genotyped children with DCM at a tertiary pediatric center from 2007-2016. Variants were reclassified with updated population/ancestry frequency information and literature reports. Results We reviewed 111 children (55% male) with a mean age of 4.4 ± 6.1 years (range 0 to 17.6 years) at time of diagnosis of DCM. A family history of DCM was present in 30%. Cardiac death (defined as transplant or patient death) occurred in 48/111 (43%); 46 were transplanted, 2 died prior to transplant, and 6 died post-transplant. Forty children (36%) had at least one likely pathogenic/pathogenic (LP/P) variant; 45 (41%) had variants of uncertain significance (VUS), but no LP/P variants; and 26 (23%) had only benign variants or no variants identified. Sarcomeric/cytoskeletal genes accounted for 131/171 VUS/LP/P variants (77%). The average number of VUS/LP/P variants per patient was 1.5 ± 1.6. VUS/LP/P variants in TPM1, MYBPC3, and LAMA4 were more prevalent in patients who presented before age one year (13/61 vs. 1/50 p=0.003). Truncating and frameshift LP/P variants in TTN were all seen after the age of 13 (3/21 vs. 0/90, p=0.01). All children with MYH7 variants occurring between amino acid residues 1 and 600 presented with dilated cardiomyopathy with left ventricular non-compaction (LVNC), accounting for 6/12 cases with MYH7 variants. With respect to outcome, DSP and MYBPC3 variants occurred more frequently in patients with transplant or death (12/51 vs. 4/60, p=0.01). Conclusion Pediatric DCM is associated with a different pattern of genetic variation than described in adult studies. Sarcomeric/cytoskeletal gene variants were more common in this population, especially MYH7 missense variants. We provide four candidate genes that may be associated with early onset of disease and cardiac death (TPM1, MYBPC3, LAMA4, and DSP) and provide support for the association between domain-specific MYH7 variants and LVNC. We plan to expand to a multi-center study for further exploration of genotype-phenotype relationships in DCM.

Combinatorial interactions of genetic variants in human cardiomyopathy.

Dilated cardiomyopathy (DCM) is a leading cause of morbidity and mortality worldwide; yet how genetic variation and environmental factors impact DCM heritability remains unclear. Here, we report that compound genetic interactions between DNA sequence variants contribute to the complex heritability of DCM. By using genetic data from a large family with a history of DCM, we discovered that heterozygous sequence variants in the TROPOMYOSIN 1 (TPM1) and VINCULIN (VCL) genes cose-gregate in individuals affected by DCM. In vitro studies of patient-derived and isogenic human-pluripotent-stem-cell-derived cardio-myocytes that were genome-edited via CRISPR to create an allelic series of TPM1 and VCL variants revealed that cardiomyocytes with both TPM1 and VCL variants display reduced contractility and sarcomeres that are less organized. Analyses of mice genetically engineered to harbour these human TPM1 and VCL variants show that stress on the heart may also influence the variable penetrance and expressivity of DCM-associated genetic variants in vivo. We conclude that compound genetic variants can interact combinatorially to induce DCM, particularly when influenced by other disease-provoking stressors.

P3169Clinical characteristics and natural history of dilated cardiomyopathy due to BAG3 mutations

P3169Clinical characteristics and natural history of dilated cardiomyopathy due to BAG3 mutations

Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death

Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G>A(p.Arg173Gln)] and BAG3 [BAG3 c.785C>T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

Acute Abdominal Aortic Occlusion Managed With Covered Stents

A 60-year-old African-American woman with a history of dilated cardiomyopathy and permanent atrial fibrillation presented to the emergency department with acute onset of bilateral lower extremity pain and partial paralysis. History was notable for recent implantable cardioverter-defibrillator

A Rare Case of Left Ventricular Non-Compaction Cardiomyopathy

SESSION TITLE: Genetic Disorders SESSION TYPE: Case Report Slide PRESENTED ON: Saturday, April 16, 2016 at 02:15 PM - 03:45 PM INTRODUCTION: Left Ventricular Non-Compaction Cardiomyopathy (LVNCC) is a rare myocardial disorder which results from failure of left ventricle to compact in embryogenesis. It is characterized by a two-layered ventricular wall, an outer compacted epicardial layer and an inner non-compacted layer composed of prominent trabeculations and deep inter-trabecular recesses which communicate with LV cavity. CASE PRESENTATION: A 44 year old male with history of dilated cardiomyopathy s/p AICD presented to our ER with complaints of SOB, dry cough, and leg edema. Patient reportedly stopped taking his Lasix two weeks ago. Exam was significant for elevated JVD, mild crackles and pedal edema. Labs showed elevated troponin (0.41 ng/ml) and BNP (1771 pg/ml). Echocardiogram revealed severely decreased LV systolic function (EF <10%) with severely dilated LV cavity, severe diastolic dysfunction, prominent LV trabeculations, and deep inter-trabecular recesses communicating with the LV cavity, consistent with LVNCC (Fig. 1). Patient was initiated on diuretics and an aldosterone antagonist, added to his regimen of beta blocker and ACE inhibitor, started on IV heparin, and subsequently bridged to Coumadin for anti-coagulation for low EF. He was discharged in stable condition to follow up with advanced heart failure for Cardiac Transplant and LVAD evaluation. DISCUSSION: LVNCC was first reported in 1932 in association with other congenital cardiac abnormalities (1). It is a genetically heterogeneous disorder with familial and sporadic forms and can be linked to mutations in mitochondrial, cytoskeletal, Z-line, and sarcomeric proteins. Reported prevalence of LVNCC varies considerably and is estimated to be between 0.014 and 1.3%, however, the true prevalence is unknown as it is often unrecognized. Patients usually present with heart failure, ventricular arrhythmias or systemic embolic events. Echocardiography is the first line imaging modality and diagnostic criteria include end-systolic ratio of non-compacted layer/compacted layer >2 and evidence of blood flow in intertrabecular recesses from the LV cavity on Color Doppler Imaging, in the absence of other cardiac abnormalities. The Cardiac MRI may be used for confirmation of the diagnosis. Treatment consists of standard heart failure therapy, management of arrhythmias and consideration of oral anti-coagulation in high risk patients to prevent systemic embolic complications. Due to high familial recurrence, genetic testing of affected individuals and screening of first-degree family members is also recommended. CONCLUSIONS: Still considered a novel entity, LVNCC is getting increasingly recognized because of heightened awareness and improved cardiac imaging modalities and physicians should be aware of this rare cardiomyopathy. Reference #1: Bellet S, Gouley BA. Congenital heart disease with multiple cardiac anomalies: report of a case showing aortic atresia, fibrous scar in myocardium and embryonal sinusoidal remains, Am J Med Sci. 1932, 183:458-65. DISCLOSURE: The following authors have nothing to disclose: Jeffrey Le, Shelly Brejt, Sameer Chadha, Nadine Montemarano, Joshua Kerstein, Jacob Shani No Product/Research Disclosure Information

Radiotherapy and implanted cardioverter defibrillators

A number of studies have reported an increase in radiation sensitivity of pacemakers or implantable cardioverter defibrillators. The type, severity and extent of radiation damage to these devices depend on the total dose and rate. We report the case of a 70-year-old male patient with non-small cell lung cancer presenting as a sub-carinal paraesophageal lesion, and a history of dilated cardiomyopathy and cardioverter-defibrillator implantation. The decision of a multidisciplinary meeting was to keep the device in place and deliver radiotherapy using an intensity-modulated radiation therapy technique by means of helical tomotherapy. The radiotherapy was well tolerated and consistent device interrogation revealed no malfunction. Innovative irradiation techniques have made radiotherapy feasible despite the presence of technological sophistications of pacemakers and cardioverter defibrillators that have potentially changed the tolerance profiles.

Regular cannon wave

A 52-year-old male with history of dilated cardiomyopathy was admitted with progressive dizziness and worsening dyspnea. His blood pressure was 100/60 with a regular pulse of 70 per minute. Jugular vein wave showed a prominent pulse like regular cannon waves. Cannon wave occurs in conditions with atrioventricular dissociation and right atrial contraction against a closed tricuspid valve. Large A waves are associated with reduced right ventricular compliance or elevated right ventricular end-diastolic pressure.

Prevalence of Titin Truncating Variants in General Population.

BackgroundTruncating titin (TTN) mutations, especially in A-band region, represent the most common cause of dilated cardiomyopathy (DCM). Clinical interpretation of these variants can be challenging, as these variants are also present in reference populations. We carried out systematic analyses of TTN truncating variants (TTNtv) in publicly available reference populations, including, for the first time, data from Exome Aggregation Consortium (ExAC). The goal was to establish more accurate estimate of prevalence of different TTNtv to allow better clinical interpretation of these findings.Methods and ResultsUsing data from 1000 Genomes Project, Exome Sequencing Project (ESP) and ExAC, we estimated the prevalence of TTNtv in the population. In the three population datasets, 52–54% of TTNtv were not affecting all TTN transcripts. The frequency of truncations affecting all transcripts in ExAC was 0.36% (0.32% - 0.41%, 95% CI) and 0.19% (0.16% - 0.23%, 95% CI) for those affecting the A-band. In the A-band region, the prevalences of frameshift, nonsense and essential splice site variants were 0.057%, 0.090%, and 0.047% respectively. Cga/Tga (arginine/nonsense–R/*) transitional change at CpG mutation hotspots was the most frequent type of TTN nonsense mutation accounting for 91.3% (21/23) of arginine residue nonsense mutation (R/*) at TTN A-band region. Non-essential splice-site variants had significantly lower proportion of private variants and higher proportion of low-frequency variants compared to essential splice-site variants (P = 0.01; P = 5.1 X 10−4, respectively).ConclusionA-band TTNtv are more rare in the general population than previously reported. Based on this analysis, one in 500 carries a truncation in TTN A-band suggesting the penetrance of these potentially harmful variants is still poorly understood, and some of these variants do not manifest as autosomal dominant DCM. This calls for caution when interpreting TTNtv in individuals and families with no history of DCM. Considering the size of TTN, expertise in DNA library preparation, high coverage NGS strategies, validated bioinformatics approach, accurate variant assessment strategy, and confirmatory sequencing are prerequisites for reliable evaluation of TTN in clinical settings, and ideally with the inclusion of mRNA and/or protein level assessment for a definite diagnosis.

Abstract 10895: The Association of Growth Patterns and Clinical Outcomes in Children With Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry Study Group

Introduction: Although malnourishment is associated with mortality in adult dilated cardiomyopathy (DCM), a paradox exists where obesity is protective. We aim to look at the role of these risk factors in pediatric DCM. Hypothesis: We hypothesize malnourishment (MN) and obesity are risk factors for death or heart transplantation. Methods: The NHLBI- funded Pediatric Cardiomyopathy Registry (PCMR) database was used for this analysis of patients (age &lt; 18 years) with idiopathic or familial DCM and myocarditis. Patients were categorized by anthropological measurements: MN (defined as BMI &lt;5% for ≥2years or weight for length &lt;5% for &lt;2 years), obese (BMI&gt; 95% for ages ≥2years or weight for length &gt;95% for &lt;2 years), and normal. Results: Of 904 DCM patients, 23.7% (214) were MN, 13.3% (120) were obese, and 63.1% (570) were normal (Table). Obese patients were significantly older (p&lt;0.001) and more likely to have a family history of DCM (both p&lt;0.05). MN were more likely to have congestive heart failure, increased cardiac dimensions, and higher ventricular mass (p&lt;0.01). In a Kaplan Meier analysis, there was a difference in time to death or transplant by groups (Figure, p=0.0498). Adjusting for age and myocarditis, MN was associated with increased risk of death (HR: 1.857, 95%CI: 1.159-2.977, p=&lt;0.001), but obesity was not (HR: 1.362, 95%CI: 0.722, 2.566). Competing outcome analysis showed an increased risk of death for MN (p=0.026) but no difference between groups in transplant rate (p=0.159). Conclusion: Malnourishment is significantly associated with poor clinical outcomes. Unlike adult DCM where obesity is protective, obesity is not associated with improved survival in pediatric DCM.

Psoriasis induced toxic shock-like syndrome mimicking hemolytic uremic syndrome

Introduction: Over the past decade the incidence of invasive group A streptococcal infections causing streptococcal toxic shock syndrome (stss) or toxic shock like syndrome has been increasing. Group A streptococcus (Streptococcus pyogenes) can cause several different conditions including simple cases such as pharyngitis to severe cases involving bacteremia. case report: A 37-year-old female with history of dilated cardiomyopathy and psoriasis presenting with multiple episodes of watery diarrhea, multi- organ dysfunction, septic shock with an unclear underlying etiology later found to be secondary to toxic shock-like syndrome. conclusion: the mortality rate associated with toxic shock-like syndrome has been found to be high and a patient normally presents with signs of high fever, hypotension, liver injury, acute renal failure, coagulopathy, and at times soft tissue infection. It can be a difficult diagnosis to make as it can involve multi-organ dysfunction and as cultures are not readily available at time of presentation; its awareness needs to be differentiated to that