Dilated Left Ventricle Research Articles

938 ARRHYTHMOGENIC CARDIOMYOPATHY IN A PATIENT CARRYING A PATHOGENIC LMNA VARIANT

Abstract Background Lamin A (LMNA) protein is one of the main constituents of the nuclear lamina. Pathogenic variants of LMNA gene have been demonstrated to be linked to a wide spectrum of disorders, including cardiac diseases. The first reported heart disease linked to LMNA was dilated cardiomyopathy (DCM), in a form typically characterized by the presence of conduction disorders and high incidence of sudden cardiac death (SCD) disrespectfully of left ventricular systolic function. Genetic variants of the same gene have been associated with Arrhythmogenic Cardiomyopathy (ACM), but its putative role as disease causing gene is still debated. Case summary a man with positive familial history for DCM presented to the Emergency Department because of palpitations. The electrocardiogram showed first degree AV-block, complete right bundle branch block and low QRS voltages on limb leads. Cardiac magnetic resonance revealed severe dilatation of the right ventricle with wall motion abnormalities in keeping with ACM, associated with mild dilatation and moderate dysfunction of left ventricle. The genetic test identified a pathogenic variant in LMNA. Moreover, non-sustained ventricular tachycardias were present on the ECG Holter. According to international guidelines on SCD prevention, the patient underwent ICD implantation, with one appropriate ICD discharge on a sustained ventricular tachycardia episode after few months. Discussion LMNA pathogenic variants can lead to a broad spectrum of cardiac manifestations, including Arrhythmogenic Cardiomyopathy. A genetic test should be considered if there is a familial cardiomyopathy associated with conduction disorders, in order to achieve a proper risk stratification for sudden death.

Anesthetic considerations in pediatric renal autotransplantation

BackgroundRenal autotransplantation is a complex procedure involving reimplantation of the renal artery and vein at a different site. Anesthetic management of renal autotransplant is challenging because of associated morbidities and intraoperative hemodynamic changes.Case presentationWe present a case of a 14-month-old male who had severe hypertension and cardiomyopathy due to renal artery stenosis. Echocardiography reported dilated left atrium and left ventricle, moderate to severe left ventricular systolic dysfunction, and a left ventricular ejection fraction of 30%. The renal artery and renal vein were anastamosed to the great vessels. Anesthetic management included maintaining normal baseline diastolic pressure, systemic vascular resistance, and preload and avoiding tachycardia. Milrinone infusion was used.ConclusionsAnesthetic management was challenging as adequate perfusion pressures had to be maintained while keeping the patient hemodynamically stable.

1121 USE OF IMPELLA 5.0 AS BRIDGE TO LVAD IN CARDIOGENIC SHOCK: REPORT OF TWO CASES

Abstract Background Left ventricle assist devices (LVAD) are an option in end stage heart failure (HF) as bridge to or alterative to heart transplantation. Adequate compensation of patient is key to obtain a good outcome. We report two cases of Impella 5.0 bridge to LVAD in patients with cardiogenic shock (CS) in which intra-aortic balloon pump (IABP) failed to obtain hemodynamic stability. Case series A) A 60 years old man developed CS after anterior myocardial infarction treated with primary PCI of left main coronary artery. At presentation patient was hypotensive with signs of hypoperfusion and pulmonary congestion: systemic blood pressure (SBP) 80/60 mmHg despite inotropic drugs, blood lactates 4 mmol/l, urine output of last 6 hours 0,4 ml/kg/h (INTERMACS 2). Echocardiography showed severe left ventricle disfunction with LVEF 15%, severe mitral regurgitation (MR) and sPAP 45 mmHg. Therefore, IABP was implanted. Right heart catheterization (RHC) showed pulmonary hypertension and high filling pressure with reduced cardiac output and increased pulmonary vascular resistance (mPAP 39 mmHg, CPWP 28 mmHg, CO 3 l/min, PVR 3.7 uW, PAPi 2.8); X-ray chest showed persistence of pulmonary congestion. After 9 days on IABP, patient underwent Impella 5.0 implant through right axillary artery as bridge to durable LVAD. Pulmonary artery catheter (PAC) monitoring showed reduction of pulmonary hypertension with mPAP 35 mmHg and CPWP 17 mmHg and chest X-ray documented improvement of lung congestion. Bedside rehabilitation was started. Two weeks later patient underwent LVAD HM3 implantation as destination therapy. The patient was discharge home on post-operative day 55. B) After subacute myocardial infarction with three-vessels disease, a 53 y.o. man developed severe congestive HF with severe left ventricular disfunction and was referred to our institution for evaluation. RHC showed pulmonary hypertension with pre-capillary component not reversible after enoximone test, contraindicating heart transplantation. Therefore, patient was candidate to receive LVAD as bridge strategy. Echocardiography at admission showed dilated and hypokinetic left ventricle (EDV 200 ml, LVEF 17% severe MR, sPAP 60 mmHg) and dilated and hypokinetic RV. During hospitalization the patient experienced CS with SBP 62/45 mmHg, 6-hours urine output of 1,4 ml/kg/h and blood lactates 8.3 mmol/l (INTERMACS 1) so femoral IABP was implanted. RHC was repeated both without IABP support (mPAP 37 mmHg, PCWP 28 mmHg, CO 1.4 l/min, CI 0.9 l/min/m2) and with IABP support (mPAP 32 mmHg, PCWP 18 mmHg, CO 2.15 l/min, CI 1.4 l/min/m2). During the following stay he developed S. Aureus sepsis requiring prolonged antibiotic therapy. Expecting a long time before LVAD, axillary Impella 5.0 was implanted in order to unload the LV and allow early patient mobilization. Subsequent PAC monitoring showed improvement of pulmonary hypertension and cardiac index (mPAP 24 mmHg, PCWP 9 mmHg, CO 5.1 l/min with Impella flow 4.2 l/min, CI 3.2 l/min/m2). After 11 days, patient received LVAD HVAD with uneventful course and was discharged on post-operative day 22. Conclusions Impella 5.0 is a surgically implanted intravascular microaxial blood pump that delivers up to 5 l/min of blood from LV to aorta, leading to improved perfusion and more efficient LV unloading. In patients with CS this can help to obtain better decongestion, RV recovery, and favorable preconditioning before LVAD implant. Moreover, axillary access allows better patient mobilization preventing cachexia after long time hospitalization.

694 DRUG INDUCED KIDNEY INFARCTION: A CASE REPORT

Abstract Isotretinoin (ISO) is a synthetic analog of vitamin A. Notwithstanding the well-known long-term efficacy in the treatment of severe resistant cystic acne, ISO induces several side effects too. Dyslipidemia, increased liver enzymes, as well as reduction of biotidinase have been already reported [1]. Homocysteine (HCY), a sulfur-containing amino acid, is recycled into methionine by a transmethylation reaction requiring folate and vitamin B12. Given that during ISO treatment elevated liver enzymes (SGOT, SGPT) are often observed, it has been hypothesized that iatrogenic liver dysfunction could affect cystathionine-b-synthase, an enzyme involved in HCY metabolism, [2]. Several studies have highlighted that elevated plasma HCY concentrations are associated with an increased risk of premature occlusive vascular disease. We hereby report a case of drug-induced kidney infarction after ISO therapy. A previously healthy 18-year-old male, on therapy with 40 mg/die isotretinoin for acne, was admitted to the Emergency Unit for abdominal pain, nausea and vomiting and dyspnea. A trans-thoracic echocardiogram showed dilated and hypocontractile left ventricle. During the hospitalization he had a total body CT that showed the presence of an ischemic lesion on left kidney without other pathological findings. He started therapy with 12 IU/kg UFH as soon as a surgical emergency was excluded. Subsequently, he underwent a coronary angiogram that resulted unremarkable. Cardiac MRI showed extensive delayed gadolinium late enhancement with intramural linear pattern. In the hypothesis of drug-induced vasculitis, an extensive serological testing was performed. Elevation of serum liver enzymes (SGOT, SGPT), CRP, LDH was found. Mutations on MTHFR gene and Leiden Factor were not detected, neither alteration in coagulation parameters. Finally the dosage of plasmatic HCY resulted over the range of normality and ISO was discontinued. The patient was discharged on optimized medical therapy for heart failure. He is currently managed as outpatient. HCY levels could be found elevated in patients with ischemic events during ISO treatment. Given the widespread use of this drug for acne, it could be reasonable to dose HCY in patients with suspected liver dysfunction. Physicians should be aware of this scenario and should act swiftly to avoid uneventful outcomes. [1] Schulpis KH et al. Elevated plasma homocysteine levels in patients on isotretinoin therapy for cystic acne. Int J Dermatol. 2001 Jan;40(1):33-6. [2] Polat M, et al. Plasma homocysteine level is elevated in patients on isotretinoin therapy for cystic acne: a prospective controlled study. J Dermatolog Treat. 2008;19(4):229-32.

142 ADVANCED HEART FAILURE IN PATIENTS WITH ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background Arrhythmogenic Cardiomyopathy (ACM) is a primary disease of the heart muscle, characterized by fibro-fatty myocardial replacement. Improvements in the clinical diagnosis and antiarrhythmic therapy, including the use of the defibrillator (ICD) and endo-epicardial catheter ablation, have increased the survival of these patients, who experience late complications such as advanced heart failure, which sometimes requires cardiac transplantation. Aim of the study To evaluate clinical, instrumental and genetic features of patients affected with ACM who developed heart failure (HF) and to sought for possible predictive factors of HF. Methods From the entire cohort of probands and family members followed at the Cardiomyopathy unit of our University (555 patients), 34 patients (29%), both probands (n= 26, 77%) and family members who experienced HF (6%) were selected (24 males, 71%). Their anamnestic, clinical, and instrumental data were compared with those without episodes of HF (n-HF). Results The mean age at diagnosis in HF cohort was 45.2 (±18) years. In 14 patients (41%) HF was the first symptom that led to diagnosis. According to 2010 TFC 30 patients (88%) had a definite diagnosis of ACM. The most frequently observed phenotype was the biventricular ACM (n=27, 79%). A disease-related genetic variant was found in 18 (53%) and DSP was the more common disease-gene, accounting for 24% of cases. The mean duration of follow-up was 12.6 (±11.0) years (min-max, 1-20 years). During this period a total of 14 subjects (41.2%) experienced life-threatening arrhythmias (LTA), while 13 patients (38.2%) died, of whom 11 (84.6%) because of refractory HF. Eighteen patients (53%) underwent cardiac transplantation (mean age 43±17 years), approximately 4 (±3.5) years after the onset of symptoms. Comparison with the n-HF cohort of ACM patients showed a significant difference on presence of T-wave inversion (TWI) in V1-V3 (p=0.001), TWI in V4-V6 (p=0.010), low QRS voltages both in precordial and limb leads (both p<0.001) and presence of left bundle-branch block and right bundle-branch block (both p<0.001). Regarding CMR, HF cohort was characterized by a significantly more dilated right and left ventricle EDV (both p<0.001), EF reduction (both p<0.001), presence of wall motion alterations (respectively, p=0.007 and p<0.001) and LGE (respectively, p=0.002 and p=0.005) compared to n-HF group. Regarding outcomes evaluation, the HF group showed more frequently LTA (HF=41.2% vs n-HF 21.5%, p=0.008). Finally, the presence of right bundle-branch block at ECG (OR=20.562, CI 1.884-224.413, p=0.013) and of impaired RV ejection fraction (OR=0.821, CI 0.719-0.937, p=0.004) were found to be independent predictors of HF. Conclusions Heart failure is a rare complication in patients affected with ACM, with a prevalence of 6% in our study. The mean age of onset of HF was 45.2 (±18) years. Furthermore, 18 patients (53%) had an unfavorable progression to heart transplantation. The presence of right bundle branch block at ECG and an impaired CMR RV-EF were found to be predictors of HF. Our results suggest the importance of scheduling a close follow-up in ACM patients who show initial signs and/or symptoms of HF, taking into consideration the fast rate of progression to refractory HF, once established.

272 A SUDDENLY RIGHT-TO-LEFT SHUNT: THE IMPORTANCE OF EVALUATING PATENT FORAMEN OVALE DURING CARDIOPULMONARY EXERCISE TESTING

Abstract A 55-years-old male affected by heart failure with reduced ejection fraction (HFrEF) was accepted into the Cardiology Department for increasing dyspnea during the last few months. He previously underwent implantation of a biventricular implantable cardioverter defibrillator (ICD) in primary prevention. Medical history included healthy coronary vessels at invasive coronary angiography and an episode of transient ischemic attack (TIA). The patient was referred to our center to evaluate the dyspnea components and to establish an etiology for the novel onset of left ventricular impairment. He underwent a left-right catheterization that did confirm the absence of obstructive coronary disease and signs of pulmonary hypertension (PH) at rest. The transthoracic echocardiogram showed a dilated left ventricle and global hypokinesia (LVEF of 35%). During the stay, the therapy was further optimized according to the latest European guidelines. Before discharge, in order to better assess the dyspnea and the limited tolerance to exercise, a cardiopulmonary exercise testing (CPET) was performed. CPET showed that the VO2 peak was severely reduced compared to the predicted value (16.8 ml/kg/min, corresponding to 51% of the predicted). After 6 minutes of exercise, at around 60 WR, a considerable increase in PETO2 and RER with a concomitant decrease in PETCO2 and a slight oxygen desaturation were observed. Also, a deep increase in VE/VCO2 slope was seen, underlying an exercise-induced pulmonary hypertension. In the suspicion of an inter-atrial shunt, a subsequent rest transthoracic echocardiogram with a bubble test was performed, demonstrating the presence of a patent foramen ovale (PFO). Discussion The foramen ovale is a vestigial communication between the atria that works as a bypass of the pulmonary circulation during fetal life and then seals at birth after the start of breathing in most people. In around 25% of adults, patency of foramen ovale persists and, in some cases, can lead to a source of a right-to-left shunt, particularly in patients with heart failure that can experience PH at rest or during exercise. This may allow a mixture of oxygenated and non-oxygenated blood that affects pulmonary gas exchange efficiency and may allow blood clots formed in the right circulation to embolize into the left circulation. From a pathophysiological point of view, a right-to-left passage of deoxygenated blood induces the activation of chemoreceptors which induce hyperventilation to adequately compensate for the high amount of CO2 in blood from the right sections of the heart. In people not experiencing pulmonary pressure increase during exercise, right-to-left shunt via a PFO is very unlikely since left atrial pressure is higher than right atrial pressure. However, in the presence of PH, right atrial pressure can overcome left atrial pressure and force venous blood through the defect directly into the systemic circulation. The concomitant increase in VE/VCO2 slope underlines exercise-induced PH, which is frequently associated with heart failure and further contributes to exercise intolerance. Conclusions In the presented case, CPET helped diagnose a misunderstood PFO with a right-to-left shunt induced by effort in a patient with a previous TIA. This observation demonstrates that it could be helpful to identify this eventuality during exercise, to discern patients with higher risk of cardiovascular events who would benefit from a percutaneous closure.

367 LEFT VENTRICULAR MALIGNANT PERIPHERAL NERVE SHEATH TUMOR, A RARE PRIMARY CARDIAC NEOPLASM

Abstract This is a case of a 71 year-old man, symptomatic for heart failure (NYHA II class), with recent weight loss and occurrence of arthralgia. In the last month episodes of non sustained ventricular tachycardia were observed. Transthoracic echocardiography showed a dilated left ventricle with reduced ejection fraction (30%) and the presence of an apical left ventricular cyst (dimensions 33×36 mm), with no doppler signal inside. No relevant valvular diseases were found. The first hypothesis was a cystic echinococcosis with left ventricle localization, but the serological testing resulted negative. In order to obtain a better characterization of the apical lesion a Cardiac Magnetic Resonance (CMR) was performed: it confirmed the apical mass with thin wall, high T2 and T1 signal and no contrast enhancement. CMR findings raised the suspicion of cardiac tumor. The case was discussed in the local heart team, and the patient was scheduled for cardiac surgery with mass removal. The histological examination showed a malignant mesenchymal neoplasm related to a primary cardiac schwannoma. Follow up outpatient visit showed a decrease of the arrhythmic burden and a progressive improvement in patient's symptoms. Echocardiography reported little improvement in EF (38%) and no suspicious lesions. MPNST (malignant peripheral nerve sheath tumor) is a type of cancer extremely rare and not fully considered in literature with a poor prognosis. CMR and echocardiography could help to early diagnose this neoplasms when dimension and localization are not prohibitive for operating.

278 A CASE OF ACCIDENTAL DIAGNOSIS OF ALCAPA SYNDROME IN ASYMPTOMATIC CHILD

Abstract A 7-year-old (y.o.) boy was referred to our center for a specialist evaluation due to alteration of the ventricular repolarization in the anterior and lateral lead on the electrocardiogram at medical evaluation for physical activity. The child was totally asymptomatic, with normal growth and unremarkable past medical history. The physical examination revealed only S4 and a minimal apical systolic murmur. Transthoracic echocardiogram demonstrated a mildly dilated left ventricle (LV) and normal left ventricular ejection fraction. Strain pattern of basal-medium segments of lateral wall was reduced. Right coronary artery (RCA) appeared dilatated and the left coronary artery (LCA) showed an inverse flow at Doppler evaluation. Findings were suspicious for ALCAPA diagnosis (Anomalous Left Coronary Artery Arising from the Pulmonary Artery); a rare congenital heart disease that, if not treated, leads to death in 90% of cases during first year of life. Adult type of ALCAPA (adolescence-60 y.o) is even more rare and can cause heart failure due to a dilatative cardiomyopathy, chronic cardiac ischemia and, in 80-90% of cases, sudden cardiac death. We performed a coronary angiography that confirmed the anomalous origin of LCA from the pulmonary artery. The RCA was dominant, enlarged and supplied an important collateral flow for LCA. Coronary angiography is indicated not only for diagnosis confirmation, but also for coronary tree demonstration, especially in adult type of ALCAPA, because of the presence of not rare anomalies or “adaptation” of peripheral coronary circulation. All these features are important positive prognostic factors that enable survival beyond infancy. LCA ostium stenosis or bronchial artery collateral vessels are also common but weren't seen in this case. In adult type of ALCAPA surgery is usually indicated at the time of diagnosis, so a coronary button transfer and pulmonary Valsalva sinus reconstruction with autologous pericardial patch were performed. This is the preferred surgical technique in adult patients as it is the most anatomic correction. Since before hospitalization heart failure therapy with betablocker was introduced and after surgery aspirin therapy was started too. Post-surgery transthoracic echocardiogram highlighted a moderate pericardial effusion without haemodynamic impact and a pleural effusion, so an anti-inflammatory therapy with ibuprofen, cortisone and then colchicine was started. After discharge anti-inflammatory therapy was under-titrated until suspension based on gradual reduction of pericardial and pleural effusion. Patient was always free of symptoms and with good performance status. ALCAPA or Bland–White–Garland syndrome is an uncommon congenital heart disease. The presence of adequate collateral circulation between RCA and LCA allows to survive beyond infancy (adult type). We described a case of early diagnosis of adult type of ALCAPA in asymptomatic child thanks to a careful examination of basal electrocardiogram for evaluation of non-competitive sport practice.

738 A RARE CASE OF UNICUSPID AORTIC VALVE WITH SEVERE STENOSIS AND REGURGITATION: CLINICAL PRESENTATION AND MANAGEMENT

Abstract A 19-year-old Pakistani migrant, who arrived in our country on foot, presented at emergency department with angina and worsening dyspnoea on exertion. The patient reported an unclear history of aortic valve disease. Clinical examination revealed a 6/6L systolic murmur with thrill. The electrocardiogram showed sinus rhythm and signs of left ventricular hypertrophy. Chest X-ray reported cardiomegaly and signs of congestion. Troponin I HS was mildly elevated (39 ng/L, n.v. < 18 ng/L). The patient was admitted to our Cardiology department. Transthoracic echocardiography revealed a mildly dilated left ventricle (LV), with severe hypertrophy, normal kinetics and systolic function (EF 63%), dilated ascending aorta (diam. 41 mm) and severe aortic steno-insufficiency. Transesophageal echocardiography was then performed, revealing a highly calcified, unicuspid unicommissural aortic valve with severe stenosis and regurgitation. A separate origin of left coronary ostia was also documented. The patient was referred to urgent cardiac surgery. A modified Bentall procedure (mechanical valve and prosthetic conduit) was performed with reimplantation of the coronary ostia. Due to a post-surgical complete atrioventricular block, a dual-chamber pacemaker (DDD) was implanted. Follow-up echocardiography showed reduction of LV volumes and wall thickness and normal prosthetic function. Unicuspid aortic valve is a very rare congenital disease, with a prevalence of about 0.02% in the adult population and is frequently associated with ascending aorta dilatation. The treatment is aortic valve replacement. Complete atrioventricular block can occur after surgery, requiring cardiac pacing.

623 PERCUTANEOUS LEFT ATRIAL APPENDAGE CLOSURE AND TRANSCATHETER CEREBRAL EMBOLIC PROTECTION: TWO CASES REPORT

Abstract Introduction Percutaneous left atrial appendage closure (LAAC) in AF patients is not inferior to oral anticoagulation (OAC) in terms of systemic embolism. LAA Closure is usually contraindicated in presence of intracardiac thrombus, a condition far from uncommon. The feasibility and safety of transcatheter cerebral embolic protection (TCEP) has been reported in literature as a successful off – label option in retrieving embolic debris during percutaneous LAAC. We present two cases of Watchman Flex insertion in the setting of LAA thrombus and prophylactic use of TCEP. Cases report The first patient was an 88-year-old male with history of symptomatic AF and post – traumatic cerebral bleeding, who was referred to LAAC because of high risk of bleeding in using OAC. Transthoracic echocardiography (TTE) documented a severely dilatated left atrial and preserved left ventricular systolic function. Transesophageal echocardiography (TEE) revealed a “chicken wing” shaped LAA with spontaneous echo-contrast and sludge effect confirmed with echo-contrast medium “SonoVue”. ECG – gated cardiac CT (CCT) showed a LAA filling defect and confirmed the diagnosis of LAA thrombus. The second patient was a 75-year-old man with valvular permanent AF and history of multiple ischemic strokes despite of OAC therapy with Warfarin. TTE documented a dilated left ventricle with severely depressed ejection fraction; TEE revealed a “windstock” shaped LAA with incompletely distal opacification with echo-contrast medium “SonoVue”. Both patients were candidate to LAAC with concomitant use of CEPDs in the event of neurological complication. TriGUARD 3 cerebral protection (TG3, Keystone Heart) was deployed in the aortic arch through right femoral artery access before LAAC procedure. Following transseptal puncture Watchman Flex device (Boston Scientific, Marlborough, MA) was deployed without complications or residual peri-device leaks. At the end the TriGurad 3 device was retracted and no debris were noted at the post operatory inspection. The first patient was discharged afterward with daily acetylsalicylic acid 100 mg and Clopidogrel 75 mg and the second patient with daily acetylsalicylic acid 100 mg and Warfarin. Both patients underwent follow-up TEE at four weeks. Neither device – related complications nor thrombotic/hemorrhagic adverse events have been not reported so far. Discussion Both patients were at very high risk for stroke and bleeding. They were not theoretically candidate to LAAC because of intracardiac thrombus. The prophylactic use of TCEP (including TG3) has been reported in a small retrospective study by Tarantini et al. and in some case series. Procedures were always successful and uneventful. Moreover, small captured debris on the device on visual examination proved its efficacy. The use of TCEP has been mentioned even by Beneduce et al. as a safer and more feasible strategy in AF patients. Conclusion Prophylactic use of TCEP during The Watchman Flex device implantation is safe and feasible.

692 THE USE OF ULTRASOUND ENHANCING AGENTS (UEA) IN THE EVALUATION OF LEFT ATRIAL APPENDAGE (LAA) THROMBUS IN PATIENT CANDIDATE TO PERCUTANEOUS LAA CLOSURE

Abstract Introduction Left atrial appendage closure (LAAC) is an emerging option in patients with atrial fibrillation (AF) and contraindication for oral anticoagulation (OAC) therapy. Patients with left atrial thrombus are usually excluded from this strategy. Therefore, pre-procedural transesophageal echocardiography (TEE) is usually performed for LAA thrombus exclusion. The application of second-generation lipid microspheres ultrasound enhancing agents (UEA) is of growing interest. The following clinical cases reports describe the benefit from UEA implication on subsequent decision-making regarding with LAAC procedure. Case report num.1 an 88-year-old male with history of symptomatic AF and post – traumatic cerebral bleeding was referred to LAAC because of high risk of bleeding in using OAC. Transthoracic echocardiography (TTE) documented a severely dilatated left atrium and preserved left ventricular systolic function. Pre – operative TEE revealed a “chicken wing” shaped LAA with severe spontaneous echo-contrast and sludge effect. Echo-contrast medium “SonoVue” showed an early filling defect with late but complete LAA opacification, excluding thrombus. Of note, ECG-gated cardiac CT (CCT) could not exclude filling defect with certainty. Consecutively, the patient was candidate to LAAC in a short time. Case report num.2 a 75-year-old man with valvular permanent AF and multi-territory ischemic ictus despite being on adequate prophylactic OAC (Warfarin). At TTE a dilated left ventricle with mildly reduced ejection fraction was documented. ECG – gated CCT with delayed phases imaging showed a possible filling defect in LAA, however imaging was suboptimal due to a reverb of voluminous hiatal hernia. TEE revealed a “windstock” shaped LAA with incomplete distal opacification when echo-contrast medium “SonoVue” was used, confirming thrombus. The patient was therefore referred for LAAC procedure with concomitant use of cerebral embolic protection devices (CEPDs). Discussion Transesophageal echocardiography is the test of choice for the exclusion of LAA thrombus. However technical difficulty, spontaneous echo contrast (SEC) and prominent pectinate musculature within the appendage may make the exclusion of LAA thrombus not easy. ECG – gated cardiac CT may be conclusive as well. UEA use is associated with higher diagnostic power for LAA thrombus exclusion and recent study have shown its utility also in terms of LAA sizing. Thus, the most recent guidelines of American Society of Echocardiography mention echo contrast use for the delineation of LAA thrombi and differentiate between them with SEC. Conclusion The use of ultrasound enhancing agents is useful and increases the interpretative confidence in exclusion of LAA thrombus.

661 TWO CARDIOMYOPATHIES IN ONE HEART: LESSONS FROM CLINICAL CASE

Abstract Case description In November 2020, a 55-years-old female with no significant past medical history, was admitted to our Emergency Department for chest pain after acute stressful event. She had a significant family history of ischemic heart disease, and unclear comatose status of her sister. At admission, she was asymptomatic, blood pressure was 115/80 mmHg, and oxygen saturation was 96%. An electrocardiogram (ECG) showed biphasic T wave in anterolateral leads. Elevated levels of troponin I (hs-TnI of 900 ng/L) and B-type natriuretic peptide (BNP) of 864 pg/mL were detected. Transthoracic echocardiogram (TTE) revealed an ejection fraction (EF) of 30% with apical ballooning of mid and apical segments of the left ventricle (LV) along with a sizable apical thrombus. Aspirin, iv diuretics, iv nitrates and unfractioned heparin were started. After 13 hours, she suffered a sudden transient neurological sign of decreased level of consciousness. Cranial MRI revealed an ischemic lesion in the territory of the apex of basilar artery (thalamic region). After 7 days from stroke, the patients underwent coronary angiography demonstrating unobstructed coronaries. Thus, the diagnosis of takotsubo syndrome was confirmed. During hospitalization, ECG evolution showed T wave inversion in precordial and lateral leads. Hs-TnI declining within normal values. Of note, ventricular arrhythmias burden with polymorphic ventricular contraction (PVC) emerged on continuous ECG-monitoring. Despite resolution of apical balloning and apical thrombosis, there were persistent wall-motion abnormalities in infero-lateral walls and mild LV dysfunction. This was also confirmed by cardiac magnetic resonance (CMR). Further, CMR also showed an intense myocardial edema with elevated LV mass. The patients was discharged on Warfarin, Bisoprolol 2.5 mg/die, Ramipril 5 mg/die, Eplerenone 25 mg/die. A clinical documentation was required to further investigate history of her sister, and neurological sequelae after cardiac arrest at 28s related to ventricular fibrillation emerged. However, no deeply evaluation of underlining heart disease was available. Despite an early favorable follow-up of patient, after six months, she suffered from palpitations and heart failure requiring diuretic therapy. Persistent repolarization abnormalities in infero-lateral leads, and low-voltage in precordial leads were noted. An extensive wall-motion abnormalities and moderate LV dysfunction were detected. Importantly, significant arrhythmic burden with PVC (13%) at 24-hr ECG monitoring was recorded. CMR was requested to further investigate the possibility of underlining coexisting cardiomyopathy. Mild LV dilation, moderate dysfunction (LVEF 39%), wall motion abnormalities and thinning of the inferior wall middle segments were reported. Surprisingly, fibro-fatty replacement in infero-lateral of LV wall was detected, and unexpectedly, right ventricular (RV) fibro-fatty replacement and mild RV dysfunction were also described. Hence, diagnosis of arrhythmogenic cardiomyopathy was made. Since persistent arrhythmic burden despite optimized medical treatment, biventricular involvement, family history of SCD, an implantable cardioverter defibrillator in primary prevention was placed. Furthermore, genetic testing was required and extensive clinical family screening was suggested. Conclusion According to the clinical data collected, takotsubo and arrhytmogenic cardiomyopathy can coexist. A potential link between two myocardial heart disease may be identified in the future, especially among patients presenting takotsubo and long-term unfavorable outcome.

177 TRANSCATHETER EDGE-TO-EDGE REPAIR OF SEVERE FUNCTIONAL MITRAL REGURGITATION TO OVERCOME ACUTE DECOMPENSATION IN A YOUNG MAN CANDIDATE TO HEART TRANSPLANTATION.

Abstract Background Chronic severe functional mitral regurgitation (FMR) is common in patients with HF as it reflects left ventricle dysfunction and portends poor prognosis. Case report A 42 years old man with cardiovascular risk factors (former smoker, obesity) but without previous cardiological history presented anterior ST-elevation myocardial infarction (STEMI) treated with primary PCI of the anterior descending artery. He developed severe ventricular dysfunction leading to congestive heart failure (HF) requiring early re-hospitalization for pulmonary edema. Despite optimal medical therapy patient remained symptomatic (NYHA class III, INTERMACS 6) with persistence of left ventricle ejection fraction (LVEF) depression, therefore he received an implantable cardiac defibrillator for primary prevention and was referred to our institution for further evaluation. Trans-esophageal echocardiography showed severe left ventricle dilatation and disfunction (EDD 6.9 cm, iEDV 113 ml/m2, LVEF 24%) and presence of severe FMR with EROA 37 mm2 and RV 44 ml. Right heart catheterization (RHC) revealed combined pulmonary hypertension (mean PA pressure 43 mmHg, PCWP 32 mmHg, PVR 4.6 WU) with severely reduced cardiac index obtained (CO 3.4 l/min, CI 1.9 l/min/m2). After infusion of inodilator (enoximone) a decrease of PA pressure and PVR was reported, concluding for reversible pulmonary hypertension. After screening for non-cardiac contraindications, the patient was listed for heart transplantation. Chances to get a donation with a short waiting list time were low because of patient's high BMI and blood group B. Therefore, after Heart Team evaluation, transcatheter edge-to-edge repair of the mitral valve (TEER) was performed as bridge to transplant. A single NTR clip was used, placed centrally between A2-P2 segments, reducing regurgitation from severe to mild. Patient was discharged on heart transplantation waiting list. At three months follow up he presented clinical improvement with reduction of NYHA class from III to II. RHC was repeated and showed normal filling pressures, reduction of pulmonary pressure (mPAP 20 mmHg) and increased cardiac output (CO 5.2 l/min, CI 2.5 l/min/m2). According to his preferences, the patient was suspended from the waiting list with indication to continue outpatient follow-up. At 1-year control he was stable in NYHA II class and the daily diuretic dose had been reduced, echocardiography showed severe LVEF depression (28%) with mild to moderate residual mitral regurgitation. Conclusions TEER recently emerged as an option for patients with FMR who are not suitable for surgery. Latest guidelines suggest its use in presence of specific criteria (LVEF 20-50%, ESD < 7 cm, sPAP <70 mmHg, hemodynamic stability, absence of right ventricle disfunction and severe TR) rarely fulfilled by patients with advanced HF requiring evaluation for transplant. On the other hand, access to surgical strategies for end stage HF is limited by scarce availability of donors and by temporary or definitive contraindications. Evidences are emerging that in this population TEER can improve hemodynamic profile and lead to reduction of pulmonary hypertension, providing temporary stability before definitive treatment or allowing candidacy. In this setting, TEER might be performed to reduce symptoms. Considering TEER as bridge strategy to transplant, candidacy or decision can expand the number of patients suitable for heart transplantation or delay urgency.

986 LEFT VENTRICULAR LEAD PLACEMENT FOR BIVENTRICULAR PACING INTO A LEFT LATERAL VEIN IN PATIENT WITH CONGENITAL ATRESIA OF THE CORONARY SINUS OSTIUM WHO UNDERWENT AORTIC VALVE REPLACEMENT

Abstract Introduction Coronary sinus ostial atresia (CSOA) is a rare congenital heart anomaly consisting in the occlusion of the coronary sinus (CS) outlet in the right atrium. It is one of the causes of placement left lead failure in CS during cardiac resynchronization therapy (CRT) device implantation. The persistence of the left superior vena cava is the most common pathway that allows venous blood flow to drain into the right atrium and can represent a new possible way to reach a left ventricular vein from the CS. Methods A 66-year-old male suffering from sarcoidosis was studied after an episode of syncope under exertion. EKG showed a 1st degree atrioventricular block and a left bundle branch block (LBBB) with wide QRS (170 ms). Echocardiography found left ventricle dilatation, severe systolic dysfunction, and a severe low-flow low-gradient aortic stenosis for which he underwent aortic valve replacement. After surgery and finding of 2nd degree type II atrioventricular block, CRT implant was performed but the procedure was complicated by the finding of CSOA. The insertion of the left quadripolar lead along a left branch of the occluded CS was achieved with a push-and-pull technique of the lead over a guidewire, after the retrieval and the cannulation of the persistent left superior vena cava. Results A new approach was applied on a rare case of CSOA found during CRT procedure. The contrast medium (CM) in the left subclavian vein revealed the existence of the left superior vena cava that was than cannulated. CM injection in CS highlighted a posterior left branch that was approached with a specific guidewire and a subselector after selective venography. With a fine technique of sliding of the lead on a tensioned guidewire, the quadripolar catheter was successfully placed in the left ventricular vein. Left-ventricle-right ventricle delays and catheter thresholds were tested and a final QSR duration of 90 msec in CRT mode was obtained. Conclusions This case-report shows a complex technique, reported in parallel with other similar procedures, to help the approach toward a rare anatomical variant of CSOA accompanied by persistent left superior vena cava when a CRT implant is needed after cardiac valve surgery in a patient suffering from sarcoidosis.

Berardinelli-Seip Congenital Lipodystrophy Discovered Following a STEMI Event.

Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare congenital lipodystrophy, with an incidence of 1-9 per million population, which is usually diagnosed at birth and is associated with pathogenic variants of the BSCL2 and AGPAT2 genes.Due to the absence of functional adipocytes, lipid storage occurs in other tissues, including skeletal muscle and liver.Diagnosis is based on the presence of three major or two major and two minor characteristics.

Pre-operative N-Acetyl Cysteine for Prevention of Atrial Fibrillation After CABG Surgery in Pakistan

Objective: To determine the effect of NAC in prevention of post-operative atrial fibrillation in patients undergoing CABG.
 Study Design: Quasi experimental study.
 Place and Duration of Study: Adult Cardiac Intensive Care Unit, Armed Forces Institute of Cardiology & National Institute of Heart Diseases (AFIC&NIHD) Rawalpindi during 6 months.
 Methodology: 146 patients of both gender undergoing elective CABG were included in the study, having age between 30-70 years. However, any patient with history of arrhythmia including AF, thyroid dysfunction, ejection fraction less than 25%, any valvular lesion, dilated left atrium, dilated left ventricle, dilated right atrium, dilated right ventricle or having right atrial tear during surgery were excluded from the study. By using non-probability consecutive sampling, patients were divided into two groups by using envelope method. One group was given standard treatment (control group) while other group was named as NAC group (experimental group). Data analysis was performed using SPSS version-23. Descriptive statistics were reported as Mean±SD. Categorical variables were reported as frequency and percentage. Chi square test and T-test was used to determine association between different variables.
 Results: A total of 146 patients with mean age 55.27±7.3 yrs. 127(87%) were male and 19(13%) were females. 28(19.2%) patients had atrial fibrillation while 11(7.5%) patients had ventricular premature contractions (VPC). There was no statistically significant difference between ages (p=0.784), gender (p=0.461), AF (p=0.207) and VPC (p=0.347). Out of 73 (50%) patients from each group; the mean age of NAC group was 55.41±7.3 yrs and of control group was 55.08±7.1 yrs (p=0.784). Gender wise distribution of NAC group had 8(11%) females and 65(89%) males while in control group 11(15%) females and 62(85%) were males. AF was found to be 11(15%) and 17(23.3%) in NAC and control group respectively. In NAC group, VPC was 4 (5.5%) and in control group it was 66 (90.4%).
 Conclusion: This study shows that NAC decreases the frequency of post-operative atrial fibrillation and ventricular premature contractions, but the decrease is statistically insignificant in Pakistani population. However, keeping in view other beneficial effects of NAC, we would recommend more studies on this subject in Pakistani population.

KBTBD13 is a novel cardiomyopathy gene.

KBTBD13 variants cause nemaline myopathy type 6 (NEM6). The majority of NEM6 patients harbors the Dutch founder variant, c.1222C>T, p.Arg408Cys (KBTBD13 p.R408C). Although KBTBD13 is expressed in cardiac muscle, cardiac involvement in NEM6 is unknown. Here, we constructed pedigrees of three families with the KBTBD13 p.R408C variant. In 65evaluated patients, 12% presented with left ventricle dilatation, 29% with left ventricular ejection fraction< 50%, 8% with atrial fibrillation, 9% with ventricular tachycardia, and 20% with repolarization abnormalities. Five patients received an implantable cardioverter defibrillator, three cases of sudden cardiac death were reported. Linkage analysis confirmed cosegregation of the KBTBD13 p.R408C variant with the cardiac phenotype. Mouse studies revealed that (1) mice harboring the Kbtbd13 p.R408C variant display mild diastolic dysfunction; (2) Kbtbd13-deficient mice have systolic dysfunction. Hence, (1) KBTBD13 is associated with cardiac dysfunction and cardiomyopathy; (2) KBTBD13 should be added to the cardiomyopathy gene panel; (3) NEM6 patients should be referred to the cardiologist.

Von Hippel–Lindau syndrome with a rare complication of dilated cardiomyopathy: a case report

BackgroundVon Hippel–Lindau (VHL) syndrome is an autosomal dominant hereditary disease affecting multiple organs, with pheochromocytoma in 26% of cases. However, VHL syndrome with congestive heart failure and dilated cardiomyopathy as the primary clinical manifestations has been rarely reported.Case presentationA 35-year-old male patient was admitted to the hospital with dyspnea. The patient had a history of cerebellar hemangioblastoma that had been resected, and a one-year history of hypertension. Echocardiography and cardiac magnetic resonance imaging demonstrated a dilated left ventricle, decreased systolic function, and nonischemic myocardial changes. Contrast-enhanced abdominal computed tomography showed pheochromocytoma, neoplastic lesions, and multiple cysts in the kidneys and pancreas. Genetic analysis revealed a missense mutation of the VHL gene, c.269 A > T (p.Asn90Ile), which was identified as the cause of the disease. Dilated cardiomyopathy and VHL syndrome type 2 were diagnosed. The patient was administered a diuretic, α-blocker, β-blocker, and an angiotensin receptor neprilysin inhibitor (ARNI), but refused pheochromocytoma resection. At the six-month follow-up, the patient was asymptomatic with improved cardiac function.ConclusionCardiac involvement is an atypical manifestation in VHL syndrome. Early diagnosis with genetic screening is essential for avoiding life-threatening complications associated with VHL. The management of this rare manifestation of VHL syndrome requires further investigation.

Abstract 9474: Trim35-Mediated Ubiquitination and Degradation of Nuclear PKM2 is Sufficient to Promote Heart Failure

Introduction: Pyruvate Kinase M2 (PKM2) is a glycolytic enzyme that can translocate to the nucleus to regulate different transcription factors (TF) in different tissues or pathologic states. Although its function has been studied extensively in cancer, its biologic role in the heart and specifically terminally differentiated adult cardiomyocytes remains unresolved. Hypothesis: PKM2 may be critical in regulating cardiomyocyte(CM)-specific TF important for cardiac survival. Methods: Transverse aortic constriction (TAC) banding model was used to assess the levels and modifications of PKM2 during heart failure (HF). CM-specific PKM2-deficient and CM-specific Trim35 overexpressing(OE) mice were generated to evaluate the role of PKM2/Trim35 in adult CM. Human Dilated Left Ventricle biopsies were used to translate mechanistic findings into a clinical setting. Results: Here we show that nuclear PKM2 ( S37 P-PKM2) in CM interacts with several pro-survival or pro-apoptotic TF, including Gata-4, Gata-6, and p53. CM-specific PKM2-deficient mice developed age-dependent dilated cardiac dysfunction and had decreased levels of Gata-4/6, but increased levels of p53, compared to control Cre+ hearts. Mechanistically, we found that nuclear PKM2 can prevent caspase-1 dependent cleavage Gata-4/Gata-6, while also providing a platform for Mdm2-mediated ubiquitination of p53. In a preclinical HF model, nuclear PKM2, along with Gata-4/6 levels decreased, but p53 levels increased (compared to sham controls). Loss of nuclear PKM2 was ubiquitination-dependent and associated with the induction of the E3 ubiquitin-ligase TRIM35. CM-specific Trim35 OE mice had decreased S37 P-PKM2 and GATA-4/6, along with increased p53 levels (compared to littermate controls) and had similar cardiac dysfunction to CM-specific PKM2-deficient mice. In a well-characterized cohort of patients with dilated left ventricles, we found a significant increase in TRIM35 levels that was associated with a decrease in S37 P-PKM2, Gata-4/6 levels, but an increase in p53 levels, compared to non-failing ventricles. Conclusion: This study provides insight into a previously unrecognized biologic role for PKM2 in providing a molecular platform for TF essential for preserving cardiac survival.

Abstract 13272: Diabetic Cardiomyopathy as a Coronary Artery Disease Mimic: A Case Report

A 49-year-old female presented with complaints of angina and dyspnea on exertion for last 4 months, which caused significant limitation of ordinary physical activity. She had poorly controlled diabetes mellitus type 2 with HbA1C of 10.3%. EKG showed complete LBBB with QRS duration of 180 milliseconds. Echocardiogram was consistent with dilated left ventricle and global hypokinesia of left ventricle with ejection fraction of 25-30%. There was marked reduction in GLS (GLPS average of -7.0%). She underwent coronary angiogram which revealed normal epicardial coronary arteries. 99m Tc-sestamibi SPECT myocardial perfusion imaging (MPI) at rest, demonstrated moderate to severe ischemia involving apical, antero-septal, adjacent anterior wall and adjacent basal 2/3 rd of inferior wall segments of LV myocardium (involving approx.~73% of RCA territory and 57% of LAD territory at 50% uptake threshold). There was wall motion abnormality in above mentioned segments on ECG gated SPECT and estimated LVEF with QGS was ~29±5%. She has been started on anti-ischemic measures, guideline directed therapy for HFrEF and comprehensive diabetes care. Diabetic cardiomyopathy is myocardial dysfunction with normal epicardial coronary arteries and absence of other cardiovascular diseases. It is characterized by myocardial fibrosis and associated systolic dysfunction preceded by diastolic dysfunction. Cardiac insulin resistance leads to advanced glycation end products, microvascular dysfunction etc. Perfusion defects observed during MPI in patients with LBBB may be due to CAD, microvascular dysfunction, or artifacts. In the setting of LBBB, isolated anteroseptal defect has low probability of CAD but presence of perfusion defects in RCA territory and apical region increases probability of ischemic events.In this case, there was ischemia with systolic dysfunction in the absence of any overt clinical coronary artery disease and no other identifiable cause.