First-degree Block Research Articles

Hyperammonemia and First-Degree Atrio-Ventricular Block in Adult Male from Valproic Acid Toxicity

AbstractIntroductionThe purpose of this case study is to review the clinical presentation and medical work of an adult male who experienced symptomatic hyperammonemia and first-degree atrio-ventricular block in the setting of valproic acid toxicity.MethodThis case involves a 28-year-old African American male with a past psychiatric history of bipolar 1 disorder with psychotic features, antisocial personality disorder, PTSD, and ASD, who was psychiatrically hospitalized for mania and psychosis at a large midwestern university hospital. At the time of evaluation in the emergency department, the patient endorsed suicidal ideation, religious/persecutory delusions, and auditory hallucinations of demons. Zyprexa Zydis was started and titrated to 20 mg every 12 hours, which did not sufficiently improve symptoms. Depakote EC/DR 1000 mg every 12 hours was then added for treatment of mania. Approximately 1 week later, the patient was observed to be somnolent and complained of malaise, nausea, and vomiting.ResultsLabs were collected which showed an elevated ammonia level of 336 umol/L and free valproic acid level of 13.3 mcg/ml. An EKG was performed which showed first-degree atrio-ventricular block with fusion complexes. The patient’s baseline EKG displayed sinus bradycardia with no evidence of atrio-ventricular block. The patient’s CMP was unremarkable except total bilirubin of 1.5 mg/dL and glucose of 104 mg/dL. His lactate was elevated at 1.95 mmol/L. The patient’s troponin and CRP were unremarkable. The patient was medically transferred for management of hyperammonemia and EKG changes. Depakote was discontinued and lactulose 20 g TID was initiated. Patient was placed on telemetry and the first-degree atrio-ventricular block resolved within 24 hours after discontinuation of Depakote. Daily ammonia level, chem 7, and magnesium were collected. Ammonia decreased to 79 and 59 umol/L on consecutive days. Sodium was mildly elevated at 144 on day 2 of medical admission. Poison control was contacted and L-carnitine 990 TID was started for suspected carnitine deficiency. The patient medically recovered after several days and was readmitted to the psychiatric hospital for further psychiatric management.ConclusionsThe patient’s presentation of hyperammonemia and first-degree atrio-ventricular block were likely due to valproic acid toxicity. We suspect that carnitine deficiency contributed to the patient’s valproic acid toxicity at lower-than-expected blood levels. Although antipsychotics can cause prolonged QTc interval, conduction disorders are not typical abnormalities. Caution should be taken when prescribing Depakote to individuals at higher risk of developing toxicity, including those with potential nutritional deficiencies as well as those with limited self-advocacy abilities secondary to psychiatric illness. Rapid identification of side effects, such as valproic acid toxicity, remain crucial for favorable patient outcomes.FundingNo Funding

Restoration of sinus rhythm in a late presentation of inferior STEMI complicated by complete heart block with percutaneous coronary intervention

An 87-year-old female patient presented with a two-day history of the chest and epigastric pain associated with generalized fatigue. She was diagnosed with late presentation inferior ST-elevation myocardial infarction complicated by complete heart block. Given her late presentation, she was not taken to the catheterization laboratory immediately. She was admitted to the cardiac care unit. Transthoracic echocardiography showed an ejection fraction of 55% - 60% with wall motion abnormalities involving the posterior and inferior walls. A coronary angiogram the next day showed a total occlusion of the proximal segment of the RCA. Despite the uncertain benefit, taking into account the complete heart block, the artery was re-canalized with stent placement. She remained in complete heart block with stable hemodynamics. The heart team took the decision with the family to delay the insertion of a permanent pacemaker to maximize the chance of spontaneous recovery. Indeed, three days after coronary revascularization, her rhythm evolved into atrial fibrillation and two days later reverted to sinus rhythm with first-degree AV block and LAFB. She remained in normal sinus rhythm and first-degree AV block at her six months follow-up clinic visit. Data regarding the role of percutaneous intervention in patients presenting with late inferior STEMI and complete heart block is lacking. Our case illustrates the possible therapeutic role of late intervention in restoring sinus rhythm and avoiding the insertion of a permanent pacemaker.

Recognizing Patterns on a Resting 12-Lead Electrocardiogram

Scenario: During an annual physical examination, a healthy 55-year-old man who works as a long-haul truck driver had a routine 12-lead electrocardiogram (ECG) recorded. Overall, he had no complaints and was asymptomatic. His body mass index was within normal limits, and he was taking simvastatin for high cholesterol and lisinopril for high blood pressure (current blood pressure, 128/78 mm Hg).Sinus rhythm at 85 beats per minute with first-degree atrioventricular (AV) block and premature ventricular contractions (PVCs) in a trigeminy pattern.Trigeminy is a pattern of PVCs occurring in a series of 3 heart beats, either 2 normal sinus beats followed by a PVC (as in this example) or 1 normal sinus beat followed by 2 PVCs. Trigeminy is not common, is often transient, and can disturb the normal contraction and cardiac output of the heart because a premature impulse interrupts sinus rhythm. In this case, there are more sinus beats than PVCs, most likely supporting normal cardiac output. The PVCs are similar in morphology, or unifocal, suggesting the origin (focus) is at 1 ventricular site. The etiology of trigeminy is not definitive, but some causes include caffeine, medications (eg, antihistamines), alcohol, anxiety, and heart disease. Of note, the PR interval is slightly prolonged (210 milliseconds), meeting criteria for a first-degree AV block. This occurs when electrical conduction through the AV node is slowed but atrial to ventricular conduction is not interrupted. In this case, the continuous rhythm strip at the bottom of the 12-lead ECG is very helpful in capturing the onset and offset of the PVCs. Also, the low R-wave amplitude may be a sign for hypertensive patients requiring further workup with echocardiography.Although this patient is asymptomatic, options to monitor the patient for a long, continuous period include portable monitors like a Holter or event recorder to improve assessment of the prevalence of the PVCs and other dysrhythmias. Potential modifications that should be recommended to this patient to avoid possible triggers include reducing caffeine intake, managing anxiety, monitoring his blood pressure, and exercising (given the sedentary nature of his profession). In general, first-degree AV block is considered benign, is not traditionally treated, and in this case was not new. However, recent epidemiological research from the Framingham study indicates a relationship between first-degree AV block and a higher risk of hospitalization for heart failure, cardiovascular mortality, and all-cause mortality. Although currently asymptomatic, the patient should monitor for potential symptoms of worsening of cardiovascular health, for example, new-onset palpitations. If symptoms develop and evidence suggests more sustained arrhythmia, an echocardiogram may be warranted.

Marked PR interval variability in a patient with Brugada syndrome.

To the Editor The authors present a clinical case of a 54-year-old woman without relevant medical history other than Brugada type 1 pattern in the electrocardiogram, without chronic medication, who was referred for the cardiology outpatient clinic with palpitations. She had a strong family history of Brugada syndrome, but no history of sudden death, and she never had syncope. A transthoracic echocardiogram was performed, ruling out structural heart disease. Blood samples were analyzed, without thyroid function or electrolyte abnormalities. A 24-hour Holter examination was performed (digital Philips Zymed Holter, Model 1810 Plus Software, Philips Medical Systems) that revealed nocturnal periods of first-degree atrioventricular block (AVB) with a markedly variable PR interval and without nonconducted P waves; no other abnormalities were seen; the patient was asymptomatic. The P wave and QRS morphology were the same throughout the examination. The PR interval either increased or decreased, but it was always followed by a QRS complex. The number of P waves was the same as the QRS complexes. There was no relation between the PR interval variability and heart rate or circadian predominance. The patient is kept under follow-up in the outpatient clinic, uneventful. No genetic test was performed. First-degree AVB is typically a benign situation1; however, it is associated with increased incidence of atrial fibrillation, heart failure, and mortality during follow-up.2 In some clinical settings, it can even be associated with markedly decreased survival.3 Some data point out that first-degree AVB on a basal ECG is an independent predictor of malignant arrhythmic events in Brugada syndrome (although this association was only demonstrated with first-degree AVB on basal ECG and not on Holter examination).4,5 The PR interval is highly affected by the autonomic nervous system.6-9 Sympathetic activation results in a decrease of the PR interval, whereas parasympathetic activation originates an increase of the PR interval.6,7 Previous studies showed that the increase in PR interval in response to vagal stimulation is well correlated with vagal stimulation frequency and can be regarded as linear.7 The Brugada syndrome is diagnosed in the presence of a spontaneous type 1 pattern in patients without other heart disease, regardless of symptoms.10 It is a genetic sodium-related (INa) channelopathy.10 The most common gene involved is the SCN5A, which is also associated with conduction diseases.11 Sodium currents are responsible for propagation of action potential through the myocardial cells. As patients with Brugada syndrome have reduced INa current, conduction disease is not unexpected to occur, if the SCN5A gene is involved.12 First-degree AVB could represent a marker of increased risk because of a stronger phenotype of INa reduction, leading to increased myocardial electrical instability.5 Other identified risk markers are the localization of type 1 Brugada pattern (Figs. 1 and 2), atrial fibrillation, fragmented QRS, QRS duration >120 ms, R wave in lead aVR, S wave in lead I (≥40 ms, amplitude ≥0.1 mV, area ≥1 mm2), early repolarization pattern in inferolateral leads, ST segment depression, T‐wave alternans, dispersion of repolarization, and Tzou criteria.11 In another recent study, the S wave in lead I was the only independent predictor of persistent risk of life-threatening arrhythmic events.13Figure 1.: ECG revealing sinus rhythm with type 1 Brugada pattern.Figure 2.: (A) Holter revealing sinus rhythm with type 2 Brugada pattern and first-degree AVB with a progressive PR interval prolongation; (B) continuation of previous Holter stripe; and (C) variable PR interval, always followed by a QRS complex. A type 1 Brugada pattern was not present in this examination.The significance of this PR interval variability, with a “harmonic” appearance, is not yet known, as well as its clinical implications.

Long first-degree AVblock during acute sickle cell crisis

Long first-degree AVblock during acute sickle cell crisis

Arrhythmia in a COVID-19 patient: A case report

In this study, we considered an 83-year-old male patient admitted to the Al-Zahra hospital emergency department in Isfahan. He complained of fatigue, weakness, headache, and cough. In addition, he had hallucinations and delusions for two days; but he had no fever and chill. His physical examination showed a blood pressure of 170/100 mm Hg, heart rate of 142 beats per minute (bpm), respiratory rate of 23 pbm, oxygen saturation (in room air) of 83%, and oxygen bag reserve mask of 93%. We realized cardiac involvement during hospitalization, including sinus bradycardia, first-degree atrioventricular (AV) block, recurrent premature ventricular from tricuspid ring, atrial tachycardia (AT) rhythm with variable AV conduction block, increased heart rate with functional bundle branch block, and negative troponin. The patient was treated with medicines to control heart rate and admitted to the cardiac care unit (CCU). Next, the patient was intubated due to a worsening lung condition. Afterward, he was admitted to the intensive care unit (ICU) and died the next day. According to the literature, compromised cardiac vascular is the most common complications in hospitalized patients due to COVID-19 infection and has a higher mortality risk. Cardiac arrhythmias are additionally common clinical manifestations. These arrhythmias seem to be caused by inflammatory responses in the myocardium, electrolyte disorders, and hypoxia. Our patient showed that the COVID-19 virus might induce different types of arrhythmias.

Oxidative stress and adverse cardiovascular effects among professional divers in Egypt

Professional divers are exposed to unique multifactorial hazards in their working environment and adverse cardiovascular effects such as ischemia, arrhythmia, stroke, and death are associated with professional diving. Cardiovascular events are aggravated by diving-induced oxidative stress and account for one-fourth of diving fatalities. This study aimed to measure oxidative and cardiovascular stress in a group of professional divers in Alexandria, Egypt using a panel of biomarkers. A comparative cross-sectional study was conducted between June 2017 and May 2018 at the General Naval Hospital in Alexandria. A total of 50 professional divers and a comparison group of 50 marine seafarers sharing similar maritime environments were enrolled in the study. Participants were clinically evaluated by electrocardiography (ECG) and plasma measurement of trace metals (Fe+, Cu+, and Zn+), electrolytes (Na+, K+, Ca+), and oxidative stress biomarkers (OSBMs; MDA, TAS, GST, GSH, GR, GPx, SOD, and CAT). Significant ECG abnormalities including short corrected QT interval, sinus bradycardia, left ventricular hypertrophy, early repolarization, first-degree heart block, and intraventricular conduction defect were identified among divers. Biochemical analyses revealed high mean levels of FBG [89.0 ± 12.46 vs. 100.5 ± 29.03 mg/dl], LDH-C [41.46 ± 4.01 vs. 39.34 ± 4.34 mg/dl], electrolyte imbalance [higher Na+ (9.44 ± 0.52 vs. 9.19 ± 0.60 mmol/L), and lower Ca+ (141.72 ± 3.53 and 143.26 ± 3.99 mmol/L)], disturbed trace metals [Fe+ and Zn+ (101.1 ± 38.17 vs. 147.6 ± 38.08 and 85.52 ± 27.37 vs. 116.6 ± 21.95 µm/dl, respectively), higher Cu+ (271.3 ± 75.01 vs. 100.8 ± 30.20 µm/dl)], and higher OSBMs (high MDA and reduced CAT, GPx, GSH, GR, and GST enzyme levels) among professional divers compared to the marine seafarers (t-test p < 0.05). Oxidative stress and trace metal imbalance are associated with the pathophysiology of cardiovascular disease; this association, together with electrophysiological changes of ECG may serve as biomarkers for cardiovascular risk assessment in diver periodic medical examinations.

Electrocardiographic changes in hospitalised children with COVID-19.

Cardiac manifestations of the coronavirus disease 2019 (COVID-19) have mainly been reported in adults. Therefore, we aimed to determine the electrocardiographic abnormalities in hospitalised paediatric patients with COVID-19 and multisystemic inflammatory syndrome in children. We retrospectively evaluated hospitalised paediatric patients <18 years of age with a diagnosis of COVID-19 (n = 168) and multisystem inflammatory syndrome in children (n = 48) between March 2021 and December 2021. A daily electrocardiography was performed for the patients who had electrocardiographic abnormalities on admission or developed electrocardiographic abnormality on the follow-up. The characteristics of these patients, underlying predisposing conditions, and clinical course were also examined. Two-hundred sixteen paediatric patients (55% were male) with a mean age of 10.7 ± 4.69 years were evaluated. There was an underlying disease in 84 (38.8%) patients and 51 (23.6%) required paediatric ICU admission. Electrocardiography abnormality was detected in 12 (5.5%) which were as follows: 7 (3.2%) had sinus bradycardia, 3 (1.4%) patients had transient ST elevation and concomitant T negativity, and 2 (0.9%) developed first-degree Atrioventricular (AV) block. The median time from the onset of disease symptoms to detecting electrocardiographic abnormality was 9 days. Electrocardiographic abnormalities returned to normal uneventfully 3 days later. The prevalence of arrhythmia in paediatric patients with COVID-19 was detected in 5.5% of the patients. While two-thirds of the electrocardiography abnormalities were sinus bradycardia, ST elevation was remarkable (1.4%). Clinicians should be aware of electrocardiographic abnormalities and consider electrocardiographic monitoring in paediatric patients with COVID-19 and multisystemic inflammatory syndrome in children.

Lifestyle habits associated with cardiac conduction disease.

Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. Research to identify modifiable risk factors has been scant. Data from the Cardiovascular Health Study, a population-based cohort study of adults ≥ 65 years with annual 12-lead electrocardiograms obtained over 10 years, were utilized to examine relationships between baseline characteristics, including lifestyle habits, and conduction disease. Of 5050 participants (mean age 73 ± 6 years; 52% women), prevalent conduction disease included 257 with first-degree atrioventricular block, 99 with left anterior fascicular block, 9 with left posterior fascicular block, 193 with right bundle branch block (BBB), 76 with left BBB, and 102 with intraventricular block at baseline. After multivariable adjustment, older age, male sex, a larger body mass index, hypertension, and coronary heart disease were associated with a higher prevalence of conduction disease, whereas White race and more physical activity were associated with a lower prevalence. Over a median follow-up on 7 (interquartile range 1-9) years, 1036 developed incident conduction disease. Older age, male sex, a larger BMI, and diabetes were each associated with incident conduction disease. Of lifestyle habits, more physical activity (hazard ratio 0.91, 95% confidence interval 0.84-0.98, P = 0.017) was associated with a reduced risk, while smoking and alcohol did not exhibit a significant association. While some difficult to control comorbidities were associated with conduction disease as expected, a readily modifiable lifestyle factor, physical activity, was associated with a lower risk.

RELATIONSHIP BETWEEN MITRAL ANNULAR CALCIFICATION AND FIRST DEGREE ATRIOVENTRICULAR BLOCK IN ELDERLY

Aim: In this study, we aimed to reveal the relationship between these two degenerative processes, mitral annular calcification, and first-degree AV block. Material and method: The data of 2347 patients over the age of 65 who were examined in the cardiology outpatient clinic. A total of 389 patients with echocardiography results and 12-lead ECGs obtained at the same visit were included in their electronic records. The patient population was divided into two groups as those with or without first-degree AV block, and those with or without mitral annular calcification. Results: Considering the relationship between mitral annular calcification and first-degree AV block, first-degree AV block was observed more frequently in patients with mitral annular calcification, and this was statistically significant. ((Odds ratio: 6.881; 3.107 – 15.236 (95% CI), p&lt;0.001)) Conclusion: In our study, it was observed that first-degree AV block was more common in patients with mitral annular calcification. When these conditions are encountered in clinical follow-ups, the association should be kept in mind, and it should be remembered that a conduction defect may develop in patients with mitral annular calcification or valve pathology may occur in patients with a conduction defect.

Electrocardiographic changes in dengue fever

Electrocardiographic changes in dengue fever

Electrocardiographic changes associated with hyperkalaemia in domestic cats

Hyperkalaemia is a life-threatening electrolyte imbalance because it affects cardiac conduction and can lead to fatal arrhythmias if left untreated. The present study describes the occurrence of hyperkalaemia in cats and the electrocardiographic changes associated with this electrolyte imbalance. Hyperkalaemia was identified in 83.33 per cent of the study group subjects. Acute kidney injury and obstructive uropathy were the main clinical conditions associated with it. Electrocardiographic findings in hyperkalaemia in different cats under study included peaked T waves in lead II and the precordial lead CV6LL, atrial standstill and sino-ventricular rhythm, normal sinus rhythm, ventricular tachycardia, first-degree atrio-ventricular block, bradycardia, sinus tachycardia, and atrio-ventricular dissociation. Electrocardiography should always be performed in cases suspected of electrolyte imbalances, particularly hyperkalaemia, so as to identify any fatal arrhythmias and initiate treatment at the earliest.

Evaluation of electrocardiographic and serum biochemical changes in arrhythmias associated with renal diseases of dogs

The present study was conducted to investigate electrocardiographical (ECG) and haemato-biochemical changes in arrhythmia associated with renal diseases in dogs. The dogs with renal affections confirmed through appropriate diagnostic methods were selected and screened for arrhythmia. The ECG and haemato-biochemical parameters of twenty dogs with arrhythmia were compared with that of the control group and ECG parameters were statistically correlated with the haemato-biochemical parameters for correlation studies. It was found that the occurrence of arrhythmia was 51.2 per cent in renal diseases. Arrhythmia was more predominant in dogs with chronic kidney disease (CKD) followed by acute kidney injury (AKI). Sinus arrhythmia followed by first-degree AV block and wandering pacemaker were the common types of arrhythmias observed. A significant increase in R-R interval and a decrease in heart rate was noticed in comparison. The haemato-biochemical analysis revealed anaemia, leukocytosis with neutrophilia, elevated blood urea nitrogen (BUN), creatinine and magnesium level. A significant positive correlation was noticed between haemoglobin, volume of packed red cells (VPRC) and red blood cell count (RBC) with T amplitude and, creatinine and BUN levels with corrected Q-T interval. A significant negative correlation was noticed between VPRC, RBC and haemoglobin with the corrected QT interval. The present study revealed ECG and haemato-biochemical parameters had a significant role in renal diseases in dogs which might help in the early diagnosis and proper management of arrhythmia associated with renal diseases.

Electrocardiography and Drug Intoxication

Intoxication is the deterioration of body functions due to different toxic substances. Poisoning by drugs constitutes an important part of all poisonings. Symptoms such as altered consciousness, tachycardia/bradycardia, or hypertension/hypotension may be seen because the cardiovascular system is affected. Changes in clinical findings and ECG may be revealed according to the degree of heart involvement. Rapid recognition and effective intervention by the emergency physician are of great importance. This review considers the use of ECG in the management of poisoned patients. Systematic evaluation of the ECG in a patient followed up with poisoning is essential for details that may be overlooked. Velocity, rhythm, intervals, and segments, QRS, wave morphologies, durations, ischemic changes should be followed carefully.&#x0D; When performing rhythm analysis, clues to drug cardiotoxicity should be sought in unstable patients. Are there ectopic beats on the EKG? The answer to this question may carry important clues. Automaticity caused by sympathomimetics may underlie ectopic beats. This may be the first sign of a problem caused by acute coronary syndrome or electrolyte disturbances. Is the rhythm supraventricular? or ventricular? Is bradycardia with AV block? Or without AV block? Is tachycardia narrow complex? Or is it a large complex? Answers to questions such as: For life-threatening rhythms, ventricular tachycardia, ventricular fibrillation, and complete AV-block, the guidelines developed should be followed, and first intervention should be made. Agents that can cause tachycardia; are sympathomimetics (methamphetamine), anticholinergics (antidepressants, antipsychotics), class 1A and 1C antidysrhythmics, and TCA. Agents that can cause bradycardia; calcium channel / beta blockers / digoxin (AV block), opioids / ethanol, organophosphates, lithium. Prolonging the PR interval may indicate beta-adrenergic antagonism, calcium channel antagonism, or digoxin poisoning. Typical ECG of TCA poisoning shows sinus tachycardia with first-degree AV block, wide QRS complexes, and positive R' wave in aVR. The ECG should be taken and evaluated in patients presenting with poisoning within the first 10 minutes. Suppose the poisoning agent is an agent that influences the cardiovascular system. In that case, it should be kept in mind that continuous cardiac monitoring and control ECG evaluation should be performed in addition to the application of ECG.

Atrioventricular dyssynchrony in patients with permanent pacemaker due to sinus node dysfunction and first-degree atrioventricular block: does the long PR syndrome exist?

Atrioventricular dyssynchrony in patients with permanent pacemaker due to sinus node dysfunction and first-degree atrioventricular block: does the long PR syndrome exist?

807 MATERNAL ANTI-RO/SSA AUTOANTIBODIES AND PROLONGED PR INTERVAL IN A COMPETITIVE ATHLETE

Abstract Background Prolongation of the PR interval is a common finding among competitive athletes. However, further investigations should be performed when the PR interval is markedly prolonged. We report the case of a young male athlete with a late progressive congenital form of autoimmune-mediated atrioventricular block. Case presentation A 26-year-old male athlete was referred to our center because of a significant prolongation of the PR interval (PR=400 ms), firstly found at the age of 7 years in a preparticipation screening and then confirmed when he was 10 years old. He has been playing soccer for 6 hours/week without symptoms or limitations. His personal remote medical history was unremarkable, he did not have a family history of sudden cardiac death, channelopathies, or cardiomyopathies. Vital parameters and physical examination were normal. Blood test results were within the limits, with negative inflammation indexes and normal thyroid function. Ambulatory 12-lead ECG monitoring, including a training session to assess the chronotropic response to exercise, showed a 1st and 2nd type 1 AV block with narrow QRS without pauses and a shortening of the PR interval during the training session, also confirmed by exercise testing. After three months of detraining, no variation in the PR interval was observed. Echocardiography and cardiac magnetic resonance were normal, as well as genetic testing. Finally, we assessed the autoimmunity status of the patient and his mother, given the potential association between damage induced by anti-Ro/SSA antibodies and AV block and we found maternal seropositivity only, compatible with a late progressive congenital form of autoimmune AV bock. Accordingly, no circulating anti-Ro/SSA-autoantibodies were found in the athlete and we did not recommend immuno-modulating therapy. Considering the absence of symptoms and of cardiac, laboratory and genetic abnormalities, no circulating autoantibodies in the patient and the stability of the PR interval, the athlete was deemed eligible for sports competition. We advised him yearly follow-up visits to exclude the possibility of conduction disturbance progression. During the follow-up period he has continued to practice competitive sports without events. Discussion According to current recommendations, 1st degree AV block (up to 399 ms) and 2nd degree type 1 AV block can be considered physiological adaptations to exercise, especially if they disappear during exercise and detraining. Otherwise, further investigations are recommended to exclude abnormalities associated with sudden cardiac death in athletes, such as structural heart diseases, primary electrical diseases and autoimmunity. The most recognized form of autoimmune AV block is congenital (neonatal lupus). Growing evidence supports the existence of a late progressive congenital form, in which the conduction system injury is mediated by transplacental passage of antibodies produced by the mother and cross-reacting with calcium channels in the fetus, with a subclinical presentation in utero/at birth/in the neonatal phase and a manifest conduction disease later in life. Finally, autoimmune AV block can be acquired, in this case autoantibodies are found in the patient only and immuno-modulating therapy can be considered. In our case, maternal only seropositivity supported the hypothesis of a late progressive congenital form.

820 VARIABLE EXPRESSIVITY OF SCN5A MUTATION IN A FAMILY WITH CARDIAC DYSFUNCTION AND SUSPECTED BRUGADA SYNDROME

Abstract Background Inherited arrhythmogenic diseases (IADs) represent a group of life-threatening genetic cardiomyopathies that predispose young individuals to sudden cardiac death (SCD), often in the absence of structural cardiac alterations. Some IADs share mutations in genes encoding for surface membrane ion channels, and the gene for the alpha subunit of the voltage-dependent channel Nav1.5 (SCN5A) is among the ones mostly involved. Brugada syndrome represents one of the possible spectrum deriving from SCN5A gene mutations, and it is characterized by “loss-of-function” genetic alterations. Interestingly, both loss-of and gain-of-function mutations have been associated with familial dilated cardiomyopathy (DCM). Materials and Methods In the context of an Italian Ministry of Health-funded research project devoted to identify genetic isolates of IADs in the Calabria region, we found a family affected by different cardiovascular manifestations including cardiac dysfunction, ventricular tachyarrhythmias, atrioventricular block and suspected Brugada syndrome pattern in first-degree relatives in association with a newly identified SCN5A mutation. Results The proband came to our attention with a diagnosis of DCM, echocardiographic assessment of reduced left ventricular ejection fraction (EF) to 38%, high occurrence of premature ventricular complexes (PVCs) and first-degree atrioventricular block (PR = 240ms) at electrocardiogram. In spite of negative electrophysiologic study, he underwent implantable cardioverter defibrillator implantation (ICD), hypothesizing lamin A/C mutation; genetic analysis turned out negative for lamin A/C and CACNA1C, while a SCN5A gene mutation (c.4554 G&amp;lt;T p.Gln1518His) was detected. Proband's sons and his brother underwent clinical evaluations as well as genetic testing: the second son's ECG showed first-degree AV block (PR = 220ms), QTc interval 426ms, and coved type ST-segment elevation of 1.5mm, in the context of normal cardiac function; the remaining male (see Figure 1) was asymptomatic, while the daughter had a hypokinetic non-dilated cardiomyopathy. The proband's brother had first-degree AV block and very frequent monomorphic ventricular couplets. Conclusions These phenotypic differences in first degree-relatives, can be explained by the concept of variable expressivity of genes, according to which individuals carrying the same mutation can have different clinical features. Therefore, the search for genetic mutations assumes a preponderant role for stratifying the risk of SCN5A-related diseases and to adopt appropriate diagnostic and therapeutic strategies.

281 CARDIAC RESYNCHRONIZATION TERHAPY IN PERSISTENT LEFT SUPERIOR VENA CAVA WITH A BRIDGING INNOMINATE VEIN

Abstract Background The Persistent Left (PL) Superior Vena Cava (SVC) is a congenital malformation of the thoracic venous return that has an incidence of 0.2-3% in the general population and an incidence of about 0.5% in patients undergoing cardiac implantable electronic device. In this case, the placement of the leads, especially for the Right Ventricle (RV) and Left Ventricle (LV) through one of the branches could be challenging. Methods A 66-year-old man with hypertension, diabetes and dyslipidemia, in optimal pharmacologic therapy for congestive heart failure (NYHA II), hospitalized for recurrent syncopal episodes, with extreme sinus bradycardia, first-degree AV block and Left Bundle Branch Block, The patient had a LV hypertrophy and mild global systolic function (LV ejection fraction of 40%) for these we opted for a pacemaker CRT device implantation. Results Isolation of left cephalic vein was used as venous access for right atrium (RA) and RV leads while Seldinger technique via subclavian vein was used as venous access for LV lead. The guidewire through the subclavian vein pointed out the presence of PLSVC. Left subclavian venogram confirmed PLSVC and revealed a bridging innominate vein. To pass through the innominate vein and reach the SVC, a 0.035-inch hydrophilic guidewire was used. A 6Fr-sheath was advanced through the hydrophilic guidewire, subsequently a second metallic guidewire was advanced through the same introducer by removing the dilator. The RV and RA leads were placed respectively on low right interventricular septum and RA appendage passing through bridging innominate vein. Electrical parameters were normal. For the placement of the LV lead a 9.5Fr sheath introducer was advanced over the guidewire through the PLSVC. A venogram showed a lateral and a postero-lateral branch of the coronary sinus with acute angulation. With a 6Fr quadripolar Josephson catheter the postero-lateral branch was entered, eventually a 9Fr peelable outer guide catheter was advanced through the electrophysiology catheter becoming selective with the interested branch. A quadripolar S shaped lead was used, it was advanced into the targeted vein through a 0,014fr hydrophilic guidewire. Adequate electrical parameters and stability were achieved. Conclusion Lead implantation in patient with PLSVC is challenging. Placing the RA and RV leads through SVC ensure a better stability along time. The cannulation of CS is easily achieved by approach via PLSVC while selective vein cannulation can be difficult due to the modified acute angulation.

954 DILATED CARDIOMYOPATHY AND ATRIOVENTRICULAR BLOCK RELATED TO THE MUTATION IN THE LMNE GENE: DESCRIPTION OF A FAMILY

Abstract The proband was patient A2, suffering by severe left ventricular dysfunction (EF 20%) and II degree Mobitz type 1 atrioventricular block, requiring dual chamber ICD implantation, and retinitis pigmentosa. He had three brothers A1, A4, A5 suffering also by dilated cardiomyopathy and ICD/CRTD recipients. His sister A3, his daughter B1 and the firstborn brother A1 were also affected by retinitis pigmentosa. Genetic analysis was performed in A2 by NGS of a panel of genes related to heart disease and retinitis pigmentosa. It documented the presence of a missense pathogenetic variant (class 4) of the LMNA gene in heterozygosis (c.949G&amp;gt;A). This variant has been described in several scientific papers as associated with cardiac impairment in patients suffering from atrioventricular block and dilated cardiomyopathy. Laminin A/C is a fundamental protein of the nuclear envelope of the cell. Germline mutations in the LMNA gene, present on chromosome 22 (1q22), encoding the A/C lamina, have been causally linked to four different diseases with 42 reported mutations: Dilated cardiomyopathy (DCM) with disease of the conduction system; Limb girdle muscular dystrophy (LGMD); Autosomal dominant variant of Emery-Dreifuss muscular dystrophy (EDMD); Autosomal dominant partial lipodystrophy. LMNA-related dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and/or reduced systolic function frequently preceded or accompanied by significant conduction system disease. Family studies suggest that conduction system disease commonly precedes the development of DCM by a few years to a decade or more. Conduction system involvement usually starts with disease of the sinus node and/or atrioventricular node that can manifest as sinus bradycardia, sinus node arrest with junctional rhythms, or heart block (commonly first-degree heart block that progresses to second- and third-degree block). The following are also common: symptomatic bradyarrhythmias requiring cardiac pacemakers, supraventricular arrhythmias including atrial flutter, atrial fibrillation, supraventricular tachycardia, and the sick sinus syndrome (i.e., tachycardia-bradycardia syndrome), ventricular arrhythmias including frequent premature ventricular contractions and ventricular tachycardia Sudden cardiac death may occur with progressive disease. Although more malignant, life-threatening arrhythmias may occur with longstanding and usually previously symptomatic DCM, sudden cardiac death can also be the presenting manifestation of LMNA-related DCM, with minimal or no left ventricular dysfunction. In the cardiological setting, the AVB associated with DCM is a reliable marker for LMNA gene molecular screening. Regarding retinitis pigmentosa, the variant in heterozygosis c538C&amp;gt;G was found in the RHO gene in the proband, classifiable as pathogenetic. This gene encodes a protein necessary for the function of retinal photoreceptors and pathogenic mutations have been found in 30-40% of hereditary forms of retinitis pigmentosa. In conclusion, we believe that the tests carried out confirmed the hypothesis of a hereditary form of cardiomyopathy and retinitis pigmentosa, which seem to segregate independently in the family. Both mutations can be transmitted in 50% of cases, regardless of sex. For this reason we recommended to extend genetic analysis to all the first-degree relatives (siblings and children).

Risk of Cardiac Lesion with Chronic and Acute Use of Loperamide-An Integrative Review.

Loperamide is a synthetic opioid commonly used as an antidiarrheal due to its activation of u-opioid receptors in the myenteric plexus. In therapeutic doses, it inhibits peristalsis and has anti-secretory and anti-motility effects, until metabolized by intestinal and hepatic CYP3A4 and CYP2C8 into inactive metabolites. Furthermore, loperamide also inhibits L-type voltage-gated calcium (Ca2+) channels, increases action potential duration, and can induce arrhythmias and even cardiotoxicity, particularly when taken in extremely high doses. Thus, the aim of this study was to perform an integrative review of the available evidence in the recent literature on the cardiac risks of acute and chronic use of loperamide. In electrocardiogram (ECG) analysis, the most common finding was QTc prolongation in 27 cases, followed by QRS prolongation, first-degree atrioventricular (AV) block, torsades de pointes, ventricular tachycardia, and right bundle branch block. As for the symptoms encountered, syncope, weakness, palpitations, lightheadedness, shortness of breath, nausea, vomiting, bradycardia, and cardiac arrest were the most common. Loperamide can inhibit hERG voltage-gated potassium (K+) channels (Kv11.1), leading to the prolongation of repolarization, QTc interval prolongation, and increased risk of torsades de pointes. In addition, loperamide can inhibit voltage-gated sodium (Na+) channels (Nav1.5), impairing electrical cardiac conduction and potentiating QRS interval widening. Therefore, QTc prolongation, torsades de pointes, and other ECG alterations are of particular concern regarding loperamide toxicity, particularly when overdosed.