Bloqueo AV completo durante el ejercicio

 Abstract

Exercise-induced atrioventricular (AV) block in patients with normal electrocardiogram at rest is uncommon. We report the clinical features of two patients with AV block during treadmill test. The first patient was a woman of 54 years of age with presyncope on exercise. She developed complete AV block during exercise testing without evidence of ischemic myocardial disease. Electrophysiologic study documented distal AV block. The second patient was a man 31 years old who developed angina and third-degree AV block with depression of ST segment during treadmill test. Myocardial perfusion study suggested ischemic heart disease. He received anti-ischemic drugs with improvement of symptoms. A control exercise testing demonstrated normal AV conduction and electrophysiologic study was normal. In the first case, exercise AV block was probably due to abnormal His Purkinje conduction system refractoriness to autonomic modulation, while in second case AV block was secondary to ischemic heart disease. Third-degree AV block at exercise can be present in patients without conduction system abnormalities at rest. Exercise-induced infra-Hisian AV block must be treated with pacing until ischemic heart disease has been ruled out. *1

Abstract

In this report we describe the case of a 56-year-old woman with normal 1:1 AV conduction at rest who developed 2:1 AV block during treadmill exercise testing. Electrophysiological study documented 2:1 AV block proximal to the His bundle with reappearance of 1:1 AV conduction at a higher pacing atrial rate. A gap phenomenon involving a proximal and distal part of the AV node may be a likely explanation of paradoxical AV conduction in our case.*2

Abstract

Exercise-induced atrioventricular block in patients with normal atrioventricular conduction at rest is uncommon. Electrophysiologic studies have documented block distal to the atrioventricular node in these patients. Implantation of a permanent pacemaker is recommended because of a high incidence of subsequent symptomatic block. We report three symptomatic patients with exercise-induced atrioventricular block. Two patients showed a bundle branch block in the baseline electrocardiogram, suggesting a distal location of the block. In the remainder, with a normal QRS, the electrophysiologic study revealed AV block within the His bundle in response to atrial pacing.*3

Abstract

Three patients with 1:1 atrio-ventricular conduction at rest developed fixed 2nd or 3rd degree atrio-ventricular block during exercise testing. In all patients electrophysiologic study documented block distal to the atrioventricular node. The exercise induced block probably occurred because of increased atrial rate and abnormal refractoriness of the His-Purkinje conduction system. These findings suggest that high degree atrioventricular block appearing during exercise reflects conduction disease of the His-Purkinje system rather than of the atrio-ventricular node, even in absence of bundle branch block. These patients should be considered for permanent cardiac pacing.*4

Abstract

Four personal cases of exercise-induced conduction defects occurring during stress testing are reported. The significance of these changes is discussed in the light of the authors' observations and of the cases published in the literature. The development of atrioventricular block is usually related to pre-existing disease of the conduction system, whilst left anterior or posterior hemiblock is usually due to transient ischaemia related to significant stenosis of the coronary artery responsible for the vascularisation of the relevant bundle branch (usually a proximal stenosis of the left anterior descending artery). Complete left bundle branch block may be due to a number of conditions (including chronic ischaemic heart disease).*5

*1 A complete atrioventricular block during exertion]

[Article in Spanish]

A Medeiros et al. Arch Inst Cardiol Mex. 1999 May-Jun.

*2Exercise-induced second-degree atrioventricular block

Loukas K Pappas et al. Int J Cardiol. 2006.

*3Exercise-induced atrioventricular block

[Article in Spanish]

J M Barbero et al. Rev Esp Cardiol. 1993

*4 Intermittent atrio-ventricular block induced by exertion. Description of 3 cases]

[Article in Italian]

M Barra et al. G Ital Cardiol. 1985 Nov.

*5 Significance of exercise-induced arrhythmias]

[Article in French]

D M Marcadet et al. Arch Mal Coeur Vaiss. 1988 Aug.

Nuevas indicaciones para marcapaseo

 Abstract

New indications have recently appeared for cardiac pacing with haemodynamic and antiarrhythmic objectives without any symptomatic bradycardia. The best documented indication, though relatively rare, is stimulation of obstructive hypertrophic cardiomyopathy; initially reserved for cases with favorable results of an acute haemodynamic test, it is now used in other cases without this criterion; hypertrophic cardiomyopathy without permanent obstruction, atrial fibrillation or left bundle branch block. The improvement observed during follow-up is always greater as a real remodeling of the myocardium seems to occur with ventricular dilatation and/or septal thinning. However, the position of the atrial, and above all, of the ventricular pacing catheters is critical as is regulation of the pacemaker which should allow complete ventricular capture with an AV delay allowing good filling. The follow-up of these patients must therefore be regular and the effects on longevity are unknown. DDD pacing has also been proposed in dilated cardiomyopathy. The results are contradictory and only very selected cases with left bundle branch block and long PR interval seem justified with, again, optimisation of the pacing sites with high septal or biventricular stimulation. Recurrent atrial tachycardia, special algorithms preventing extrasystoles have been tried with variable results. In cases with inter-atrial block, atrial resynchronisation by bi-atrial stimulation has been assessed with promising results but many technical problems remain unsolved.*1

Abstract

In view of the large number of inappropriate shocks observed in patients with implanted defibrillators, improved detection of ventricular arrhythmias has become a major objective. The addition of an atrial catheter has been proposed to improve discrimination between ventricular and non-ventricular arrhythmias. Besides this function, the additional catheter could be used for DDD pacing without risk of interaction between the pacemaker and defibrillator. The authors report their initial experience in 16 patients implanted with a DDD pacemaker. The indication was resuscitated sudden death (N = 5) or ventricular tachycardia (N = 11). The choice of a DDD defibrillator was justified by a bradycardia (N = 9), haemodynamic factors (N = 4) or supraventricular tachycardia (N = 3). The devices used were the Defender 9001 (ELA Medical SA, France, N = 3), the Ventak AV 1810 and the Ventak AV II DR 1821 (Guidant/CPI, Inc. USA, N = 11 and N = 2 respectively). There were three immediate complications. After 2 to 29 months' follow-up, 5 patients had received appropriate treatment by their devices. Five patients had inappropriate shocks : one patient received a shock triggered by electrical interference, two others had no active sensing algorithme when the shocks were delivered, and the other two had an activated algorithme with 1/1 conduction of a supraventricular arrhythmia. No recurrences were recorded after reprogramming the device. DDD or VDD pacing was permanent in 9 patients and intermittent in 3 others. Seven patients had dilated cardiomyopathy and severe cardiac failure and were clinically improved by dual chamber pacing. In many patients, candidates for a defibrillator, this new generation of devices has improved specificity of arrhythmia detection and cardiac pacing without risk of interaction. The authors propose a classification of the indications for a DDD defibrillator.*2

Abstract

T he Dual Chamber and VVI Implantable Defibrillator (DAVID) trial randomized 506 patients and tested the hypothesis that the dual-chamber pacing mode would produce improved hemodynamics and would in turn reduce congestive heart failure, heart failure hospitalizations, heart failure deaths, atrial fibrillation, strokes, ventricular arrhythmias, and total mortality compared to backup ventricular pacing in patients indicated for implantable defibrillator therapy. Patients had either primary prevention indications (47%) or secondary prevention indications (53%) for implantable defibrillator therapy but had no indications for bradycardia pacemaker support. All the patients had moderate to severe left ventricular dysfunction with a left ventricular ejection fraction of 40% or less (mean = 27%) and were consistently treated with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (86%) and beta adrenergic blocking agents (85%). The primary combined endpoint of hospitalization for congestive heart failure or death was paradoxically increased and statistically significant ( p = 0.03) at one year in the patients paced in the dual chamber mode (22.6%) compared to patients randomized to ventricular backup pacing (13.3%). Both heart failure hospitalization and mortality contributed outcome. Another perspective would consider this a randomized controlled study of presence or absence of pacemaker therapy in patients with left ventricular dysfunction and indications for implantable defibrillator therapy. Ventricular backup pacing produced less than 3% ventricular and no atrial pacing, while dual chamber pacing produced approximately 60% atrial and ventricular paced heart beats. The poor outcome in the dual chamber paced group correlated with the percentage of right ventricular pacing and suggests that right ventricular pacing caused ventricular dyssynchrony. The poor outcome associated with right ventricular pacing compared to intrinsic activation in the control group of the DAVID trial is reminiscent of the poor outcome associated with prolonged intraventricular conduction activation in the control groups compared to biventricular pacing in the intervention groups of the cardiac resynchronization trials. The direct conclusion from these results are that patients with indications for implantable defibrillators and no indication for pacing should not be paced in the dual chamber pacing mode. It is not appropriate to conclude that only single chamber implantable defibrillators should be implanted. There are other potential advantages to having an implanted atrial lead including improved secondary outcomes. However the DAVID trial results suggest that the dual chamber paced mode was not associated with improved quality of life or decreased frequency of hospitalization, inappropriate shocks from the defibrillator or atrial fibrillation. The more important question is what is the optimal pacing mode in these patients? The AAIR mode is under investigation in the DAVID II study in an attempt to identify a pacing mode that preserves atrio-ventricular synchrony, normal atrio-ventricular timing, prevents bradycardia and also prevents right ventricular stimulation. Caution should be taken to not directly apply these results to patients with either an indication for pacemaker therapy or to patients with an indication for cardiac resynchronization therapy since patients from neither population were included. However, considering the large magnitude of the deleterious effects associated with dual chamber pacing in the DAVID trial future studies should explore the possibility that left ventricular stimulation may be the only pacing mode capable of preventing bradycardia without increasing death and congestive heart failure.*3

Abstract

We compared 2 studies of implantable cardiac defibrillators (ICDs) to determine the effects of device mode on outcomes. The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial (1993 to 1997) demonstrated improved survival with the ICD compared with antiarrhythmic drug therapy. The Dual-chamber And VVI Implantable Defibrillator (DAVID) trial (2000 to 2002) showed that VVI pacing at 40 beats/min in patients with ICDs reduced the combined end point of death and hospitalization for congestive heart failure compared with DDDR pacing at 70 beats/min. Patients in the AVID trial (631 of 1,016) and the DAVID trial (221 of 506) meeting common inclusion and all exclusion criteria were studied. The major end points were the time to death, and the composite end point of time to death or hospitalization for congestive heart failure. Patients in the AVID and DAVID trials were similar, but more AVID patients had coronary artery disease (p = 0.04), history of myocardial infarction (p = 0.005), and previous ventricular arrhythmias (p = 0.03). DAVID patients underwent more previous revascularization procedures (coronary artery bypass surgery, p = 0.03; percutaneous coronary intervention, p = 0.001), and were more often taking beta-blocking drugs at hospital discharge (p <0.001). The backup VVI ICD groups in both studies had similar outcomes (p = 0.4), even when corrected for the previous demographic differences. The time-to- composite end point was similar in AVID patients treated with antiarrhythmic drugs and DAVID patients treated with DDDR ICDs (p = 0.6). Despite improved pharmacologic therapy and revascularization, outcomes have not improved with backup VVI pacing ICDs. If DDDR ICDs had been used in the AVID trial, benefit from ICDs for patients with serious ventricular arrhythmias could have been missed.*4

Abstract

Context: Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure.

Objective: To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing.

Design: The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial.

Setting and participants: A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias.

Interventions: All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients.

Main outcome measure: Composite end point of time to death or first hospitalization for congestive heart failure.

Results: One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming.

Conclusion: For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.*5

*1New indications for cardiac pacing

[Article in French]

J M Davy et al. Arch Mal Coeur Vaiss. 1995 Dec

*2Dual-chamber implantable automatic defibrillators. Experiences apropos of 16 cases]

[Article in French]

P Le Franc et al. Arch Mal Coeur Vaiss. 1998 Jun.

*3The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial: rationale, design, results, clinical implications and lessons for future trials

Bruce L Wilkoff et al. Card Electrophysiol Rev. 2003 Dec.

*4A comparison of the AVID and DAVID trials of implantable defibrillators.

Arjun Sharma et al. Am J Cardiol. 2005.

*5Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial

Bruce L Wilkoff et al. JAMA. 2002.

Sindrome de brugada inducido.

 Abstract

Brugada syndrome is an inherited cardiac condition with the potential for development of life-threatening arrhythmias in relatively young individuals without significant structural cardiac abnormalities. The condition is characterized by a distinct coved-type ST segment elevation in the right precordial leads (V1-V3). This hallmark pattern (type 1) is often dynamic and sometimes concealed, and may be unmasked in certain conditions or under the effect of certain agents, which include variation of sympathovagal balance, hormones, metabolic factors and drugs. These factors may not only modulate electrocardiographic morphology and induce the characteristic type 1 pattern, but also predispose to ventricular arrhythmias. The risk of malignant arrhythmias in acute events with induced type 1 pattern may be imminent, particularly if the patient in fact has Brugada syndrome. The physician should be aware of the modulating factors that may underlie a Brugada pattern, and be able to recognize, identify and promptly correct them. The mechanisms responsible for the type 1 pattern and possible associated ventricular arrhythmias induced by these modulating factors have attracted growing attention and interest. Furthermore, not all induced Brugada ECG patterns are observed in patients with Brugada syndrome, existing the possibility for acquired Brugada patterns/syndrome and Brugada phenocopies. This paper reviews the modulating factors associated with induced type 1 pattern as possible causes of arrhythmogenesis, particularly in Brugada syndrome patients, describes some of the probable underlying mechanisms, and discusses the concepts of acquired Brugada syndrome and Brugada phenocopies.

Keywords: Arritmia ventricular; Brugada phenocopy; Brugada syndrome; Exercise; Exercício; Febre; Fenocópias; Fever; Iatrogenia farmacológica; Iatrogenic drugs; Síndrome de Brugada; Ventricular arrhythmia.

Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved. *1

Abstract

When an ECG shows (or is suspicious for) a Brugada pattern, i.e., the association of a positive terminal deflection and ST segment elevation in the right precordial leads, the cardiologist often faces several problems. Three important questions are raised by this ECG pattern: (1) is this really a Brugada ECG pattern? (2) How can be determined whether this patient is at risk for sudden death? and (3) Should this patient receive an implantable cardioverter-defibrillator (ICD)? The term "Brugada syndrome" should be restricted to patients who have diagnostic ECG changes, as well as a history of symptoms. Asymptomatic subjects, in contrast, should be categorized as having a "Brugada ECG pattern" rather than the syndrome. Diagnostic ECG (type 1) is characterized by a J wave (a terminal positive wave) whose amplitude is > or =2 mm, and a "coved" type ST segment elevation located in the right precordial leads. These signs are usually present in leads V1 and/or V2 (lead V3 is more rarely involved, and is never the only affected one), but occasionally also can be observed in some of the limb leads. Types 2 and 3 ECGs, which are not truly diagnostic of Brugada pattern, are characterized by a "saddle back" ST segment elevation, that is > or =1 mm in type 2 and <1 mm in type 3. In Brugada ECG pattern, the QRS complex characteristically shows a positive terminal deflection that mimics an r' prime wave (the wave occurring in right bundle branch block), in the right precordial leads. Actually, it is a J wave that is very similar to the "Osborn" one observed during hypothermia. The J wave of Brugada ECG pattern is generated by a voltage gradient across the myocardial wall of the right ventricular outflow tract. This abnormal potential can be recorded only by electrodes located very close to the site where that phenomenon is originating. Displacement of the right precordial leads electrodes one or two intercostal spaces above their normal positions may, at times, disclose the diagnostic pattern when conventional leads, recorded at the fourth intercostal space, are non-diagnostic or even normal. High right precordial leads should be recorded whenever standard V1-V3 leads raise the suspicion of Brugada pattern. For example, when a relatively large positive terminal wave, even of low amplitude, is recorded, placing high right precordial leads is an option that should be considered. The ECG may show a marked variation over time, ranging from the typical pattern to a completely normal ECG and back again. In subjects with a non-diagnostic ECG, a pharmacological test with sodium channel blockers may disclose the typical Brugada pattern. In order to establish the diagnosis, several conditions that can mimic Brugada pattern must be excluded. These include right bundle branch block, early repolarization, acute myocardial ischemia, pericarditis, hypercalcemia, hyperkalemia, hypothermia and primary right ventricular diseases, particularly arrhythmogenic right ventricular dysplasia. Some drugs (e.g., some antiarrhythmic drugs, psychotropic agents or antihistamines), hyperthermia and enhanced vagal tone, as it occurs after a full meal, may render Brugada pattern more evident on the ECG. Typical ventricular arrhythmia in Brugada syndrome is a polymorphic ventricular tachycardia, that can evolve into ventricular fibrillation; its mechanism is assumed to be phase 2 reentry. Monomorphic ventricular tachycardia is rarely seen. Atrial fibrillation occurs more frequently in patients with the Brugada ECG pattern than in the general population. A mutation in the SCN5A gene, which encodes the alpha subunit of the cardiac sodium channel, is found in about 20% of the subjects with Brugada pattern; mutations in other genes have less frequently been described. Genetic testing is not very helpful in formulating the diagnosis, but when a mutation is found it could be useful to extend testing to first degree relatives, enabling early detection of abnormal gene carriers. Patients who have experienced an aborted sudden death have a high risk of recurrence and should receive an ICD. A history of syncope, spontaneous type 1 ECG and male sex, not family history of sudden death, are independent risk factors. The role of programmed ventricular stimulation in risk stratification remains the subject of debate. Asymptomatic patients with a Brugada ECG pattern should: (1) receive adequate information on current knowledge concerning this topic, (2) be given the list of forbidden drugs, (3) be informed to promptly treat hyperthermia, (4) be informed that clinical evaluation should be extended to their first degree relatives, 5) undergo regular cardiology follow-up. Also in this group the role of programmed ventricular stimulation in risk stratification is debated. Subjects showing a Brugada pattern after a pharmacological challenge should be followed-up with ECG and 12-lead Holter monitoring, if available, to identify the appearance of spontaneous type 1 ECG. Symptoms should be promptly reported.*2

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Abstract

Objectives: We examined the modulatory effects of autonomic nervous system and antiarrhythmic drugs on the ST segment in patients with Brugada syndrome to gain an insight into the mechanism of ST segment elevation.

Background: Right bundle branch block, ST segment elevation and ventricular tachyarrhythmias define a distinct clinical and electrocardiographic (ECG) syndrome (Brugada syndrome). However, the mechanism of ST segment elevation and the causes of this syndrome are unknown.

Methods: The study included four patients in whom structural heart or coronary artery disease was excluded by noninvasive and invasive tests. High take-off ST segment elevation of either the coved or saddle-back type in precordial leads V1, V2 and V3 was seen in all patients. Three patients experienced recurrent episodes of syncope or aborted sudden cardiac death, and the remaining patient had palpitation. Autonomic receptor stimulation and blockade and intravenous administration of antiarrhythmic drugs were performed during sinus rhythm while the 12-lead ECG was recorded. Metaiodobenzylguanidine (MIBG) scanning and Holter monitoring were also performed.

Results: Beta-adrenoceptor stimulation by intravenous isoproterenol consistently reduced (> or = 0.1 mV) ST segment elevation at or 80 ms after the J point in all four patients. Selective alpha-adrenoceptor stimulation by intravenous norepinephrine in the presence of propranolol or by intravenous methoxamine consistently augmented, whereas alpha-adrenoceptor blockade reduced, ST segment elevation in three patients. Intracoronary acetylcholine or intravenous edrophonium or neostigmine augmented ST segment elevation without inducing coronary spasm in three of four patients. Class IA antiarrhythmic drugs also consistently augmented (three patients), whereas class IB drugs had no effect on (two patients) ST segment elevation. No abnormality was found on MIBG imaging or heart rate variability in three patients, suggesting that autonomic dysfunction is not a primary disease process. Class IA drugs had no effect on ST segment in three control patients, suggesting that the ST segment elevation seen in patients with Brugada syndrome in response to the drugs is not a nonspecific response.

Conclusions: ST segment elevation in patients with Brugada syndrome was augmented by selective stimulation of alpha-adrenoceptors or muscarinic receptors or by class IA drugs but was mitigated by beta-adrenoceptor stimulation or alpha-adrenoceptor blockade. These responses might be explained by postulating the presence of an area of early repolarization or a local "depolarized" area in the ventricle causing ST segment elevation in this syndrome. Because only a small number of patients were studied, these possibilities need further evaluation.*3

Abstract

In 1992 a new syndrome was described consisting of syncopal episodes and/or sudden death in patients with a structurally normal heart and an electrocardiogram (ECG) characteristic of right bundle branch block with ST segment elevation in leads V1 to V3. The disease is genetically determined, with an autosomal dominant pattern of transmission. Three different mutations that affect the structure and function of the cardiac sodium channel gene SCN5A have been identified. Two mutations result in total loss of function of the sodium channel. The other mutation results in acceleration of the recovery of the sodium channel from inactivation. The incidence of the disease is difficult to estimate, but it causes 4 to 10 sudden deaths per 10000 inhabitants per year in areas like Thailand and Laos. In these countries, the disease represents the most frequent cause of death in young adults. Up to 50% of the yearly sudden deaths in patients with a structurally normal heart are caused by this syndrome. The diagnosis is easily made by means of the ECG. The presence of concealed and intermittent forms, however, make the diagnosis difficult in some patients. The ECG can be modulated by changes in autonomic balance and the administration of antiarrhythmic drugs. Beta-adrenergic stimulation normalizes the ECG, while intravenous ajmaline, flecainide or procainamide accentuate ST segment elevation and are capable of unmasking concealed and intermittent forms of the disease. Recent data suggest that loss of the action potential dome in the right ventricular epicardium but not the endocardium underlies ST segment elevation seen in the Brugada syndrome. Also, electrical heterogeneity within the right ventricular epicardium leads to the development of closely coupled extrasystoles via a phase 2 reentrant mechanism, which then precipitates ventricular tachycardia-ventricular fibrillation. Right ventricular epicardium is preferentially affected because of the predominance of transient outward current in this tissue. Antiarrhythmic drugs like amiodarone and beta-blockers do not prevent sudden death in symptomatic or asymptomatic individuals. Gene therapy may offer a cure in future years. Implantation of an automatic cardioverter-defibrillator is the only currently proven effective therapy.*4

Abstract

In 1992 we described a new syndrome characterized by syncopal or sudden death episodes in patients with a structurally normal heart and a characteristic electrocardiogram 9 showing a pattern of right bundle branch block and ST segment elevation in right precordial leads V1 to V3. The disease is genetically determined with and autosomic dominant pattern of transmission. Until now three mutations and one polymorphism in the sodium cardiac channel gene have been identified in two families and one sporadic patient. As in many other genetically determined diseases, the disease is heterogeneous, caused by more than one gene. The syndrome has been identified in almost all countries in the world. Its incidence is difficult to evaluate, but it seems to be responsible for 4 to 10 sudden deaths per year per 10,000 inhabitants in areas like Laos or Thailand, and it represents the most frequent cause of death in young male adults in these countries. Up to 50% of all sudden deaths in patients with structurally normal heart are caused by the disease. The diagnosis can be easily made thanks to the characteristic electrocardiographic pattern. In some patients, the presence of concealed and intermittent forms might make the diagnosis more difficult. The electrocardiogram can be modulated by autonomic changes and administration of antiarrhythmic drugs. Beta-adrenergic stimulation normalizes the electrocardiogram, whereas ajmaline, flecainide or procainamide administration increase ST segment elevation. These drugs allow the unmasking of concealed or intermittent forms of the disease. Prognosis of patients with the syndrome is poor without an implantable defibrillator and antiarrhythmic drugs like amiodarone or betablockers do not protect against sudden death. The poor prognosis is similar in patients with a history of aborted sudden death or syncope and in asymptomatic patients in whom the abnormal electrocardiogram characteristic of the syndrome, was identified during a routine examination.*5

*1Induced Brugada syndrome: Possible sources of arrhythmogenesis

[Article in English, Portuguese]

Gonçalo Tomé et al. Rev Port Cardiol. 2017 Dec.

*2Doubts of the cardiologist regarding an electrocardiogram presenting QRS V1-V2 complexes with positive terminal wave and ST segment elevation. Consensus Conference promoted by the Italian Cardiology Society

[Article in Italian]

Giuseppe Oreto et al. G Ital Cardiol (Rome). 2010 Nov.

*3Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome.

T Miyazaki et al. J Am Coll Cardiol. 1996 Apr.

*4The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome

J Brugada et al. Europace. 1999 Jul.

*5 Sudden death (VI). The Brugada syndrome and right myocardiopathies as a cause of sudden death. The differences and similarities]

[Article in Spanish]

J Brugada et al. Rev Esp Cardiol. 2000 Feb.

Síndrome QT largo congenito

 Abstract in English, Spanish

Congenital long QT syndrome (LQTS) represents a group of heart diseases of genetic origin characterized by prolongation of the QT interval and an abnormal T wave on the electrocardiogram (ECG). They can have a dominant or recessive expression, the latter associated with sensorineural deafness. In both cases, its clinical presentation is associated with recurrent syncope and sudden death as a consequence of ventricular tachycardia, specifically Torsades de Pointes. Currently they are classified according to the specific genetic defect, being able to compromise around 16 genes and almost 2000 mutations. It should be suspected in individuals with related symptoms, electrocardiographic findings, and family history. Management is based on the reduction or elimination of symptoms, and concomitantly the prevention of sudden death (SD), in those children with congenital deafness, the management requires the application of the otolaryngologist specialist's own measures. The cardiovascular management implies the modification of lifestyles, mainly the prohibition of competitive sports, including swimming, avoiding exposure to loud sounds or triggers. The medications used include beta-blockers, and more rarely flecainide, ranozaline, and verapamil; invasive management consists of the implantation of a cardioverter defibrillator or even left sympathetic denervation, each with its own risks and benefits. In any of the cases, we must avoid the circumstances that increase the QT interval, as well as carry out the appropriate analysis of the benefits and risks of each possible invasive measure.

Keywords: Death, Sudden; Long QT Syndrome; Pediatrics; Torsades de Pointes.*1

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Abstract

Long QT syndrome (LQTS) is a rare cardiac channelopathy associated with syncope and sudden death due to torsades de pointes and ventricular fibrillation. Syncope and sudden death are frequently associated with physical and emotional stress. Management of patients with LQTS consists of life-style modification, β-blockers, left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillator (ICD) implantation. Prohibition of competitive exercise and avoidance of QT-prolonging drugs are important issues in life-style modification. Although β-blockers are the primary treatment modality for patients with LQTS, these drugs are not completely effective in some patients. Lifelong ICD implantation in young and active patients is associated with significant complications. LCSD is a relatively simple and highly effective surgical procedure. However, LCSD is rarely used.

Keywords: Adrenergic beta-blocker; Defibrillators, implantable; Long QT syndrome; Sympathectomy.

PubMed Disclaimer

Conflict of interest statement

The authors have no financial conflicts of interest.*2

Abstract

Objectives: This study sought to report our single-center experience with left cardiac sympathetic denervation (LCSD) for long QT syndrome (LQTS) since 1973.

Background: LCSD is still underutilized because clinicians are often uncertain whether to use it versus an implantable cardioverter-defibrillator (ICD).

Methods: We performed LCSD in 125 patients with LQTS (58% women, mean QT interval corrected for frequency [QTc] 527 ± 60 ms, 90% on beta blockers) with a follow-up of 12.9 ± 10.3 years. They were retrospectively divided into 4 groups according to the clinical/genetic status: very high risk (n = 18, symptomatic in the first year of life or with highly malignant genetics), with aborted cardiac arrest (ACA) (n = 31), with syncope and/or ICD shocks on beta blockers (n = 45), in primary prevention (n = 31).

Results: After LCSD, 17% in the very high risk group remained asymptomatic, compared with 52%, 47%, and 97% in the other 3 groups (P < 0.0001), with an overall 86% decrease in the mean yearly cardiac event rate (P < 0.0001). Among 45 patients with only syncope/ICD shocks before LCSD, none had ACA/sudden death as first symptom after LCSD and a 6-month post-LCSD QTc <500 ms predicted excellent outcome. Patients with a QTc ≥500 ms have a 50% chance of shortening it by an average of 60 ms. LCSD results are not affected by common genotypes.

Conclusions: We provide definitive evidence for the long-term efficacy of LCSD in LQTS. The degree of antiarrhythmic protection is influenced by patient's specificity and amount of QTc shortening. This novel approach to the analysis of the outcome allows cardiologists to rationally decide and tailor their management strategies to the individual features of their patients.

Keywords: cardiac sympathetic denervation; genetics; implantable cardioverter-defibrillator; long QT syndrome; sudden death; sympathetic nervous system.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.*3

Abstract

Long QT syndrome (LQTS) is a potentially life-threatening, but highly treatable genetic heart disease. LQTS-directed therapies often consist of beta-blockers (BBs), left cardiac sympathetic denervation (LCSD), and/or an implantable cardioverter defibrillator (ICD). However, in clinical practice, many patient-specific and genotype-directed permutations exist. Herein, we aim to review the spectrum of treatment configurations utilized at a single, tertiary center specializing in the care of patients with LQTS to demonstrate optimal LQTS-directed management is not amenable to a "one-size-fits-all" approach but instead benefits from patient- and genotype-tailored strategies.

Keywords: Genetic testing; Long QT syndrome; Precision therapy; Sudden cardiac death.

Copyright © 2022 Elsevier Inc. All rights reserved. *4

Abstract in English, Chinese

Objective: To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD) for long QT syndrome(LQTS) patients with either recurrence on drug therapy intolerance/refusal. Methods: This study was a retrospective cohort study. The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012. This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People's Hospital or Beijing Tongren Hospital. The patients were allocated into 3 groups: high-risk group(n=13, baseline QTc ≥550 ms or symptomatic in the first year of life or highly malignant genetics); intermediate-risk group(n=10, 500 ms≤baseline QTc<550 ms, symptomatic after the first year and without highly malignant genetics); low-risk group(n=5, baseline QTc<500 ms, symptomatic after the first year and without highly malignant genetics). LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery (VATS). Patients were regularly followed up until 20 years after the surgery. Data were collected before and 1 year after surgery and at the last follow-up. Patients' electrocardiograph(ECG), cardiac events and surgery-related complications were recorded. Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes. Results: A total of 28 LQTS patients, aged 20.5 (15.0, 37.5) and underwent LCSD surgery, were enrolled in this study, including 23(82.1%) women. There were 11(39.3%) patients treated with traditional approach while 17(60.7%) with VATS-LCSD. There were 19(67.9%) patients had positive genetic test results, including 4 LQT1, 12 LQT2, 1 LQT1/LQT2 mixed type, and 2 Jervell-Lange-Nielsen (JLN) syndrome. The median follow-up period was 189.3(138.7, 204.9) months. The dropout rate was 10.7%(3/28) while 3 patients in the intermediate-risk group were lost to follow-up. Horner syndrome occurred in 1 patient (in the high-risk group). Sudden cardiac deaths were observed in 3 (12.0%) patients (all in the high-risk group), and 12 patients (48.0%) had syncope recurrences (2 in low-risk group, 3 in intermediate-risk group and 7 in high-risk group). A significant reduction in the mean yearly episodes of cardiac events was observed, from (3.5±3.3) before LCSD to(0.2±0.1) at one year after LCSD and (0.5±0.8) at last follow up(P<0.001). The mean QTc was shortened from (545.7±51.2)ms before the surgery to (489.0±40.1)ms at the last follow-up (P<0.001). Among the 20 patients with basic QTc ≥500 ms and completing the follow-up, the QTc intervals of 11(55.0%) patients were shortened to below 500 ms. The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-, intermediate- and high-risk groups, and the difference was statistically significant (χ²=7.24, log-rank P=0.026). No difference was found in the event free survival rates among LQT1, LQT2 and undefined gene patients (χ²=5.20, log-rank P>0.05). Conclusions: LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up. LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy. However, high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.*5

*1Congenital long QT syndrome

[Article in Spanish]

Luis Alfredo Melgar Quicaño et al. Arch Peru Cardiol Cir Cardiovasc. 2021.

*2Management of Patients with Long QT Syndrome

Yongkeun Cho. Korean Circ J. 2016 Nov.

*3Left Cardiac Sympathetic Denervation for Long QT Syndrome: 50 Years' Experience Provides Guidance for Management

Veronica Dusi et al. JACC Clin Electrophysiol. 2022 Mar.

Free article

*4Precision therapy in congenital long QT syndrome

Raquel Neves et al. Trends Cardiovasc Med. 2024 Jan.

*5The long-term efficacy of left cardiac sympathetic denervation in long QT syndrome

[Article in Chinese]

X Li et al. Zhonghua Xin Xue Guan Bing Za Zhi. 2022.

Sindrome aórtico agudo

 Abstract

Acute aortic syndrome embraces a group of heterogenous pathological entities involving the aortic wall with a common clinical profile. The current epidemiology, clinical presentation, diagnosis and treatment strategy are discussed in this review. Besides, the importance of multidisciplinary aortic teams, aortic centers and the implementation of an aortic code are emphasized.

Keywords: Acute aortic syndrome; Aortic code; Aortic dissection; Código aorta; Disección aórtica; Hematoma intramural aórtico; Intramural aortic hematoma; Penetrating aortic ulcer; Síndrome aórtico agudo; Úlcera penetrante aórtica.*1

Abstract

Background: Acute aortic syndromes comprise a spectrum of diseases including aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcers. Early diagnosis, rapid intervention, and multidisciplinary team care are vital to efficiently manage time-sensitive aortic emergencies, mobilize appropriate resources, and optimize clinical outcomes.

Objective: This comprehensive review outlines the multidisciplinary team approach from initial presentation to definitive interventional treatment and post-operative care.

Discussion: Acute aortic syndromes can be life-threatening and require prompt diagnosis and aggressive initiation of blood pressure and pain control to prevent subsequent complications. Early time to diagnosis and intervention are associated with improved outcomes.

Conclusions: A multidisciplinary team can help promptly diagnose and manage aortic syndromes.

Keywords: Aortic dissection; Aortic syndromes; Cardiac surgery; Vascular surgery.*2

Abstract

Acute aortic syndromes are disorders of the thoracic and abdominal aorta that are usually symptomatic and require urgent evaluation and treatment. They include acute aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer. Knowledge of the natural history of these conditions, prompt diagnosis, and surgical intervention, when indicated, are the keys to successful outcomes.

PubMed Disclaimer

Figures *3

Abstract

Objective: For intramural hematoma and penetrating atherosclerotic ulcer, long-term behavior and treatment are controversial. This study evaluates the long-term behavior of intramural hematoma and penetrating atherosclerotic ulcer, including radiologic follow-up and survival analysis.

Methods: Between 1995 and 2014, 108 patients (mean age, 70.8 ± 10 years; 56% female) presented with intramural hematoma or penetrating atherosclerotic ulcer to Yale-New Haven Hospital (New Haven, Conn). We reviewed the medical records, radiology, and online mortality databases.

Results: Ten of 55 patients (18%) with intramural hematoma and 17 of 53 patients (32%) with penetrating atherosclerotic ulcer had rupture state symptoms on admission, both greater than type A (8%) or type B dissection (4%) (P < .001). No branch vascular occlusion occurred. For patients with intramural hematoma with follow-up imaging, 8 of 14 (57%) worsened (mean follow-up, 9.4 months) and 6 (43%) underwent late surgery. For patients with penetrating atherosclerotic ulcer with follow-up imaging, 6 of 20 (30%) worsened and underwent late surgery, and 11 (55%) showed no change (mean follow-up, 34.3 months). Overall survivals were 77%, 70%, 58%, and 33% at 1, 3, 5, and 10 years, respectively. No operative deaths occurred for patients with nonrupture state. Patients with penetrating atherosclerotic ulcer with initial surgical treatment had better long-term survival than patients treated medically (P = .037). In the intramural hematoma group, no such difference was observed (P = .10).

Conclusions: At presentation, the incidence of early rupture of intramural hematoma and penetrating atherosclerotic ulcer was higher than for typical dissection. For branch vessels, intramural hematoma never occludes branch arteries. On imaging follow-up, patients with intramural hematoma and penetrating atherosclerotic ulcer rarely improved, with late surgery commonly needed. Better survival was observed for the initial surgical management of patients with penetrating atherosclerotic ulcer compared with initial medical management.

Keywords: intramural hematoma; long-term follow-up; penetrating atherosclerotic ulcer.

Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

PubMed Disclaimer *4

Abstract

Background: The aim of the study was to analyze aortic-related outcomes after diagnosis of aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU) from a population-based approach.

Methods: Retrospective review of an incident cohort of AD, IMH, and PAU patients in Olmsted County, Minnesota from 1995 to 2015. Primary end point was aortic death. Secondary end points were subsequent aortic events (aortic intervention, new dissection, or rupture not present at presentation) and first-time diagnosis of an aortic aneurysm. Outcomes were compared with randomly selected population referents matched for age and sex in a 3:1 ratio using Cox proportional hazards regression adjusting for comorbidities.

Results: Among 133 patients (77 AD, 21 IMH, and 35 PAU), 57% were males, and mean age was 71.8 years (standard deviation, 14). Median follow-up was 10 years. Of 73 deaths among AD/IMH/PAU patients, 23 (32%) were aortic-related. Estimated freedom from aortic death was 84%, 80%, and 77% at 5, 10, and 15 years. There were no aortic deaths among population referents (adjusted hazard ratio [HR] for aortic death in AD/IMH/PAU, 184.7; 95% confidence interval [95% CI], 10.3-3,299.2; P < 0.001). Fifty (38%) AD/IMH/PAU patients had a subsequent aortic event (aortic intervention, new dissection, or rupture), whereas there were 8 (2%) aortic events among population referents (all elective aneurysm repairs; adjusted HR for any aortic event and aortic intervention in AD/IMH/PAU patients, 33.3; 95% CI, 15.3-72.0; P < 0.001 and 31.5; 95% CI, 14.5-68.4; P < 0.001, respectively). After excluding aortic events/interventions ≤14 days of diagnosis, AD/IMH/PAU patients remained at increased risk of any aortic event (adjusted HR, 10.8; 95% CI, 3.9-29.8; P < 0.001) and aortic intervention (adjusted HR, 9.6; 95% CI, 3.4-26.8; P < 0.001). Among those subjects with available follow-up imaging, the risk of first-time diagnosis of aortic aneurysm was significantly increased for AD/IMH/PAU patients when compared with population referents (adjusted HR, 10.9; 95% CI, 5.4-21.7; P < 0.001 and 8.3; 95% CI, 4.1-16.7; P < 0.001 for thoracic and abdominal aneurysms, respectively) and remained increased when excluding aneurysms that formed within 14 days of AD/IMH/PAU (adjusted HR, 6.2; 95% CI, 1.8-21.1; P = 0.004 and 2.8; 95% CI, 1.0-7.6; P = 0.040 for thoracic and abdominal aneurysms, respectively).

Conclusions: AD/IMH/PAU patients have a substantial risk of aortic death, any aortic event, aortic intervention, and first-time diagnosis of aortic aneurysm that persists even when the acute phase (≤14 days after diagnosis) is uncomplicated. Advances in postdiagnosis treatment are necessary to improve the prognosis in these patients.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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Figures

*1Acute aortic syndrome

[Article in English, Spanish]

Isidre Vilacosta et al. Med Clin (Barc). 2024.

*2Management of acute aortic syndromes from initial presentation to definitive treatment

Christopher K Mehta et al. Am J Emerg Med. 2022 Jan.

*3Acute Aortic Syndromes: Diagnosis and Treatment

Michael C Murphy et al. Mo Med. 2017 Nov-Dec.

*4Long-term behavior of aortic intramural hematomas and penetrating ulcers

Alan S Chou et al. J Thorac Cardiovasc Surg. 2016 Feb.

*5 Population-Based Assessment of Aortic-Related Outcomes in Aortic Dissection, Intramural Hematoma, and Penetrating Aortic Ulcer

Salome Weiss et al. Ann Vasc Surg. 2020 Nov.

Hipertrigliceridemia y rasgo poligenico

 Familial combined hyperlipidaemia (FCH) is the most prevalent form of familial hyperlipidaemia with a multigenic origin and a complex pattern of inheritance. In this respect, FCH is an oligogenic primary lipid disorder due to interaction of genetic variants and mutations with environmental factors. Patients with FCH are at increased risk of cardiovascular disease and often have other associated metabolic conditions. Despite its relevance in cardiovascular prevention, FCH is frequently underdiagnosed and very often undertreated. In this review, emphasis is placed on the most recent advances in FCH, in order to increase its awareness and ultimately contribute to improving its clinical control.

Keywords: Dislipidemia; Dyslipidaemia; Familial combined hyperlipidaemia; Hipercolesterolemia; Hiperlipemia familiar combinada; Hipertrigliceridemia; Hypercholesterolaemia; Hypertriglyceridaemia. *1

Abstract

Familial combined hyperlipidemia (FCH) is the most frequent genetic dyslipidemia (DLP) with high risk of early atherosclerosis manifestation. It is characterized by elevated both triglycerides 1.5 mmol/l and apolipoprotein B 1.2 g/l (hyper-TG/hyper-ApoB fenotype), with at least two affected family members. Despite the fact that plasmatic levels of total cholesterol and LDL-C are usually lower than in familial hypercholesterolemia and full expression of DLP in FCH occurs in adulthood, risk of premature manifestation of atherosclerosis is similar in both these familial DLP. It is probably due to the presence of other atherogenic lipid and non-lipid risk factors, such as increased levels of triglyceride rich lipoprotein remnants, presence of small dense LDL, reduction of HDL-C, presence of insulin resistance with impaired glucose homeostasis, hepatic steatosis, arterial hypertension, hyperuricemia and presence of increased markers of systemic inflammation. The term "familial" usually implicates a monogenic trait. However, FCH is almost always nonmendelian. According to recent knowledge FCH is mostly polygenic with variable presence of large effect mutations, accumulation of several small-effect polymorphisms and some environmental influences. Therefore, FCH is rather a syndrome with common clinical presentation but multigenic causes. The term "familial combined hyperlipidemia" is embedded in clinical practice and so it is not necessary to abandon it, as it nearly urges to examination of first degree relatives. This might help to identify a great number of risk subjects who deserve appropriate management.Key words: apolipoprotein B - familial combined hyperlipidemia - genetics - insulin resistance - premature atherosclerosis - triglycerides.*2

Abstract

Purpose of review: : Familial combined hyperlipidemia (FCH), defined by concurrently elevated plasma triglyceride (TG) and low-density lipoprotein (LDL) cholesterol, has long been investigated to characterize its genetic basis. Despite almost half a century of searching, a single gene cause for the phenotype has not yet been identified.

Recent findings: : Recent studies using next-generation genetic analytic methods confirm that FCH has a polygenic basis, with a clear large contribution from the accumulation of small-to-moderate effect common single nucleotide polymorphisms (SNPs) throughout the genome that is associated with raising TG, and probably also those raising LDL cholesterol. On the other hand, rare monogenic variants, such as those causing familial hypercholesterolemia, play a negligible role, if any. Genetic profiling suggests that patients with FCH and hypertriglyceridemia share a strong polygenic basis and show a similar profile of multiple TG-raising common SNPs.

Summary: : Recent progress in genomics has shown that most if not all of the genetic susceptibility to FCH is polygenic in nature. Future research should include larger cohort studies, with wider ancestral diversity, ancestry-specific polygenic scores, and investigation of epigenetic and lifestyle factors to help further elucidate the causative agents at play in cases where the genetic etiology remains to be defined.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. *3

Abstract

Purpose of review: Combined hyperlipidemia is the most common lipid disorder and is strongly polygenic. Given its prevalence and associated risk for atherosclerotic cardiovascular disease, this review describes the potential for utilizing polygenic risk scores for risk prediction and management of combined hyperlipidemia.

Recent findings: Different diagnostic criteria have led to inconsistent prevalence estimates and missed diagnoses. Given that individuals with combined hyperlipidemia have risk estimates for incident coronary artery disease similar to individuals with familial hypercholesterolemia, early identification and therapeutic management of those affected is crucial. With diagnostic criteria including traits such apolipoprotein B, low-density lipoprotein cholesterol, and triglyceride, polygenic risk scores for these traits strongly associate with combined hyperlipidemia and could be used in combination for clinical risk prediction models and developing specific treatment plans for patients.

Summary: Polygenic risk scores are effective tools in risk prediction of combined hyperlipidemia, can provide insight into disease pathophysiology, and may be useful in managing and guiding treatment plans for patients. However, efforts to ensure equitable polygenic risk score performance across different genetic ancestry groups is necessary before clinical implementation in order to prevent the exacerbation of racial disparities in the clinic.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

PubMed Disclaimer *4

Abstract

Background and aims: Familial combined hyperlipidemia (FCHL) is one of the most common inherited lipid phenotypes, characterized by elevated plasma concentrations of apolipoprotein B-100 and triglycerides. The genetic inheritance of FCHL remains poorly understood. The goals of this study were to investigate the polygenetic architecture and cardiovascular risk associated with FCHL.

Methods and results: We identified individuals with an FCHL phenotype among 349,222 unrelated participants of European ancestry in the UK Biobank using modified versions of 5 different diagnostic criteria. The prevalence of the FCHL phenotype was 11.44% (n = 39,961), 5.01% (n = 17,485), 1.48% (n = 5,153), 1.10% (n = 3,838), and 0.48% (n = 1,688) according to modified versions of the Consensus Conference, Dutch, Mexico, Brunzell, and Goldstein criteria, respectively. We performed discovery, case-control genome-wide association studies for these different FCHL criteria and identified 175 independent loci associated with FCHL at genome-wide significance. We investigated the association of genetic and clinical risk with FCHL and found that polygenic susceptibility to hypercholesterolemia or hypertriglyceridemia and features of metabolic syndrome were associated with greater prevalence of FCHL. Participants with an FCHL phenotype had a similar risk of incident coronary artery disease compared to participants with monogenic familial hypercholesterolemia (adjusted hazard ratio vs controls [95% confidence interval]: 2.72 [2.31-3.21] and 1.90 [1.30-2.78]).

Conclusions: These results suggest that, rather than being a single genetic entity, the FCHL phenotype represents a polygenic susceptibility to dyslipidemia in combination with metabolic abnormalities. The cardiovascular risk associated with an FCHL phenotype is similar to that of monogenic familial hypercholesterolemia, despite being ∼5x more common.

Keywords: Apolipoprotein B-100; Combined hyperlipidemia; FCHL; Familial hypercholesterolemia; Genome-wide association study; UK Biobank.

Copyright © 2021 Elsevier B.V. All rights reserved.*5

*1Familial combined hyperlipidaemia/polygenic mixed hyperlipidaemia

[Article in English, Spanish]

Juan Pedro-Botet et al. Clin Investig Arterioscler. 2021 May.

*2Familial combined hyperlipidemia - the most common genetic dyslipidemia in population and in patients with premature atherothrombotic cardiovascular disease]

[Article in Czech]

Helena Vaverková et al. Vnitr Lek. 2018 Winter

*3Familial combined hyperlipidemia is a polygenic trait

Praneet K Gill et al. Curr Opin Lipidol. 2022.

*4The clinical utility of polygenic risk scores for combined hyperlipidemia

Jacqueline S Dron. Curr Opin Lipidol. 2023.

*5Polygenic architecture and cardiovascular risk of familial combined hyperlipidemia

Mark Trinder et al. Atherosclerosis. 2022 Jan.

Feocromocitoma

 Abstract

The presentation of pheochromocytoma is quite variable. We report a case of previously undiscovered pheochromocytoma which was manifested by traumatic retroperitoneal hemorrhage. A 79-year-old man fell from his bicycle and was admitted to the emergency room complaining of right flank pain. Enhanced computed tomography (CT) revealed hemorrhage around the right adrenal gland. Since the plasma catecholamine levels were elevated, we suspected the presence of pheochromocytoma. After absorption of the hematoma, the tumor appeared clearly. The diagnosis of pheochromocytoma was confirmed through urine catecholamine testing and 131I-MIBG scintigraphy. Six months after the injury, the tumor was surgically resected. Traumatic hemorrhage of pheochromocytoma is extremely rare; only 3 cases have been reported in the literature.-*1

Abstract

A 35-year-old man was delivered to the emergency room complaining of right flank pain because of blunt abdominal trauma sustained while playing baseball. Enhanced computed tomography (CT) revealed a right adrenal mass and fluid collection around the mass. We diagnosed the mass as pheochromocytoma by endocrinological examination and radioisotopical imaging test. After absorption of the hematoma three months after the injury, laparoscopic right adrenalectomy was performed. He had an uncomplicated postoperative course without supplementation of catecholamine. Pathological findings were compatible with pheochromocytoma. Eight months after the operation, he had no evidence of recurrence.*2

Abstract 

A 55-year-old female presented with subarachnoid hemorrhage and was admitted to the department of neurosurgery. Because she had severe hypertension, systemic evaluation was performed. Computed tomography showed a right adrenal tumor which was suspected to be a pheochromocytoma because catecholamine levels were very high in both serum and 24-hour urine. She did not awaken from anesthesia after laparoscopic adrenalectomy and laboratory tests showed that her blood sugar concentration was 33 mg/dl. This hypoglycemia was controlled by continuous infusion of a 50% glucose solution at 40 ml/h and she became conscious the next morning. We gradually decreased the amount of glucose infused and stopped the infusion on postoperative day 4. The tumor was pathologically diagnosed as a pheochromocytoma.*3

Abstract

A 54-year-old woman was scheduled for resection of pheochromocytoma. Anesthesia was maintained with general anesthesia combined with thoracic epidural anesthesia. The blood glucose decreased to 30 mg x dl(-1) about four hours after⁸ the tumor resection, despite intravenous administration of glucose at a rate of 15 g x hr(-1) with intermittent boluses of 5 g of glucose. The blood glucose levels increased over 100 mg x dl(-1) with intravenous administration of 15 g x hr(-1) glucose, 6 hours after tumor resection.*4

Abstract

A 74-year-old woman underwent radical nephrectomy for an adrenaline predominant pheochromocytoma in the left adrenal gland. She was pretreated with doxazosin for 3 weeks before surgery. Anesthesia was induced with intravenous fentanyl, midazolam and vecuronium, and inhaled sevoflurane in oxygen. A central venous catheter was inserted into the right internal jugular vein and a PiCCO catheter was inserted into the femoral artery for the monitoring of cardiac function and hemodynamics. In addition, continuous monitoring and automatic control of blood glucose were started using STG-22. Target concentration of blood glucose was set at 120-140 mg x dl(-1). Anesthesia was maintained with sevoflurane and remifentanil. Prostaglandin E1, nitroglycerin and dexmedetomidine were infused continuously from the start of surgery, and the systolic blood pressure was kept within 120-160 mmHg. During surgical manipulation around the tumor, there were sudden increases in blood pressure, heart rate and blood glucose concentration. Thus, phentolamine and landiolol were also administered to control blood pressure and heart rate. On the contrary, after the tumor removal, noradrenaline, dobutamine and milrinone were required to maintain blood pressure. The STG-22 worked well to maintain blood glucose concentrations during surgery without any hyper- and hypoglycemic events.*5

*1Pheochromocytoma manifested by traumatic adrenal hemorrhage.Article in Japanese]

Futoshi Sano et al. Hinyokika Kiyo. 2006 Jan.

*2Pheochromocytoma with retroperitoneal hemorrhage after abdominal trauma]

[Article in Japanese]

Takuji Hayashi et al. Hinyokika Kiyo. 2009 Nov

*3Severe hypoglycemia after resection of adrenal pheochromocytoma: a case report]

[Article in Japanese]

Shun Umeda et al. Hinyokika Kiyo. 2009 Mar.

*4Postoperative profound hypoglycemia after resection of adrenaline-predominant pheochromocytoma]

[Article in Japanese]

Tomoaki Yanaru et al. Masui. 2007 Dec.

*5Management of anesthesia with artificial pancreas STG-22 for pheochromocytoma resection]

[Article in Japanese]

Tomoaki Yatabe et al. Masui. 2009 Jan.