Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis.

BACKGROUND: Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown. OBJECTIVE: To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia. METHODS: A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated. RESULTS: The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P<0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P<0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004). CONCLUSIONS: Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant.

A case of bidirectional conduction block within the superior vena cava induced by cryoballoon pulmonary vein isolation.

A 53-year-old male underwent a pulmonary vein isolation (PVI) of atrial fibrillation (AF) with a second-generation cryoballoon (CB). Although the patient maintained sinus rhythm after the PVI, a superior vena cava (SVC) fibrillation was recorded by a circular-multipolar-electrode catheter positioned inside the SVC that suggested conduction block between the right atrium (RA)-SVC connection. An adenosine triphosphate intravenous injection induced a dormant reconnection of the SVC myocardial sleeve and converted sinus rhythm to an AF rhythm. This case demonstrated that a CB application for the isolation of a right superior pulmonary vein could induce an electrical conduction block between the RA-SVC connection.

Transient receptor potential melastatin 4 cation channel in pediatric heart block.

OBJECTIVE: Progressive cardiac conduction disease (PCCD) is a common pediatric heart conduction disorder. It is an autosomal inheritance of rare mutations, which leads to familial cases of PCCD. In these cases, the His-Purkinje system's conductive capacity is progressively deranged, involving either right or left bundle branch block. Also, QRS complexes display widening is an important characteristic that culminates in complete AV block, syncope, and sudden death. Mutations in TRPM4 gene that encodes for transient receptor potential melastatin 4 have recently been reported to cause familial cases of PCCD and heart block. TRPM4 conducts a Ca2+-activated non-selective monovalent cationic current leading to a negative plasma membrane potential. TRPM4 channels let Na+ ion influx, causing membrane depolarization, whereas, at positive membrane potentials, TRPM4 channels repolarize the membrane by facilitating K+ ion efflux from the cell. TRPM4 protein contains many regulatory motifs that confer voltage dependence, ATP/ADP sensitivity, and Ca2+ responsiveness. Mutational studies revealed the significance of the two-calmodulin binding sites at the N-terminus of for Ca2+ dependent activation of this channel. Mutations that reduce deSUMOylation increase the steady-state levels of active TRPM4 channels on the membrane without alteration of its sensitivity to Ca2+ or ATP or its voltage dependence of activation. Increased TRPM4 function interferes with cardiac conduction and eventually contributes to heart block. Both gain and loss of function mutations of TRPM4 are implicated in the cardiac block. Currently, the major therapeutic management of cardiac block due to TRPM4 mutations is implantation of a pacemaker to reinstate normal current propagation through AV node.

Autologous biological pacing function with adrenergic-responsiveness in porcine of complete heart block.

AIMS: To assess the efficacy of autologous biological pacing function by autograft of gene-transferred mesenchymal stem cells in a porcine model of complete heart block. METHODS AND RESULTS: Fourteen healthy young male pigs were randomized into active group (n=8) and control group (n=6). Porcine MSCs were transfected with Ad.HCN4 or Ad.Null. The pacemaker function of transfected MSCs was studied by whole-cell patch clamp. The CHB model of porcine was created with transthoracic ablation technique and the transfected MSCs were autografted into the free wall of right ventricle. The pacing function was studied by ECG and ambulatory Holter recording weekly. The adrenergic responsiveness was evaluated by the variation of heart rate after isoprenaline infusion or food provision following an overnight fasting. HCN4-MSCs expressed a robust time-dependent inward current (If) and the current density of If was 4.3±0.6 pA/pF at -105 mV. In week 2 after autograft, the heart rate of active group became significantly higher than control (53±5 bpm vs. 38±4 bpm, P<0.05) and the percent of pacing beats in active group was higher than control (69±10% vs. 28±8%, P<0.05). By infusion of isoprenaline, the heart rate was increased significantly in both groups. However, there was a significant increase of heart rate when presenting food for active group (P<0.05) while not in control. CONCLUSIONS: Our findings demonstrated that autografted HCN4-MSCs could increase the heart rate by providing an adrenergic-responsive biological pacing function, indicating a promising approach without immunological or ethical issues for the treatment of complete heart block.

Cardiac conduction block at multiple levels caused by arsenic trioxide therapy.

We present a rare case of a woman aged 62 years with refractory acute promyelocytic leukemia treated with arsenic trioxide leading to progressive, multilevel cardiac conduction block. After chelation treatment with dimercaprol, there was normalization of conduction.

A case study of a pregnant patient with a congenital heart block accompanied by left isomerism and uncontrolled type 2 diabetes who was treated successfully with ritodrine.

We present a case study of a patient with a congenital heart block associated with a left isomerism that was diagnosed during the 26th week of gestation. The mother had type 2 diabetes mellitus that was difficult to control during the early stages of the pregnancy. A fetal echocardiogram revealed an atrioventricular dissociation, with an atrial rate of 120 bpm and a ventricular rate of 55 bpm. Subsequent examinations also revealed a left isomerism in the fetus. To increase the fetal heart rate, a continuous intravenous infusion of ritodrine was administered. The fetal ventricular rate rapidly increased to 65 bpm. The pregnancy successfully continued until term and a female infant weighing 3,182 g was born via a cesarean section. A subsequent surgery was performed to provide the infant with a permanent cardiac pacemaker, and notably, the child is now 4 months of age and her growth has been within the normal range.

Intracoronary aminophylline for management of bradyarrhythmias during thrombectomy with the AngioJet catheter.

Thrombectomy with the AngioJet rheolytic thrombectomy catheter frequently causes bradyarrhythmias. This necessitates temporary pacemaker insertion and limits the device's use. Novel approaches for treatment of bradyarrhythmias are being tested. This article focuses on the evidence supporting the role of adenosine in bradyarrhythmias during thrombectomy and presents; data from a porcine model and the first human experience supporting the use of aminophylline, a competitive inhibitor of the adenosine receptor, via an intracoronary route, for prevention of bradyarrhythmias during thrombectomy.

Relationship between arrhythmogenesis and disease activity in cardiac sarcoidosis.

BACKGROUND: In patients with cardiac sarcoidosis, ventricular arrhythmias and/or conduction disturbances are frequently observed and sometimes fatal. However, few reports on disease activity and arrhythmic events in cardiac sarcoidosis are available. OBJECTIVE: The purpose of this study was to investigate the relationship between disease activity and arrhythmic events in cardiac sarcoidosis and the effect of corticosteroid therapy. METHODS: The study population consisted of 15 cardiac sarcoidosis patients with new-onset symptomatic arrhythmia, including eight patients admitted once for complete atrioventricular block (CAVB), five patients admitted once for sustained ventricular tachycardia (VT), and two patients admitted twice for two arrhythmic events (one for CAVB and the other for sustained VT). Disease activity was evaluated by gallium-67 citrate (Ga) scintigraphy. All patients with positive Ga uptake were treated with corticosteroids, and arrhythmic events were evaluated by repeat Holter recordings. RESULTS: Positive uptake of Ga was observed in 8 (80%) of the 10 CAVB events and in 1 (14%) of the 7 sustained VT events (80% vs 14%, P = .02). Corticosteroids abolished myocardial Ga uptake in all nine patients with positive Ga uptake. After corticosteroid therapy was started, AV conduction improved in 5 of 9 CAVB patients (including 8 patients with new-onset CAVB and one patient with history of CAVB). However, ventricular arrhythmias were not improved after corticosteroid therapy. CONCLUSION: In cardiac sarcoidosis patients, CAVB develops mainly during the active phase of the disease. Early treatment with corticosteroids might improve AV conduction disturbance. However, sustained VT is not closely linked with disease activity and frequently develops in the advanced stage of disease.

Cardiac sarcoidosis responding to monotherapy with infliximab.

Cardiac involvement is a rare and potentially life-threatening complication of sarcoidosis. We report the case of a young previously healthy woman who presented with complete atrioventricular heart block. Further evaluation revealed non-caseating granulomas in the hilar and mediastinal regions. A pacemaker was inserted, and she was treated with four doses of infliximab after she refused treatment with steroids. Rapid resolution of the pulmonary lymph nodes was documented and repeated interrogations of the pacemaker 1 year after her last infliximab infusion documented that she was in sinus rhythm. Infliximab may be considered as an alternative first-line therapy in sarcoidosis with serious organ involvement.

Perioperative cardiac issues: postoperative arrhythmias.

This article reviews current concepts about the diagnosis and acute management of postoperative arrhythmias. A systematic approach to diagnosis of arrhythmias and evaluation of predisposing factors is presented, followed by consideration of common bradyarrhythmias and tachyarrhythmias in the postoperative setting. Postoperative arrhythmias are common and represent a major source of morbidity after surgical procedures, both cardiac and noncardiac. Postoperative dysrhythmias are most likely to occur in patients with structural heart disease. The initiating factor for an arrhythmia following surgery is usually a transient insult such as hypoxemia, cardiac ischemia, catecholamine excess, or electrolyte abnormality. Management includes correction of these imbalances and, if clinically indicated, medical therapy directed at the arrhythmia itself.

Incidence, predictors, and outcomes of high-degree atrioventricular block complicating acute myocardial infarction treated with thrombolytic therapy.

BACKGROUND: In the fibrinolytic era, several studies have suggested that the rate of atrioventricular block (AVB) in the setting of acute myocardial infarction (MI) is high and is associated with increased short-term mortality. We sought to delineate predictors of AVB and determine long-term mortality of patients developing AVB in the setting of ST-segment elevation MI (STEMI) treated with thrombolytic therapy. METHODS: We combined data on patients from 4 similar studies of STEMI. We identified independent predictors of AVB and compared the 6-month and 1-year mortality rates of patients with AVB (5251) to the rates of patients without AVB (70 742). RESULTS: The incidence of AVB was 6.9%. Significant independent predictors of AVB included inferior MI, older age, worse Killip class at presentation, female sex, enrollment in the United States, current smoking, hypertension, and diabetes. Adjusted mortality was significantly higher in patients with AVB than in patients without AVB within 30 days (OR 3.2, 95% CI 2.7-3.7), 6 months (OR 1.6, 95% CI 1.5-1.8), and 1 year (OR 1.5, 95% CI 1.3-1.6). For patients with AVB and inferior MI, mortality odds ratios (ORs) were 2.2 (95% CI 1.7-2.7), 2.6 (95% CI 2.4-2.9), and 2.4 (95% CI 2.2-2.6) within 30 days, 6 months, and 1 year, respectively. For patients with AVB and anterior MI, mortality ORs were 3.0 (95% CI 2.2-4.1), 3.5 (95% CI 3.1-3.8), and 3.3 (95% CI 3.0-3.7) within 30 days, 6 months, and 1 year, respectively. CONCLUSIONS: In the thrombolytic era, AVB in the setting of STEMI is common and associated with higher mortality. Future studies should focus on determining therapies that are effective at reducing mortality rates in such patients.

[A case of severe bradycardia and AV block during administration of propofol].

A 69-yr-old man underwent emergency laparotomy. He was in endotoxic shock. Preoperative evaluation including a full blood count, chest X-ray and ECG were normal. Body temperature was 37.4 degrees C. Preoperative arterial pressure was 140/80 mmHg and heart rate 65 bpm. Anesthesia was induced with ketamine 100 mg, propofol 20 mg, fentanyl 50 micrograms and vecuronium 4 mg and maintained with propofol 4 mg.kg-1.hr-1 and fentanyl. Soon after opening the abdominal peritoneum, severe bradycardia (< 20 bpm) occurred, but it was effectively treated by ephedrine 16 mg. After that, surgery was performed uneventfully. In the intensive care unit (ICU), the patient developed four episodes of severe atrioventricular (AV) block after stimulation of the trachea by suction drainage under sedation with propofol, although there was no AV block during sedation with ketamine and propofol. After stopping propofol, the AV block was no longer observed. He was discharged from the ICU on the 12th postoperative day. Postoperative Holter ECG and echocardiography showed no abnormalities. It is likely that stimulation of the trachea triggered vagovagal reflex and propofol prolonged AV conduction, causing the AV block.

[Conduction defects as the presenting feature of sarcoidosis or observed during the course of the disease: regression with corticoid steroid therapy]. / Troubles conductifs révélant une sarcoïdose ou apparaissant au cours de son évolution: régression sous corticoïdes.

Cardiac sarcoidosis is often unrecognised because of the absence of specific clinical and electrical signs. The consequences are serious, the main risk being sudden death due to conduction defects (24 to 31% of cases) or ventricular arrhythmias. Any conduction defect without an obvious cause in a young patient should suggest a possible diagnosis of sarcoidosis. The confirmation is histological when giant cell non-caseuting epithelioid granuloma is demonstrated but myocardial biopsies are only positive in 20% of cases. Therefore, biopsy of accessible organs such as salivary glands is recommended. Diagnostic strategy consists in searching for signs of systemic sarcoidosis, and, when the diagnosis has been established, perform a complete work-up with echocardiography, dipyridamole myocardial scintigraphy, cardiac MRI and 24 hour ambulatory ECG recordings (Holter). The only proven treatment is steroid therapy with occasional spectacular observations of reversibility of arrhythmias or conduction defects.

Prenatal diagnosis and treatment of fetal long QT syndrome: a case report.

We report a case of a fetus presenting with bradycardia, intermittent atrioventricular (AV) block, ventricular tachycardia (VT) and the signs of fetal congestive heart failure (ascites and scrotal hydrocele) during mid-gestation. Prenatal treatment with beta-adrenergic blocker (propranolol) and digitalis glycosides was prescribed because of suspicion of long QT syndrome occurring with fetal congestive heart failure. The male baby was born at 39 weeks of gestation and showed a prolonged QT interval (QTc = 492 ms) and frequent variable AV block or alternating left and right bundle branch block, depending on the atrial rate. Prenatal administration of lidocaine failed to correct the fetal VT. Conversely, propranolol decreased the attack frequency of fetal VT. Postnatal administration of the K(+) channel opener (nicorandil) successfully shortened the QT interval and improved the outcome.

[Prinzmetal's variant angina with transient complete atrio-ventricular block--case report]. / Napadowy blok calkowity z poronnymi zespolami MAS w przebiegu dlawicy naczynioskurczowej.

A case of 44-year-old women with episodes of chest pain with ST-T segment elevation and paroxysmal atrioventricular complete block with syncopal episodes is presented. Coronary angiography did not reveal atheromatous lesions. A patient was treated with nitrates and calcium channel blockers. However syncopal episodes with A-V block reoccurred. A single-chamber (ventricular demand) pacemaker was implanted. A six month follow-up was uneventful.

Triggers of ventricular tachyarrhythmias and therapeutic effects of nicorandil in canine models of LQT2 and LQT3 syndromes.

OBJECTIVES: We sought to identify the triggers of ventricular tachyarrhythmia (VTA) in experimental models of long QT type 2 (LQT2) and long QT type 3 (LQT3) syndromes. BACKGROUND: Most adverse cardiac events occurring in the long QT type 1 syndrome are related to sympathetic nerve activity. In contrast, various factors may trigger VTA in patients with LQT2 and LQT3. METHODS: The mode of onset of VTA and therapeutic effects of the potassium-adenosine triphosphate channel opener nicorandil were compared in canine models of LQT2 and LQT3, using three induction protocols: 1) bradycardia produced by atrioventricular block (BRADY); 2) programmed ventricular stimulation; and 3) electrical stimulation of the left stellate ganglion (left stellate stimulation [LSS]). Transmural unipolar electrograms were recorded, and the activation-recovery interval (ARI) was measured. RESULTS: Ventricular tachyarrhythmias developed during BRADY in all six experiments in the LQT3 model, but in none of the six experiments in LQT2. Programmed ventricular stimulation induced VTA in two experiments of the LQT2 model, but in none of the LQT3 experiments. Stimulation of the left stellate ganglion induced VTA in three experiments in LQT2 and in two experiments in LQT3. Nicorandil caused greater shortening of ARI and greater attenuation of transmural ARI dispersion in the LQT2 model than in the LQT3 model. After treatment with nicorandil, a single VTA was induced in the LQT2 model by LSS, whereas in the LQT3 model, VTA remained inducible by BRADY in four experiments and LSS in one experiment. CONCLUSIONS: An abrupt increase in sympathetic activity appeared arrhythmogenic in both models. Nicorandil attenuated the heterogeneity of ventricular repolarization and suppressed the induction of VTA in the LQT2 model, but had a limited therapeutic effect in the LQT3 model.

Congenital long QT syndrome with functionally impaired atrioventricular conduction: successful treatment by mexiletine and propranolol.

Congenital long QT syndrome (LQTS) with atrioventricular block is a rare and malignant arrhythmia, which usually responds poorly to traditional beta-blocker therapy. We describe a male neonate with LQTS with ventricular tachycardia and 2:1 atrioventricular block. This patient's sister had similar presentation and died suddenly at the age of 8 months despite beta-blocker and pacemaker therapy. Our patient responded to a combination of sodium channel blocker (mexiletine) and beta-blocker (propranolol) therapy. He was asymptomatic during a 2-year follow-up period. This case suggests that propranolol combined with mexiletine might be useful in the treatment of patients with LQTS with atrioventricular block.