Mortality After Total Thyroidectomy for Amiodarone-Induced Thyrotoxicosis According to Left Ventricular Ejection Fraction.

OBJECTIVE: To report cardiac outcomes after total thyroidectomy for amiodarone-induced thyrotoxicosis according to the baseline left ventricular ejection fraction in a tertiary referral center. STUDY DESIGN: Retrospective, monocentric. SETTING: The tertiary health care system. METHODS: Patients who underwent total thyroidectomy for amiodarone-induced thyrotoxicosis between 2010 and 2020 with age >18 and available preoperative left ventricular ejection fraction were included in this study. Patients were dichotomized into: group 1 with left ventricular ejection fraction ≥40% (mildly reduced/normal ejection fraction), and group 2 with left ventricular ejection fraction <40% (reduced ejection fraction). RESULTS: There were 34 patients in group 1 and 17 to group 2. The latter were younger (median 58.4 [Q1-Q3 48.0-64.9] vs. 69.8 years in group 1 [59.8-78.3], p = .0035) and they presented more cardiomyopathy (58.8 vs. 26.5%, p = .030). Overall, the median time until surgery referral was 3.1 [1.9-7.1] months and 47.1% underwent surgery after restoration of euthyroidism. Surgical complications accounted for 7.8%. In group 2, the median left ventricular ejection fraction was significantly improved after surgery (22.5 [20.0-25.0] vs. 29.0% [25.3-45.5], p = .0078). Five-year cardiac mortality was significantly higher in group 2 (p < .0001): 47.0% died of cardiac causes versus 2.9% in group 1. A baseline left ventricular ejection fraction <40% and a longer time until surgery referral were significantly associated with cardiac mortality (multivariable Cox regression analysis, p = .015 and .020, respectively). CONCLUSION: These results reinforce the idea that surgery, if chosen, should be performed quickly in patients with left ventricular ejection fraction <40%.

Septal versus apical pacing sites in permanent right ventricular pacing: The multicentre prospective SEPTAL-PM study.

BACKGROUND: The optimal right ventricular pacing site for patients requiring pacemaker implantation for permanent atrioventricular block is a matter of debate. Long-term right ventricular apical pacing has been associated with left ventricular ejection fraction impairment and heart failure. Right ventricular septal pacing has been proposed as an alternative. AIM: The aim of this randomized prospective multicentre trial was to compare left ventricular remodelling and outcomes between right ventricular apical and septal pacing after mid-term follow-up. METHODS: Patients requiring pacemaker implantation for high-degree atrioventricular block were enrolled and randomized in a 1:1 fashion to receive a right ventricular apical or septal lead. RESULTS: A total of 141 patients were included, 69 in the septal group and 72 in the apical group. Both groups exhibited similar left ventricular ejection fractions after 18 months of follow-up (septal 57.1±11.9% vs. apical 57.4±13.4%), and left ventricular ejection fraction variation was similar in the two groups at the end of follow-up (septal -1.5±13.2% vs. apical 0.3±13.3%). Additionally, left ventricular volume, quality of life and 6-minute walk distance were similar in the two groups. However, patients in the septal group were more likely to be asymptomatic, with a significantly lower concentration of N-terminal prohormone of brain natriuretic peptide. Lastly, lead position did not impact 18-month survival. CONCLUSION: Pacing from the right ventricular apex does not have any detrimental effect on left ventricular systolic function compared with septal pacing over an 18-month period.

Preventing atrial fibrillation by combined right isthmus ablation and cryoballoon pulmonary vein isolation in patients with typical atrial flutter: PAF-CRIOBLAF study.

BACKGROUND: Although less common, typical atrial flutter shares similar pathophysiological roots with atrial fibrillation. Following successful cavo-tricuspid isthmus ablation using radiofrequency, many patients, however, develop atrial fibrillation in the mid-to-long-term. This study sought to assess whether pulmonary vein isolation conducted at the same time as cavo-tricuspid isthmus ablation would significantly modify the atrial fibrillation burden upon follow-up in patients suffering from typical atrial flutter. METHODS: This was a multicenter randomized controlled study involving typical atrial flutter patients with history of non-predominant atrial fibrillation (1 atrial fibrillation episode only, in 67% of population) who were scheduled for cavo-tricuspid isthmus radiofrequency ablation. Patients were randomly assigned to either undergo cavo-tricuspid isthmus ablation alone or cavo-tricuspid isthmus plus pulmonary vein isolation (CTI+). Pulmonary vein isolation was performed using cryoballoon technology. An outpatient consultation with ECG and 1-week Holter monitoring was performed at 3, 6 months, 1 year, and 2 years postprocedure. The primary endpoint was atrial fibrillation recurrences lasting more than 30 s at 2 years postablation. RESULTS: Of the patients enrolled, 36 were included in each group. At 2-year follow-up, the atrial fibrillation recurrence rate was significantly higher in the CTI vs CTI+group (25/36, 69% vs. 12/36, 33% respectively; P < .001), with similar typical atrial flutter recurrence rates. There were no differences in undesirable events, except for transient phrenic nerve palsy reported from three CTI+patients (8.3%). CONCLUSION: Pulmonary vein isolation using cryoballoon technology was proven to significantly reduce the atrial fibrillation incidence at 2 years postcavo-tricuspid isthmus ablation.

Electrical Storm Ablation in a Patient in Cardiogenic Shock Supported by Impella 5.0.

Intra-axial pumps are increasingly used to support cardiogenic shock. The occurrence of electrical storms in this setting is a rising issue, and data remain scarce about optimal management. We report the feasibility of ventricular tachycardia ablation in the presence of a recent surgically inserted Impella 5.0 device (Abiomed, Danvers, Massachusetts). (Level of Difficulty: Intermediate.).

Cardiac aging and heart disease in humans.

The world population continues to grow older rapidly, mostly because of declining fertility and increasing longevity. Since age represents the largest risk factor for cardiovascular disease, the prevalence of these pathologies increases dramatically with increasing age. In order to improve patient care and prevention for age-related cardiac diseases, insight should be gained from the analysis of processes involved in and leading to cardiac aging. It is from this perspective that we provide here an overview of changes associated with age in the heart on four levels: functional, structural, cellular and molecular. We highlight those changes that are in common with the development of the two major age-associated cardiac pathologies: heart failure and atrial fibrillation. These commonly affected processes in aging and cardiac pathophysiology may provide an explanation for the age risk factor in cardiac disease.

Cardiac remote monitoring in France.

The increase in number of implanted cardiac medical devices and the announced decrease in number of cardiologists have led to remote monitoring being considered as a pivotal tool for patient follow-up. For 10 years, remote monitoring has been the subject of multiple clinical studies. In these studies, reliability and clinical efficacy have been demonstrated, but the use of remote monitoring remains quite limited in France compared with other countries. To explain this delay in uptake, some organizational difficulties and the lack of reimbursement of remote monitoring are often mentioned. The results of medico-economic studies might provide answers about the value of remote monitoring and enable the supervisory authorities to define how its use will be financed. This review provides a global view of remote monitoring in France, and covers the principle, clinical efficacy, organizational and regulatory aspects, and medico-economic data.

The psychological impact of implantable cardioverter defibrillator implantation on Brugada syndrome patients.

AIMS: Brugada syndrome (BrS) is a hereditary arrhythmic disease, responsible for sudden death in patients without known heart disease. An implantable cardioverter defibrillator (ICD) is recommended in patients at high risk of sudden death, but the resulting psychological impact has never been studied. The aim of our study was to assess the impact on quality of life of BrS and ICD implantation. METHODS AND RESULTS: Patients were selected from the reference centre for hereditary arrhythmic disease database in Nantes. This population was divided into three groups: Group 1 (G1), symptomatic implanted patients; Group 2 (G2), asymptomatic implanted patients; and Group 3 (G3), asymptomatic patients without ICD. One hundred and ninety questionnaires [36-item short-form health survey (SF-36) and subsidiary questions] were analysed (60 in G1, 78 in G2, and 52 in G3). We failed to identify any difference in the evaluation of the SF-36 between the three groups and the SF-36 score was similar to the French population score. However, specific questions regarding tolerance of the ICD showed that ICD implantation resulted in significant negative impact, especially for professional careers and purchasing insurance, even though the patient considered ICD implantation as reassuring. CONCLUSION: Whatever the group, BrS patients have a good quality of life with no difference between implanted and non-implanted patients. However, ICD implantation is accompanied by difficulties in their social and professional life. This work emphasizes the need to propose specific recommendations applicable to insurance to reduce the complications experienced by these patients.

Remote implantable cardioverter defibrillator monitoring in a Brugada syndrome population.

AIMS: The diagnosis of Brugada syndrome (BS) is typically made in a young and otherwise healthy population. In patients with a high risk of sudden cardiac death (SCD), the only currently recommended therapy is an implantable cardioverter defibrillator (ICD), but these are not without complications. We investigated whether remote ICD monitoring could simplify follow-up and detect potential complications in these patients. METHODS AND RESULTS: Thirty-five consecutive patients (26 males, 44 +/- 11 years) implanted with an ICD for BS with a remote monitoring ['Home Monitoring' (HM), Biotronik, Germany] system were prospectively enrolled in this study. They were matched for age, sex, and follow-up duration with 35 BS patients implanted with an ICD without this capability. During a mean follow-up of 33 +/- 17 months, the number of cardiology consultations was significantly lower in the HM group (3 +/- 2 vs. 7 +/- 3; P < 0.001). Inappropriate shock(s) [IS(s)] occurred in three patients (8.5%) in the HM group vs. six (17%) in the control group (P = NS). Ten patients in the HM group had a median of four alerts ('ventricular tachycardia/ventricular fibrillation detection' in all patients, 'shock' in three, 'ineffective shock' in two patients with shock on noise, 'extreme ventricular pacing impedance' in one patient due to lead failure, and 'deactivated therapy' in two patients with lead failure before replacement). In 5 of these 10 patients, prompt reprogramming of the ICD may have prevented IS(s). CONCLUSION: Remote ICD monitoring in patients with BS decreases outpatient consultations and may help prevent ISs.

Are women with severely symptomatic brugada syndrome different from men?

UNLABELLED: Women with Brugada Syndrome. INTRODUCTION: Spontaneous type-1 ECG has been recognized as a risk factor for sudden cardiac death (SCD) in Brugada syndrome (BrS), but studied populations predominantly consisted of men. We sought to investigate whether a spontaneous type-1 ECG pattern was also associated in women with severely symptomatic BrS. Other known risk factors were also examined for gender specificity. METHODS: Patients with severely symptomatic BrS, defined as resuscitated SCD and/or appropriate implantable cardioverter-defibrillator (ICD) shock, were included from 11 European centers. Clinical data, investigation of family history, 12-lead ECG, and results of electrophysiological study (EPS) were collected. The average follow-up was 4 +/- 3 years. RESULTS: Fifty-eight patients fulfilled the inclusion criteria (mean age 47 +/- 11 years, 8 women). Thirty-six men (72%) but only two women (25%) had a spontaneous type-1 ECG at baseline (P = 0.02). Maximal ST elevation before or after drug challenge was 3.7 +/- 1.3 mm in men versus 2.4 +/- 0.7 mm in women (P = 0.007). The proportion of patients with a family history of SCD or an SCN5A mutation was not significantly different between both groups. Of those patients with high-risk BrS who underwent EPS, 76%(12/25) of men and 50%(2/4) of women had a positive study. CONCLUSION: In contrast to men, most women with BrS and resuscitated SCD or appropriate ICD shock do not have a spontaneous type-1 ECG pattern. In addition, the degree of ST elevation is less pronounced in women than men. While women represent a lower-risk group overall, risk factors established from a predominantly male population may not be helpful in identifying high-risk females.

Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study.

BACKGROUND: The Prospective Evaluation of Pacemaker Lead Endocarditis study is a multicenter, prospective survey of the incidence and risk factors of infectious complications after implantation of pacemakers and cardioverter-defibrillators. METHODS AND RESULTS: Between January 1, 2000, and December 31, 2000, 6319 consecutive recipients of implantable systems were enrolled at 44 medical centers and followed up for 12 months. All infectious complications were recorded, and their occurrence was related to the baseline demographic, clinical, and procedural characteristics. Among 5866 pacing systems, 3789 included 2 and 117 had >2 leads; among 453 implantable cardioverter-defibrillators, 178 were dual-lead systems. A total of 4461 de novo implantations occurred and 1858 pulse generator or lead replacements. Reinterventions were performed before hospital discharge in 101 patients. Single- and multiple-variable logistic regression analyses were performed to identify risk factors; adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. At 12 months, device-related infections were reported in 42 patients (0.68%; 95% CI, 0.47 to 0.89). The occurrence of infection was positively correlated with fever within 24 hours before the implantation procedure (aOR, 5.83; 95% CI, 2.00 to 16.98), use of temporary pacing before the implantation procedure (aOR, 2.46; 95% CI, 1.09 to 5.13), and early reinterventions (aOR, 15.04; 95% CI, 6.7 to 33.73). Implantation of a new system (aOR, 0.46; 95% CI, 0.24 to 0.87) and antibiotic prophylaxis (aOR, 0.4; 95% CI, 0.18 to 0.86) were negatively correlated with risk of infection. CONCLUSIONS: This study identified several factors of risk of device infection and confirmed the efficacy of antibiotic prophylaxis in recipients of new or replacement pacemakers or implantable cardioverter-defibrillators.

Gene expression profile associated with chronic atrial fibrillation and underlying valvular heart disease in man.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. The pathophysiology of AF involves electrical, structural and contractile remodeling, which is associated with changes in cardiac gene expression. Previous studies of gene-expression changes in clinical AF have mostly been limited to a small number of candidate genes and have not all been well controlled for underlying heart disease. The present study assessed AF-related gene-expression changes in valve-disease patients with microarrays representing the cardiac transcriptome. Right atrial appendages from 11 patients with chronic AF and underlying valvular heart disease (AF-VHD) and seven patients in sinus rhythm with VHD (SR-VHD) were individually compared to an age-matched sinus-rhythm control group (SR-CTRL, 11 patients) using cardiac-specific microarray analysis. One-class statistical analysis was used to identify genes differentially expressed between SR-VHD and SR-CTRL patients. Two-class statistical analysis was used to identify genes differentially expressed between AF-VHD and SR-VHD patients. Out of 3863 analyzed genes, 832 genes were differentially expressed between SR-VHD and SR-CTRL patients, and 169 genes were differentially expressed between AF-VHD and SR-VHD patients. Striking AF-related changes included altered expression of nine genes pointing towards the development of fibrosis (e.g. upregulation of transforming growth factor beta1), and changes in eight genes potentially related to an increased risk of thromboembolic events (e.g. upregulation of alpha2 macroglobulin). Microarray results were confirmed by quantitative PCR. Our results suggest that AF produces a characteristic profile of gene-expression changes that may be related to the pathophysiology of the arrhythmia.

Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias.

BACKGROUND: Small scale clinical trials suggested the feasibility and the efficacy of autologous myoblast transplantation to improve ventricular function after myocardial infarction. However, these trials were hampered by unexpected episodes of life-threatening ventricular tachyarrhythmias (VT). We investigated cardiac electrical stability after myoblast transplantation to the myocardium. METHODS AND RESULTS: Seven days after coronary ligation, Wistar rats were randomized into 3 groups: a control group receiving no further treatment, a vehicle group injected with culture medium into the infarcted myocardium, and a myoblast group injected with autologous myoblasts. Holter monitoring did not discriminate the myoblast from the vehicle groups. Programmed Electrical Stimulation (PES) was performed to evaluate further a cardiac substrate for arrhythmia susceptibility. The occurrence of sustained VT during PES was similar in control and vehicle groups (5/17 and 4/19 rats, respectively; p=0.50). In contrast, 13/20 rats (65%) from the myoblast group showed at least one episode of sustained VT during PES (p<0.05 and p<0.005 versus control and vehicle groups). As a further control group, rats injected with autologous bone marrow mononuclear cells into the infarcted myocardium did not show increased susceptibility to PES. CONCLUSIONS: In an infarcted rat model, myoblast transplantation but not bone marrow mononuclear cells or myocardial injection per se induces electrical ventricular instability. Because ventricular arrhythmias are life-threatening disorders, we suggest that such preclinical evaluation should be conducted for any new source of cells to be injected into the myocardium.

Human atrial ion channel and transporter subunit gene-expression remodeling associated with valvular heart disease and atrial fibrillation.

BACKGROUND: Valvular heart disease (VHD), which often leads to atrial fibrillation (AF), and AF both cause ion-channel remodeling. We evaluated the ion-channel gene expression profile of VHD patients, in permanent AF (AF-VHD) or in sinus rhythm (SR-VHD), in comparison with patients without AF or VHD, respectively. METHODS AND RESULTS: We used microarrays containing probes for human ion-channel and Ca2+-regulator genes to quantify mRNA expression in atrial tissues from 7 SR-VHD patients and 11 AF-VHD patients relative to 11 control patients in SR without structural heart disease (SR-CAD). From the data set, we selected for detailed analysis 59 transcripts expressed in the human heart. SR-VHD patients differentially expressed 24/59 ion-channel and Ca2+-regulator transcripts. There was significant overlap between VHD groups, with 66% of genes altered in SR-VHD patients being similarly modified in AF-VHD. Statistical differences between the AF- and SR-VHD groups identified the specific molecular portrait of AF, which involved 12 genes that were further confirmed by real-time reverse transcription-polymerase chain reaction. For example, phospholamban, the beta-subunit MinK (KCNE1) and MIRP2 (KCNE3), and the 2-pore potassium channel TWIK-1 were upregulated in AF-VHD compared with SR-VHD, whereas the T-type calcium-channel Cav3.1 and the transient-outward potassium channel Kv4.3 were downregulated. Two-way hierarchical clustering separated SR-VHD from AF-VHD patients. AF-related changes in L-type Ca2+-current and inward-rectifier current were confirmed at protein and functional levels. Finally, for 13 selected genes, SR restoration reversed ion-channel remodeling. CONCLUSIONS: VHD extensively remodels cardiac ion-channel and transporter expression, and AF alters ion-channel expression in VHD patients.

Expression of human ERG K+ channels in the mouse heart exerts anti-arrhythmic activity.

OBJECTIVE: The K(+) channel encoded by the human ether-a-go-go-related gene (HERG) is crucial for repolarization in the human heart. In order to investigate the impact of HERG current (I(Kr)) on the incidence of cardiac arrhythmias, we generated a transgenic mouse expressing HERG specifically in the heart. METHODS AND RESULTS: ECG recordings at baseline showed no obvious difference between transgenic and wild-type (WT) mice with the exception of the T wave, which was more negative in transgenic mice than in WT mice. E4031 (20 mg/kg) prolonged the QTc interval and flattened the T wave in transgenic mice, but not in WT mice. Injection of BaCl(2) (25 mg/kg) induced short runs of ventricular tachycardia in 9/10 WT mice, but not in transgenic animals. Atrial pacing reproducibly induced atrial tachyarrhythmias in 11/15 WT mice. In contrast, atrial arrhythmia was inducible in only 2/11 transgenic mice. When pretreated with dofetilide (10 mg/kg), transgenic mice were as sensitive to experimental arrhythmias as WT mice. Microelectrode studies showed that atrial action potentials have a steeper slope of duration-rate adaptation in WT than in transgenic mice. Transgenic mice were also characterized by a post-repolarization refractoriness, which could result from the substantial amount of I(Kr) subsisting after repolarization as assessed with action potential-clamp experiments and simulations with a model of the transgenic mouse action potential. CONCLUSION: HERG expression in the mouse heart can protect against experimental induction of arrhythmias. This is the first report of such a protective effect of HERG in vivo.

Long-term amiodarone administration remodels expression of ion channel transcripts in the mouse heart.

BACKGROUND: The basis for the unique effectiveness of long-term amiodarone treatment on cardiac arrhythmias is incompletely understood. The present study investigated the pharmacogenomic profile of amiodarone on genes encoding ion-channel subunits. METHODS AND RESULTS: Adult male mice were treated for 6 weeks with vehicle or oral amiodarone at 30, 90, or 180 mg x kg(-1) x d(-1). Plasma and myocardial levels of amiodarone and N-desethylamiodarone increased dose-dependently, reaching therapeutic ranges observed in human. Plasma triiodothyronine levels decreased, whereas reverse triiodothyronine levels increased in amiodarone-treated animals. In ECG recordings, amiodarone dose-dependently prolonged the RR, PR, QRS, and corrected QT intervals. Specific microarrays containing probes for the complete ion-channel repertoire (IonChips) and real-time reverse transcription-polymerase chain reaction experiments demonstrated that amiodarone induced a dose-dependent remodeling in multiple ion-channel subunits. Genes encoding Na+ (SCN4A, SCN5A, SCN1B), connexin (GJA1), Ca2+ (CaCNA1C), and K+ channels (KCNA5, KCNB1, KCND2) were downregulated. In patch-clamp experiments, lower expression of K+ and Na+ channel genes was associated with decreased I(to,f), I(K,slow), and I(Na) currents. Inversely, other K+ channel alpha- and beta-subunits, such as KCNA4, KCNK1, KCNAB1, and KCNE3, were upregulated. CONCLUSIONS: Long-term amiodarone treatment induces a dose-dependent remodeling of ion-channel expression that is correlated with the cardiac electrophysiologic effects of the drug. This profile cannot be attributed solely to the amiodarone-induced cardiac hypothyroidism syndrome. Thus, in addition to the direct effect of the drug on membrane proteins, part of the therapeutic action of long-term amiodarone treatment is likely related to its effect on ion-channel transcripts.

Microarray analysis reveals complex remodeling of cardiac ion channel expression with altered thyroid status: relation to cellular and integrated electrophysiology.

Although electrophysiological remodeling occurs in various myocardial diseases, the underlying molecular mechanisms are poorly understood. cDNA microarrays containing probes for a large population of mouse genes encoding ion channel subunits ("IonChips") were developed and exploited to investigate remodeling of ion channel transcripts associated with altered thyroid status in adult mouse ventricle. Functional consequences of hypo- and hyperthyroidism were evaluated with patch-clamp and ECG recordings. Hypothyroidism decreased heart rate and prolonged QTc duration. Opposite changes were observed in hyperthyroidism. Microarray analysis revealed that hypothyroidism induces significant reductions in KCNA5, KCNB1, KCND2, and KCNK2 transcripts, whereas KCNQ1 and KCNE1 expression is increased. In hyperthyroidism, in contrast, KCNA5 and KCNB1 expression is increased and KCNQ1 and KCNE1 expression is decreased. Real-time RT-PCR validated these results. Consistent with microarray analysis, Western blot experiments confirmed those modifications at the protein level. Patch-clamp recordings revealed significant reductions in I(to,f) and I(K,slow) densities, and increased I(Ks) density in hypothyroid myocytes. In addition to effects on K+ channel transcripts, transcripts for the pacemaker channel HCN2 were decreased and those encoding the alpha1C Ca2+ channel (CaCNA1C) were increased in hypothyroid animals. The expression of Na+, Cl-, and inwardly rectifying K+ channel subunits, in contrast, were unaffected by thyroid hormone status. Taken together, these data demonstrate that thyroid hormone levels selectively and differentially regulate transcript expression for at least nine ion channel alpha- and beta-subunits. Our results also document the potential of cDNA microarray analysis for the simultaneous examination of ion channel transcript expression levels in the diseased/remodeled myocardium.