Didier Klug

Systemic Infection Related to Endocarditis on Pacemaker Leads Clinical Presentation and Management

BACKGROUND Endocarditis related to pacemaker (PM)-lead infection is a rare but serious complication of permanent transvenous pacing. To determine in which situations the diagnosis should be evoked and to determine optimal management, we reviewed our experience with endocarditis related to PM-lead infection. METHODS AND RESULTS Fifty-two patients were admitted for endocarditis related to PM-lead infection. The presentation was acute in 14 patients, with onset of symptoms in the first 6 weeks after the last procedure on the implant site, and chronic in 38 patients. Fever occurred in 86.5%. Clinical and/or radiological evidences of pulmonary involvement were observed in 38.4%. Pulmonary scintigraphy disclosed pulmonary infarcts in 31.2%. Local complications were found in 51.9%. Elevated C-reactive protein was found in 96.2%. A germ was isolated in 88.4% of patients and was a Staphylococcus in 93.5%. Transthoracic echocardiography demonstrated vegetations in only 23% of patients, whereas transesophageal echocardiography disclosed abnormal appearances on the PM lead in 94%. We systematically tried to ablate all the material. Two techniques were used: percutaneous ablation or surgical removal during extracorporeal circulation. All patients were treated with antibiotics after removal of the infected material. Two patients died before lead removal and 2 after surgical removal; the predischarge mortality was 7.6%, and the overall mortality was 26.9% after a follow-up of 20.1+/-13 months. CONCLUSIONS The diagnosis of endocarditis related to PM-lead infection should be suspected in the presence of fever, complications, or pulmonary lesions after PM insertion. Transesophageal echocardiography should be performed to look for vegetations. Staphylococci are involved in the majority of these infections. The endocardial system must be entirely removed and appropriate antibiotic therapy pursued for 6 weeks.

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.

Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia

Background— The pathophysiological background of catecholaminergic polymorphic ventricular tachycardia is well understood, but the clinical features of this stress-induced arrhythmic disorder, especially the incidence and risk factors of arrhythmic events, have not been fully ascertained. Methods and Results— The outcome in 101 catecholaminergic polymorphic ventricular tachycardia patients, including 50 probands, was analyzed. During a mean follow-up of 7.9 years, cardiac events defined as syncope, aborted cardiac arrest, including appropriate discharges from implantable defibrillators, or sudden cardiac death occurred in 27 patients, including 2 mutation carriers with normal exercise tests. The estimated 8-year event rate was 32% in the total population and 27% and 58% in the patients with and without &bgr;-blockers, respectively. Absence of &bgr;-blockers (hazard ratio [HR], 5.48; 95% CI, 1.80 to 16.68) and younger age at diagnosis (HR, 0.54 per decade; 95% CI, 0.33 to 0.89) were independent predictors. Fatal or near-fatal events defined as aborted cardiac arrest or sudden cardiac death occurred in 13 patients, resulting in an estimated 8-year event rate of 13%. Absence of &bgr;-blockers (HR, 5.54; 95% CI, 1.17 to 26.15) and history of aborted cardiac arrest (HR, 13.01; 95% CI, 2.48 to 68.21) were independent predictors. No difference was observed in cardiac and fatal or near-fatal event rates between probands and family members. Conclusions— Cardiac and fatal or near-fatal events were not rare in both catecholaminergic polymorphic ventricular tachycardia probands and affected family members during the long-term follow-up, even while taking &bgr;-blockers, which was associated with a lower event rate. Further studies evaluating concomitant therapies are necessary to improve outcome in these patients.

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice

AIMS Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.

Local symptoms at the site of pacemaker implantation indicate latent systemic infection

Background: To determine whether local complications at the site of pacemaker implantation indicate infection of the intravascular part of the lead as well as of the pacemaker pocket. Methods: 105 patients admitted for local inflammatory findings, impending pacemaker or lead exteriorisation, frank pacemaker or lead exteriorisation, or overt infection were studied prospectively. After systematic lead extraction, the initial clinical presentation was related to the results of lead cultures. Results: Regardless of the initial presentation, the intravascular parts of the leads gave positive cultures in 79.3% of patients. Additionally, 91.6% of the cultures of the extravascular lead segments were positive, in contrast to 38.1% positivity for wound swab cultures. No clinical observations or laboratory investigations permitted identification of patients with negative lead cultures. In a subgroup of 50 patients with manifestations strictly limited to the pacemaker implantation site, cultures of intravascular lead segments were positive in 72%. Infection recurred in 4/8 patients without complete lead body extraction (50%) v 1/97 patients (1.0%) whose leads were totally extracted (p < 0.001). Conclusions: Local complications at the site of pacemaker implantation are usually associated with infection of the intravascular part of the leads, with a risk of progressing to systemic infection. Such local symptoms should prompt the extraction of leads even in the absence of other infectious manifestations.

Notched T Waves on Holter Recordings Enhance Detection of Patients With LQT2 ( HERG ) Mutations

Background —The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potassium channels, are the most common cause of the dominant long-QT syndrome (LQTS). In addition to QT-interval prolongation, notched T waves have been proposed as a phenotypic marker of LQTS patients. Methods and Results —The T-wave morphology of carriers of mutations in KCNQ1 (n=133) or HERG (n=57) and of 100 control subjects was analyzed from Holter ECG recordings. Averaged T-wave templates were obtained at different cycle lengths, and potential notched T waves were classified as grade 1 (G1) in case of a bulge at or below the horizontal, whatever the amplitude, and as grade 2 (G2) in case of a protuberance above the horizontal. The highest grade obtained from a template defined the notch category of the subject. T-wave morphology was normal in the majority of LQT1 and control subjects compared with LQT2 (92%, 96%, and 19%, respectively, P <0.001). G1 notches were relatively more frequent in LQT2 (18% versus 8% [LQT1] and 4% [control], P <0.01), and G2 notches were seen exclusively in LQT2 (63%). Predictors for G2 were young age, missense mutations, and core domain mutations in HERG. Conclusions —This study provides novel evidence that Holter recording analysis is superior to the 12-lead ECG in detecting G1 and G2 T-wave notches. These repolarization abnormalities are more indicative of LQT2 versus LQT1, with G2 notches being most specific and often reflecting HERG core domain missense mutations.

Novel Calmodulin Mutations Associated With Congenital Arrhythmia Susceptibility

Background—Genetic predisposition to life-threatening cardiac arrhythmias such as congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2) have been associated with severe forms of LQTS and CPVT, with life-threatening arrhythmias occurring very early in life. Additional mutation-positive cases are needed to discern genotype–phenotype correlations associated with calmodulin mutations. Methods and Results—We used conventional and next-generation sequencing approaches, including exome analysis, in genotype-negative LQTS probands. We identified 5 novel de novo missense mutations in CALM2 in 3 subjects with LQTS (p.N98S, p.N98I, p.D134H) and 2 subjects with clinical features of both LQTS and CPVT (p.D132E, p.Q136P). Age of onset of major symptoms (syncope or cardiac arrest) ranged from 1 to 9 years. Three of 5 probands had cardiac arrest and 1 of these subjects did not survive. The clinical severity among subjects in this series was generally less than that originally reported for CALM1 and CALM2 associated with recurrent cardiac arrest during infancy. Four of 5 probands responded to &bgr;-blocker therapy, whereas 1 subject with mutation p.Q136P died suddenly during exertion despite this treatment. Mutations affect conserved residues located within Ca2+-binding loops III (p.N98S, p.N98I) or IV (p.D132E, p.D134H, p.Q136P) and caused reduced Ca2+-binding affinity. Conclusions—CALM2 mutations can be associated with LQTS and with overlapping features of LQTS and CPVT.

Pacemaker Lead Infection in Young Patients

Transvenous pacing has become widespread in the pediatric population, but related pacemaker lead infection in young patients has rarely been reported. To determine prevalence and optimal management of pacemaker lead infection in children and young adults, the authors reviewed their pacing database including 4,476 patients who previously had pacemaker implantations from 1975 to 2001. A pacemaker was implanted in 304 patients under the age of 40. Of these patients 217 of them had congenital heart disease: 108 with structural defect, 109 without (mainly complete AV blocks). Among patients with congenital heart disease, 12 developed a pacemaker lead infection (5.5%, 6 patients with structural defect, 6 without). This incidence was significantly higher than in patients < 40 years at first implantation without congenital heart disease (2.3%) and in > 40‐year‐old patients (1.2%, P < 0.001) . However, the number of reinterventions at the pulse generator site was higher in patients having had their first implantation before the age of 40. In patients with structural cardiac defect: two died after surgical lead extraction and one died before the scheduled lead extraction. The three remaining patients had successful surgical (n = 1) or percutaneous (n = 2) lead extractions. In patients without structural cardiac defect successful percutaneous extraction (5/6) or surgical extraction (1/6 with vegetation > 25 mm) was performed. One patient with percutaneous extraction developed chronic cor pulmonale during follow‐up. One infection recurred in one patient with structural cardiac defect although complete removal of the pacing material had been performed. The prevalence of pacemaker lead infection is higher in younger patients, perhaps in part due to a higher number of procedures at the pacemaker site than in the general population of patients with a pacemaker. Patients with structural cardiac defect who underwent surgical lead removal were at high risk for death. Patients with percutaneous lead extraction may develop cor pulmonale. (PACE 2003; 26[Pt. I]:1489–1493)

Contributions of remote monitoring to the follow-up of implantable cardioverter–defibrillator leads under advisory

Aims Automatic daily transmission of data from implantable cardioverter–defibrillators (ICDs) enables the remote monitoring of device status and leads function. We report on a 2-year experience with remote monitoring in 40 recipients of high-voltage ICD leads, prone to fracture and under advisory since October 2007. Methods and results The ICDs were remotely monitored as well as systematically interrogated in the ambulatory department every 3 months. The patients were also seen in case of abnormal lead impedance, or other manifestations consistent with lead dysfunction. Over a mean follow-up of 22 ± 4 months after ICD implantation, four lead dysfunctions were suspected because of remotely transmitted oversensing of noise artifacts, abrupt rise in pacing impedance, or both. A lead fracture needing lead replacement was confirmed in three patients (7.5%), two of them before any inappropriate therapy and one after the delivery of three inappropriate shocks. No lead failure was observed in the remaining 36 patients, either at the time of ambulatory visits or during remote monitoring. Conclusion Remote monitoring allowed the early and reliable detection of ICD leads failure without requiring any patient intervention.

Prevalence and prognostic significance of psychiatric disorders in patients evaluated for recurrent unexplained syncope.

We aimed to assess the psychiatric profile and prognostic value of psychiatric disorders (PDs) in patients presenting with unexplained syncope. Forty patients with recurrent unexplained syncope referred for head-up tilt testing were compared with age- and sex-matched patients free of known chronic PDs referred for arrhythmia. All patients underwent a semistandardized psychiatry questionnaire (Mini-International Neuropsychiatric Interview) to assess their profile. Additional stress coping was performed to study adaptational processes to stressful situations. After tilt testing and psychiatric evaluation, a drug-free follow-up was performed in patients with syncope. Of the 80 patients who referred to the psychiatric interview, 40 had evidence of at least 1 psychiatric disorder. They were 26 patients (65%) in the syncope group and 14 patients (35%) in the control group (p = 0.01). Detailed analysis revealed a more frequent subprofile of anxiety and panic disorders in patients with syncope than in controls (30% vs 12% and 20% vs 10%, respectively), whereas the subprofile of depression was similar in both groups. Moreover, those with syncope were more likely to have a high anxiety index (25 +/- 5 vs 22 +/- 4, p = 0.004), and were more prone to avoidance-oriented coping strategies when experiencing undesirable life events than controls. Considering syncope patients, no difference could be found between the 25 with a positive tilt test and the 15 with a negative tilt test with respect to the number of syncopal episodes and psychiatric profile. After a 3-year drug-free follow-up, 15 patients (37.5%) had at least 1 recurrent syncope. The recurrence rate was similar in patients with positive and negative head-up tilt test results (9 of 25 vs 6 of 15, respectively). In contrast, the syncopal recurrence rate was higher in patients who fulfilled criteria for affective disorders (13 of 26 vs 2 of 14, 95% confidence interval 1.09 to 2.55, relative risk 1.7, p = 0.04). Thus, patients with recurrent unexplained syncope are more anxious and are more prone to panic disorders and avoidance-oriented coping strategies than control patients with arrhythmia. The presence of a psychiatric disorder is associated with an increased risk of recurrence. The outcome of such patients may be improved with recognition and treatment of PDs.