Primary prevention by implantable cardioverter defibrillators: shock proof?

In the last two decades, the focus of implantable cardioverter defibrillator {ICD} trials has mainly been on prophylactic implantation of ICDs in high-risk populations for the prevention of sudden cardiac death. In particular, prophylactic ICDs in high-risk post-MI patients with a depressed left ventricular ejection fraction has resulted in significantly improved survival. These benefits are in addition to those of optimal pharmacological therapy and ICD therapy should be considered the standard of care in these patients.     

Treatment failure with antagonists of TNF-α: mechanisms and implications for the care of patients

The use of TNF-α antagonists has substantially improved the care of many patients with inflammatory and autoimmune diseases. However, approximately one third of such patients fail to respond well to treatment, regardless of the antagonist used or of the underlying disease. The mechanisms underlying these failures are analyzed in this review, and proposals made concerning how best to adapt therapeutic decisions in these instances.     

Are geomagnetic disturbances a risk factor for the sudden unexplained death of epileptic children?

The relationship between geomagnetic disturbances (with amplitudes above 50 nT) and the sudden unexplained death (SUD) of epileptic adults has been controversial up to now. In an autopsy-based cohort study (from 1964 to 1992) 15 epileptic children with SUD aged 1-14 years were compared to 63 epileptic children whose cause of death was known (KCD). The time of death as well as two international geomagnetic indices were assessed: Bartels' planetary 3-h signs (Kp) for the time of death and 2 h before, and the mean planetary daily amplitudes (Ap) on the day of death and on the 4 critical days before (and on the 4 post-mortem days as a control). Among the 15 SUD patients 9 died between 6 a.m. and 9 a.m. (universal time) whereas the KCD group showed an approximately uniform distribution of the time of death ( P = 0.026, Kolmogorov-Smirnov test). The Kp signs at death and 2 h before as well as the Ap indices at death and for the 4 pre-mortem days or after were not different in comparisons between the SUD and the KCD group ( P > 0.2, Mann-Whitney test). Furthermore the frequency of sudden storm commencement at death and for the 4 days before revealed no deviation of the SUD (26.7%) from the KCD group (23.8%) ( P > 0.2, Fisher test). The results do not support the hypothesis that geomagnetic disturbances are a risk factor for the sudden unexplained death of epileptic children.     

Do all of the neurologic diseases in patients with DNA repair gene mutations result from the accumulation of DNA damage?

The classic model for neurodegeneration due to mutations in DNA repair genes holds that DNA damage accumulates in the absence of repair, resulting in the death of neurons. This model was originally put forth to explain the dramatic loss of neurons observed in patients with xeroderma pigmentosum neurologic disease, and is likely to be valid for other neurodegenerative diseases due to mutations in DNA repair genes. However, in trichiothiodystrophy (TTD), Aicardi-Goutières syndrome (AGS), and Cockayne syndrome (CS), abnormal myelin is the most prominent neuropathological feature. Myelin is synthesized by specific types of glial cells called oligodendrocytes. In this review, we focus on new studies that illustrate two disease mechanisms for myelin defects resulting from mutations in DNA repair genes, both of which are fundamentally different than the classic model described above. First, studies using the TTD mouse model indicate that TFIIH acts as a co-activator for thyroid hormone-dependent gene expression in the brain, and that a causative XPD mutation in TTD results in reduction of this co-activator function and a dysregulation of myelin-related gene expression. Second, in AGS, which is caused by mutations in either TREX1 or RNASEH2, recent evidence indicates that failure to degrade nucleic acids produced during S-phase triggers activation of the innate immune system, resulting in myelin defects and calcification of the brain. Strikingly, both myelin defects and brain calcification are both prominent features of CS neurologic disease. The similar neuropathology in CS and AGS seems unlikely to be due to the loss of a common DNA repair function, and based on the evidence in the literature, we propose that vascular abnormalities may be part of the mechanism that is common to both diseases. In summary, while the classic DNA damage accumulation model is applicable to the neuronal death due to defective DNA repair, the myelination defects and brain calcification seem to be better explained by quite different mechanisms. We discuss the implications of these different disease mechanisms for the rational development of treatments and therapies.     

Do all patients with implantable cardioverter defibrillator need a generator change? A health service evaluation of patients who underwent generator changes from a single tertiary center

BackgroundThe patient characteristics, therapy received and outcomes after one or more implantable cardioverter defibrillator (ICD) generator changes from contemporary practice is not well known.MethodsWe conducted a health service evaluation of patients who underwent ICD implantation and generator change. Patients who had generator changes from February 2016 to October 2019 were identified from our database and electronic records were reviewed for patient characteristics, number of generator changes, receipt of therapy and death.ResultsOur database included 88 patients with a generator change. A total of 22 patients (25.0%) received dual chamber ICD, 10 patients (11.4%) received single chamber ICD, 54 patients (61.3%) received cardiac resynchronization therapy defibrillator and 2 patients (2.3%) received subcutaneous ICD. A second generator change occurred in 18 patients and a third generator changes was performed in 6 patients. There were 29 deaths and a follow up period of 9.4 ± 2.9 years. From implant to initial generator change 39 patients had appropriate antitachycardia pacing (ATP), 6 patient had inappropriate ATP, 29 patients had appropriate shocks and 5 patients had an inappropriate shock. Between the 1st and 2nd generator change and the 2nd and 3rd there were no cases of inappropriate ATP or shock. Overall, 42 patients out of the 88 had appropriate therapy (47.7%) and 7 patients had inappropriate therapy (8.0%).ConclusionsMost patients with ICDs do not receive therapy and a minority have inappropriate therapy which typically occur before the first generator change as we observed no inappropriate therapy beyond the first generator change.     

Malignant familial hypertrophic cardiomyopathy in a family with a 453Arg→Cys mutation in the β-myosin heavy chain gene: Coexistence of sudden death and end-stage heart failure

Recent genotype-phenotype correlation studies in familial hypertrophic cardiomyopathy (FHC) have revealed that some mutations in the β-myosin heavy chain (BMHC) gene may be associated with a high incidence of sudden death and a poor prognosis. Coexistence of sudden death and end-stage heart failure in several families with FHC has recently being reported; however, the genetic basis of such families has not been clearly demonstrated. A three-generation Chinese familial hypertrophic cardiomyopathy (FHC) family (family HL1) with two cases of end-stage heart failure and three cases of sudden death was analyzed. The average age of death in the affected members in this family was 34 years old. Genetic linkage analysis using polymorphisms in the α- and β-myosin heavy chain genes revealed that FHC in this family is significantly linked to the BMHC gene without recombinations. Single-strand conformation polymorphism analysis of exons 8, 9 and 13 to 23 in the BMHC gene showed a polymorphic band on exon 14 that is in complete linkage with the disease status in this family. DNA sequencing analysis in the affected members revealed an 453Arg→Cys mutation in the BMHC gene. To our knowledge this is the first reported mutation of FHC in Chinese. Our data suggest that the 453Arg→Cys mutation is associated with a malignant clinical course in FHC due not only to sudden death but also to end-stage heart failure. Received: 6 July 1995 / Revised: 20 September 1995     

Long-term monitoring for patients after surgical ablation of atrial fibrillation: are all devices the same?

In recent years, the nonmedical management of atrial fibrillation (AF) has rapidly evolved, with more options available to address the arrhythmia. Determining the successful return of sinus rhythm and the medical management after ablation requires the selection of the correct diagnostic method. In May 2007, the Heart Rhythm Society in conjunction with the Society for Thoracic Surgeons, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society identified the need for programs to adopt a consistent method of follow-up and monitoring. Choosing the right monitor for the determination of the success, postsurgical ablation that meets the Heart Rhythm Society guidelines for monitoring especially for asymptomatic patients is imperative. Therefore, we reviewed the current devices available to assist practitioners in determining which monitor best meets their needs The criteria selected to perform the review include (1) ease of use for patients (compliance), (2) ability of the monitor to perform internal analysis, (3) the monitor has >24 hours of storage capability, and (4) external support. Our selection criteria revealed six cardiac rhythm monitors currently available for use. This review compared the different arrhythmia monitors from an established monitoring program perspective to assist practitioners in choosing a monitor that meets their practice needs for determining the return to sinus rhythm postsurgical ablation.     

Implementation of guidelines for implantable cardioverter-defibrillator therapy in clinical practice: Which patients do benefit?

Purpose

Based on multiple large clinical trials conducted over the last decades guidelines for implantable cardioverter-defibrillator (ICD) implantations have been evolving. The increase in primary prophylactic ICD implantations challenges us to be critical towards the indications in certain patient populations.

Methods

We retrospectively collected patient characteristics and rates of appropriate and inappropriate ICD therapy, appropriate and inappropriate ICD shock and mortality of all patients who received an ICD in the University Medical Center Utrecht (UMCU) over the years 2006–2011.

Results

A total of 1075 patients were included in this analysis (74 % male, mean age 61 ± 13 years, left ventricular ejection fraction 30 ± 13 %); 61 % had a primary indication and 58 % had ischaemic heart disease. During a mean follow-up period of 31 ± 17 months, 227 of the patients (21 %) received appropriate ICD therapy (149 (14 %) patients received an appropriate ICD shock). Females, patients with a primary prophylactic indication and patients with non-ischaemic heart disease experienced significantly less ICD therapy. Only a few patients (54, 5 %) received inappropriate ICD therapy; 33 (3 %) patients received an inappropriate ICD shock. Fifty-five patients died within one year after ICD implantation and were therefore, in retrospect, not eligible for ICD implantation.

Conclusion

Our study confirms the benefit of ICD implantation in clinical practice. Nevertheless, certain patients experience less benefit than others. A more patient-tailored risk stratification based on electrophysiological parameters would be lucrative to improve clinical benefit and cost-effectiveness.     

When is connectivity important? A case study of the spatial pattern of sudden oak death

Although connectivity has been examined from many different angles and in many ecological disciplines, few studies have tested in which systems and under what conditions connectivity is important in determining ecological dynamics. Identifying general rules governing when connectivity is important is crucial not only for basic ecology, but also for our ability to manage natural systems, particularly as increasing fragmentation may change the degree to which connectivity influences ecological dynamics. In this study, we used statistical regression, least‐cost path analysis, and model selection techniques to test the relative importance of potential connectivity in determining the spatial pattern of sudden oak death, a tree disease that is killing millions of oak and tanoak trees along coastal forests of California and Oregon. We hypothesized that potential connectivity, in addition to environmental conditions, is important in determining the spatial distribution of sudden oak death, the importance of connectivity is more apparent when measured using biologically meaningful metrics that account for the effects of landscape structure on disease spread, and the relative importance of environmental variables and connectivity is approximately equal. Results demonstrate that potential connectivity was important in determining the spatial pattern of sudden oak death, though it was relatively less important than environmental variables. Moreover, connectivity was important only when using biologically meaningful metrics as opposed to simple distance‐based metrics that ignore landscape structure. These results demonstrate that connectivity can be important in systems not typically considered in connectivity studies – highlighting the importance of examining connectivity in a variety of different systems – and demonstrate that the manner in which connectivity is measured may govern our ability to detect its importance.     

Tachyarrhythmia in patients with congenital heart disease: inevitable destiny?

The prevalence of patients with congenital heart disease (CHD) has increased over the last century. As a result, the number of CHD patients presenting with late, postoperative tachyarrhythmias has increased as well. The aim of this review is to discuss the present knowledge on the mechanisms underlying both atrial and ventricular tachyarrhythmia in patients with CHD and the advantages and disadvantages of the currently available invasive treatment modalities.     

Mate for the heart: pulsatile or continuous?

At the AHA meeting 2009 it was reported by the press media (and meanwhile published in the N Engl J Med by Slaughter et al., 3 December 2009), that a ‘new type of device more than doubles the two-year survival rate among heart failure patients. The new device, called HeartMate II, improves survival, is more durable, and is linked to better quality of life. The device works by pumping blood continuously rather than simulating a heart beat as older pumps do. The pump is connected to equipment outside the body – a small computer and batteries that the patient wears in a belt pack or harness using a wire from the patient’s abdomen. The FDA has approved the device only as a temporary bridge to transplant.’