Iatrogenic pacemaker-induced ventricular arrhythmia: a case report.

Background: Minimizing right ventricular (RV) pacing to reduce the progression of heart failure is an established practice. Proprietary algorithms to reduce unnecessary RV pacing have been incorporated into both simple and complex cardiac pacemaker devices, for reducing the possibility of heart failure and arrhythmias. Case summary: We present a case of a 43-year-old male implanted with a dual-chamber primary prevention implantable cardioverter-defibrillator (AUTOGEN EL, Boston Scientific) for sudden cardiac death. At the time of implant, the patient had hypertrophic cardiomyopathy with mild left ventricular (LV) systolic impairment, and sinus rhythm with intact atrioventricular (AV) conduction. The patient developed progression of his disease with symptoms (dyspnoea) and LV impairment. This led to a decision to activate the minimal RV pacing algorithm (RYTHMIQ™). A deterioration in AV conduction caused intrinsic ventricular beats to fall in the atrial blanking period, and subsequent VVI backup pacing resulted in R on T pacing. This induced ventricular arrhythmia. RYTHMIQ™ was subsequently deactivated, and the patient has had no further device-induced arrhythmias. Discussion: Numerous studies have demonstrated the adverse effect of RV pacing on LV function. Minimizing RV pacing is, therefore, encouraged in individuals with intact AV conduction. However, underlying conduction abnormalities must be assessed prior to activating algorithms designed to minimize RV pacing. This case demonstrates the importance of careful intracardiac electrogram interpretation and individual case-based device programming, to avoid device-induced complications.

Non-invasive markers for sudden cardiac death risk stratification in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common yet challenging cardiac disease. Great strides have been made in improving DCM prognosis due to heart failure but sudden cardiac death (SCD) due to ventricular arrhythmias remains significant and challenging to predict. High-risk patients can be effectively managed with implantable cardioverter defibrillators (ICDs) but because identification of what is high risk is very limited, many patients unnecessarily experience the morbidity associated with an ICD implant and many others are not identified and have preventable mortality. Current guidelines recommend use of left ventricular ejection fraction and New York Heart Association class as the main markers of risk stratification to identify patients who would be at higher risk of SCD. However, when analysing the data from the trials that these recommendations are based on, the number of patients in whom an ICD delivers appropriate therapy is modest. In order to improve the effectiveness of therapy with an ICD, the patients who are most likely to benefit need to be identified. This review article presents the evidence behind current guideline-directed SCD risk markers and then explores new potential imaging, electrophysiological and genetic risk markers for SCD in DCM.

Disparity in implantable cardioverter defibrillator therapy among minority South Asians in the United Kingdom.

OBJECTIVE: There are large geographical differences in implantable cardioverter defibrillator (ICD) implantation rates for reasons not completely understood. In an increasingly multiethnic population, we sought out to investigate whether ethnicity influenced ICD implantation rates. METHODS: This was a retrospective, cohort study of new ICD implantation or upgrade to ICD from January 2006 to February 2019 in recipients of Caucasian or South Asian ethnicity at a single tertiary centre in the UK. Data were obtained from a routinely collected local registry. Crude rates of ICD implantation were calculated for the population of Leicestershire county and were age-standardised to the UK population using the UK National Census of 2011. RESULTS: The Leicestershire population was 980 328 at the time of the Census, of which 761 403 (77.7%) were Caucasian and 155 500 (15.9%) were South Asian. Overall, 2650 ICD implantations were performed in Caucasian (91.9%) and South Asian (8.1%) patients. South Asians were less likely than Caucasians to receive an ICD (risk ratio (RR) 0.43, 95% CI 0.37 to 0.49, p<0.001) even when standardised for age (RR 0.75, 95% CI 0.74 to 0.75, p<0.001). This remained the case for primary prevention indication (age-standardised RR 0.91, 95% CI 0.90 to 0.91, p<0.001), while differences in secondary prevention ICD implants were even greater (age-standardised RR 0.49, 95% CI 0.48 to 0.50, p<0.001). CONCLUSION: Despite a universal and free healthcare system, ICD implantation rates were significantly lower in the South Asian than the Caucasian population residing in the UK. Whether this is due to cultural acceptance or an unbalanced consideration is unclear.

Whole Genome Sequencing in an Acrodermatitis Enteropathica Family from the Middle East.

We report a family from Tabuk, Saudi Arabia, previously screened for Acrodermatitis Enteropathica (AE), in which two siblings presented with typical features of acral dermatitis and a pustular eruption but differing severity. Affected members of our family carry a rare genetic variant, p.Gly512Trp in the SLC39A4 gene which encodes a zinc transporter; disease is thought to result from zinc deficiency. Similar mutations have been reported previously; however, the variable severity within cases carrying the p.Gly512Trp variant and in AE overall led us to hypothesise that additional genetic modifiers may be contributing to the disease phenotype. Therefore whole genome sequencing was carried out in five family members, for whom material was available to search for additional modifiers of AE; this included one individual with clinically diagnosed AE. We confirmed that the p.Gly512Trp change in SLC39A4 was the only candidate homozygous change which was sufficiently rare (ExAC allele frequency 1.178e-05) and predicted deleterious (CADD score 35) to be attributable as a fully penetrant cause of AE. To identify other genes which may carry relevant genetic variation, we reviewed the relevant literature and databases including Gene Ontology Consortium, GeneMANIA, GeneCards, and MalaCards to identify zinc transporter genes and possible interacting partners. The affected individual carried variants in RECQL4 and GPAA1 genes with ExAC allele frequency <0.01 and CADD score >10. p.Gly512Trp is highly likely to be the pathogenic variant in this family. This variant was previously detected in a Tunisian proband with perfect genotype-phenotype segregation suggestive of pathogenicity. Further research is required in this area due to small sample size, but attention should be given to RECQL4 and GPAA1 to understand their role in the skin disease.