Physiological pacing: just a lot of buzz or the next paradigm shift in bradycardia pacing?

ABSTRACT: Cardiac pacing has been an established therapy for bradyarrhythmia due to sinus or atrioventricular nodal disease since the 1950s. However, contemporary studies have shown that conventional right ventricular pacing (RVP) causes electromechanical dyssynchrony, which can lead to atrial fibrillation, heart failure and even death. Recently, the push for a more physiological cardiac pacing has seen a revival in the utilisation and development of conduction system pacing (CSP). There has been a shift towards adopting His bundle pacing (HBP) or left bundle branch area pacing (LBBaP) in bradycardia patients worldwide and in Singapore. This review serves to outline the electrophysiological concepts behind CSP and illustrate the different paced electrocardiogram characteristics of HBP, LBBaP and RVP to aid understanding of this revolutionary pacing approach among medical practitioners in Singapore.

Contemporary wearable and handheld technology for the diagnosis of cardiac arrhythmias in Singapore.

Twelve-lead electrocardiography (ECG) remains the gold standard for the diagnosis of cardiac arrhythmias. It provides a snapshot of the cardiac electrical activity while the leads are attached to the patient. As medical training is required to use the ECG machine, its use remains restricted to the clinic and hospital settings. These aspects limit the usefulness of 12-lead ECG in the diagnosis of cardiac arrhythmias, especially in individuals with short-lasting and infrequent paroxysmal symptoms. The introduction of ECG recording features in wearable and handheld smart devices has changed the paradigm of cardiac arrhythmia diagnosis, empowering patients to record their ECG as and when symptoms occur. This review describes contemporary ambulatory heart rhythm monitors commonly available in Singapore and their expanding role in the diagnosis of cardiac rhythm abnormalities.

Practical and systematic approach using the steerable catheter and stylet-driven lead to deliver safe and effective left bundle branch area pacing.

INTRODUCTION: Current delivery tools were not designed for left bundle branch area pacing (LBBAP). Challenges using these tools include lack of reach into the right ventricle and poor support for the lead to penetrate the interventricular septum. Concerns using stylet-driven leads (SDL) for LBBAP have been previously highlighted. Knowledge and the technical know-how of using SDL for LBBAP need to be evaluated in a fair and consistent manner. A stepwise approach is devised for use of Agilis HisProTM steerable catheter with Tendril STS Model 2088TC lead for LBBAP and evaluated for safety and reproducibility. METHODS: Consecutive patients undergoing LBBAP using the stepwise approach with Agilis HisProTM steerable catheter were analyzed. The safety, efficacy and reproducibility of the technique were evaluated. The lead parameters were analyzed in the immediate (1 day) and short-term period (3-6 months) post implantation. RESULTS: LBBAP was attempted in 41 patients using the stepwise approach of which 37 (90.7%) were successful. The lead parameters were stable in the immediate and short-term post implantation in all our patients. There was no significant difference between the group of patients with multiple repositioning of the lead compared to those successful at the 1st attempt. There were no acute or short-term lead and procedural complications. CONCLUSION: A stepwise and systematic approach using the Agilis HisProTM steerable catheter and proper handling of the Tendril STS Model 2088TC stylet-driven lead is an important part of the armamentarium to deliver LBBAP in a practical, effective and reproducible manner.

Predicting atrial fibrillation after ischemic stroke: clinical, genetics and electrocardiogram modelling.

INTRODUCTION: Detection of atrial fibrillation (AF) is challenging in patients after ischemic stroke due to its paroxysmal nature. We aim to determine the utility of a combined clinical, electrocardiographic and genetic variables model to predict AF in a post-stroke population. MATERIALS AND METHODS: We performed a cohort study at a single comprehensive stroke centre from 09/11/2009 to 31/10/2017. All patients recruited were diagnosed with acute ischemic stroke or transient ischemic attacks. Electrocardiographic variables including p-wave terminal force (PWTF), corrected QT interval (QTc) and genetic variables including single nucleotide polymorphisms (SNP) at the 4q25 (rs2200733) were evaluated. Clinical, electrocardiographic and genetic variables of patients without AF and those who developed AF were compared. Multiple logistic regression analysis and receiver operating characteristics were performed to identify parameters and determine their ability to predict the occurrence of AF. RESULTS: Out of 709 patients (median age of 59 years, IQR 52-67) recruited, sixty (8.5%) were found to develop AF on follow-up. Age (odds ratio (OR): 3.49, 95% confidence interval (CI): 2.03-5.98, p<0.0001), hypertension (OR: 2.76, 95% CI: 1.36-5.63, p=0.0052) and valvular heart disease (OR: 8.49, 95% CI: 2.62-27.6, p<0.004 were the strongest predictors of AF, with area under receiver operating value of 0.76 (95% CI: 0.70-0.82), and 0.82 (95% CI: 0.77-0.87) when electrocardiographic variables (PWTF and QTc) were added. SNP did not improve prediction modelling. CONCLUSION: We demonstrated that a model combining clinical and electrocardiographic variables provided robust prediction of AF in our post-stroke population. Role of SNP in prediction of AF was limited.

Motion characteristics of subclinical tremors in Parkinson's disease and normal subjects.

The characteristics of the Parkinson's disease tremor reported previously are not applicable to the full spectrum of severity. The characteristics of high- and low-amplitude tremors differ in signal regularity and frequency dispersion, a phenomenon that indicates characterisation should be studied separately based on the severity. The subclinical tremor of Parkinson's disease is close to physiological tremor in terms of amplitude and frequency, and their distinctive features are still undetermined. We aimed to determine joint motion characteristics that are unique to subclinical Parkinson's disease tremors. The tremors were characterised by four hand-arm motions based on displacement and peak frequencies. The rest and postural tremors of 63 patients with Parkinson's disease and 62 normal subjects were measured with inertial sensors. The baseline was established from normal tremors, and the joint motions were compared within and between the two subject groups. Displacement analysis showed that pronation-supination and wrist abduction-adduction are the most and least predominant tremor motions for both Parkinson's disease and normal tremors, respectively. However, the subclinical Parkinson's disease tremor has significant greater amplitude and peak frequency in specific predominant motions compared with the normal tremor. The flexion-extension of normal postural tremor increases in frequency from the proximal to distal segment, a phenomenon that is explainable by mechanical oscillation. This characteristic is also observed in patients with Parkinson's disease but with amplification in wrist and elbow joints. The contributed distinctive characteristics of subclinical tremors provide clues on the physiological manifestation that is a result of the neuromuscular mechanism of Parkinson's disease.

A South East Asian perspective of neuropsychiatric startle syndromes of latah.

Latah is a culture-specific syndrome characterized by exaggerated startle response, echolalia, palilalia, echopraxia, coprolalia, forced obedience and involuntary vocalization in response to startle. Latah is stimulus-induced and is associated with behavior and psychiatric features. The aim of this review is to provide a comprehensive description on latah from a regional perspective based on previous literature and clinical experiences and highlight the clinical characteristics of latah from a movement disorders perspective. The pathophysiology of latah is complex and poorly understood although psychological stressors have been implicated. In view of the distressing psychosocial impact of latah, this neuropsychiatric startle syndrome warrants further studies to understand the pathophysiology and identify the appropriate treatments.

Left ventricular systolic dysfunction with concomitant bradyarrhythmia in a patient with POEMS syndrome: a case report.

BACKGROUND: POEMS syndrome (PS) is a paraneoplastic disorder from plasma cell dyscrasia, characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. Vascular endothelial growth factors (VEGFs)-driven fluid extracellular matrix expansion plays a key role in this condition. Associated cardiac involvement has been sparsely reported thus far. CASE SUMMARY: A 55-year-old woman with PS presented with a pleural effusion and respiratory failure requiring mechanical ventilation. Transthoracic echocardiogram revealed left ventricular (LV) systolic dysfunction with a moderate pericardial effusion. She developed intermittent complete heart block and ventricular standstill, requiring temporary transcutaneous pacing. Further evaluation revealed no significant coronary stenosis on coronary angiogram and cardiac magnetic resonance (CMR) showed elevated T1 and extracellular volume suggestive of myocardial oedema with possible early cardiac infiltration. She had a dual-chamber permanent pacemaker implanted in view of recurrent high-grade heart block. She was initiated on a daratumumab-based chemotherapy regimen prior to discharge. She recovered well subsequently with a promising clinical response to chemotherapy. DISCUSSION: We describe the first case of LV systolic dysfunction with concomitant significant bradyarrhythmia in a patient with PS. CMR revealed evidence suggestive of LV myocardial oedema and/or possible early infiltration. VEGF overexpression could explain oedema-related LV dysfunction which reversed with adequate diuresis, as well as damage to the conduction system. Early cardiac amyloidosis, which can be associated with PS, is an important differential diagnosis. Pacemaker implantation, adequate diuresis, and definitive chemotherapy are key to the management of concomitant ventricular myocardial and electrical dysfunction in such rare case.

Rhythm blues in the time of coronavirus disease 2019 (COVID-19): how the cardiac electrophysiologist adapts to a viral pandemic in Singapore.

Coronavirus disease 2019 (COVID-19) is a major healthcare disaster in the modern times. Healthcare services must adapt to effectively juggle between pandemic management and maintenance of business-as-usual services so that both COVID-19 and non-COVID-19 patients receive appropriate clinical care. We share our experience of significant cardiac rhythm abnormalities seen in COVID-19 patients in Singapore, how the viral pandemic has affected the cardiac electrophysiology and pacing service in a large acute care general hospital and the steps taken to alleviate the negative impact.

Hypertensive brainstem encephalopathy: a diagnosis often overlooked.

Hypertensive encephalopathy (HE) is a subset of posterior reversible encephalopathy syndrome. It typically involves the posterior supratentorial structures, but variations do occur. However, isolated brainstem involvement in HE is rare, with a few cases reported in the literature. Herein, we report a case of acute hypertensive brainstem encephalopathy in which the patient had mild symptoms with very high blood pressure and normal neurological examination. The computed tomography of the brain showed diffuse hypodensity at brainstem. The patient's symptoms improved drastically after hypertension had been controlled. Marked clinical-radiologic dissociation in this particular case was highly suggestive of hypertensive brainstem encephalopathy. Prompt recognition of the condition and aggressive treatment of hypertension in such patients is crucial to relieve oedema and to prevent life-threatening progression. Nevertheless, there is still a lack of awareness among physicians and radiologists regarding this rare clinical entity.

Biomechanical System Versus Observational Rating Scale for Parkinson's Disease Tremor Assessment.

There is a lack of evidence that either conventional observational rating scale or biomechanical system is a better tremor assessment tool. This work focuses on comparing a biomechanical system and the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale in terms of test-retest reliability. The Parkinson's disease tremors were quantified by biomechanical system in joint angular displacement and predicted rating, as well as assessed by three raters using observational ratings. Qualitative comparisons of the validity and function are made also. The observational rating captures the overall severity of body parts, whereas the biomechanical system provides motion- and joint-specific tremor severity. The tremor readings of the biomechanical system were previously validated against encoders' readings and doctors' ratings; the observational ratings were validated with previous ratings on assessing the disease and combined motor symptoms rather than on tremor specifically. Analyses show that the predicted rating is significantly more reliable than the average clinical ratings by three raters. The comparison work removes some of the inconsistent impressions of the tools and serves as guideline for selecting a tool that can improve tremor assessment. Nevertheless, further work is required to consider more variabilities that influence the overall judgement.

Assessment of Caregiver Burden in Huntington's Disease.

Huntington's disease (HD) is a rare neurodegenerative disease associated with disability and loss of patient independence. The caregivers of HD patients are at high risk for burnout. We aimed to identify variables that impact caregiver burden, as measured by the Modified Caregiver Strain Index (MCSI) and the Huntington's disease Quality of Life Battery for Carers Short Form (HD-SF). Total functional capacity and being sole caregiver were significantly associated with higher caregiver burden via MCSI. There was not good correlation between MCSI and HDQoLC-SF. This study highlights the need for more research to effectively identify at-risk caregivers for early intervention.

An In-Laboratory Validity and Reliability Tested System for Quantifying Hand-Arm Tremor in Motions.

Despite the advancement of the tremor assessment systems, the current technology still lacks a method that can objectively characterize tremors in relative segmental movements. This paper presents a measurement system, which quantifies multi-degrees-of-freedom coupled relative motions of hand-arm tremor, in terms of joint angular displacement. In-laboratory validity and reliability tests of the system algorithm to provide joint angular displacement was carried out by using the two-degrees-of-freedom tremor simulator with incremental rotary encoder systems installed. The statistical analyses show that the developed system has high validity results and comparable reliability performances using the rotary encoder system as the reference. In the clinical trials, the system was tested on 38 Parkinson's disease patients. The system readings were correlated with the observational tremor ratings of six trained medical doctors. The moderate to very high clinical correlations of the system readings in measuring rest, postural and task-specific tremors add merits to the degree of readiness of the developed tremor measurement system in a routine clinical setting and/or intervention trial for tremor amelioration.

Thymoma-associated myasthenia gravis and LGI1-encephalitis, with nephrotic syndrome post-thymectomy.

Thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes, though it is uncommon for multiple paraneoplastic syndromes to be present in a single individual. We report a rare case of an elderly gentleman who was found to have thymoma-associated myasthenia gravis and LGI1-encephalitis with myokymia, who presented with nephrotic syndrome (minimal change glomerulopathy) after thymectomy. The latter two paraneoplastic syndromes had manifested when prednisolone was tapered down to low dose. This case serves to remind neurologists that apart from paraneoplastic neurological manifestations, thymoma may also be associated with renal disease. Nephropathy in myasthenia patients with thymoma should be properly evaluated, as it is treatable with immunotherapy, and it may even occur post-thymectomy.

Prevalence of neuromyelitis optica spectrum disorder in the multi-ethnic Penang Island, Malaysia, and a review of worldwide prevalence.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) occurs worldwide in all ethnicities. Recently, population-based studies have shown that NMOSD is more common among non-White populations. There is scarce data about NMOSD prevalence in South East Asian populations. METHODS: (1) A population-based study was undertaken to estimate NMOSD prevalence in the multi-ethnic Penang Island, Malaysia, comprising Chinese, Malays, and Indians. Medical records of NMOSD patients followed up at the Penang General Hospital (the neurology referral centre in Penang Island) were reviewed. The 2015 diagnostic criteria of the International Panel for NMO Diagnosis were used for case ascertainment. (2) A review of population-based prevalence studies of NMOSD worldwide was carried out. PubMed and conference proceedings were searched for such studies. RESULTS: Of the 28 NMOSD patients, 14 were residents of Penang Island on prevalence day [13 (93%) Chinese and one (7%) Malay]. All 14 patients were females and aquaporin 4 seropositive. The prevalence of NMOSD in Penang Island was 1.99/100,000 population; according to ethnicities, the prevalence in Chinese was significantly higher than in Malays (3.31/100,000 vs 0.43/100,000, respectively, p = 0.0195). CONCLUSION: Based on our and other population-based studies, among Asians, East Asian origin populations (Chinese and Japanese) appear to have higher NMOSD prevalence than other Asian ethnic groups. Worldwide, Blacks seem to have the highest NMOSD prevalence. More studies in different geographical regions and ethnic groups will be useful to further inform about potential factors in NMOSD pathogenesis.

Benefits and barriers to participating in longitudinal research of youth-onset type 2 diabetes: Results from the TODAY retention survey.

BACKGROUND/AIMS: Conducting longitudinal research related to chronic illness in adolescents is inherently challenging due to developmental changes and psychosocial stressors. Participants in the Treatment Options for type 2 Diabetes in Adolescents and Youth clinical trial were socioeconomically disadvantaged as well. This study assessed attitudes and beliefs about retention in Treatment Options for type 2 Diabetes in Adolescents and Youth to shed light on the factors that potentially promote and detract from the likelihood of sustained participation. METHODS: After an average 7.3 years of follow-up (range 4.9-9.5), Treatment Options for type 2 Diabetes in Adolescents and Youth participants completed a survey examining their perceptions of the benefits and barriers to sustained involvement in the protocol. RESULTS: The most common reasons for staying in Treatment Options for type 2 Diabetes in Adolescents and Youth included having a strong relationship with the medical team, getting study-provided diabetes care, access to free diabetes medicine and supplies, and being part of a large study to learn more about how to care for youth-onset type 2 diabetes. The most commonly endorsed challenges included scheduling conflicts, possibly disappointing others, difficulties getting to study visits, and the occurrence of other medical issues. CONCLUSIONS: Similar to other published reports, a supportive relationship with study staff was commonly endorsed as a benefit of engagement in the longitudinal study, suggesting that rapport, staff consistency, and relationship quality are important components of optimal retention. Moreover, our findings suggest the value of trying to remove logistical barriers, such as transportation and scheduling challenges, in order to promote long-term participation in research. Further research is recommended to evaluate factors that contribute to attrition versus retention in an a priori manner within longitudinal studies, especially protocols involving cohorts that are more vulnerable to attrition due to developmental transitions and/or socioeconomic challenges. Additional efforts to optimize quantitative and qualitative measurement of barriers would also help to expand our understanding of how to optimally retain participants in longitudinal protocols.

Diethylstilboestrol (1 mg) in the management of castration-resistant prostate cancer.

OBJECTIVE: To investigate the efficacy of diethylstilboestrol (DES) in patients with advanced prostate cancer refractory to androgen suppression. METHODS: This retrospective study comprises 194 patients with prostate cancer treated with DES (1 mg daily) between 1976 and 2010. Study outcome parameters included demographic data, tumour characteristics, treatment history, prostate-specific antigen (PSA) responses, radiologic studies, adverse events and overall survival. RESULTS: At initiation of oestrogen therapy the mean patient age was 69 years (range: 48-89) and the median PSA was 96 ng/ml (range: 1.9-9,500). The median duration of prior prostate cancer treatment was 29 months (range: 1-365). DES was the second-line treatment in 58 patients and the third/fourth-line therapy in 136 men. A formal (≥50%) PSA response was observed in 95 patients (48.9%) and the median time to progression (TTP) was 250 days (95% CI, 180-360) for this group. An additional 62 patients (31.9%) had a partial PSA response with a median TTP of 150 days (95% CI, 92-180). Thirty-seven patients (19.1%) did not have a PSA response and the median TTP was 90 days (95% CI, 90-97). The median overall survival from the start of oestrogen therapy for the entire cohort was 576 days (95% CI, 482-690). The median overall survival of patients who had a formal (≥50%), partial (<50%) and no PSA response was 756 (95% CI, 670-1,429), 428 (95% CI, 340-630) and 329 (95% CI, 287-510) days, respectively. Thirty-nine patients (20.1%) were still alive at the end of the study. No treatment-related deaths occurred. CONCLUSIONS: In the age of chemotherapy this study highlights the efficacy of oestrogen therapy in castration-refractory prostate cancer. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.