Lower Risks of New-Onset Hepatocellular Carcinoma in Patients With Type 2 Diabetes Mellitus Treated With SGLT2 Inhibitors Versus DPP4 Inhibitors.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i. METHODS: This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors. RESULTS: A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses. CONCLUSIONS: SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study.

OBJECTIVE: To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a). DESIGN: This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD). Propensity score matching (1:1) using the nearest neighbour search was performed, and multivariable Cox regression was applied. A three-arm comparison between SGLT2I, DPP4I and GLP1a was conducted using propensity scores with inverse probability of treatment weighting. RESULTS: A total of 62,858 patients (median age: 62.2 years old [SD: 12.8]; 55.93% males; SGLT2I: n = 23,442; DPP4I: n = 39,416) were included. In the matched cohort, the incidence of gastric cancer was lower in SGLT2I (Incidence rate per 1000 person-year, IR: 0.32; 95% confidence interval, CI 0.23-0.43) than in DPP4I (IR per 1000 person-year: 1.22; CI 1.03-1.42) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of gastric cancer (HR 0.30; 95% CI 0.19-0.48), PU, acute gastritis, non-acute gastritis, and GERD (p < 0.05) compared to DPP4I use. In the three-arm analysis, GLP1a use was associated with higher risks of gastric cancer and GERD compared to SGLT2I use. CONCLUSIONS: The use of SGLT2I was associated with lower risks of new-onset gastric cancer, PU, acute gastritis, non-acute gastritis, and GERD after matching and adjustments compared to DPP4I use. SGLT2I use was associated with lower risks of GERD and gastric cancer compared to GLP1a use.

Lower risk of gout in sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors in type-2 diabetes.

OBJECTIVES: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks. METHODS: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between 1 January 2015 and 31 December 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. RESULTS: This study included 43 201 patients [median age: 63.23 years old (Interquartile range, IQR): 55.21-71.95, 53.74% males; SGLT2I group: n = 16 144; DPP4I group: n = 27 057] with a median follow-up of 5.59 years (IQR: 5.27-5.81 years) since initial drug exposure. The incidence rate of developing gout [Incidence rate (IR): 2.5; 95% CI: 2.2, 2.9] among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8, 5.8). SGLT2I was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) and 51% lower risks of all-cause mortality (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory results. The results remained consistent on competing risk and other propensity score approaches. CONCLUSIONS: SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use.

Comparison of Sodium-Glucose Cotransporter-2 Inhibitor and Dipeptidyl Peptidase-4 Inhibitor on the Risks of New-Onset Atrial Fibrillation, Stroke and Mortality in Diabetic Patients: A Propensity Score-Matched Study in Hong Kong.

OBJECTIVE: To compare the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and dipeptidyl peptidase-4 inhibitors (DPP4Is) on adverse outcomes in diabetic patients in Hong Kong. METHODS: This was a retrospective population-based cohort study of type 2 diabetes mellitus patients (n = 72,746) treated with SGLT2I or DPP4I between January 1, 2015, and December 31, 2020, in Hong Kong. Patients with exposure to both DPP4I and SGLT2I therapy, without complete demographics or mortality data, or who had prior atrial fibrillation (AF) were excluded. The study outcomes were new-onset AF, stroke/transient ischemic attack, cardiovascular mortality and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed. RESULTS: The unmatched study cohort included 21,713 SGLT2I users and 39,510 DPP4I users (total: n = 61,233 patients; 55.37% males, median age: 62.7 years [interquartile range (IQR): 54.6-71.9 years]). Over a median follow-up of 2030 (IQR: 1912-2117) days, 2496 patients (incidence rate [IR]: 4.07%) developed new-onset AF, 2179 patients (IR: 3.55%) developed stroke/transient ischemic attack, 1963 (IR: 3.20%) died from cardiovascular causes and 6607 patients (IR: 10.79%) suffered from all-cause mortality. After propensity score matching (SGLT2I: n = 21,713; DPP4I: n = 21,713), SGLT2I users showed lower incidence of new-onset AF (1.96% vs. 2.78%, standardized mean difference [SMD] = 0.05), stroke (1.80% vs. 3.52%, SMD = 0.11), cardiovascular mortality (0.47% vs. 1.56%, SMD = 0.11) and all-cause mortality (2.59% vs. 7.47%, SMD = 0.22) compared to DPP4I users. Cox regression found that SGLT2I users showed lower risk of new-onset AF (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: [0.56, 0.83], P = 0.0001), stroke (HR: 0.64, 95% CI: [0.53, 0.79], P < 0.0001), cardiovascular mortality (HR: 0.39, 95% CI: [0.27, 0.56], P < 0.0001) and all-cause mortality (HR: 0.44, 95% CI: [0.37, 0.51], P < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory tests. CONCLUSIONS: Based on real-world data of type 2 diabetic patients in Hong Kong, SGLT2I use was associated with lower risk of incident AF, stroke/transient ischemic attack, and cardiovascular and all-cause mortality outcomes compared to DPP4I use.

Risk stratification of sudden cardiac death in asymptomatic female Brugada syndrome patients: A literature review.

BACKGROUND AND OBJECTIVES: Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk-scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome. FINDINGS: Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted. CONCLUSIONS: Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female-specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender-specific risk stratification approach amongst asymptomatic BrS patients.

Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score-Matched Study.

BACKGROUND: The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM). METHODS: This population-based retrospective cohort study included male patients with T2DM presenting to public hospitals/clinics in Hong Kong between January 1, 2000, and December 31, 2009. We only included patients prescribed either, but not both, metformin or sulfonylurea. All patients were followed up until December 31, 2019. The primary outcome was new-onset prostate cancer and the secondary outcome was all-cause mortality. One-to-one propensity score matching was performed between metformin and sulfonylurea users based on demographics, comorbidities, antidiabetic and cardiovascular medications, fasting blood glucose level, and hemoglobin A1c level. Subgroup analyses based on age and use of androgen deprivation therapy were performed. RESULTS: The final study cohort consisted of 25,695 metformin users (mean [SD] age, 65.2 [11.8] years) and 25,695 matched sulfonylurea users (mean [SD] age, 65.3 [11.8] years) with a median follow-up duration of 119.6 months (interquartile range, 91.7-139.6 months) after 1:1 propensity score matching of 66,411 patients. Metformin users had lower risks of new-onset prostate cancer (hazard ratio, 0.80; 95% CI, 0.69-0.93; P=.0031) and all-cause mortality (hazard ratio, 0.89; 95% CI, 0.86-0.92; P<.0001) than sulfonylurea users. Metformin use was more protective against prostate cancer but less protective against all-cause mortality in patients aged <65 years (P for trend <.0001 for both) compared with patients aged ≥65 years. Metformin users had lower risk of all-cause mortality than sulfonylurea users, regardless of the use of androgen deprivation therapy (P for trend <.0001) among patients who developed prostate cancer. CONCLUSIONS: Metformin use was associated with significantly lower risks of new-onset prostate cancer and all-cause mortality than sulfonylurea use in male patients with T2DM.

A remote mentorship model for empowering students to undertake electrocardiology research: Effects on gender equity.

Over the past years, there has been increasing awareness on female representation in cardiology, in particular senior academic ranks. Given the gender disparity in cardiology, female talents in cardiovascular academic medicine are significantly under-represented. In addition, whilst women have a slightly higher frequency of earning first authorships, it has been reported that women are 50% less likely to hold a senior authorship position. The drop in female representation in senior ranks of academic medicine may be contributed by a lack of female talent engagement, particularly during their early-career advancement, in high-impact journals and leadership roles. We present a remote, accessible-distributed research team model to help raise the female representation and tackle the challenges faced by female academics in the field of cardiovascular medicine. The group celebrates accessibility through open communication and collaboration, where mentees can seek research advice and ideas virtually from senior members and principal investigators. The decentralized system allows easy access for research guidance and inspirationand break down barriers in the lack of mentorship for early-career female talents. Students are empowered to lead their projects, and be involved in all phases- from the generation of study ideas to publication. The early development of holistic independent research skills equips students to become principal investigators and leaders in the future. The distributive element of the group is demonstrated through the decentralized research approach employed. Authorship is allocated based on intellectual contribution rather than on the acquisition of funding or seniority level.

Predictive risk models for forecasting arrhythmic outcomes in Brugada syndrome: A focused review.

Brugada syndrome (BrS) is a rare disorder characterized by coved or saddle-shaped ST-segment elevation in the right precordial leads on the electrocardiogram. Risk stratification in BrS remains challenging. A number of clinical, electrocardiographic, programmed ventricular stimulation and genetic risk factors have been identified as important predictors of future major arrhythmic events. There is a positive association between the number of risk factors and arrhythmic events. Hence, a multi-parametric approach would provide comprehensive risk assessment and more accurate risk stratification, assisting in therapeutic decisions making, including implantable cardioverter-defibrillator placement or identification of low-risk individuals. However, the extent to which each variable influences the risk and non-linear interactions between the different risk variables make risk stratification challenging. This paper aims to provide a focused review of the multi-parametric risk models for BrS risk stratification published in the literature.

Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

Heart failure (HF) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems. While some studies have demonstrated the value of CRP in predicting (i) the development of HFpEF and (ii) long-term clinical outcomes in HFpEF patients, others have shown no such correlation. As a result, we conducted the following systematic review and meta-analysis to assess both the diagnostic and prognostic role of CRP in HFpEF. PubMed and Embase were searched for studies that assess the relationship between CRP and HFpEF using the following search terms: (((C-reactive protein) AND ((preserved ejection fraction) OR (diastolic heart failure))). The search period was from the start of database to August 6, 2019, with no language restrictions. A total of 312 and 233 studies were obtained from PubMed and Embase respectively, from which 19 studies were included. Our meta-analysis demonstrated the value of a high CRP in predicting the development of not only new onset HFpEF (HR: 1.08; 95% CI: 1.00-1.16; P = 0.04; I2 = 22%), but also an increased risk of cardiovascular mortality when used as a categorical (HR: 2.52; 95% CI: 1.61-3.96; P < 0.0001; I2 = 19%) or a continuous variable (HR: 1.24; 95% CI: 1.04-1.47; P = 0.01; I2 = 28%), as well as all-cause mortality when used as a categorical (HR: 1.78; 95% CI: 1.53-2.06; P < 0.00001; I2 = 0%) or a continuous variable: (HR: 1.06; 95% CI: 1.02-1.06; P = 0.003; I2 = 61%) in HFpEF patients. CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients, in turn justifying its use as a simple, accessible parameter to guide clinical management in this patient population. However, more prospective studies are still required to not only explore the utility and dynamicity of CRP in HFpEF but also to determine whether risk stratification algorithms incorporating CRP actually provide a material benefit in improving patient prognosis.

Glycemic and lipid variability for predicting complications and mortality in diabetes mellitus using machine learning.

INTRODUCTION: Recent studies have reported that HbA1c and lipid variability is useful for risk stratification in diabetes mellitus. The present study evaluated the predictive value of the baseline, subsequent mean of at least three measurements and variability of HbA1c and lipids for adverse outcomes. METHODS: This retrospective cohort study consists of type 1 and type 2 diabetic patients who were prescribed insulin at outpatient clinics of Hong Kong public hospitals, from 1st January to 31st December 2009. Standard deviation (SD) and coefficient of variation were used to measure the variability of HbA1c, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride. The primary outcome is all-cause mortality. Secondary outcomes were diabetes-related complications. RESULT: The study consists of 25,186 patients (mean age = 63.0, interquartile range [IQR] of age = 15.1 years, male = 50%). HbA1c and lipid value and variability were significant predictors of all-cause mortality. Higher HbA1c and lipid variability measures were associated with increased risks of neurological, ophthalmological and renal complications, as well as incident dementia, osteoporosis, peripheral vascular disease, ischemic heart disease, atrial fibrillation and heart failure (p <  0.05). Significant association was found between hypoglycemic frequency (p <  0.0001), HbA1c (p <  0.0001) and lipid variability against baseline neutrophil-lymphocyte ratio (NLR). CONCLUSION: Raised variability in HbA1c and lipid parameters are associated with an elevated risk in both diabetic complications and all-cause mortality. The association between hypoglycemic frequency, baseline NLR, and both HbA1c and lipid variability implicate a role for inflammation in mediating adverse outcomes in diabetes, but this should be explored further in future studies.

Arrhythmias and electrocardiographic findings in Coronavirus disease 2019: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) primarily causes lung infection, but recent studies have shown that cardiac involvement is associated with a worse prognosis. OBJECTIVES: We conducted a systematic review and meta-analysis to examine the prevalence of cardiac arrhythmias detected by the electrocardiogram and their relationships with adverse outcomes in patients with COVID-19. METHODS: PubMed and Google were searched for studies that reported on cardiac arrhythmias and/or examined the relationship between arrhythmias and adverse outcomes. RESULTS: Thirty studies with 12,713 participants were included in the systematic review, and 28 studies (n = 12,499) in the meta-analysis. The mean age was 61.3 ± 16.8 years; 39.3% were female. In 25 studies with 7578 patients, the overall prevalence of cardiac arrhythmias was 10.3% (95% confidence interval [CI]: 8.4%-12.3%). The most common arrhythmias documented during hospitalization were supraventricular arrhythmias (6.2%, 95% CI: 4.4%-8.1%) followed by ventricular arrhythmias (2.5%, 95% CI: 1.8%-3.1%). The incidence of cardiac arrhythmias was higher among critically ill patients (relative risk [RR]: 12.1, 95% CI: 8.5-17.3) and among non-survivors (RR: 3.8, 95%, CI: 1.7-8.7). Eight studies reported changes in the QT interval. The prevalence of QTc > 500 ms was 12.3% (95% CI: 6.9%-17.8%). ST-segment deviation was reported in eight studies, with a pooled estimate of 8.7% (95% CI: 7.3% to 10.0%). CONCLUSION: Our meta-analysis showed that QTc prolongation, ST-segment deviation, and various other cardiac arrhythmias were observed in patients hospitalized with COVID-19. The presence of cardiac arrhythmias was associated with a worse prognosis.

Multi-parametric system for risk stratification in mitral regurgitation: A multi-task Gaussian prediction approach.

BACKGROUND: We hypothesized that a multi-parametric approach incorporating medical comorbidity information, electrocardiographic P-wave indices, echocardiographic assessment, neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) calculated from laboratory data can improve risk stratification in mitral regurgitation (MR). METHODS: Patients diagnosed with mitral regurgitation between 1 March 2005 and 30 October 2018 from a single centre were retrospectively analysed. Outcomes analysed were incident atrial fibrillation (AF), transient ischemic attack (TIA)/stroke and mortality. RESULTS: This study cohort included 706 patients, of whom 171 had normal inter-atrial conduction, 257 had inter-atrial block (IAB) and 266 had AF at baseline. Logistic regression analysis showed that age, hypertension and mean P-wave duration (PWD) were significant predictors of new-onset AF. Low left ventricular ejection fraction (LVEF), abnormal P-wave terminal force in V1 (PTFV1) predicted TIA/stroke. Age, smoking, hypertension, diabetes mellitus, hypercholesterolaemia, ischemic heart disease, secondary mitral regurgitation, urea, creatinine, NLR, PNI, left atrial diameter (LAD), left ventricular end-diastolic dimension, LVEF, pulmonary arterial systolic pressure, IAB, baseline AF and heart failure predicted all-cause mortality. A multi-task Gaussian process learning model demonstrated significant improvement in risk stratification compared to logistic regression and a decision tree method. CONCLUSIONS: A multi-parametric approach incorporating multi-modality clinical data improves risk stratification in mitral regurgitation. Multi-task machine learning can significantly improve overall risk stratification performance.

Value of electrocardiography in coronavirus disease 2019 (COVID-19).

In December 2019, reports of an unknown pneumonia not responsive to traditional treatments arose in Wuhan, China. The pathogen was subsequently identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to be responsible for the coronavirus disease-2019 (COVID-19) illness, and public health emergency of international concern was declared by the World Health Organization. There is increasing awareness of the cardiovascular manifestations of COVID-19 disease, and the adverse impact of cardiovascular involvement on its prognosis. In this setting, the electrocardiogram (ECG) is one of the leading tools to assess the extent of cardiac involvement in COVID-19 patients, due to its wide disponibility, low cost, and the possibility of remote evaluation. In this article, we review the role of the ECG in the identification of cardiac involvement in COVID-19, highlighting relevant clinical implications.

Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. METHODS: High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. RESULTS: Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. CONCLUSIONS: Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.

Electrographic indices in migraine patients: A systematic review and meta-analysis.

BACKGROUND AND AIM: Migraine patients can exhibit autonomic dysregulation, in turn leading to cardiac conduction and repolarization abnormalities. This systematic review and meta-analysis evaluated the electrocardiographic changes in migraineurs. METHOD: PubMed and Embase databases were searched for human studies using the search terms 'migraine' and 'electrocardiogram' until 15th December 2018, identifying 108 and 131 studies. RESULTS: Thirteen studies involving 667 migraineurs and 208 normal subjects included (mean age=30.7, total male percentage=19.8%) were included. A longer mean QTc interval (standard mean difference=7.89, 95% confidence interval=[3.29, 12.49], p=0.0008) and higher frequency of QTc prolongation (risk ratio [RR]=6.23, [2.86-13.58], p<0.00001), but no difference in PR-interval (SMD=4.33, [-3.90-12.56], p=0.30) were observed during migraine attacks compared to pain-free periods. P-wave dispersion was higher in migraine patients compared to controls (mean difference=3.62, [1.03-6.21], p=0.006). RR-interval were statistically indistinguishable between migraine patients and controls (SMD=0.08, [-0.65-0.81], p=0.83), or between migraineurs with and without aura (SMD=-0.03, [-0.44-0.38], p=0.89). Deep breathing ratio was significantly lower in migraineurs compared to controls (SMD=-0.27, 95% CI=[-0.46, -0.08], p=0.006) but similar between migraineurs with and without aura (SMD=-0.04, [-0.27-0.19], p=0.74). No significant difference in Valsalva ratio is found between migraineurs and controls (SMD=0.10, [-0.32-0.53], p=0.63) or between migraineurs with and without aura (SMD=-0.17, [-0.40-0.06], p=0.14). Root mean square of successive differences (RMSSD) (SMD=-0.07, [-1.10-0.95], p=0.89) and standard deviation of NN intervals (SDNN) (SMD=-0.10, [-0.61-0.41], p=0.71) did not significantly differ between migraine patients and controls. CONCLUSION: Electrocardiographic alterations are observed in migraine patients compared to controls, especially during migraine attacks.

Electrocardiographic evidence of abnormal atrial phenotype in Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is an inherited ion channelopathy that may predispose affected individuals to atrial cardiomyopathy. We tested the hypothesis that BrS patients have higher degrees of atrial electrophysiological abnormalities compared to controls, and these can be reflected by changes in P-wave parameters determined on the electrocardiogram (ECG). METHODS: This was a single-center retrospective study comparing BrS patients to age- and gender-matched control subjects. Mean P-wave duration (PWDmean), maximum PWD (PWDmax) and minimum PWD (PWDmin), P-wave dispersion (PWDmax - PWDmin), and P-wave terminal force in V1 (PTFV1) were measured. PWDmax ≥ 120 ms, in the presence and absence of biphasic P-waves in the inferior leads, were termed advanced and partial inter-atrial block (IAB), respectively. RESULTS: The proportion of IAB was significantly higher in BrS patients (28/51; 55%) than in control subjects (14/51; 27%; Fisher's Exact test; P < 0.01). Advanced IAB was observed in two BrS patients but none of the control subjects (P = 0.50). Compared to controls, BrS patients showed higher PWDmean (107 [98-113] vs. 97 [90-108] ms; KWANOVA, P < 0.01), PWDmax (123 [110-132] vs. 113 [107-121] ms; P < 0.001) but statistically indistinguishable PWDmin (82 [72-92] vs. 77 [69-85]; P = 0.09), and P-wave dispersion (38 [26-52] vs. 37 [23-45] ms; P = 0.14). PTFV1 was significantly higher in BrS patients than in control subjects (24 [0-40] vs. 0 [0-27] mm.ms; P < 0.05). CONCLUSION: Atrial conduction abnormalities are frequently observed in BrS. These patients may require monitoring for future development of atrial fibrillation and stroke.