A Multicenter External Validation of a Score Model to Predict Risk of Events in Patients With Brugada Syndrome.

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al. Data were compiled summatively over follow-up to mimic regular risk re-evaluation as per current guidelines. Sudden cardiac death survivor data were considered perievent to ascertain the utility of the score before cardiac arrest. Scores were compared with actual outcomes. Sensitivity in our cohort was 22.7%, specificity was 57.6%, and C-index was 0.58. In conclusion, up to 75% of cardiac arrest survivors in this cohort would not have been offered a defibrillator if evaluated before their event. This casts doubt on the utility of the score model for primary prevention of sudden death. Inherent issues with modern risk scoring strategies decrease the likelihood of success even in robustly designed tools such as the Sieira score model.

QT Interval Dynamics and Cardiovascular Outcomes: A Cohort Study in an Integrated Health Care Delivery System.

Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within-person QT change over time in relation to risk of incident CVD and all-cause mortality in a real-world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non-White) with 3 or more ECGs (baseline in 2005-2009; mean±SD follow-up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all-cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all-cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all-cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long-term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.

Plasma Omega-3 Fatty Acids and the Risk of Cardiovascular Events in Patients After an Acute Coronary Syndrome in MERLIN-TIMI 36.

Background Plasma omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been shown to be inversely correlated with the risk of cardiovascular death in primary prevention. The risk relationship in the setting of an acute coronary syndrome is less well established. Methods and Results Baseline plasma ω3-PUFA composition (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) was assessed through gas chromatography with flame ionization detection in a case-cohort study involving 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event-free subjects as controls from MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation-Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36), a trial of patients hospitalized with non-ST-segment-elevation -acute coronary syndrome. After inverse-probability-weighted multivariable adjustment including all traditional risk factors, a higher relative proportion of long-chain ω3-PUFAs (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid) were associated with 18% lower odds of cardiovascular death (adjusted [adj] odds ratio [OR] per 1 SD, 0.82; 95% CI, 0.68-0.98) that was primarily driven by 27% lower odds of sudden cardiac death (adj OR per 1 SD, 0.73; 95% CI, 0.55-0.97). Long-chain ω3-PUFA levels in the top quartile were associated with 51% lower odds of cardiovascular death (adj OR 0.49; 95% CI, 0.27-0.86) and 63% lower odds of sudden cardiac death (adj OR, 0.37; 95% CI, 0.16-0.56). An attenuated relationship was seen for α-linolenic acid and subsequent odds of cardiovascular (adj OR, 0.92; 95% CI, 0.74-1.14) and sudden cardiac death (adj OR, 0.91; 95% CI, 0.67-1.25). No significant relationship was observed between any ω3-PUFAs and the odds of cardiovascular death unrelated to sudden cardiac death, myocardial infarction, atrial fibrillation, or early post-acute coronary syndrome ventricular tachycardia. Conclusions In patients after non-ST-segment-elevation-acute coronary syndrome, plasma long-chain ω3-PUFAs are inversely associated with lower odds of sudden cardiac death, independent of traditional risk factors and lipids. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00099788.

Public health impact of daily life triggers of sudden cardiac death: A systematic review and comparative risk assessment.

BACKGROUND: Sudden cardiac death (SCD) may be triggered by daily circumstances and activities such as stressful psycho-emotional events, physical exertion or substance misuse. We calculated population attributable fractions (PAFs) to estimate the public health relevance of daily life triggers of SCD and to compare their population impacts. METHODS: We searched PubMed, Scopus and the Web of Science citation databases to retrieve studies of triggers of SCD and cardiac arrest that would enable a computation of PAFs. When more studies investigated the same trigger, a meta-analytical pooled risk random-effect estimate was used. RESULTS: Of the retrieved studies, eight provided data enabling computation of PAFs. The prevalence of exposure within population for SCD triggers in the control periods ranged from 1.06% for influenza infection to 8.73% for recent use of cannabis. Triggers ordered from the highest to the lowest risk increase were: physical exertion, recent cocaine use, episodic alcohol consumption, recent amphetamine use, episodic coffee consumption, psycho-emotional stress within the previous month, influenza infection, and recent cannabis use. The relative risk increase ranged from 1.10 to 4.98. By accounting for both the magnitude of the risk increase and the prevalence in the population, the present estimates of PAF assign 14.5% (95% confidence interval [CI] 4.9-28.5) of all SCDs to episodic alcohol consumption, 9.4% (95% CI 1.2-29.3) to physical exertion, 6.9% (95% CI 0.3-25.0) to cocaine, 6% (95% CI 1.2-14.6) to episodic coffee consumption, 3% (95% CI 0.4-6.8) to psycho-emotional stress in the previous month, 1.7% (95% CI -0.9 to 12.9) to amphetamines, 0.9% (95% CI -4.9 to 12.5) to cannabis, and 0.3% (95% CI 0.2-0.4) to influenza infections. CONCLUSIONS: In addition to episodic alcohol consumption, a trigger with the greatest public health importance for SCD, episodic physical exertion, cocaine use and coffee consumption also show a considerable population impact.

Sex Differences in Electrophysiology, Ventricular Tachyarrhythmia, Cardiac Arrest and Sudden Cardiac Death Following Acute Myocardial Infarction.

BACKGROUND: Women experience less appropriate implantable cardioverter-defibrillator (ICD) interventions and are underrepresented in randomised ICD trials. Sex-differences in inducible and spontaneous ventricular tachycardia/fibrillation (VT/VF), cardiac arrest and sudden cardiac death (SCD) early post-myocardial infarction (MI) require further study. METHODS: Consecutive ST-elevation MI patients with left ventricular ejection fraction (LVEF)≤40% underwent electrophysiology study (EPS) to target early prevention of SCD. An ICD was implanted for a positive (inducible monomorphic VT) but not a negative (no arrhythmia or inducible VF) EPS. The combined primary endpoint of VT/VF (spontaneous or ICD-treated), cardiac arrest or SCD was assessed using competing risk survival analysis in women versus men with adjustment for confounders. Logistic regression was used to determine independent predictors of inducible VT at EPS. RESULTS: A total of 403 patients (16.9% female) underwent EPS. Women were significantly older than men but with similar LVEF (31.5 ± 6.3 versus 31.6 ± 6.4%, p = 0.91). Electrophysiology study was positive for inducible VT in 22.1% and 33.4% (p = 0.066) and an ICD implanted in 25.0% and 33.4% (p = 0.356) of women versus men. Appropriate ICD activations (VT/VF) occurred in 5.9% of women and 36.6% of men (p = 0.012). The adjusted cumulative primary endpoint incidence was significantly lower in women than men (1.6% versus 26.5%, p = 0.03). Female sex was not an independent predictor of inducible VT at EPS (HR 0.63, 95% CI 0.33-1.23, p = 0.178). CONCLUSIONS: Women with early post-MI cardiomyopathy had lower VT/VF, cardiac arrest and SCD, compared to men. In ICD recipients the rate of appropriate activations was six-fold less in women compared to men.

Association of Dietary Magnesium Intake with Fatal Coronary Heart Disease and Sudden Cardiac Death.

Background: Postmenopausal women represent the highest population-based burden of cardiovascular disease, including sudden cardiac death (SCD). Our understanding of the etiology and risk factors contributing to fatal coronary heart disease (CHD) and SCD, particularly among women, is limited. This study examines the association between dietary magnesium intake and fatal CHD and SCD. Materials and Methods: We examined 153,569 postmenopausal women who participated in the Women's Health Initiative recruited between 1993 and 1998. Magnesium intake at baseline was assessed using a validated food frequency questionnaire, adjusting for energy via the residual method. Fatal CHD and SCD were identified over an average follow-up of 10.5 years. Results: For every standard deviation increase in magnesium intake, there was statistically significant risk reduction, after adjustment for confounders, of 7% for fatal CHD (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.89-0.97), and 18% risk reduction for SCD (HR 0.82, 95% CI 0.58-1.15) the latter of which did not reach statistical significance. In age-adjusted quartile analysis, women with the lowest magnesium intake (189 mg/day) had the greatest risk for fatal CHD (HR 1.54, 95% CI 1.40-1.69) and SCD (HR 1.70, 95% CI 0.94-3.07). This association was attenuated in the fully adjusted model, with HRs of 1.19 (95% CI 1.06-1.34) for CHD and 1.24 (95% CI 0.58-2.65) for SCD for the lowest quartile of magnesium intake. Conclusions: This study provides evidence of a potential inverse association between dietary magnesium and fatal CHD and a trend of magnesium with SCD in postmenopausal women. Future studies should confirm this association and consider clinical trials to test whether magnesium supplementation could reduce fatal CHD in high-risk individuals.

Why docosapentaenoic acid is not included in the Omega-3 Index.

As currently defined, the Omega-3 Index comprises eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), but not docosapentaenoic acid (DPA) in erythrocytes. In fish and many fish oils DPA is detectable (along with EPA and DHA), but sources rich in DPA are scarce. Purified DPA is available, and DPA is a precursor of biologically active molecules, but much remains to be learned about the effects of DPA in humans. In epidemiologic studies, erythrocyte DPA did not predict risk for total mortality, sudden cardiac death, or other relevant cardiovascular events, and, more importantly, did not improve prediction of these events when included along with EPA and DHA, the original Omega-3 Index. We conclude that current scientific evidence does not support including DPA into the Omega-3 Index.

Status of cardiac arrhythmia services in Africa in 2018: a PASCAR Sudden Cardiac Death Task Force report.

BACKGROUND: There is limited information on the availability of health services to treat cardiac arrhythmias in Africa. METHODS: The Pan-African Society of Cardiology (PASCAR) Sudden Cardiac Death Task Force conducted a survey of the burden of cardiac arrhythmias and related services over two months (15 October to 15 December) in 2017. An electronic questionnaire was completed by general cardiologists and electrophysiologists working in African countries. The questionnaire focused on availability of human resources, diagnostic tools and treatment modalities in each country. RESULTS: We received responses from physicians in 33 out of 55 (60%) African countries. Limited use of basic cardiovascular drugs such as anti-arrhythmics and anticoagulants prevails. Non-vitamin K-dependent oral anticoagulants (NOACs) are not widely used on the continent, even in North Africa. Six (18%) of the sub-Saharan African (SSA) countries do not have a registered cardiologist and about one-third do not have pacemaker services. The median pacemaker implantation rate was 2.66 per million population per country, which is 200-fold lower than in Europe. The density of pacemaker facilities and operators in Africa is quite low, with a median of 0.14 (0.03-6.36) centres and 0.10 (0.05-9.49) operators per million population. Less than half of the African countries have a functional catheter laboratory with only South Africa providing the full complement of services for cardiac arrhythmia in SSA. Overall, countries in North Africa have better coverage, leaving more than 110 million people in SSA without access to effective basic treatment for cardiac conduction disturbances. CONCLUSION: The lack of diagnostic and treatment services for cardiac arrhythmias is a common scenario in the majority of SSA countries, resulting in sub-optimal care and a subsequent high burden of premature cardiac death. There is a need to improve the standard of care by providing essential services such as cardiac pacemaker implantation.

Combined Effect of Sauna Bathing and Cardiorespiratory Fitness on the Risk of Sudden Cardiac Deaths in Caucasian Men: A Long-term Prospective Cohort Study.

Both cardiorespiratory fitness (CRF) and frequency of sauna bathing (FSB) are each strongly and independently associated with sudden cardiac death (SCD) risk. However, the combined effect of CRF and FSB on SCD risk has not been previously investigated. We evaluated the joint impact of CRF and FSB on the risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of 2291 men aged 42-61 years at recruitment. Objectively measured CRF and self-reported sauna bathing habits were assessed at baseline. CRF was categorized as low and high (median cutoffs) and FSB as low and high (defined as ≤2 and 3-7 sessions/week respectively). Multivariable adjusted hazard ratios (HRs) with confidence intervals (CIs) were calculated for SCD. During a median follow-up of 26.1 years, 226 SCDs occurred. Comparing high vs low CRF, the HR (95% CIs) for SCD in analysis adjusted for several established risk factors was 0.48 (0.34-0.67). Comparing high vs low FSB, the corresponding HR was 0.67 (0.46-0.98). Compared to men with low CRF & low FSB, the multivariate-adjusted HRs of SCD for the following groups: high CRF & high FSB; high CRF & low FSB; and low CRF & high FSB were 0.31 (0.16-0.63), 0.49 (0.34-0.70), and 0.71 (0.45-1.10) respectively. In a general male Caucasian population, the combined effect of high aerobic fitness (as measured by CRF) and frequent sauna baths is associated with a substantially lowered risk of future SCD compared with high CRF or frequent sauna bathing alone.

Risk Stratification for Sudden Cardiac Death After Myocardial Infarction.

Sudden cardiac death (SCD) accounts for ∼50% of mortality after myocardial infarction (MI). Most SCDs result from ventricular tachyarrhythmias, and the tachycardias that precipitate cardiac arrest result from multiple mechanisms. As a result, it is highly unlikely that any single test will identify all patients at risk for SCD. Current guidelines for use of implantable cardioverter-defibrillators (ICDs) to prevent SCD are based primarily on measurement of left ventricular ejection fraction (LVEF). Although reduced LVEF is associated with increased total cardiac mortality after MI, the focus of current guidelines on LVEF omits ∼50% of patients who die suddenly. In addition, there is no evidence of a mechanistic link between reduced LVEF and arrhythmias. Thus, LVEF is neither sensitive nor specific as a tool for post-MI risk stratification. Newer tests to screen for predisposition to ventricular arrhythmias and SCD examine abnormalities of ventricular repolarization, autonomic nervous system function, and electrical heterogeneity. These tests, as well as older methods such as programmed stimulation, the signal-averaged electrocardiogram, and spontaneous ventricular ectopy, do not perform well in patients with LVEF ≤30%. Recent observational studies suggest, however, that these tests may have greater utility in patients with LVEF >30%. Because SCD results from multiple mechanisms, it is likely that combinations of risk factors will prove more precise for risk stratification. Prospective trials that evaluate the performance of risk stratification schema to determine ICD use are necessary for cost-effective reduction of the incidence of SCD after MI.

Hypertrophic cardiomyopathy. / Miocardiopatía hipertrófica.

Hypertrophic cardiomyopathy is the most common inherited cardiovascular disease. It is characterized by increased ventricular wall thickness and is highly complex due to its heterogeneous clinical presentation, several phenotypes, large number of associated causal mutations and broad spectrum of complications. It is caused by mutations in sarcomeric proteins, which are identified in up to 60% of cases of the disease. Clinical manifestations of Hypertrophic Cardiomyopathy include shortness of breath, chest pain, palpitations and syncope, which are related to the onset of diastolic dysfunction, left ventricular outflow tract obstruction, ischemia, atrial fibrillation and abnormal vascular responses. It is associated with an increased risk of sudden cardiac death, heart failure and thromboembolic events. In this article, we discuss the diagnostic and therapeutic aspects of this disease.

Clinical outcome of patients with the Brugada type 1 electrocardiogram without prophylactic implantable cardioverter defibrillator in primary prevention: a cumulative analysis of seven large prospective studies.

Aims: Patients with the Brugada type 1 ECG (Br type 1) without previous aborted sudden death (aSD) who do not have a prophylactic ICD constitute a very large population whose outcome is little known. The objective of this study was to evaluate the risk of SD or aborted SD (aSD) in these patients. Methods and results: We conducted a meta-analysis and cumulative analysis of seven large prospective studies involving 1568 patients who had not received a prophylactic ICD in primary prevention. Patients proved to be heterogeneous. Many were theoretically at low risk, in that they had a drug-induced Br type 1 (48%) and/or were asymptomatic (87%), Others, in contrast, had one or more risk factors. During a mean/median follow-up ranging from 30 to 48 months, 23 patients suffered SD and 1 had aSD. The annual incidence of SD/aSD was 0.5% in the total population, 0.9% in patients with spontaneous Br type 1 and 0.08% in those with drug-induced Br type 1 (P = 0.0001). The paper by Brugada et al. reported an incidence of SD more than six times higher than the other studies, probably as a result of selection bias. On excluding this paper, the annual incidence of SD/aSD in the remaining 1198 patients fell to 0.22% in the total population and to 0.38 and 0.06% in spontaneous and drug-induced Br type 1, respectively. Of the 24 patients with SD/aSD, 96% were males, the mean age was 39 ± 15 years, 92% had spontaneous Br type 1, 61% had familial SD (f-SD), and only 18.2% had a previous syncope; 43% had a positive electrophysiological study. Multiple meta-analysis of individual trials showed that spontaneous Br type 1, f-SD, and previous syncope increased the risk of SD/aSD (RR 2.83, 2.49, and 3.03, respectively). However, each of these three risk factors had a very low positive predictive value (PPV) (1.9-3.3%), while negative predictive values (NPV) were high (98.5-99.7%). The incidence of SD/aSD was only slightly higher in patients with syncope than in asymptomatic patients (2% vs. 1.5%, P = 0.6124). Patients with SD/aSD when compared with the others had a mean of 1.74 vs. 0.95 risk factors (P = 0.026). Conclusion: (i) In patients with Br type 1 ECG without an ICD in primary prevention, the risk of SD/aSD is low, particularly in those with drug-induced Br type 1; (ii) spontaneous Br type 1, f-SD, and syncope increase the risk. However, each of these risk factors individually has limited clinical usefulness, owing to their very low PPV; (iii) patients at highest risk are those with more than one risk factor.

Spatiotemporal Progression of Early Human Ventricular Fibrillation.

Objectives: The objective of this study was to evaluate the spatio-temporal organization and progression of human ventricular fibrillation (VF) in the left (LV) and right (RV) ventricles. Background: Studies suggest that localized sources contribute to VF maintenance, but the evolution of VF episodes has not been quantified. Methods: Synchrony between electrograms recorded from 25 patients with induced VF is computed and used to define the Asynchronous Index (ASI), indicating regions which are out-of-step with surrounding tissue. Computer simulations show that ASI can identify the location of VF-maintaining sources, where larger values of ASImax correlate with more stable sources. Results: Automated synchrony analysis shows elevated values of ASI in a majority of self-terminating episodes (LV: 8/9, RV: 7/8) and sustained episodes (LV: 11/11, RV: 12/12). The locations of ASImax in sustained episodes co-localize with rotor cores when rotational activity is simultaneously present in phase maps (LV: 8/8, RV: 5/7, p<.05). The distribution of ASImax differentiates self-terminating from sustained episodes (mean ASImax = 0.60±0.14 and 0.70±0.16, respectively; p=0.01). Across sustained episodes the LV exhibits an increase in ASImax with time. Conclusions: Quantitative analysis identifies localized asynchronous regions that correlate with sources in VF, with sustained episodes evolving to exhibit more stable activation in the LV. This successive increase in stability indicates a stabilizing agent may be responsible for perpetuating fibrillation in a "migrate-and-capture" mechanism in the LV.

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators.

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks.

Sleep Disordered Breathing and Heart Failure: What Does the Future Hold?

Most patients with heart failure (HF) have sleep-disordered breathing (SDB), with central (rather than obstructive) sleep apnea becoming the predominant form in patients with more severe disease. Cyclical apnea and hypopneas are associated with sleep disturbance, hypoxemia, hemodynamic changes, and sympathetic activation. These patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and can partially normalize the sleep and respiratory physiology. However, recent randomized trials of cardiovascular outcomes in central sleep apnea in chronic HF with reduced ejection fraction have had neutral findings or suggested the possibility of harm, likely from an increased rate of sudden death. Further randomized outcome studies are required to determine whether mask-based treatment is appropriate for patients with chronic HF with reduced ejection fraction and obstructive sleep apnea, for patients with heart failure with preserved ejection fraction, and for patients with decompensated heart failure. New therapies for sleep apnea (e.g., implantable phrenic nerve stimulators) also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with HF and sleep apnea.

Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency.

Importance: Controversy exists regarding the safety of testosterone replacement therapy (TRT) following recent reports of an increased risk of adverse cardiovascular events. Objective: To investigate the association between TRT and cardiovascular outcomes in men with androgen deficiency. Design, Setting, and Participants: A retrospective cohort study was conducted within an integrated health care delivery system. Men at least 40 years old with evidence of androgen deficiency either by a coded diagnosis and/or a morning serum total testosterone level of less than 300 ng/dL were included. The eligibility window was January 1, 1999, to December 31, 2010, with follow-up through December 31, 2012. Exposures: Any prescribed TRT given by injection, orally, or topically. Main Outcomes and Measures: The primary outcome was a composite of cardiovascular end points that included acute myocardial infarction (AMI), coronary revascularization, unstable angina, stroke, transient ischemic attack (TIA), and sudden cardiac death (SCD). Multivariable Cox proportional hazards models were used to investigate the association between TRT and cardiovascular outcomes. An inverse probability of treatment weight, propensity score methodology, was used to balance baseline characteristics. Results: The cohorts consisted of 8808 men (19.8%) ever dispensed testosterone (ever-TRT) (mean age, 58.4 years; 1.4% with prior cardiovascular events) and 35 527 men (80.2%) never dispensed testosterone (never-TRT) (mean age, 59.8 years; 2.0% with prior cardiovascular events). Median follow was 3.2 years (interquartile range [IQR], 1.7-6.6 years) in the never-TRT group vs 4.2 (IQR, 2.1-7.8) years in the ever-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person-years in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67 (95% CI, 0.62-0.73. Similar results were seen when the outcome was restricted to combined stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0.62-0.84) and combined cardiac events (AMI, SCD, unstable angina, revascularization procedures) (HR, 0.66; 95% CI, 0.60-0.72). Conclusions and Relevance: Among men with androgen deficiency, dispensed testosterone prescriptions were associated with a lower risk of cardiovascular outcomes over a median follow-up of 3.4 years.

Associations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury with heart rate-corrected QT and JT intervals in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

PURPOSE: Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish have been associated with risk of cardiovascular diseases (CVD), especially sudden cardiac death (SCD). Mercury exposure, mainly due fish consumption, has been associated with higher risk. However, the impact of PUFAs or mercury on the ventricular cardiac arrhythmias, which often precede SCD, is not completely known. We investigated the associations of the serum long-chain omega-3 PUFAs and hair mercury with ventricular repolarization, measured by heart rate-corrected QT and JT intervals (QTc and JTc, respectively). METHODS: A total of 1411 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years and free of CVD in 1984-1989, were studied. RESULTS: Serum long-chain omega-3 PUFA concentrations were inversely associated with QTc and JTc (multivariate-adjusted P trend across quartiles = 0.02 and 0.002, respectively) and, during the mean 22.9-year follow-up, with lower SCD risk. However, further adjustments for QTc, JTc or hair mercury did not attenuate the associations with SCD. Hair mercury was not associated with QTc, JTc or SCD risk, but it slightly attenuated the associations of the serum long-chain omega-3 PUFA with QTc and JTc. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentrations, mainly a marker for fish consumption, were inversely associated with QTc and JTc in middle-aged and older men from Eastern Finland, but QTc or JTc did not attenuate the inverse associations of the long-chain omega-3 PUFA with SCD risk. This suggests that prevention of prolonged ventricular repolarization may not explain the inverse association of the long-chain omega-3 PUFA with SCD risk.

Prognostic value of coronary computed tomography angiography in diabetic patients without chest pain syndrome.

AIMS: Diabetic patients with coronary artery disease (CAD) are often free of chest pain syndrome. A useful modality for non-invasive assessment of CAD is coronary computed tomography angiography (CTA). However, the prognostic value of CAD on coronary CTA in diabetic patients without chest pain syndrome is relatively unknown. Therefore, the aim was to investigate the long-term prognostic value of coronary CTA in a large population diabetic patients without chest pain syndrome. METHODS: Between 2005 and 2013, 525 diabetic patients without chest pain syndrome were prospectively included to undergo coronary artery calcium (CAC)-scoring followed by coronary CTA. During follow-up, the composite endpoint of all-cause mortality, non-fatal myocardial infarction (MI), and late revascularization (>90 days) was registered. RESULTS: In total, CAC-scoring was performed in 410 patients and coronary CTA in 444 patients (431 interpretable). After median follow-up of 5.0 (IQR 2.7-6.5) years, the composite endpoint occurred in 65 (14%) patients. Coronary CTA demonstrated a high prevalence of CAD (85%), mostly non-obstructive CAD (51%). Furthermore, patients with a normal CTA had an excellent prognosis (event-rate 3%). An incremental increase in event-rate was observed with increasing CAC-risk category or coronary stenosis severity. Finally, obstructive (50-70%) or severe CAD (>70%) was independently predictive of events (HR 11.10 [2.52;48.79] (P = .001), HR 15.16 [3.01;76.36] (P = .001)). Obstructive (50-70%) or severe CAD (>70%) provided increased value over baseline risk factors. CONCLUSION: Coronary CTA provided prognostic value in diabetic patients without chest pain syndrome. Most importantly, the prognosis of patients with a normal CTA was excellent.

Electrophysiology testing and catheter ablation are helpful when evaluating asymptomatic patients with Wolff-Parkinson-White pattern: the con perspective.

The association between asymptomatic Wolff-Parkinson-White (WPW) syndrome and sudden cardiac death (SCD) has been well documented. The inherent properties of the accessory pathway determine the risk of SCD in WPW, and catheter ablation essentially eliminates this risk. An approach to WPW syndrome is needed that incorporates the patient's individualized considerations into the decision making. Patients must understand that there is a trade-off of a small immediate risk of an invasive approach for elimination of a small lifetime risk of the natural history of asymptomatic WPW. Clinicians can minimize the invasive risk by only performing ablation for patients with at-risk pathways.