The prognostic significance of single-lead ST-segment resolution in ST-segment elevation myocardial infarction patients treated with primary PCI - A substudy of the randomized TOTAL trial.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality worldwide. Simple electrocardiogram (ECG) tools, including ST-segment resolution (STR) have been developed to identify high-risk STEMI patients after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We evaluated the prognostic impact of STR in the ECG lead with maximal baseline ST-segment elevation (STE) 30-60 minutes after primary PCI in 7,654 STEMI patients included in the TOTAL trial. Incomplete or no STR was defined as < 70% STR and complete STR as ≥ 70% STR. The primary outcome was the composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or new or worsening New York Heart Association (NYHA) class IV heart failure at 1-year follow-up. RESULTS: Of 7,654 patients, 42.9% had incomplete or no STR and 57.1% had complete STR. The primary outcome occurred in 341 patients (10.4%) in the incomplete or no STR group and in 234 patients (5.4%) in the complete STR group. In Cox regression analysis, adjusted hazard ratio for STR < 70% to predict the primary outcome was 1.56 (95% confidence interval 1.32-1.89; P < .001) (model adjusted for all baseline comorbidities, clinical status during hospitalization, angiographic findings, and procedural techniques). CONCLUSION: In a large international study of STEMI patients, STR < 70% 30-60 minutes post primary PCI in the ECG lead with the greatest STE at admission was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 1-year follow-up. Clinicians should pay attention to this simple ECG finding.

The association between GRACE score at admission for myocardial infarction and the incidence of sudden cardiac arrests in long-term follow-up - the MADDEC study.

Background. Sudden cardiac arrest (SCA), often also leading to sudden cardiac death (SCD), is a common complication in coronary artery disease. Despite the effort there is a lack of applicable prediction tools to identify those at high risk. We tested the association between the validated GRACE score and the incidence of SCA after myocardial infarction. Material and methods. A retrospective analysis of 1,985 patients treated for myocardial infarction (MI) between January 1st 2015 and December 31st 2018 and followed until the 31st of December of 2021. The main exposure variable was patients' GRACE score at the point of admission and main outcome variable was incident SCA after hospitalization. Their association was analyzed by subdistribution hazard (SDH) model analysis. The secondary endpoints included SCA in patients with no indication to implantable cardioverter-defibrillator (ICD) device and incident SCD. Results. A total of 1985 patients were treated for MI. Mean GRACE score at baseline was 118.7 (SD 32.0). During a median follow-up time of 5.3 years (IQR 3.8-6.1 years) 78 SCA events and 52 SCDs occurred. In unadjusted analyses one SD increase in GRACE score associated with over 50% higher risk of SCA (SDH 1.55, 95% CI 1.29-1.85, p < 0.0001) and over 40% higher risk for SCD (1.42, 1.12-1.79, p = 0.0033). The associations between SCA and GRACE remained statistically significant even with patients without indication for ICD device (1.57, 1.30-1.90, p < 0.0001) as well as when adjusting with patients LVEF and omitting the age from the GRACE score to better represent the severity of the cardiac event. The association of GRACE and SCD turned statistically insignificant when adjusting with LVEF. Conclusions. GRACE score measured at admission for MI associates with long-term risk for SCA.

What is already known about this subject?Nearly 50% of cardiac mortality is caused by sudden cardiac death, often due to sudden cardiac arrest.Despite the effort, there is a lack of applicable prediction tools to identify those at high risk.What does this study add?This study shows that GRACE score measured at the point of admission for myocardial infarction can be used to evaluate patients' risk for sudden cardiac arrest in a long-term follow-up.How might this impact on clinical practice?Based on our findings, the GRACE score at the point of admission could significantly affect the patients' need for an ICD device after hospitalization for MI and should be considered as a contributing factor when evaluating the patients' follow-up care.

Anterior ST elevation in a patient with RBBB.

A 79-year-old male with a history of coronary artery disease presented to the Emergency Department with chest pain. ECG showed RBBB with mild ST elevation and positive T waves in I, aVL and V2. In patients with RBBB lack of ST depression and T wave inversion in the anterior leads could signify ischemia secondary to left anterior descending coronary artery occlusion. However, the patient did not have acute coronary syndrome and the presenting ECG was comparable to an ECG recorded five years earlier.

Congenital short QT syndrome: A review focused on electrocardiographic features.

Congenital short QT syndrome is a very low prevalence inherited primary arrhythmia syndrome first reported in 2000 by Gussak et al., who described two families with a short QT interval, syncope, and sudden cardiac death. In 2004, Ramon Brugada et al. identified the first genetic type of this entity. To date, a total of nine genotypes have been described. The diagnosis is easy from the electrocardiogram (ECG), not only due to the short QT duration, but also based on other aspects covered in this review. During 24-h Holter monitoring, paroxysmal atrial fibrillation spontaneously converting to sinus rhythm may be found. Even though the T wave may appear symmetric on the ECG, the T loop of the vectorcardiogram confirms that the T wave is constantly asymmetric due to the presence of dashes closer to each other in the efferent branch. In this review, we also describe the minus-plus T wave sign that we have described in a previously published article. In addition to congenital causes, we briefly highlight the existence of numerous acquired causes of short QT interval.

Acute chest pain in a patient with left bundle branch pacing.

We present a patient with left bundle branch (LBB) electronic ventricular pacing with chest pain. ECG showed ventricular pacing and ST elevation in the inferolateral leads. At first it was felt that the Sgarbossa criteria for STEMI in electronic ventricular pacing are not met. However, as symptoms persisted, emergency coronary angiography was performed showing complete occlusion of the left circumflex artery. As LBB pacing results in narrow QRS complexes with incomplete right bundle branch block, ST-segment deviation should not be ignored and the Sgarbossa criteria for patients with LBB block or right ventricular electronic pacing should not be applied.

The prognostic significance of Q waves and T wave inversions in the ECG of patients with STEMI: A substudy of the TOTAL trial.

BACKGROUND: The prognostic significance of Q waves and T-wave inversions (TWI) combined and separately in STEMI patients undergoing primary PCI has not been well established in previous studies. METHODS: We included 7,831 patients from the TOTAL trial and divided the patients into categories based on Q waves and TWIs in the presenting ECG. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock or new or worsening NYHA class IV heart failure within one year. The study evaluated the effect of Q waves and TWI on the risk of primary outcome and all-cause death, and whether patient benefit of aspiration thrombectomy differed between the ECG categories. RESULTS: Patients with Q+TWI+ (Q wave and TWI) pattern had higher risk of primary outcome compared to patients with Q-TWI- pattern [33 (10.5%) vs. 221 (4.2%); adjusted hazard ratio (aHR) 2.10; 95% CI, 1.45-3.04; p<0.001] within 40-days' period. When analyzed separately, patients with Q waves had a higher risk for the primary outcome compared to patients with no Q waves in the first 40 days [aHR 1.80; 95% CI, 1.48-2.19; p<0.001] but there was no additive risk after 40 days. Patients with TWI had a higher risk for primary outcome only after 40 days when compared to patients with no TWI [aHR 1.63; 95% CI, 1.04-2.55; p=0.033]. There was a trend towards a benefit of thrombectomy in patients with the Q+TWI+ pattern. CONCLUSIONS: Q waves and TWI combined (Q+TWI+ pattern) in the presenting ECG is associated with unfavourable outcome within 40-days. Q waves tend to affect short-term outcome, while TWI has more effect on long-term outcome.

Underweight and obesity are related to higher mortality in patients undergoing coronary angiography: The KARDIO invasive cardiology register study.

BACKGROUND: In patients with some cardiovascular disease conditions, slightly elevated body mass index (BMI) is associated with a lower mortality risk (termed "obesity paradox"). It is uncertain, however, if this obesity paradox exists in patients who have had invasive cardiology procedures. We evaluated the association between BMI and mortality in patients who underwent coronary angiography. METHODS: We utilised the KARDIO registry, which comprised data on demographics, prevalent diseases, risk factors, coronary angiographies, and interventions on 42,636 patients. BMI was categorised based on WHO cut-offs or transformed using P-splines. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for all-cause mortality. RESULTS: During a median follow-up of 4.9 years, 4688 all-cause deaths occurred. BMI was nonlinearly associated with mortality risk: compared to normal weight category (18.5-25 kg/m2 ), the age-adjusted HRs (95% CIs) for all-cause mortality were 1.90 (1.49, 2.43), 0.96 (0.92, 1.01), 1.04 (0.99, 1.09), 1.08 (0.96, 1.20), and 1.45 (1.22, 1.72) for underweight (<18.5 kg/m2 ), preobesity (25 to <30 kg/m2 ), obesity class I (30 to <35 kg/m2 ), obesity class II (35 to <40 kg/m2 ), and obesity class III (>40 kg/m2 ), respectively. The corresponding multivariable adjusted HRs (95% CIs) were 2.00 (1.55, 2.58), 0.92 (0.88, 0.97) 1.01 (0.95, 1.06), 1.10 (0.98, 1.23), and 1.49 (1.26, 1,78), respectively. CONCLUSIONS: In patients undergoing coronary angiography, underweight and obesity class III are associated with increased mortality risk, and the lowest mortality was observed in the preobesity class. It appears the obesity paradox may be present in patients who undergo invasive coronary procedures.

Evaluation of the QRS score for diagnosing coronary artery disease in women: A Finnish cardiovascular study.

BACKGROUND: Exercise electrocardiography is a widely used diagnostic modality for diagnosing coronary artery disease. This method has been used for both sexes; however, its diagnostic accuracy in women is limited. METHODS: The study analyzed 332 women participating in the Finnish Cardiovascular Study. Among 332 women, 125 with angiographically proven coronary artery disease (mean age 62.1 ± 9.5 years), 91 with a low likelihood of coronary artery disease (mean age 47.3 ± 13.5 years), and 116 without angiographically proven coronary artery disease (mean age 56.3 ± 9.9 years) were analyzed. The Q, R, S, and ST-segment changes and QRS score were determined by subtracting the Q, R, S, and ST-segment amplitudes immediately after the maximal exercise changes from their rest values (Δ). Receiver operating characteristic curve analysis was performed to evaluate the overall diagnostic performance of the parameters for predicting coronary artery disease. RESULTS: The areas under the receiver operating characteristic curve between coronary artery disease and low likelihood of coronary artery disease groups for the QRS score and ΔSTV5, ΔQaVF, and ΔRaVF were 0.75, 0.73, 0.71, and 0.71, respectively. These areas were lower (0.62, 0.57, 0.60, and 0.60, respectively) between the groups with and without angiographically proven coronary artery disease. QRS score demonstrated the highest sensitivity at 80% specificity (61.5%) and the highest specificity at 80% sensitivity (57.6%). CONCLUSIONS: This study suggests that the QRS and ST-segment depression have a moderate diagnostic ability to predict coronary artery disease in women. Q and R waves in lead aVF showed good diagnostic ability.

Transient ascending ST-segment depression and widening of the S wave in 3-channel Holter monitoring-A sign of dromotropic disturbance in the right ventricular outflow tract in the Brugada syndrome: A report of five cases.

BACKGROUND: Brugada syndrome (BrS) is somewhat a challenging diagnosis, due to its dynamic pattern. One of the aspects of this disease is a significant conduction disorder located in the right ventricular outflow tract (RVOT), which can be explained as a consequence of low expression of Connexin-43. This decreased conduction speed is responsible for the typical electrocardiographic pattern. Opposite leads located preferably in inferior leads of the electrocardiogram may show a deep and widened S wave associated with ascending ST segment depression. Holter monitoring electrocardiographic (ECG) aspects is still a new frontier of knowledge in BrS, especially in intermittent clinical presentations. METHODS: We describe, as an exploratory analysis, five case series of intermittent type 1 BrS to demonstrate the appearance of ascending ST segment depression and widening of the S wave, during 3-channel 24h-Holter monitoring (C1, C2 and C3) with bipolar leads. RESULTS: In the five cases described, the ST segment depression was observed mainly in C2, but in some cases also in C1 and C3. Only case 1 presented concomitant intermittent elevation of the ST segment in C1. All cases were intermittent. CONCLUSION: The recognition of an ECG pattern with ascending ST-segment depression and widening of the S wave in 3-channel Holter described in this case series should raise a suspicion of the BrS and suggests the counterpart of a dromotropic disturbance registered in the RVOT and/or reciprocal changes.

The Role of ECG in the Diagnosis and Risk Stratification of Acute Coronary Syndromes: an Old but Indispensable Tool.

PURPOSE OF REVIEW: Since its inception in 1902 by Willem Einthoven, the electrocardiogram (ECG) has fundamentally undergone minimal technological advances. Nevertheless, its clinical utility is critical, and it remains an essential tool to diagnose, risk stratify, and guide reperfusion and invasive strategies in patients with suspected acute coronary syndromes. ECG reading can be demanding, with many healthcare professionals lacking the necessary expertise to accurately interpret them. This is exacerbated by the need to constantly revisit old dogmas pertinent to the interpretation of ECGs. RECENT FINDINGS: Notably, ECG leads record the global electrical activity of the heart toward and away from each electrode rather than local events. The long-held central paradigm that the various ECG leads record local events underneath specific electrodes should therefore be reassessed. For example, ST segment elevation in leads V1 and V2 usually denote antero-apical rather than septal infarction, often a misnomer utilized by the majority of clinicians. The ECG diagnosis of ST-elevation myocardial infarction (STEMI) is sometimes challenging and discerning it from non-ST-elevation myocardial infarction (NSTEMI) is of paramount importance to implement timely acute reperfusion therapy. In fact, when qualifications for emergency reperfusion therapy are based on STEMI ECG criteria, nearly one-third of cases with acute coronary occlusion are missed. Diagnostic ST elevation in the absence of left ventricular (LV) hypertrophy or left bundle-branch block (LBBB) is defined by a specific set of sex-specific criteria for new ST elevation at the J point in contiguous precordial or limb leads. However, other ECG criteria need to be kept in mind. These include, but are not limited to, new or presumably new left bundle branch block (LBBB), which is often considered as an STEMI-equivalent; ST depression in two or more precordial leads (V1-V4), denoting a true inferolateral transmural myocardial infarction; and the infrequent presentation with hyperacute T-wave changes. As our understanding of the pathology of ischemic reperfusion injury has evolved and following the introduction of new imaging modalities such as cardiac magnetic resonance imaging, we need to re-assess the old dogmas pertinent to the interpretation of ECGs and update the terms and classifications.

High-risk ECG patterns in ST elevation myocardial infarction for mortality prediction.

AIM: We explored the pre-intervention (first medical contact) electrocardiographic (ECG) patterns and their relation to survival among patients with acute myocardial infarction, who presented either with ST elevation (ST elevation myocardial infarction, STEMI) or LBBB, and who underwent emergent coronary angiography in a region with a 24/7/365 STEMI network. METHODS: This is a retrospective analysis of 1363 consecutive patients hospitalized for first STEMI between the years 2014 and 2018. We assessed the prognostic significance of a variety of ECG categories, including location of ST elevation, severity of ischemia, intraventricular and atrioventricular conduction disorders, atrial fibrillation or flutter, junctional rhythms, heart rate, left ventricular hypertrophy and Q waves. The primary outcome was all-cause mortality between January 2014 and the end of 2020. RESULTS: The mean age of the patients was 67.9 (SD 12.8) years. The majority were treated by percutaneous coronary intervention (93.8%, n = 1278). Median follow-up time was 3.7 years (IQR 2.5-5.1 years) during which 22.5% (n = 307) of the patients died. According to Cox regression analysis, adjusted for pre-existing conditions and age, the ECG variables with statistically significant association with survival were elevated heart rate (>100 bpm) (HR 2.34, 95% CI 1.75-3.12), atrial fibrillation or flutter (HR 1.94, 95% CI 1.41-2.67), left bundle branch block (LBBB) (HR 2.62, 95% CI 1.49-4.63) and non-specific intraventricular conduction delay (NIVCD) (HR 1.85, 95% CI 1.22-2.89). CONCLUSION: Higher heart rate, atrial fibrillation or flutter, LBBB and NIVCD are associated with worse outcome in all-comers with STEMI. Ischemia severity was not associated with impaired prognosis.

Non-specific intraventricular conduction delay or atypical LBBB - How to predict acute coronary occlusion?

We describe two patient cases with acute coronary syndrome (ACS) and broad QRS in the acute phase electrocardiogram (ECG). The patients' ECG findings resembled left bundle branch block (LBBB), but with atypical features. Broad QRS not fulfilling the criteria for LBBB or right bundle branch block (RBBB) is diagnosed as non-specific intraventricular conduction delay (NSIVCD). The case report deals with the challenges of predicting acute coronary occlusion in patients with NSIVCD in their acute phase ECG. In one of the cases, the ECG changed from typical LBBB to NSIVCD or atypical LBBB with the development of systolic dysfunction and clinical heart failure.

Early ischemic ST-segment and T-wave changes during balloon angioplasty.

BACKGROUND: Acute coronary occlusion results in increased T-wave amplitude and ST-segment elevation in the ECG leads facing the ischemic region. MATERIAL AND METHODS: We performed continuous ECG recording in 34 patients during balloon occlusion of the left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA). Delta (Δ) ST and ΔT amplitudes were calculated by subtracting the preinflation values from the values measured during balloon inflation. RESULTS: Occlusion of the LAD resulted in greater increase in the amplitude of the T wave than of the ST segment in lead V2 (ΔT +3.4 mm, inter-quartile range [IQR] 1-6 mm; ΔST +1.4 mm, 0.5-3 mm). During RCA occlusion, ΔST and ΔT didn't differ significantly. LCx occlusion resulted in significant differences between ΔST and ΔT in all leads, except aVF and V3-V4. In two patients (LCx), we observed a biphasic ST-T response: an initial negative change of the T-wave amplitude was followed by a positive change in leads V1-V2. In leads II, III, aVF and V4-V6, there was an initial positive change, followed by a final negative change towards the end of the occlusion. CONCLUSION: Continuous 12­lead ECG recording during balloon occlusion of the LCx resulted in significant differences between the ΔST and ΔT values in all leads except aVF and V3-V4. LAD and RCA occlusion resulted in less evident differences between the ST-segment and T-wave changes. A change in polarity of T-wave changes during balloon occlusion (initial negative and final positive change, or vice versa) proved to be a rare finding.

Northwest axis in the electrocardiogram - A sign of right ventricular remodeling in tetralogy of Fallot. A case report.

The typical ECG changes in tetralogy of Fallot are right axis deviation, large R waves in the anterior precordial leads and large S waves in the lateral precordial leads. We present a patient with extreme deviation of the frontal QRS axis between -90° and ± 180°. The child underwent open heart surgery twice before one year of age and a third time at nine years of age. The axis change persisted into adulthood.

The S1S2S3 electrocardiographic pattern - Prevalence and relation to cardiovascular and pulmonary diseases in the general population.

BACKGROUND: There is lack of studies exploring the incidence and association with diseases of the S1S2S3 electrocardiogram (ECG) pattern in the general population. SUBJECTS AND METHODS: This population study included 6299 individuals aged 30+, and explored the prevalence and association between S1S2S3 and cardiovascular and pulmonary diseases. Criteria for the S1S2S3-I and S1S2S3-II ECG pattern were fulfilled when there was an S wave in the leads I, II and III, and the S-wave amplitude was greater than the R-wave amplitude in one or two of the leads, respectively. RESULTS: The S1S2S3-I ECG pattern was found in 2332 subjects (36.9%). After age adjustment, hypertension was associated with S1S2S3-I (Odds ratio [OR] 1.25, 95% CI 1.12-1.41, p < 0.001). This age-adjusted association was statistically significant among men but not among women (OR 1.37, 1.16-1.62, p < 0.001 and OR 1.13, 0.97-1.33, p = 0.126, respectively). The S1S2S3-II ECG pattern was present in 193 subjects (3.1%). After age adjustment, heart failure proved to be associated with S1S2S3-II (OR 1.85, 1.18-2.90, p = 0.007). Dividing the population by sex, resulted in a statistically significant age-adjusted association for men but not for women (OR 2.30, 1.22-4.33, p = 0.010 and OR 1.59, 0.83-3.03, p = 0.159, respectively). Interactions with sex were statistically non-significant. CONCLUSION: In the general adult population, the prevalence of the S1S2S3 ECG pattern is markedly affected by the diagnostic ECG criteria. The S1S2S3-I pattern was associated with hypertension, while S1S2S3-II was associated with heart failure, and both associations were enhanced in men. The associations with other studied cardiovascular and pulmonary diseases were minor and not clinically useful for risk stratification.

Interatrial block and P terminal force in the general population - Longitudinal changes, risk factors and prognosis.

BACKGROUND: Partial and advanced interatrial block (IAB) and P terminal force (PTF) in lead V1 are markers of atrial remodeling and risk factors for atrial fibrillation (AF). There is a lack of information about constancy and possible factors influencing the development of these P-wave abnormalities. METHODS: The study sample consisted of 6058 Finnish participants (mean age 52.16 ± 14.60 years, 45.0% male) from the general population with an ECG taken in a health examination, and from 3224 of these participants, who had a re-examination 11 years later. Risk factors for incident partial and advanced IAB and PTF were studied using binomial logistic regression analysis, and the prognostic significance of these ECG changes for new AF was studied using time-varying Cox regression analysis. RESULTS: The rate of reversal to normal of the studied ECG parameters were 47.4% for partial IAB, 40.0% for advanced IAB and 79.3% for PTF. Age, male sex, hypertension, higher BMI, higher LDL cholesterol, ECG left ventricular hypertrophy, use of beta blocker, and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist were independently associated with a risk to develop incident P-wave abnormality. Partial IAB was independently associated with increased AF risk (HR 1.28 [95% CI 1.04-1.58]), as was also advanced IAB (HR 1.72 [95% CI 1.07-2.75]). CONCLUSION: Traditional cardiovascular risk factors increase the risk of a new P-wave abnormality. Partial and advanced IAB are associated with increased AF risk. Surprisingly, P-wave abnormalities are often reversible during long-term follow-up in the general population.

The prognostic significance of the electrical QRS axis on long-term mortality in acute coronary syndrome patients - The TACOS study.

INTRODUCTION: There are several potential causes of QRS-axis deviation in the ECG, but there is limited data on the prognostic significance of QRS-axis deviation in ACS patients. SUBJECTS AND METHODS: We evaluated the long-term prognostic significance of acute phase frontal plane QRS-axis deviation and its shift during hospital stay in ACS patients. A total of 1026 patients who met the inclusion criteria were divided into three categories: normal (n = 823), left (n = 166) and right/extreme axis (n = 37). RESULTS: The median survival time was 9.0 years (95% CI 7.9-10.0) in the normal, 3.6 years (95% CI 2.4-4.7) in the left and 1.3 years (95% CI 0.2-2.4) in the right/extreme axis category. Both short and long-term all-cause mortality was lowest in the normal axis category and highest in the right/extreme axis category. Compared to normal axis, both admission phase QRS-axis deviation groups were independently associated with a higher risk of all-cause mortality. When including left ventricular hypertrophy in the ECG, only the right/extreme axis retained its statistical significance (aHR 1.76; 95% CI 1.16-2.66, p = 0.007). Axis shift to another axis category had no effect on mortality. CONCLUSION: In ACS patients, acute phase QRS-axis deviation was associated with higher risk of all-cause mortality. Among the axis deviation groups, right/extreme QRS-axis deviation was the strongest predictor of mortality in the multivariable analysis. Further studies are required to investigate to what extent this association is caused by pre-existing or by ACS-induced axis deviations. QRS-axis shift during hospital stay had no effect on all-cause mortality.

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. CONCLUSIONS: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.

Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning.

MOTIVATION: Selecting the optimal machine learning (ML) model for a given dataset is often challenging. Automated ML (AutoML) has emerged as a powerful tool for enabling the automatic selection of ML methods and parameter settings for the prediction of biomedical endpoints. Here, we apply the tree-based pipeline optimization tool (TPOT) to predict angiographic diagnoses of coronary artery disease (CAD). With TPOT, ML models are represented as expression trees and optimal pipelines discovered using a stochastic search method called genetic programing. We provide some guidelines for TPOT-based ML pipeline selection and optimization-based on various clinical phenotypes and high-throughput metabolic profiles in the Angiography and Genes Study (ANGES). RESULTS: We analyzed nuclear magnetic resonance-derived lipoprotein and metabolite profiles in the ANGES cohort with a goal to identify the role of non-obstructive CAD patients in CAD diagnostics. We performed a comparative analysis of TPOT-generated ML pipelines with selected ML classifiers, optimized with a grid search approach, applied to two phenotypic CAD profiles. As a result, TPOT-generated ML pipelines that outperformed grid search optimized models across multiple performance metrics including balanced accuracy and area under the precision-recall curve. With the selected models, we demonstrated that the phenotypic profile that distinguishes non-obstructive CAD patients from no CAD patients is associated with higher precision, suggesting a discrepancy in the underlying processes between these phenotypes. AVAILABILITY AND IMPLEMENTATION: TPOT is freely available via http://epistasislab.github.io/tpot/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

FDG-PET in possible cardiac sarcoidosis: Right ventricular uptake and high total cardiac metabolic activity predict cardiovascular events.

BACKGROUND: Cardiac involvement accounts for the majority of morbidity and mortality in sarcoidosis. Pathological myocardial fluorodeoxyglucose (FDG)-uptake in positron emission tomography (PET) has been associated with cardiovascular events and quantitative metabolic parameters have been shown to add prognostic value. Our aim was to study whether the pattern of pathological cardiac FDG-uptake and quantitative parameters are able to predict cardiovascular events in patients with suspected cardiac sarcoidosis (CS). METHODS: 137 FDG-PET examinations performed in Tampere University Hospital were retrospectively analyzed visually and quantitatively. Location of pathological uptake was noted and pathological metabolic volume, average standardized uptake value (SUV), and total cardiac metabolic activity (tCMA) were calculated. Patients were followed for ventricular tachycardia, decrease in left ventricular ejection fraction, and death. RESULTS: Eleven patients had one or more cardiovascular events during the follow-up. Five patients out of 12 with uptake in both ventricles had an event during follow-up. Eight patients had high tCMA (> 900 MBq) and three of them had a cardiovascular event. Right ventricular uptake and tCMA were significantly associated with cardiovascular events during follow-up (P-value .001 and .018, respectively). CONCLUSIONS: High tCMA and right ventricular uptake were significant risk markers for cardiac events among patient with suspected CS.