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Aims: Chronotropic incompetence and impaired heart rate (HR) recovery are related to mortality. Guidelines lack specific reference values for HR recovery. We defined normal values and studied blunted HR response and recovery and mortality risk., Methods and Results: We included 9917 subjects (45% females) aged 18-85 years who performed a cycle exercise test. We defined normal values for peak HR, HR reserve, and HR recovery at 1 and 2 min (HRR1 and HRR2) based on individuals apparently healthy (N = 2242). Associations between blunted HR indices (<5th percentile) and mortality over a median follow-up of 8.6 years were analysed using Cox regression and competing risk analysis. All HR indices were age-dependent and independent predictors of all-cause and cardiovascular (CV) mortality. The 5th percentiles of HR reserve, HRR1, and HRR2 correlated weakly with existing reference values. Heart rate recovery variables were the strongest predictors of all-cause mortality in both the overall population [HRR1, hazard ratio 1.70 (95% confidence interval, 1.49-1.94), and HRR2, 1.57 (1.37-1.79)] and in subjects with normal exercise capacity [HRR1, 1.96 (1.61-2.39), and HRR2, 1.76 (1.46-2.12)]. Combining HR indices appeared to increase the risk of all-cause [HRR1 and HRR2, 1.96 (1.68-2.29), and peak HR and HRR1, 1.87 (1.56-2.23)] and CV mortality, although no specific combination was superior for predicting CV mortality., Conclusion: All HR indices were age-dependent and associated with all-cause and CV mortality. Blunted HR recovery variables were the strongest predictors of all-cause mortality, even in subjects with normal exercise capacity. Combined blunted HR indices appeared to add prognostic value., Competing Interests: Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The hemodynamic definitions of pulmonary hypertension consider resistive loading (pulmonary vascular resistance [PVR]), but there are increasing evidence that pulsatile loading (pulmonary artery compliance [PAC]) has functional and prognostic importance. The aims of the present study on patients with left heart disease, were to evaluate a novel echocardiographic right ventricular (RV) afterload score and to investigate its relation to risk of mortality or implantation of a left ventricular assist device. Patients ( n  = 220) with left ventricular ejection fraction < 50% consecutively referred for heart transplant or heart failure workup underwent echocardiography and right heart catheterization. Four metrics were included in the afterload score: the systolic pulmonary artery pressure (sPAP Doppler ) and three variables related to pressure reflection in the pulmonary circulation. Two points were allocated for sPAP Doppler  ≥ 60 mmHg and for each pressure reflection variable indicating PVR > 3 Wood units (WU). One point was allocated for sPAP Doppler 36-59 mmHg and for pressure reflection variables above the upper normal limit. Low afterload was defined as 0-to-1 points, intermediate as 2-to-4 points, and high as 5-to-8 points. There were in-between the groups significant differences in PAC and PVR. A 5-point RV dysfunction score showed with stepwise increased RV afterload more severe dysfunction. Unadjusted hazard ratio for endpoint was 3.34 (1.69-6.79) for intermediate score, and 5.11 (2.52-10.40) for patients with high score. In conclusion, in patients with severe heart failure, a novel echocardiographic RV afterload score is related to increased pulsatile and resistant load, more severe RV dysfunction, and increased risk of adverse outcome., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Exertional breathlessness is a key symptom in cardiorespiratory disease and can be quantified using incremental exercise testing, but its prognostic significance is unknown. We evaluated the ability of abnormally high breathlessness intensity during incremental cycle exercise testing to predict all-cause, respiratory, and cardiac mortality., Study Design and Methods: Longitudinal cohort study of adults referred for exercise testing followed prospectively for mortality assessed using the Swedish National Causes of Death Registry. Abnormally high exertional breathlessness was defined as a breathlessness intensity response (Borg 0-10 scale) > the upper limit of normal using published reference equations. Mortality was analyzed using multivariable Cox regression, unadjusted and adjusted for age, sex, and body mass index. A further mortality analysis was also done adjusted for select common comorbidities in addition to age, sex and body mass index., Results: Of the 13,506 people included (46% female, age 59±15 years), 2,867 (21%) had abnormally high breathlessness during exercise testing. Over a median follow up of 8.0 years, 1,687 (12%) people died. No participant was lost to follow-up. Compared to those within normal predicted ranges, people with abnormally high exertional breathlessness had higher mortality from all causes (adjusted hazard ratio [aHR] 2.3, [95% confidence interval] 2.1-2.6), respiratory causes (aHR 5.2 [3.4-8.0]) and cardiac causes (aHR 3.0 [2.5-3.6]). Even among people with normal exercise capacity (defined as peak Watt ≥75% of predicted exercise capacity, n = 10,284) those with abnormally high exertional breathlessness were at greater risk of all-cause mortality than people with exertional breathlessness within the normal predicted range (aHR 1.5 [1.2-1.8])., Conclusion: Among people referred for exercise testing, abnormally high exertional breathlessness, quantified using healthy reference values, independently predicted all-cause, respiratory and cardiac mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Elmberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background : The assessment of left ventricular (LV) filling pressure in heart failure (HF) poses a diagnostic challenge, as HF patients may have normal LV filling pressures at rest but often display elevated LV filling pressures during exercise. Rapid preload increase during passive leg lift (PLL) may unmask HF in such challenging scenarios. We explored the dynamic interplay between simultaneous left atrial (LA) function and volume using LA strain/volume loops during rest and PLL and compared its diagnostic performance with conventional echocardiographic surrogates to detect elevated LV filling pressure. Methods : We retrospectively reviewed 35 patients with clinical HF who underwent simultaneous echocardiography and right heart catheterization before and immediately after PLL. Patients with atrial fibrillation ( n = 4) were excluded. Twenty age-matched, healthy controls were added as controls. LA reservoir strain (LASr) was analyzed using speckle-tracking echocardiography. LA strain-volume loops were generated, including the best-fit linear regression line employing simultaneous LASr and LA volume. Results : LA strain-volume slope was lower for HF patients when compared with controls (0.71 vs. 1.22%/mL, p < 0.001). During PLL, the LA strain-volume slope displayed a moderately strong negative correlation with invasive pulmonary arterial wedge pressure (PAWP) (r = -0.71, p < 0.001). At a 0.74%/mL cut-off, the LA strain-volume slope displayed 88% sensitivity and 86% specificity to identify elevated PAWP (AUC 0.89 [0.76-1.00]). In comparison, LASr demonstrated strong but numerically lower diagnostic performance (AUC 0.82 [0.67-0.98]), and mitral E/e' showed poor performance (AUC 0.57 [0.32-0.82]). Conclusions : In this proof-of-concept study, LA strain-volume characteristics provide incremental diagnostic value over conventional echocardiographic measures in the identification of elevated LV filling pressure.

Aims: An explainable advanced electrocardiography (A-ECG) Heart Age gap is the difference between A-ECG Heart Age and chronological age. This gap is an estimate of accelerated cardiovascular aging expressed in years of healthy human aging, and can intuitively communicate cardiovascular risk to the general population. However, existing A-ECG Heart Age requires sinus rhythm. We aim to develop and prognostically validate a revised, explainable A-ECG Heart Age applicable to both sinus and non-sinus rhythms., Methods and Results: An A-ECG Heart Age excluding P-wave measures was derived from the 10-s 12-lead ECG in a derivation cohort using multivariable regression machine learning with Bayesian 5-min 12-lead A-ECG Heart Age as reference. The Heart Age was externally validated in a separate cohort of patients referred for cardiovascular magnetic resonance imaging by describing its association with heart failure hospitalization or death using Cox regression, and its association with comorbidities. In the derivation cohort ( n = 2771), A-ECG Heart Age agreed with the 5-min Heart Age ( R 2 = 0.91, bias 0.0 ± 6.7 years), and increased with increasing comorbidity. In the validation cohort [ n = 731, mean age 54 ± 15 years, 43% female, n = 139 events over 5.7 (4.8-6.7) years follow-up], increased A-ECG Heart Age gap (≥10 years) associated with events [hazard ratio, HR (95% confidence interval, CI) 2.04 (1.38-3.00), C-statistic 0.58 (0.54-0.62)], and the presence of hypertension, diabetes mellitus, hypercholesterolaemia, and heart failure ( P ≤ 0.009 for all)., Conclusion: An explainable A-ECG Heart Age gap applicable to both sinus and non-sinus rhythm associates with cardiovascular risk, cardiovascular morbidity, and survival., Competing Interests: Conflict of interest: Z.S.A., T.L., I.L.-P., A.L., E.B.S., L.N., and M.M.: none; T.T.S. is owner and founder of Nicollier-Schlegel SARL, which performs ECG interpretation consultancy using software that can quantify the advanced ECG measures used in the current study. T.T.S. and M.U. are the owners and founders of Advanced ECG Systems, a company that is developing commercial applications of advanced ECG technology used in the current study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: We aimed to investigate the association between the exercise systolic blood pressure (SBP) response and future hypertension (HTN) in normotensive individuals referred for cycle ergometry, with special regard to reference exercise SBP values and exercise capacity., Methods and Results: In this longitudinal cohort study, data from 14 428 exercise tests were cross-linked with Swedish national registries on diagnoses and medications. We excluded individuals with a baseline diagnosis of cardiovascular disease or HTN. The peak exercise SBP (SBPpeak) was recorded and compared with the upper limit of normal (ULN) derived from SBPpeak reference equations incorporating age, sex, resting SBP, and exercise capacity. To evaluate the impact of exercise capacity, three SBP to work rate slopes (SBP/W-slopes) were calculated, relative to either supine or seated SBP at rest or to the first exercise SBP. Adjusted hazard ratios [HRadjusted (95% confidence interval, CI)] for incident HTN during follow-up, in relation to SBP response metrics, were calculated. We included 3895 normotensive individuals (49 ± 14 years, 45% females) with maximal cycle ergometer tests. During follow-up (median 7.5 years), 22% developed HTN. Higher SBPpeak and SBPpeak > ULN were associated with incident HTN [HRadjusted 1.19 (1.14-1.23) per 10 mmHg, and 1.95 (1.54-2.47), respectively]. All three SBP/W-slopes were positively associated with incident HTN, particularly the SBP/W-slope calculated as supine-to-peak SBP [HRadjusted 1.25 (1.19-1.31) per 1 mmHg/10 W]., Conclusion: Both SBPpeak > ULN based on reference values and high SBP/W-slopes were associated with incident HTN in normotensive individuals and should be considered in the evaluation of the cycle ergometry SBP response., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Grading of diastolic function can be useful, but indeterminate classifications are common. We aimed to invasively derive and validate a quantitative echocardiographic estimation of pulmonary artery wedge pressure (PAWP) and to compare its prognostic performance to diastolic dysfunction grading., Methods and Results: Echocardiographic measures were used to derive an estimated PAWP (ePAWP) using multivariable linear regression in patients undergoing right heart catheterization (RHC). Prognostic associations were analysed in the National Echocardiography Database of Australia (NEDA). In patients who had undergone both RHC and echocardiography within 2 h (n = 90), ePAWP was derived using left atrial volume index, mitral peak early velocity (E), and pulmonary vein systolic velocity (S). In a separate external validation cohort (n = 53, simultaneous echocardiography and RHC), ePAWP showed good agreement with invasive PAWP (mean ± standard deviation difference 0.5 ± 5.0 mmHg) and good diagnostic accuracy for estimating PAWP >15 mmHg [area under the curve (95% confidence interval) 0.94 (0.88-1.00)]. Among patients in NEDA [n = 38,856, median (interquartile range) follow-up 4.8 (2.3-8.0) years, 2756 cardiovascular deaths], ePAWP was associated with cardiovascular death even after adjustment for age, sex, and diastolic dysfunction grading [hazard ratio (HR) 1.08 (1.07-1.09) per mmHg] and provided incremental prognostic information to diastolic dysfunction grading (improved C-statistic from 0.65 to 0.68, P < 0.001). Increased ePAWP was associated with worse prognosis across all grades of diastolic function [HR normal, 1.07 (1.06-1.09); indeterminate, 1.08 (1.07-1.09); abnormal, 1.08 (1.07-1.09), P < 0.001 for all]., Conclusion: Echocardiographic ePAWP is an easily acquired continuous variable with good accuracy that associates with prognosis beyond diastolic dysfunction grading., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflicts of Interest None.

Background: Electrocardiographic detection of patients with occlusion myocardial infarction (OMI) can be difficult in patients with left bundle branch block (LBBB) or ventricular paced rhythm (VPR) and several ECG criteria for the detection of OMI in LBBB/VPR exist. Most recently, the Barcelona criteria, which includes concordant ST deviation and discordant ST deviation in leads with low R/S amplitudes, showed superior diagnostic accuracy but has not been validated externally. We aimed to describe the diagnostic accuracy of four available ECG criteria for OMI detection in patients with LBBB/VPR at the emergency department., Methods: The unweighted Sgarbossa criteria, the modified Sgarbossa criteria (MSC), the Barcelona criteria and the Selvester criteria were applied to chest pain patients with LBBB or VPR in a prospectively acquired database from five emergency departments., Results: In total, 623 patients were included, among which 441 (71%) had LBBB and 182 (29%) had VPR. Among these, 82 (13%) patients were diagnosed with AMI, and an OMI was identified in 15 (2.4%) cases. Sensitivity/specificity of the original unweighted Sgarbossa criteria were 26.7/86.2%, for MSC 60.0/86.0%, for Barcelona criteria 53.3/82.2%, and for Selvester criteria 46.7/88.3%. In this setting with low prevalence of OMI, positive predictive values were low (Sgarbossa: 4.6%; MSC: 9.4%; Barcelona criteria: 6.9%; Selvester criteria: 9.0%) and negative predictive values were high (all >98.0%)., Conclusions: Our results suggests that ECG criteria alone are insufficient in predicting presence of OMI in an ED setting with low prevalence of OMI, and the search for better rapid diagnostic instruments in this setting should continue., Competing Interests: Declaration of Competing Interest SWS: Shareholder of Powerful Medical, consultant for Heartbeam, Cardiologs, Welch Allen, and RapidAI., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Dormant coronary collaterals are highly prevalent and clinically beneficial in cases of coronary occlusion. However, the magnitude of myocardial perfusion provided by immediate coronary collateral recruitment during acute occlusion is unknown. We aimed to quantify collateral myocardial perfusion during balloon occlusion in patients with coronary artery disease (CAD)., Methods: Patients without angiographically visible collaterals undergoing elective percutaneous transluminal coronary angioplasty (PTCA) to a single epicardial vessel underwent two scans with 99mTc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT). All subjects underwent at least three minutes of angiographically verified complete balloon occlusion, at which time an intravenous injection of the radiotracer was administered, followed by SPECT imaging. A second radiotracer injection followed by SPECT imaging was performed 24 h after PTCA., Results: The study included 22 patients (median [interquartile range] age 68 [54-72] years. The perfusion defect extent was 19 [11-38] % of the LV, and the collateral perfusion at rest was 64 [58-67]% of normal., Conclusion: This is the first study to describe the magnitude of short-term changes in coronary microvascular collateral perfusion in patients with CAD. On average, despite coronary occlusion and an absence of angiographically visible collateral vessels, collaterals provided more than half of the normal perfusion., (© 2023. The Author(s).)

Quantification of pulmonary edema and congestion is important to guide diagnosis and risk stratification, and to objectively evaluate new therapies in heart failure. Herein, we review the validation, diagnostic performance, and clinical utility of noninvasive imaging modalities in this setting, including chest x-ray, lung ultrasound (LUS), computed tomography (CT), nuclear medicine imaging methods (positron emission tomography [PET], single photon emission CT), and magnetic resonance imaging (MRI). LUS is a clinically useful bedside modality, and fully quantitative methods (CT, MRI, PET) are likely to be important contributors to a more accurate and precise evaluation of new heart failure therapies and for clinical use in conjunction with cardiac imaging. There are only a limited number of studies evaluating pulmonary congestion during stress. Taken together, noninvasive imaging of pulmonary congestion provides utility for both clinical and research assessment, and continued refinement of methodologic accuracy, validation, and workflow has the potential to increase broader clinical adoption., Competing Interests: Funding Support and Author Disclosures Dr Lindow is supported by the Swedish Heart Lung Foundation (20200553), Swedish Cardiac Society, Royal Swedish Academy of Sciences (LM2019-0013), Women and Health Foundation, Region Kronoberg (8301), Swedish Heart and Lung Association, Swedish Association of Clinical Physiology, and Scandinavian Society of Clinical Physiology and Nuclear Medicine. This review was supported in part by grants to Dr Ugander from the University of Sydney, New South Wales Health, and Heart Research Australia. All of the authors are affiliated with the University of Sydney or Karolinska Institute, and both institutions have research and developments agreements with Siemens for cardiac magnetic resonance. Siemens had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Deep neural network artificial intelligence (DNN-AI)-based Heart Age estimations have been presented and used to show that the difference between an electrocardiogram (ECG)-estimated Heart Age and chronological age is associated with prognosis. An accurate ECG Heart Age, without DNNs, has been developed using explainable advanced ECG (A-ECG) methods. We aimed to evaluate the prognostic value of the explainable A-ECG Heart Age and compare its performance to a DNN-AI Heart Age., Methods and Results: Both A-ECG and DNN-AI Heart Age were applied to patients who had undergone clinical cardiovascular magnetic resonance imaging. The association between A-ECG or DNN-AI Heart Age Gap and cardiovascular risk factors was evaluated using logistic regression. The association between Heart Age Gaps and death or heart failure (HF) hospitalization was evaluated using Cox regression adjusted for clinical covariates/comorbidities. Among patients [ n = 731, 103 (14.1%) deaths, 52 (7.1%) HF hospitalizations, median (interquartile range) follow-up 5.7 (4.7-6.7) years], A-ECG Heart Age Gap was associated with risk factors and outcomes [unadjusted hazard ratio (HR) (95% confidence interval) (5 year increments): 1.23 (1.13-1.34) and adjusted HR 1.11 (1.01-1.22)]. DNN-AI Heart Age Gap was associated with risk factors and outcomes after adjustments [HR (5 year increments): 1.11 (1.01-1.21)], but not in unadjusted analyses [HR 1.00 (0.93-1.08)], making it less easily applicable in clinical practice., Conclusion: A-ECG Heart Age Gap is associated with cardiovascular risk factors and HF hospitalization or death. Explainable A-ECG Heart Age Gap has the potential for improving clinical adoption and prognostic performance compared with existing DNN-AI-type methods., Competing Interests: Conflict of interest: T.T.S. is owner and founder of Nicollier-Schlegel SARL, which performs ECG interpretation consultancy using software that can quantify the advanced ECG measures used in the current study. T.T.S. and M.U. are owners and founders of Advanced ECG Systems, a company that is developing commercial applications of advanced ECG technology used in the current study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Left ventricular diameter (LVEDD) increases with systematic endurance training but also in various cardiac diseases. High exercise capacity associates with favorable outcomes. We hypothesized that peak work rate (W peak ) indexed to LVEDD would carry prognostic information and aimed to evaluate the association between W peak /LVEDD rest and cardiovascular mortality. W peak /LVEDD rest (W/mm) was calculated in patients with an echocardiographic examination within 3 months of a maximal cycle ergometer exercise test. Low W peak /LVEDD rest was defined as a value below the sex- and age-specific 5th percentile among lower-risk subjects. The association with cardiovascular mortality was evaluated using Cox regression. In total, 3083 patients were included (8.0 [5.4-11.1] years of follow-up, 249 (8%) cardiovascular deaths). W peak /LVEDD rest (W/mm) was associated with cardiovascular mortality (adjusted hazard ratio (HR) 0.28 [0.22-0.36]), similar to W peak in % of predicted, with identical prognostic strength when adjusted for age and sex (C-statistics 0.87 for both). A combination of low W peak /LVEDD rest and low W peak was associated with a particularly poor prognosis (adjusted HR 6.4 [4.0-10.3]). W peak /LVEDD rest was associated with cardiovascular mortality but did not provide incremental prognostic value to W peak alone. The combination of a low W peak /LVEDD rest and low W peak was associated with a particularly poor prognosis., (© 2023. The Author(s).)

Background: Exertional breathlessness is commonly assessed using incremental exercise testing (IET), but reference equations for breathlessness responses are lacking. We aimed to develop reference equations for breathlessness intensity during IET., Methods: A retrospective, consecutive cohort study of adults undergoing IET was carried out in Sweden. Exclusion criteria included cardiac or respiratory disease, death or any of the aforementioned diagnoses within 1 year of the IET, morbid obesity, abnormally low exercise capacity, submaximal exertion or an abnormal exercise test. Probabilities for breathlessness intensity ratings (Borg CR10) during IET in relation to power output (%predW max ), age, sex, height and body mass were analysed using marginal ordinal logistic regression. Reference equations for males and females were derived to predict the upper limit of normal (ULN) and the probability of different Borg CR10 intensity ratings., Results: 2581 participants (43% female) aged 18-90 years were included. Mean breathlessness intensity was similar between sexes at peak exertion (6.7±1.5 versus 6.4±1.5 Borg CR10 units) and throughout exercise in relation to %predW max . Final reference equations included age, height and %predW max for males, whereas height was not included for females. The models showed a close fit to observed breathlessness intensity ratings across %predW max values. Models using absolute W did not show superior fit. Scripts are provided for calculating the probability for different breathlessness intensity ratings and the ULN by %predW max throughout IET., Conclusion: We present the first reference equations for interpreting breathlessness intensity during incremental cycle exercise testing in males and females aged 18-90 years., Competing Interests: Conflict of interest: No conflicts of interest exist for the authors., (Copyright ©The authors 2023.)

Competing Interests: Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Premature ventricular contractions (PVCs) during recovery of exercise stress testing are associated with increased cardiovascular mortality, but the cause remains unknown. We aimed to evaluate the association of PVCs during recovery with echocardiographic abnormalities, and their combined prognostic performance. Echocardiographic abnormalities [reduced left ventricular (LV) ejection fraction, valvular heart disease, LV dilatation, LV hypertrophy, or increased filling pressures] and PVCs during recovery were identified among patients having undergone both echocardiography and exercise stress test. Among included patients (n = 3106, age 59 ± 16 years, 55% males), PVCs during recovery were found in 1327 (43%) patients, among which the prevalence of echocardiographic abnormalities was increased (58% vs. 43%, p < 0.001). Overall, PVCs during recovery were associated with increased cardiovascular mortality (219 total events, 7.9 [5.4-11.1] years follow-up; adjusted hazard ratio (HR [95% confidence interval]) 1.6 [1.2-2.1], p < 0.001). When analyzed in combination with either presence or absence of echocardiographic abnormalities, PVCs during recovery were associated with increased risk when such were present (HR 3.3 [1.9-5.5], p < 0.001) but not when absent (HR 1.5 [0.8-2.8], p = 0.22), in reference to those with neither. Our findings provide mechanistic insights to the increased CV risk reported in patients with PVCs during recovery., (© 2022. The Author(s).)

Electrocardiographic (ECG) Heart Age conveying cardiovascular risk has been estimated by both Bayesian and artificial intelligence approaches. We hypothesised that explainable measures from the 10-s 12-lead ECG could successfully predict Bayesian 5-min ECG Heart Age. Advanced analysis was performed on ECGs from healthy subjects and patients with cardiovascular risk or proven heart disease. Regression models were used to predict patients' Bayesian 5-min ECG Heart Ages from their standard, resting 10-s 12-lead ECGs. The difference between 5-min and 10-s ECG Heart Ages were analyzed, as were the differences between 10-s ECG Heart Age and the chronological age (the Heart Age Gap). In total, 2,771 subjects were included (n = 1682 healthy volunteers, n = 305 with cardiovascular risk factors, n = 784 with cardiovascular disease). Overall, 10-s Heart Age showed strong agreement with the 5-min Heart Age (R 2  = 0.94, p < 0.001, mean ± SD bias 0.0 ± 5.1 years). The Heart Age Gap was 0.0 ± 5.7 years in healthy individuals, 7.4 ± 7.3 years in subjects with cardiovascular risk factors (p < 0.001), and 14.3 ± 9.2 years in patients with cardiovascular disease (p < 0.001). Heart Age can be accurately estimated from a 10-s 12-lead ECG in a transparent and explainable fashion based on known ECG measures, without deep neural network-type artificial intelligence techniques. The Heart Age Gap increases markedly with cardiovascular risk and disease., (© 2022. The Author(s).)

Objectives: This study aimed to evaluate the risk of all-cause mortality and incident cardiovascular disease associated with peak systolic blood pressure (PeakSBP) at clinical exercise testing., Methods: Data from 10 096 clinical exercise tests (54% men, age 18-85 years) was cross-linked with outcome data from national registries. PeakSBP was compared with recently published reference percentiles as well as expressed as percentage predicted PeakSBP using reference equations.Natural cubic spline modelling and Cox regression were used to analyse data stratified by sex and baseline cardiovascular risk profile., Results: Median [IQR] follow-up times were 7.9 [5.7] years (all-cause mortality) and 5.6 [5.9] years (incident cardiovascular disease), respectively. The adjusted risk of all-cause mortality [hazard ratio, 95% confidence interval (95% CI)] for individuals with PeakSBP below the 10th percentile was 2.00 (1.59-2.52) in men and 2.60 (1.97-3.44) in women, compared with individuals within the 10th--90th percentile. The corresponding risk for incident cardiovascular disease was 1.55 (1.28-1.89, men) and 1.34 (1.05-1.71, women). For males in the upper 90th percentile, compared with individuals within the 10th--90th percentile, the adjusted risks of all-cause death and incident cardiovascular disease were 0.35 (0.22-0.54) and 0.72 (0.57-0.92), respectively, while not statistically significant in women. Spline modelling revealed a continuous increase in risk with PeakSBP values less than 100% of predicted in both sexes, with no increase in risk more than 100% of predicted., Conclusion: Low, but not high, PeakSBP was associated with an increased risk of mortality and future cardiovascular disease. Using reference standards for PeakSBP could facilitate clinical risk stratification across patients of varying sex, age and exercise capacity., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Guidelines recommend considering workload in interpretation of the systolic blood pressure (SBP) response to exercise, but reference values are lacking., Design: This was a retrospective, consecutive cohort study., Methods: From 12,976 subjects aged 18-85 years who performed a bicycle ergometer exercise test at one centre in Sweden during the years 2005-2016, we excluded those with prevalent cardiovascular disease, comorbidities, cardiac risk factors or medications. We extracted SBP, heart rate and workload (watt) from ≥ 3 time points from each test. The SBP/watt-slope and the SBP/watt-ratio at peak exercise were calculated. Age- and sex-specific mean values, standard deviations and 90th and 95th percentiles were determined. Reference equations for workload-indexed and peak SBP were derived using multiple linear regression analysis, including sex, age, workload, SBP at rest and anthropometric variables as predictors., Results: A final sample of 3839 healthy subjects (n = 1620 female) were included. While females had lower mean peak SBP than males (188 ± 24 vs 202 ± 22 mmHg, p < 0.001), workload-indexed SBP measures were markedly higher in females; SBP/watt-slope: 0.52 ± 0.21 versus 0.41 ± 0.15 mmHg/watt (p < 0.001); peak SBP/watt-ratio: 1.35 ± 0.34 versus 0.90 ± 0.21 mmHg/watt (p < 0.001). Age, sex, exercise capacity, resting SBP and height were significant predictors of the workload-indexed SBP parameters and were included in the reference equations., Conclusions: These novel reference values can aid clinicians and exercise physiologists in interpreting the SBP response to exercise and may provide a basis for future research on the prognostic impact of exercise SBP. In females, a markedly higher SBP in relation to workload could imply a greater peripheral vascular resistance during exercise than in males., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Advanced interatrial block (aIAB), which is associated with incident atrial fibrillation and stroke, occurs in the setting of blocked interatrial conduction. Atrial amyloid deposition could be a possible substrate for reduced interatrial conduction, but the prevalence of aIAB in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown. We aimed to describe the prevalence of aIAB and its relationship to left atrial function in patients with ATTR-CA in comparison to patients with HF and left ventricular hypertrophy but no CA., Methods: The presence of aIAB was investigated among 75 patients (49 patients with ATTR-CA and 26 with HF but no CA). A comprehensive echocardiographic investigation was performed in all patients, including left atrial strain and strain rate measurements., Results: Among patients with ATTR-CA, 27% had aIAB and in patients with HF but no CA, this figure was 21%, ( p = 0.78). The presence of aIAB was associated with a low strain rate during atrial contraction (<0.91 s -1 ) (OR: 5.2 (1.4-19.9)), even after adjusting for age and LAVi (OR: 4.5 (1.0-19.19))., Conclusions: Advanced interatrial block is common among patients with ATTR-CA, as well as in patients with heart failure and left ventricular hypertrophy but no CA. aIAB is associated with reduced left atrial contractile function.

Objectives: To evaluate the diagnostic yield of the ECG criteria for ST-elevation myocardial infarction in a large cohort of emergency department chest pain patients, and to determine whether extended ECG criteria or reciprocal ST depression can improve accuracy. Design: Observational, register-based diagnostic study on the accuracy of ECG criteria for ST-elevation myocardial infarction. Between Jan 2010 and Dec 2014 all patients aged ≥30 years with chest pain who had an ECG recorded within 4 h at two emergency departments in Sweden were included. Exclusion criteria were: ECG with poor technical quality; QRS duration ≥120 ms; ECG signs of left ventricular hypertrophy; or previous coronary artery bypass surgery. Conventional and extended ECG criteria were applied to all patients. The main outcome was acute myocardial infarction (AMI) and an occluded/near-occluded coronary artery at angiography. Results: Finally, 19932 patients were included. Conventional ECG criteria for ST elevation myocardial infarction were fulfilled in 502 patients, and extended criteria in 1249 patients. Sensitivity for conventional ECG criteria in diagnosing AMI with coronary occlusion/near-occlusion was 17%, specificity 98% and positive predictive value 12%. Corresponding data for extended ECG criteria were 30%, 94% and 8%. When reciprocal ST depression was added to the criteria, the positive predictive value rose to 24% for the conventional and 23% for the extended criteria. Conclusions: In unselected chest pain patients at the emergency department, the diagnostic yield of both conventional and extended ECG criteria for ST-elevation myocardial infarction is low. The PPV can be increased by also considering reciprocal ST depression.

Introduction: The prognostic value of angina during exercise stress testing is controversial, possibly due to previous studies not differentiating typical from non-typical angina. We aimed to assess the prognostic value of typical angina alone, or in combination with ST depression, during exercise stress testing for predicting cardiovascular events., Methods: We conducted a prospective observational cohort study including all patients who performed a clinical exercise stress test at the department of Clinical Physiology, Kalmar County Hospital between 2005 and 2012. The association between typical angina/ST depression and incident acute coronary syndrome (ACS) and cardiovascular mortality were analysed using Cox regression for long-term and 1-year follow-up., Results: Out of 11605 patients (median follow-up 6.7 years), 623 (5.4%) developed ACS and 319 (2.7%) died from cardiovascular causes. Compared to patients with no angina and no ST depression, typical angina and ST depression were associated with increased risk of future ACS; hazard ratio (HR) 3.5 ([95%CI] 2.6-4.7). This association was even stronger for ACS within one year (typical angina with and without concomitant ST depression; HR 20.8 (13.9-31.3) and 9.7 (6.1-15.4), respectively). Concordance statistics for ST depression in predicting ACS during long-term follow-up was 0.58 (0.56-0.60) and 0.69 (0.65-0.73) for ACS within one year, and 0.64 (0.62-0.66) and 0.77 (0.73-0.81), respectively, when typical angina was added to the model., Conclusions: Typical angina during exercise stress testing is predictive of future ACS, especially in combination with ST depression, and during the first year after the test., (© 2021 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

During four decades, the ECG limb lead display has differed between Sweden and the rest of the world. In the classical, or international, display, the limb leads are presented in two groups in non-contiguous order: I, II, III, and aVR, aVL, aVF. When ECG recording and presentation was standardized in Sweden, a joint decision between several medical specialty associations was made to use the so-called Cabrera presentation, in which limb leads are presented in contiguous order: aVL, I, -aVR, II, aVF and III. This presentation is logical and easily understood.

Objectives. Pericarditis, takotsubo cardiomyopathy and early repolarization syndrome (ERS) are well-known to mimic ST elevation myocardial infarction (STEMI). We aimed to study whether ECG findings of reciprocal ST depression, PR depression, ST-segment convexity or terminal QRS distortion can discriminate between ST elevation due to ischemia and non-ischemic conditions. Design. Eighty-five patients with STEMI and 94 patients with non-ischemic ST elevation were included. All patients had acute chest pain and at least 0.1 mV ST elevation. Presence of PR depression, ST-segment convexity, terminal QRS distortion or reciprocal ST depression was assessed in each ECG. Results. In anterior ST elevation, ST depression in lead II (≥0.025 mV) occurred in 40% of patients with STEMI but in none of the non-ischemic cases. In inferior ST elevation, ST depression in lead I (≥0.025 mV) was present in 83% of patients with STEMI but in none of the non-ischemic cases. Chest-lead PR depression was uncommon in STEMI (12%) compared to non-ischemic cases (38%; p  < .001). Convex ST elevation occurred in 22% of STEMI cases and in 9% of non-ischemic cases ( p  = .01). Terminal QRS distortion was more prevalent in STEMI (40%) than in non-ischemic ST elevation (7%). In multivariable analysis, reciprocal ST depression was associated with an ischemic diagnosis, whereas ST depression in aVR and chest-lead PR depression were associated with a non-ischemic diagnosis. Conclusions. Identification of true STEMI among patients with different ST-elevation etiology may be improved by considering reciprocal ST depression, ST depression in aVR and chest-lead PR depression.

Introduction: A new grading of exercise capacity during bicycle stress testing has been proposed in Sweden based on the new reference material ('the Kalmar material'), which has not been validated. We aimed to examine the prognostic information of the new grading of exercise capacity during exercise stress testing., Methods: Data on all bicycle exercise tests performed at the Department of Clinical Physiology in Kalmar between May 2005 and October 2016 were cross-linked with the Causes of Death Register (until 30 April 2019) and the National Patient Register (until 12 December 2017). Exercise capacity was graded based on predicted exercise capacity: ≥120% (good), 75 to <120% (normal), 70 to <75% (mildly reduced), 50 to <70% (moderately reduced) and <50% (severely reduced). Associations with all-cause mortality, cardiovascular mortality and hospitalization for ischaemic heart disease (IHD) and heart failure were analysed using Cox regression., Results: A total of 13 887 patients were followed a median of 7·7 years (interquartile range 5·0-10·8); 1809 patients died (546 from cardiovascular disease). Compared to normal exercise capacity, reduction of exercise capacity was strongly associated with increased all-cause mortality [(hazard ratio; 95% confidence interval): mild (3·0; 2·6-3·5); moderate (4·4; 3·9-4·9); and severe reduction (8·5; 7·2-10·0)]. Reduced exercise capacity was also associated with increased risks of cardiovascular hospitalization and mortality., Conclusion: Reduced exercise capacity is associated with increased all-cause and cardiovascular mortality, as well as increased risk of future IHD and heart failure diagnosis and hospitalization. In patients with reduced exercise capacity, mortality is progressively increased with worsening grade of exercise capacity., (© 2019 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Electrocardiographic Decision Support - Myocardial Ischaemia (EDS-MI) is a graphical decision support for detection and localization of acute transmural ischaemia. A recent study indicated that EDS-MI performs well for detection of acute transmural ischaemia. However, its performance has not been tested in patients with non-ischaemic ST-deviation. We aimed to optimize the diagnostic accuracy of EDS-MI in patients with verified acute coronary occlusion as well as patients with non-ischaemic ST deviation and compare its performance with STEMI criteria. We studied 135 patients with non-ischaemic ST deviation (perimyocarditis, left ventricular hypertrophy, takotsubo cardiomyopathy and early repolarization) and 117 patients with acute coronary occlusion. In 63 ischaemic patients, the extent and location of the ischaemic area (myocardium at risk) was assessed by both cardiovascular magnetic resonance imaging and EDS-MI. Sensitivity and specificity of ST elevation myocardial infarction criteria were 85% (95% confidence interval (CI) 77, 90) and 44% (95% CI 36, 53) respectively. Using EDS-MI, sensitivity and specificity increased to 92% (95% CI 85, 95) and 81% (95% CI 74, 87) respectively (p=0.035 and p<0.001). Agreement was strong (83%) between cardiovascular magnetic resonance imaging and EDS-MI in localization of ischaemia. Mean myocardium at risk was 32% (± 10) by cardiovascular magnetic resonance imaging and 33% (± 11) by EDS-MI when the estimated infarcted area according to Selvester QRS scoring was included in myocardium at risk estimation. In conclusion, EDS-MI increases diagnostic accuracy and may serve as an automatic decision support in the early management of patients with suspected acute coronary syndrome. The added clinical benefit in a non-selected clinical chest pain population needs to be assessed.

Pheochromocytoma is a rare catecholamine-secreting tumor in the adrenal medulla. In some cases, the first symptoms are cardiovascular. We report on two patients with pheochromocytoma, who both presented with bidirectional ventricular tachycardia (BDVT). We elaborate on the mechanisms of BDVT in the setting of pheochromocytoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To describe the incidence of incorrect computerized ECG interpretations of atrial fibrillation or atrial flutter in a Swedish primary care population, the rate of correction of computer misinterpretations, and the consequences of misdiagnosis. Design: Retrospective expert re-analysis of ECGs with a computer-suggested diagnosis of atrial fibrillation or atrial flutter. Setting: Primary health care in Region Kronoberg, Sweden. Subjects: All adult patients who had an ECG recorded between January 2016 and June 2016 with a computer statement including the words 'atrial fibrillation' or 'atrial flutter'. Main outcome measures: Number of incorrect computer interpretations of atrial fibrillation or atrial flutter; rate of correction by the interpreting primary care physician; consequences of misdiagnosis of atrial fibrillation or atrial flutter. Results: Among 988 ECGs with a computer diagnosis of atrial fibrillation or atrial flutter, 89 (9.0%) were incorrect, among which 36 were not corrected by the interpreting physician. In 12 cases, misdiagnosed atrial fibrillation/flutter led to inappropriate treatment with anticoagulant therapy. A larger proportion of atrial flutters, 27 out of 80 (34%), than atrial fibrillations, 62 out of 908 (7%), were incorrectly diagnosed by the computer. Conclusions: Among ECGs with a computer-based diagnosis of atrial fibrillation or atrial flutter, the diagnosis was incorrect in almost 10%. In almost half of the cases, the misdiagnosis was not corrected by the overreading primary-care physician. Twelve patients received inappropriate anticoagulant treatment as a result of misdiagnosis.Key pointsData regarding the incidence of misdiagnosed atrial fibrillation or atrial flutter in primary care are lacking. In a Swedish primary care setting, computer-based ECG interpretations of atrial fibrillation or atrial flutter were incorrect in 89 of 988 (9.0%) consecutive cases.Incorrect computer diagnoses of atrial fibrillation or atrial flutter were not corrected by the primary-care physician in 47% of cases.In 12 of the cases with an incorrect computer rhythm diagnosis, misdiagnosed atrial fibrillation or flutter led to inappropriate treatment with anticoagulant therapy.

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Electrocardiographic diagnosis of acute coronary occlusion can be difficult in the setting of left bundle branch block. If presumably new bundle branch block is considered equivalent to ST-elevation myocardial infarction, unnecessary coronary angiographies will be performed. On the other hand, the diagnosis of an acute coronary occlusion should not be delayed. Presence of concordant ST-segment changes are specific, but not sensitive, findings in the diagnosis of acute coronary occlusion in patients with left bundle branch block.