Ratio of early transmitral inflow velocity to early diastolic strain rate predicts atrial fibrillation following acute myocardial infarction.

The ratio of early transmitral filling velocity to early diastolic strain rate (E/SRe) has been proposed as a new non-invasive measurement of left ventricular filling pressure. We aimed to investigate the ability of E/SRe to predict atrial fibrillation (AF) after ST-elevation myocardial infarction (STEMI). This was a prospective cohort study of patients (n = 369) with STEMI. Patients underwent an echocardiographic examination a median of two days after pPCI. By echocardiography, transmitral early filling velocity (E) was measured by pulsed-wave Doppler, and early diastolic strain rate (SRe) was measured by speckle tracking of the left ventricle. E was indexed to SRe and the early myocardial relaxation velocity (e') to obtain the E/SRe and E/e', respectively. The endpoint was new-onset AF. During follow-up (median 5.6 years, IQR: 5.0-6.1 years), 23 (6%) of the 369 patients developed AF. In unadjusted analyses, both E/SRe and E/e' were significantly associated with AF [E/SRe: HR = 1.06; (1.03-1.10); p < 0.001, per 10 increase] and [E/e': HR = 1.11 (1.05-1.17); p < 0.001, per 1 increase] and had equal Harrell's C-statistic of 0.71. However, only E/SRe remained an independent predictor after multivariable adjustments for clinical and echocardiographic parameters [E/SRe: HR = 1.06 (1.00-1.11); p = 0.044, per 10 increase]. E/SRe was further significantly associated with AF in patients with E/e' < 14 HR = 1.09 (1.01-1.17); p = 0.030, per 10 increase), also after multivariable adjustments. E/SRe is an independent predictor of AF in STEMI patients, even in subjects with seemingly normal filling pressure.

Myocardial Flow Reserve, an Independent Prognostic Marker of All-Cause Mortality Assessed by 82Rb PET Myocardial Perfusion Imaging: A Danish Multicenter Study.

BACKGROUND: Rubidium-82 positron emission tomography (82Rb PET) myocardial perfusion imaging is used in clinical practice to quantify regional perfusion defects. Additionally, 82Rb PET provides a measure of absolute myocardial flow reserve (MFR), describing the vasculature state of health. We assessed whether 82Rb PET-derived MFR is associated with all-cause mortality independently of the extent of perfusion defects. METHODS: We conducted a multicenter clinical registry-based study of patients undergoing 82Rb PET myocardial perfusion imaging on suspicion of chronic coronary syndromes. Patients were followed up in national registries for the primary outcome of all-cause mortality. Global MFR ≤2 was considered reduced. RESULTS: Among 7169 patients studied, 38.1% were women, the median age was 69 (IQR, 61-76) years, and 39.0% had MFR ≤2. A total of 667 (9.3%) patients died during a median follow-up of 3.1 (IQR, 2.6-4.0) years, more in patients with MFR ≤2 versus MFR >2 (15.7% versus 5.2%; P<0.001). MFR ≤2 was associated with all-cause mortality across subgroups defined by the extent of perfusion defects (all P<0.05). In a Cox survival regression model adjusting for sex, age, comorbidities, kidney function, left ventricular ejection fraction, and perfusion defects, MFR ≤2 was a robust predictor of mortality with a hazard ratio of 1.62 (95% CI, 1.31-2.02; P<0.001). Among patients with no reversible perfusion defects (n=3101), MFR ≤2 remained strongly associated with mortality (hazard ratio, 1.86 [95% CI, 1.26-2.73]; P<0.01). The prognostic value of impaired MFR was similar for cardiac and noncardiac death. CONCLUSIONS: MFR ≤2 predicts all-cause mortality independently of the extent of perfusion defects. Our results support the inclusion of MFR when assessing the prognosis of patients suspected of chronic coronary syndromes.

Impact of chronic kidney disease and diabetes on clinical outcomes in women undergoing PCI.

BACKGROUND: For women undergoing drug-eluting stent (DES) implantation, the individual and combined impact of chronic kidney disease (CKD) and diabetes mellitus (DM) on outcomes is uncertain. AIMS: We sought to assess the impact of CKD and DM on prognosis in women after DES implantation. METHODS: We pooled patient-level data on women from 26 randomised controlled trials comparing stent types. Women receiving DES were stratified into 4 groups based on CKD (defined as creatine clearance <60 mL/min) and DM status. The primary outcome at 3 years after percutaneous coronary intervention was the composite of all-cause death or myocardial infarction (MI); secondary outcomes included cardiac death, stent thrombosis and target lesion revascularisation. RESULTS: Among 4,269 women, 1,822 (42.7%) had no CKD/DM, 978 (22.9%) had CKD alone, 981 (23.0%) had DM alone, and 488 (11.4%) had both conditions. The risk of all-cause death or MI was not increased in women with CKD alone (adjusted hazard ratio [adj. HR] 1.19, 95% confidence interval [CI]: 0.88-1.61) nor DM alone (adj. HR 1.27, 95% CI: 0.94-1.70), but was significantly higher in women with both conditions (adj. HR 2.64, 95% CI: 1.95-3.56; interaction p-value <0.001). CKD and DM in combination were associated with an increased risk of all secondary outcomes, whereas alone, each condition was only associated with all-cause death and cardiac death. CONCLUSIONS: Among women receiving DES, the combined presence of CKD and DM was associated with a higher risk of the composite of death or MI and of any secondary outcome, whereas alone, each condition was associated with an increase in all-cause and cardiac death.

Coronary Microvascular Disease Assessed by 82-Rubidium Positron Emission Tomography Myocardial Perfusion Imaging Is Associated With Small Vessel Disease of the Kidney and Brain.

Background Coronary microvascular disease (CMD) may be part of a systemic small vessel disease that also manifests as neurological impairment and kidney disease. However, clinical evidence supporting a potential link is scarce. We assessed whether CMD is associated with an increased risk of small vessel disease in the kidney and brain. Methods and Results A retrospective multicenter (n=3) study of patients clinically referred to 82-rubidium positron emission tomography myocardial perfusion imaging was conducted between January 2018 and August 2020. Exclusion criterion was reversible perfusion defects >5%. CMD was defined as myocardial flow reserve (MFR) ≤2. The primary outcome, microvascular event, was defined by hospital contact for chronic kidney disease, stroke, or dementia. Among 5122 patients, 51.7% were men, median age 69.0 [interquartile range, 60.0-75.0] years, 11.0% had left ventricular ejection fraction ≤40%, and 32.4% had MFR ≤2. MFR was associated with baseline estimated glomerular filtration rate after multivariable adjustment (ß=0.04 [95% CI, 0.03-0.05]; P<0.001). During a median follow-up of 3.05 years, 383 (7.5%) patients suffered an event (253 cerebral and 130 renal), more frequently in patients with MFR ≤2 versus MFR >2 (11.6% versus 5.5%, P<0.001). MFR ≤2 was associated to outcome with a hazard ratio (HR) of 2.30 (95% CI, 1.88-2.81, P<0.001) and an adjusted HR of 1.62 (95% CI, 1.32-2.00, P<0.001). Results were consistent across subgroups defined by presence of irreversible perfusion defects, estimated glomerular filtration rate, diabetes, left ventricular ejection fraction, and previous revascularization. Conclusions This is the first large-scale cohort study to link CMD to microvascular events in the kidney and brain. Data support the hypothesis that CMD is part of a systemic vascular disorder.

Left atrial functional measurements' utility in predicting long-term risk of atrial fibrillation after isolated CABG.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia following coronary artery bypass grafting (CABG). We hypothesized that measures of left atrial (LA) function would be useful in predicting AF in patients undergoing CABG. METHODS AND RESULTS: In the study, 611 patients were included after CABG. All patients had echocardiograms performed preoperatively and LA functional measurements were assessed. These measurements were LA maximum volume index (LAVmax), LA minimum volume index (LAVmin) and LA emptying fraction (LAEF). The endpoint was AF occurring >14 days after surgery. During the follow-up period of a median of 3.7 years, 52 (9%) developed AF. The mean age was 67 years, 84% were male and the average left ventricle ejection fraction was 50%. Patients who developed AF had a lower CCS class and lower LAEF (40 vs. 45%), otherwise no clinical differences were observed between outcome groups. No functional LA measurements were significant predictors of AF in the whole CABG population. However, in patients with normal-sized LA (n = 532, events: 49), both LAEF and LAVmin were univariable predictors of AF. When the functional measurements were adjusted for the CHADS2 score, both LAVmin (HR = 1.07 [1.01-1.13], p = .014) and LAEF (HR: 1.02 [1.00-1.03], p = .023), remained significant predictors. CONCLUSION: No echocardiographic measurements were significant predictors of AF after CABG. In patients with a normal LA size, LAVmin as well as LAEF were significant predictors of AF.

Left atrial reservoir strain predicts ischaemic stroke after coronary artery bypass grafting independent of postoperative atrial fibrillation.

Aims: Measures of left atrial (LA) function are known to predict both ischaemic stroke and atrial fibrillation in specific patient groups. The aim of this study was to investigate the value of LA reservoir strain for predicting ischaemic stroke in patients undergoing coronary artery bypass grafting (CABG) and investigate whether the presence of postoperative atrial fibrillation (POAF) modified this relationship. Methods and results: Patients undergoing isolated CABG were included. The primary endpoint was ischaemic stroke. The association between LA reservoir strain and ischaemic stroke was investigated in uni- and multivariable Cox proportional hazards regression models including adjustment for POAF.We included 542 patients (mean age 67.3±8.9 years, 16.4% female). During a median follow-up period of 3.9 years, 21 patients (3.9%) experienced an ischaemic stroke. In total, 96 patients (17.7%) developed POAF during the index hospitalization. In a multivariable-adjusted Cox proportional hazards regression model, LA reservoir strain was significantly associated with the development of ischaemic stroke [HR (hazard ratio) 1.09 (95% CI 1.02-1.17) per 1% decrease, P = 0.011]. The presence of POAF did not modify this association (p for interaction = 0.07). The predictive value of the LA reservoir strain persisted in multiple sensitivity analyses including restricting the analysis to patients with normal left atrial volumes (LAV<34 ml/m2), patients without POAF, patients without prior stroke, and when excluding patients who developed atrial fibrillation at any time during follow-up. Conclusion: LA reservoir strain was independently associated with ischaemic stroke in CABG patients. The predictive value of LA reservoir strain was unaffected by the presence of POAF. Prospective studies are warranted to validate the potential usefulness of LA reservoir strain to predict postoperative ischaemic stroke in the setting of CABG.

Prognostic implications of myocardial perfusion imaging by 82-rubidium positron emission tomography in male and female patients with angina and no perfusion defects.

AIMS: Myocardial perfusion imaging with 82-rubidium positron emission tomography (82Rb-PET) is increasingly used to assess stable coronary artery disease (CAD). We aimed to evaluate the prognostic value of 82Rb-PET-derived parameters in patients with symptoms suggestive of CAD but no significant reversible or irreversible perfusion defects. METHODS AND RESULTS: Among 3726 consecutive patients suspected of stable CAD who underwent 82Rb-PET between January 2018 and August 2020, 2175 had no regional perfusion defects. Among these patients, we studied the association of 82Rb-PET-derived parameters with a composite endpoint of all-cause mortality, hospitalization for unstable angina pectoris, acute myocardial infarction, heart failure, or ischaemic stroke. During a median follow up of 1.7 years (interquartile range 1.1-2.5 years), there were 148 endpoints. Myocardial blood flow (MBF) reserve (MFR), MBF during stress, left ventricular ejection fraction (LVEF), LVEF-reserve, heart rate reserve, and Ca score were associated with adverse outcomes. In multivariable Cox model adjusted for patient and 82Rb-PET characteristics, MFR < 2 (hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.24-2.48), LVEF (HR 1.38 per 10% decrease, 95% CI 1.24-1.54), and LVEF-reserve (HR 1.19 per 5% decrease, 95% CI 1.07-1.31) were significant predictors of endpoints. Results were consistent in subgroups defined by gender, history of ischaemic heart disease, low LVEF, and atrial fibrillation. CONCLUSION: MFR, LVEF, and LVEF-reserve derived from 82Rb-PET provide prognostic information on cardiovascular outcomes in patients with no perfusion defects. This may aid in identifying patients at risk and might provide an opportunity for preventive interventions.

Predictive value of left atrial strain in relation to atrial fibrillation following acute myocardial infarction.

BACKGROUND: Atrial fibrillation (AF) is the most common arrythmia following ST-segment elevation myocardial infarction (STEMI) and can lead to stroke and other heart-related diseases. This study aimed to determine the prognostic value of left atrial (LA) strain, obtained by speckle tracking echocardiography (STE), in predicting incident AF outcomes following STEMI treated with primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: This prospective study comprised of 392 STEMI patients treated with pPCI. The patients had an echocardiography performed at a median of two days after their STEMI. Along with conventional measures, LA strain was obtained by speckle tracking from two apical projections. The outcome was new-onset atrial fibrillation. LA reservoir, contractile and conduit strain were measurable from echocardiograms of 303 included patients. At a median follow-up time of 5.6 years (IQR: 5.0-6.1 years), 18 patients (6,3%) developed incident AF. Mean age was 62.0 years ±11.5 and follow-up was 100%. Significantly lower LA strain values were observed in patients who experienced AF during follow-up as compared to patients who didn't. Both reservoir, contractile and conduit strain were significant univariable predictors. In the multivariable model, only LA reservoir strain remained a significant independent predictor of AF. CONCLUSION: Left atrial reservoir strain obtained by two-dimensional speckle tracking echocardiography is an independent predictor of incident AF following STEMI.

Prediction models as gatekeepers for diagnostic testing in angina patients with suspected chronic coronary syndrome.

AIMS: Assessment of pre-test probability (PTP) is an important gatekeeper when selecting patients for diagnostic testing for coronary artery disease (CAD). The 2019 European Society of Cardiology (ESC) guidelines recommend upgrading PTP based on clinical risk factors but provide no estimates of how these affect PTP. We aimed to validate two published PTP models in a contemporary low-CAD-prevalence cohort and compare with the ESC 2019 PTP. METHODS AND RESULTS: Previously published basic and clinical prediction models and the ESC 2019 PTP were validated in 42 328 patients (54% women) ≥30 years old without previous CAD referred for cardiac computed tomography angiography in a region of Denmark from 2008 to 2017. Obstructive CAD prevalence was 8.8%. The ESC 2019 PTP and basic model included angina symptoms, sex, and age, while the clinical model added diabetes mellitus family history of CAD, and dyslipidaemia. Discrimination was good for all three models [area under the receiver operating curve (AUC) 0.76, 95% confidence interval (CI) (0.75-0.77), 0.74 (0.73-0.75), and 0.76 (0.75-0.76), respectively]. Using the clinically relevant low predicted probability ≤5% of CAD cut-off, the clinical and basic models were well calibrated, whereas the ESC 2019 PTP overestimated CAD prevalence. At a cut-off of ≤5%, the clinical model ruled out 36.2% more patients than the ESC 2019 PTP, n = 23 592 (55.7%) vs. n = 8 245 (19.5%), while missing 824 (22.2%) vs. 132 (3.6%) cases of obstructive CAD. CONCLUSION: A prediction model for CAD including cardiovascular risk factors was successfully validated. Implementation of this model would reduce the need for diagnostic testing and serve as gatekeeper if accepting a watchful waiting strategy for one-fifth of the patients.

Right ventricular strain predicts adverse outcomes in patients undergoing coronary artery bypass grafting.

Patients undergoing coronary artery bypass grafting (CABG) face an elevated risk of heart failure (HF) and cardiovascular (CV) death. Detailed myocardial tissue analyses of the right ventricle are now possible and may hold prognostic value in these patients. Accordingly, we aimed to evaluate the usefulness of right ventricular (RV) layer-specific RV free wall strain (RVFWS) for predicting HF and/or CV death. Patients undergoing CABG at Gentofte Hospital from 2006 to 2011 with a preoperative echocardiogram underwent RVWFS analysis. RVFWS was obtained by speckle tracking. The outcome was defined as a composite of HF and/or CV death. Cox proportional hazards regression, Harrell's C-statistics, and competing risk regression were used to assess the prognostic value of RVFWS. Of 317 patients, 30 (9.5%) reached the endpoint at a median follow-up of 3.5 years. The mean age was 67 years, 83% were men, and the mean LVEF was 50%. In univariable analyses, endo-RVFWS (HR 1.08, P < 0.001), mid-RVFWS (HR 1.07, P = 0.002), and epi-RVFWS (HR 1.07, P = 0.004, per 1% absolute decrease) were associated with a higher risk of HF or/and CV death. Furthermore, all three layers remained independently associated with the outcome after multivariable adjustment for baseline clinical and echocardiographic measurements. Low endo-RVFWS was associated with a more than threefold increased risk of the outcome (HR = 3.04 (1.45-6.38) P = 0.003). The same was observed for mid-RVFWS (HR = 3.16 (1.45-6.91) P = 0.004), and epi-RVFWS (HR = 3.00 (1.46-6.17) P = 0.003). In patients undergoing CABG, RVFWS assessed by speckle-tracking is a predictor of adverse outcomes.

Longitudinal change in cardiac structure and function following acute coronary syndrome according to culprit coronary artery lesion.

Acute coronary syndrome (ACS) may lead to adverse remodelling and impaired cardiac function. Limited data exists on the effect of culprit coronary artery lesion site and impact on longitudinal cardiac remodelling. The present study included a total of 299 patients suffering from ACS treated with percutaneous coronary intervention (PCI). All patients had two echocardiographic examinations. The first echocardiography was median 2(IQR: 1;3) days following PCI, while the follow-up echocardiography (FUE) was median 257(IQR: 96;942) days following the first. Patients were grouped based on coronary artery PCI location; left anterior descending artery (LAD), right coronary artery (RCA) or circumflex artery (Cx). Patients with multiple lesions were excluded. Mean age was 63 ± 11 years and 77% were male. At FUE, mean left ventricular ejection fraction was 42 ± 9% and global longitudinal strain (GLS) was - 13 ± 4%. PCI treatment was allocated as 168 LAD lesions, 95 RCA lesions, and 36 Cx lesions. Linear regression analysis showed that patients with a LAD lesion displayed worsening in E/A (mean ∆ = 0.05, ß = - 0.196, p = 0.001) and a larger increase in LVEDV (mean ∆ = 33.18 mL, ß = 0.135, p = 0.012). Meanwhile patients with Cx lesion were significantly associated with a larger decrease in E/e' (mean ∆ = 2.6, ß = - 0.120, p = 0.028). Patients with Cx lesion were observed to have elevated E/e' at baseline, which normalized at FUE. The present study suggests that culprit coronary artery lesion has a differential impact on myocardial remodelling. This information may potentially aid in understanding the pathophysiological differences in cardiac structure and function amongst patients with ACS.

Early diastolic strain rate in relation to long term prognosis following isolated coronary artery bypass grafting.

BACKGROUND: The ratio of early mitral inflow velocity to early diastolic strain rate (E/e'sr) is a novel echocardiographic measure to estimate early left ventricular (LV) filling pressure. We hypothesize that E/e'sr is a predictor of outcome following coronary artery bypass grafting (CABG) and that it is superior to the conventionally used E/e'. METHODS & RESULTS: Consecutive patients undergoing isolated CABG at Gentofte Hospital (n = 652) were included. The mean age of the study population was 67 ± 9 years, 84% were male, mean LVEF was 50 ± 11%. Prior to surgery, all patients underwent an extensive echocardiographic examination. The outcome was all-cause mortality. During follow-up (median 3.8 years [IQR: 2.7; 4.9 years]), a total of 73 (11.2%) died. Both E/e' and E/e'sr were significant predictors in univariable models. In a multivariable model, E/e'sr remained an independent predictor of outcome (HR:1.05 [1.01-1.10], p = 0.049, per 10 cm increase) whereas E/e' did not (HR:1.05 [0.99-1.11], p = 0.053, per 1-unit increase). The relationship between E/e'sr, and the outcome was significantly modified by GLS (p for interaction = 0.043). In the multivariable model, E/e'sr was still significantly associated with the outcome in patients with high GLS (≥13.6%) (HR:1.18 [1.02-1.36], p = 0.029) but not in patients with low GLS (HR 1.04 CI95%: [0.99-1.10], p = 0.14). E/e' was not a significant predictor of all-cause mortality after multivariable adjustment in neither of the groups. E/e'sr improved net reclassification with 33% when added to EuroSCOREII. CONCLUSION: Following CABG, preoperative E/e'sr is an independent predictor of all-cause mortality, especially in patients with preserved systolic function and superior to E/e'.

Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial.

INTRODUCTION: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. METHODS AND ANALYSIS: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022. ETHICS AND DISSEMINATION: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible. TRIAL REGISTRATION NUMBER: NCT04121949; Pre-results.

Early systolic lengthening by speckle tracking echocardiography predicts outcome after coronary artery bypass surgery.

BACKGROUND: Early systolic lengthening (ESL), a paradoxical stretch of myocardial fibers, has been linked to loss of myocardial viability and contractile dysfunction. We assessed the long-term prognostic potential of ESL in coronary artery bypass graft (CABG) patients. METHODS: We retrospectively included patients (n = 709; mean age 68 years; 85% men) who underwent speckle tracking echocardiography (median 15 days) prior to CABG. Endpoints were cardiovascular death (CVD) and all-cause mortality. We assessed amplitude of ESL (%), defined as peak positive strain, and duration of ESL (ms), determined as time from Q-wave on the ECG to peak positive strain. We applied Cox models adjusted for clinical risk assessed as EuroSCORE II. RESULTS: During median follow-up of 3.8 years [IQR 2.7-4.9 years], 45 (6%) experienced CVD and 80 (11%) died. In survival analyses adjusted for EuroSCORE II, each 1% increase in amplitude of ESL was associated with CVD (HR 1.35 [95%CI 1.09-1.68], P = 0.006) and all-cause mortality (HR 1.29 [95%CI 1.08-1.54], P = 0.004). Similar findings applied to duration of ESL (per 10ms increase) and CVD (HR 1.12 [95%CI 1.02-1.23], P = 0.016) and all-cause mortality (HR 1.09 [95%CI 1.01--1.17], P = 0.031). The prognostic value of ESL amplitude was modified by sex (P interaction < 0.05), such that the prognostic value was greater in women for both endpoints. When adding ESL duration to EuroSCORE II, the net reclassification index improved significantly for both CVD and all-cause mortality. CONCLUSIONS: Assessment of ESL provides independent and incremental prognostic information in addition to the EuroSCORE II for CVD and all-cause mortality in CABG patients.

Change in global longitudinal strain following acute coronary syndrome and subsequent risk of heart failure.

Global Longitudinal Strain (GLS) is a well-established predictor of heart failure (HF) following acute coronary syndrome (ACS). We aim to investigate the prognostic value of GLS obtained at a follow-up consultation, as well as the change in GLS for long-term risk of incident HF. A total of 235 ACS patients had an echocardiogram performed immediately after percutaneous coronary intervention (PCI) and a follow-up echocardiogram (FUE) median 215 (IQR: 71; 878) days after the first echocardiogram. Endpoint was incident HF. Follow-up time after FUE was median 4.8 (IQR: 3.7; 5.6) years. Patients diagnosed with HF before FUE were excluded. Mean age was 63 ± 11 years and 77% were male. Baseline GLS was on average 12.7 ± 3.9%, FUE GLS was on average 13.5 ± 3.9% and mean improvement in GLS was 0.73 ± 3.68% between the 2 echocardiograms. A total of 57 (24%) patients suffered incident HF following the FUE. FUE GLS provided significantly higher prognostic information for risk of incident HF than ∆GLS when assessed by the C-statistics (C-statistics: 0.71 vs. 0.61, P = 0.021). Furthermore, after multivariable adjustments only FUE GLS [HR = 1.15, 95% CI (1.02; 1.29), P = 0.018, per 1% decrease] remained an independent predictor of incident HF. In patients with ACS, who do not develop HF before FUE, FUE GLS was an independent predictor of long-term risk of incident HF while ∆GLS was not.

Left ventricular end-diastolic pressure is associated with left atrial functional measures by echocardiography.

Echocardiography guidelines recommend the assessment of maximal LA volume (LAVmax). Evidence, however, suggests additional value of functional LA measures. We investigated the association between functional LA measures and left ventricular end-diastolic pressure (LVEDP). Patients suspected of coronary artery disease referred for invasive coronary angiography (ICA) underwent, in addition to ICA, invasive pressure measurements. LVEDP > 12 mmHg was considered elevated. LA measurements by echocardiography included: LAVmax, minimal LA volume (LAVmin), total LA emptying fraction (LAEFtotal), passive LA emptying fraction (LAEFpassive), and active LA emptying fraction (LAEFactive). Of 43 patients, 28 (65%) had elevated LVEDP. These patients more frequently had coronary vessel disease (VD) and impaired LA mechanics for all measures except LAVmax. All LA measures except LAVmax were associated with LVEDP in unadjusted linear regression analyses. After adjustment for age and VD, only LA emptying fractions remained associated with LVEDP (2.6 (1.2-4.0) mmHg increase, p = 0.001, per 5% decrease in LAEFtotal; 1.4 (0.1-2.8) mmHg increase, p = 0.040, per 5% decrease in LAEFactive; 1.8 (0.1-3.4) mmHg increase, p = 0.038, per 5% decrease in LAEFpassive). In logistic regression, only LAEFpassive was significantly associated with elevated LVEDP after adjusting for age and VD (OR = 1.11 (1.01-1.21), p = 0.023, per 1% decrease). Similar findings were made in subgroup analyses among patients without dilated LA and patients without conventional indicators of elevated filling pressure. Left ventricular end-diastolic pressure is significantly associated with LA functional measures but not LA volumes. Additionally, LAEFpassive is associated with elevated LVEDP. Future studies examining LA function should include all components of LAEF.

Association of fatal myocardial infarction with past level of physical activity: a pooled analysis of cohort studies.

AIMS: To assess the association between past level of physical activity (PA) and risk for death during the acute phase of myocardial infarction (MI) in a pooled analysis of cohort studies. METHODS AND RESULTS: European cohorts including participants with a baseline assessment of PA, conventional cardiovascular (CV) risk factors, and available follow-up on MI and death were eligible. Patients with an incident MI were included. Leisure-time PA was grouped as sedentary (<7 MET-hours), low (7-16 MET-hours), moderate (16.1-32 MET-hours), or high (>32 MET-hours) based on calculated net weekly energy expenditure. The main outcome measures were instant and 28-day case fatality of MI. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate random-effects models. Adjustments for age, sex, CV risk factors, alcohol consumption, and socioeconomic status were made. From 10 cohorts including a total of 1 495 254 participants, 28 140 patients with an incident MI comprised the study population. A total of 4976 (17.7%) died within 28 days-of these 3101 (62.3%) were classified as instant fatal MI. Compared with sedentary individuals, those with a higher level of PA had lower adjusted odds of instant fatal MI: low PA [OR, 0.79 (95% CI, 0.60-1.04)], moderate PA [0.67 (0.51-0.89)], and high PA [0.55 (0.40-0.76)]. Similar results were found for 28-day fatal MI: low PA [0.85 (0.71-1.03)], moderate PA [0.64 (0.51-0.80)], and high PA [0.72 (0.51-1.00)]. A low-to-moderate degree of heterogeneity was detected in the analysis of instant fatal MI (I2 = 47.3%), but not in that of 28-day fatal MI (I2 = 0.0%). CONCLUSION: A moderate-to-high level of PA was associated with a lower risk of instant and 28-day death in relation to a MI.

Global longitudinal strain predicts cardiovascular events after coronary artery bypass grafting.

OBJECTIVE: To determine the prognostic value of global longitudinal strain (GLS) after coronary artery bypass grafting (CABG). METHODS: We performed a retrospective cohort study on patients undergoing CABG between 2006 and 2011 who had an echocardiogram available for strain analysis. The patients were followed up through nationwide registries for development of all-cause mortality, cardiovascular death (CVD) and major adverse cardiovascular events (MACEs) defined as heart failure hospitalisation and/or CVD. Multivariable Cox regression was applied to adjust for the European System for Cardiac Operative Risk Evaluation II (EuroSCORE-II). Additive value was assessed by Net Reclassification Index (NRI) improvement. RESULTS: Of the 709 patients included, 80 died during a median follow-up of 3.8 years. Of these, 45 had CVD, and 72 patients experienced MACE. Mean age was 68 years and 85% were men. Left ventricular ejection fraction (LVEF) was 50% and GLS was -13%.GLS was an independent predictor when adjusted for the EuroSCORE-II (all-cause mortality: HR=1.07 (1.01-1.13), p=0.018; CVD: HR=1.11 (1.03-1.20), p=0.007; MACE: HR=1.12 (1.06-1.19), p<0.001, per 1% absolute decrease). GLS significantly improved the NRI score by 0.30 when added to the EuroSCORE-II for predicting MACE, but not significantly for the other endpoints.LVEF modified the association between GLS and outcomes (p for interaction<0.05 for CVD and MACE). GLS remained an independent predictor of outcomes in patients with preserved LVEF (LVEF≥50%) and improved the NRI score when added to the EuroSCORE-II for predicting CVD and MACE, but not all-cause mortality in these patients. CONCLUSION: GLS is an independent predictor of long-term outcomes after CABG. The predictive value appears strongest among patients with preserved LVEF.

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Prognostic Value and Interplay Between Myocardial Tissue Velocities in Patients Undergoing Coronary Artery Bypass Grafting.

Early diastolic tissue velocity (e') by tissue Doppler imaging represents an early marker of left ventricular (LV) dysfunction in ischemic heart disease. We assessed the value of e' for predicting mortality in patients undergoing coronary artery bypass grafting (CABG). We retrospectively investigated patients treated with CABG between 2006-2011. Before surgery, all patients underwent an echocardiogram with tissue Doppler imaging to measure tissue velocities: systolic (s'), e', and late diastolic (a'). The primary outcome was all-cause mortality. Survival analysis was applied. Improvement of EuroSCORE-II was assessed by net reclassification index. Of 660 patients, 72 (11%) died during a median follow-up time of 3.8 years. Mean age was 68 years, LVEF 50%, and 84% were men. All tissue velocities showed a significant negative association with outcome and e' provided highest Harrell's C-statistics (c-stat=0.68). After multivariable adjustment for EuroSCORE-II, LV hypertrophy, LV internal diameter, and global longitudinal strain, declining e' was associated with a higher risk of mortality (HR=1.35 (1.12 to 1.61), p = 0.001, per 1cm/s absolute decrease). LVEF≤40% modified the relationship between both s' and e' and outcome (p for interaction=0.021 and 0.024, respectively), such that neither predicted mortality when LVEF was ≤40%. In patients with LVEF>40%, only e' remained a predictor after multivariable adjustments (HR=1.36 (1.10 to 1.69), p = 0.005, per 1cm/s absolute decrease). A net reclassification index improvement of 0.14 was observed when adding global e' to the EuroSCORE-II. In conclusion, e' is an independent predictor of all-cause mortality in patients undergoing CABG, especially in patients with LVEF>40%, and improves the predictive value of EuroSCORE-II.