Plasma Lipidomics and Coronary Plaque Changes: A Substudy of the SMARTool Clinical Trial.

AIMS: To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by plasma lipidomic analysis, with coronary plaque changes according to composition assessed by quantitative serial analysis of coronary computed tomography angiography (CTA). METHODS AND RESULTS: Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by 7 EU Centers in the SMARTool study and submitted to clinical, molecular and coronary CTA re-evaluation at follow-up (interscan period 6.39 ± 1.17 years). From the 202 patients that were analysed in the SMARTool main clinical study, lipidomic analysis was performed in 154 patients before the baseline coronary CTA, and this group was included in the present study. Quantitative CTA analysis was performed by a separate core laboratory blinded from clinical data. In univariable analysis, no lipid species were significantly associated with annual total and calcified plaque changes. After adjusting for clinical variables at baseline and statin use, 3 lipid species were significantly associated with non-calcified plaque progression. In detail, cholesteryl ester (CE)(20:3), sphingomyelin (SM)(40:3) and SM(41:1) were found positively related to non-calcified plaque progression (Bonferroni adjusted P-value = 0.005, 0.016 and 0.004, respectively). CONCLUSION: The current study showed an independent relationship between specific lipid species determined by plasma lipidomic analysis, and non-calcified coronary plaque progression assessed by serial, quantitative coronary CTA analysis.

Association of Left Atrial Appendage Morphology and Function With Stroke and Transient Ischemic Attack in Atrial Fibrillation Patients.

We aimed to correlate left atrial appendage (LAA) structure and function with the history of stroke/transient ischemic attack (TIA) in patients with atrial fibrillation (AF). We analyzed the data of 649 patients with AF who were scheduled for catheter ablation. Patients underwent cardiac computed tomography and transesophageal echocardiography before ablation. The LAA morphologies depicted by cardiac computed tomography were categorized into 4 groups: cauliflower, chicken wing, swan, and windsock shapes. The mean age was 61.3 ± 10.5 years, 33.9% were women. The prevalence of stroke/TIA was 7.1%. After adjustment for the main risk factors, the LAA flow velocity ≤35.3 cm/s (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.09 to 4.61, p = 0.033) and the swan LAA shape (OR 2.69, 95% CI 0.96 to 6.86, p = 0.047) independently associated with a higher risk of stroke/TIA, whereas the windsock LAA morphology proved to be protective (OR 0.32, 95% CI 0.12 to 0.77, p = 0.017) compared with the cauliflower LAA shape. Comparing the differences between the LAA morphology groups, we measured a significantly smaller LAA orifice area (389.3 ± 137.7 mm2 in windsock vs 428.3 ± 158.9 ml in cauliflower, p = 0.021) and LAA volume (7.4 ± 3.0 mm2 in windsock vs 8.5 ± 4.8 mm2 in cauliflower, p = 0.012) in patients with windsock LAA morphology, whereas the LAA flow velocity did not differ significantly. Reduced LAA function and swan LAA morphology were independently associated with a higher prevalence of stroke/TIA, whereas the windsock LAA shape proved to be protective. Comparing the differences between the various LAA morphology types, significantly lower LAA volume and LAA orifice area were measured in the windsock LAA shape than in the cauliflower LAA shape.

Relation Between Coronary Plaque Composition Assessed by Intravascular Ultrasound Virtual Histology and Myocardial Ischemia Assessed by Quantitative Flow Ratio.

Coronary plaque composition may play an important role in the induction of myocardial ischemia. Our objective was to further clarify the relation between coronary plaque composition and myocardial ischemia in patients with chest pain symptoms. The study population consisted of 103 patients who presented to the outpatient clinic or emergency department with chest pain symptoms and were referred for diagnostic invasive coronary angiography. Intravascular ultrasound virtual histology was used for the assessment of coronary plaque composition. A noncalcified plaque was defined as a combination of necrotic core and fibrofatty tissue. Quantitative flow ratio (QFR), which is a coronary angiography-based technique used to calculate fractional flow reserve without the need for hyperemia induction or for a pressure wire, was used as the reference standard for the evaluation of myocardial ischemia. Coronary artery plaques with QFR of ≤0.80 were considered abnormal-that is, ischemia-generating. In total, 149 coronary plaques were analyzed, 21 of which (14%) were considered abnormal according to QFR. The percentage of noncalcified tissue was significantly higher in plaques with abnormal QFR (38.2 ± 6.5% vs 33.1 ± 9.0%, p = 0.014). After univariable analysis, both plaque load (odds ratio [OR] per 1% increase 1.081, p <0.001) and the percentage of noncalcified tissue (OR per 1% increase 1.070, p = 0.020) were significantly associated with reduced QFR. However, after multivariable analysis, only plaque load remained significantly associated with abnormal QFR (OR per 1% increase 1.072, p <0.001). In conclusion, the noncalcified plaque area was significantly higher in hemodynamically significant coronary lesions than in nonsignificant lesions. Although an increase in the noncalcified plaque area was significantly associated with a reduced QFR, this association lost significance after adjustment for localized plaque load.

Association of MMP9 with adverse features of plaque progression and residual inflammatory risk in patients with chronic coronary syndrome (CCS).

BACKGROUND AND AIMS: MMP-9 is a predictor of atherosclerotic plaque instability and adverse cardiovascular events, but longitudinal data on the association between MMP9 and coronary disease progression are lacking. This study is aimed at investigating whether MMP9 is associated with atherosclerotic plaque progression and the related molecular basis in stable patients with chronic coronary syndrome (CCS). METHODS: MMP9 serum levels were measured in 157 CCS patients (58 ± 8 years of age; 66% male) undergoing coronary computed tomography angiography at baseline and after a follow up period of 6.5 ± 1.1 years to assess progression of Total, Fibrous, Fibro-fatty, Necrotic Core, and Dense Calcium plaque volumes (PV). Gene expression analysis was evaluated in whole blood using a transcriptomic approach by RNA-seq. RESULTS: At multivariate analysis, serum MMP9 was associated with annual change of Total and Necrotic Core PV (Coefficient 3.205, SE 1.321, P = 0.017; 1.449, SE 0.690, P = 0.038, respectively), while MMP9 gene expression with Necrotic Core PV (Coefficient 70.559, SE 32.629, P = 0.034), independently from traditional cardiovascular risk factors, medications, and presence of obstructive CAD. After transcriptomic analysis, MMP9 expression was linked to expression of genes involved in the innate immunity. CONCLUSIONS: Among CCS patients, MMP9 is an independent predictive marker of progression of adverse coronary plaques, possibly reflecting the activity of inflammatory pathways conditioning adverse plaque phenotypes. Thus, blood MMP9 might be used for the identification of patients with residual risk even with optimal management of classical cardiovascular risk factors who may derive the greatest benefit from targeted anti-inflammatory drugs.

Association between left atrial epicardial fat, left atrial volume, and the severity of atrial fibrillation.

AIMS: Left atrial (LA) volume and LA epicardial fat are both substrates for atrial fibrillation (AF), but may relate with AF at different (early vs. late) stages in the AF disease process. We evaluated associations between LA epicardial fat and LA volume in patients with sinus rhythm (SR), paroxysmal AF (PAF), and persistent/permanent AF. METHODS AND RESULTS: In total, 300 patients (100 with SR, 100 with PAF, and 100 with persistent/permanent AF) who underwent cardiac computed tomography angiography (CTA) were included. The epicardial fat mass posterior to the LA and the LA volume were quantified from CTA and compared between patients with SR, PAF, and persistent/permanent AF. Furthermore, four groups were created by classifying LA epicardial fat and LA volume into large or small according to their median. The mean age of the population was 58.9 ± 10.5 years and 69.7% was male. Left atrial epicardial fat mass was larger in patients with PAF compared with SR, but did not further increase from PAF to persistent/permanent AF. Left atrial volume increased significantly from SR to PAF and to persistent/permanent AF. Left atrial epicardial fat and LA volume were both concordantly large or small in 184 (61%) patients, and discordant in 116 (39%). When both were small, 65.2% of the patients had SR, 23.9% PAF, and 10.9% persistent/permanent AF. When the LA epicardial fat mass was large and the LA volume small (compared with both being small), patients were significantly more often in PAF (55.2 vs. 23.9, P < 0.05), less frequently in SR (32.8% vs. 65.2%, P < 0.05) but showed comparable rates of persistent/permanent AF (12.0% vs. 10.9%, P < 0.05). When the LA volume was large, most patients had persistent/permanent AF. CONCLUSION: Left atrial epicardial fat mass was larger in PAF vs. SR, possibly indicating a marker of early disease, while large LA volumes were associated with a high prevalence of persistent/permanent AF. Elevated LA epicardial fat mass without large LA volume may reflect the early AF disease process.

Coronary volume to left ventricular mass ratio in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial mass. The aim of this study was to examine the V/M derived from coronary computed tomography angiography (CCTA) in patients with diabetes. METHODS: Patients with clinically suspected CAD enrolled in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry and known diabetic status were included. Coronary artery volume and left ventricular myocardial mass were analyzed from CCTA and the V/M ratio was calculated and compared between patients with and without diabetes. RESULTS: Of the 3053 patients (age 66 â€‹± â€‹10 years; 66% male) with known diabetic status, diabetes was present in 21.9%. Coronary volume was lower in patients with diabetes compared to those without diabetes (2850 â€‹± â€‹940 â€‹mm3 vs. 3040 â€‹± â€‹970 â€‹mm3, p â€‹< â€‹0.0001), whereas the myocardial mass was comparable between the 2 groups (122 â€‹± â€‹33 â€‹g vs. 122 â€‹± â€‹32 â€‹g, p â€‹= â€‹0.70). The V/M ratio was significantly lower in patients with diabetes (23.9 â€‹± â€‹6.8 â€‹mm3/g vs. 25.7 â€‹± â€‹7.5 â€‹mm3/g, p â€‹< â€‹0.0001). Among subjects with obstructive CAD (n â€‹= â€‹2191, 24.0% diabetics) and non-obstructive CAD (16.7% diabetics), the V/M ratio was significantly lower in patients with diabetes compared to those without (23.4 â€‹± â€‹6.7 â€‹mm3/g vs. 25.0 â€‹± â€‹7.3 â€‹mm3/g, p â€‹< â€‹0.0001 and 25.6 â€‹± â€‹6.9 â€‹mm3/g vs. 27.3 â€‹± â€‹7.6 â€‹mm3/g, respectively, p â€‹= â€‹0.006). CONCLUSION: The V/M ratio was significantly lower in patients with diabetes compared to non-diabetics, even after correcting for obstructive coronary stenosis. The clinical value of the reduced V/M ratio in diabetic patients needs further investigation.

Left atrial appendage size is a marker of atrial fibrillation recurrence after radiofrequency catheter ablation in patients with persistent atrial fibrillation.

INTRODUCTION: There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long-term recurrence of AF after catheter ablation, depending on AF type. METHODS: AF patients who underwent point-by-point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni- and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence. RESULTS: In total, 561 AF patients (61.9 ± 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence-free time of 22.7 (9.3-43.1) months. Patients with persistent AF had significantly higher body surface area-indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38-3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01-1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF. CONCLUSION: The current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF.

A specific plasma lipid signature associated with high triglycerides and low HDL cholesterol identifies residual CAD risk in patients with chronic coronary syndrome.

BACKGROUND AND AIMS: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Aim of the present study was to assess whether TG/HDL-C ratio, coronary atherosclerosis and their change over time are characterized by a specific lipidomic profiling in stable patients with chronic coronary syndrome (CCS). METHODS: TG/HDL-C ratio was calculated in 193 patients (57.8 ± 7.6 years, 115 males) with CCS characterized by clinical, bio-humoral profiles and cardiac imaging. Patient-specific plasma targeted lipidomics was defined through a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) strategy. Patients underwent coronary computed tomography angiography (CTA) and an individual CTA risk score, combining extent, severity, composition, and location of plaques, was calculated. All patients entered a follow-up (6.39 ± 1.17 years), including clinical, lipidomics and coronary CTA assessments. RESULTS: Patients were divided in groups according to baseline TG/HDL-C quartiles: IQ (<1.391), IIQ (1.392-2.000), IIIQ (2.001-3.286), and IVQ (≥3.287). A specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters, phosphatidylcholines and sphingomyelins, was associated with higher TG/HDL-C both at baseline and follow-up (IVQ vs IQ). The CTA risk score increased over time and this lipid signature was also associated with higher CTA score at follow-up. CONCLUSIONS: In stable CCS, a specific lipidomic signature identifies those patients with higher TG/HDL- C ratio and higher CTA score over time, suggesting possible molecular pathways of residual CAD risk not tackled by current optimal medical treatments.

Triglycerides and low HDL cholesterol predict coronary heart disease risk in patients with stable angina.

We assessed whether high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, expressed by an increased TG/HDL-C ratio, predict coronary atherosclerotic disease (CAD) outcomes in patients with stable angina. We studied 355 patients (60 ± 9 years, 211 males) with stable angina who underwent coronary computed tomography angiography (CTA), were managed clinically and followed for 4.5 ± 0.9 years. The primary composite outcome was all-cause mortality and non-fatal myocardial infarction. At baseline, the proportion of males, patients with metabolic syndrome, diabetes and obstructive CAD increased across TG/HDL-C ratio quartiles, together with markers of insulin resistance, hepatic and adipose tissue dysfunction and myocardial damage, with no difference in total cholesterol or LDL-C. At follow-up, the global CTA risk score (HR 1.06, 95% confidence interval (CI) 1.03-1.09, P = 0.001) and the IV quartile of the TG/HDL-C ratio (HR 2.85, 95% CI 1.30-6.26, P < 0.01) were the only independent predictors of the primary outcome. The TG/HDL-C ratio and the CTA risk score progressed over time despite increased use of lipid-lowering drugs and reduction in LDL-C. In patients with stable angina, high TG and low HDL-C levels are associated with CAD related outcomes independently of LDL-C and treatments.Trial registration. EVINCI study: ClinicalTrials.gov NCT00979199, registered September 17, 2009; SMARTool study: ClinicalTrials.gov NCT04448691, registered June 26, 2020.

Anatomical Characteristics of the Left Atrium and Left Atrial Appendage in Relation to the Risk of Stroke in Patients With Versus Without Atrial Fibrillation.

[Figure: see text].

Prognostic Value of Multilayer Left Ventricular Global Longitudinal Strain in Patients with ST-segment Elevation Myocardial Infarction with Mildly Reduced Left Ventricular Ejection Fractions.

Multilayer (epi-, mid- and endocardium) left ventricular (LV) global longitudinal strain (GLS) reflects the extent of myocardial damage after ST-segment myocardial infarction (STEMI). However, the prognostic implications of multilayer LV GLS remain unclear. We studied the association between multilayer LV GLS and prognosis in patients with mildly reduced or preserved LV ejection fraction (EF) after STEMI. Patients with first STEMI and LVEF>45% were evaluated retrospectively. Baseline multilayer (endocardial, mid-myocardial and epicardial) LV GLS were measured on 2-dimensional speckle tracking echocardiography. Patients were followed up for of all-cause mortality. A total of 569 patients (77% male, 60 ± 11 years) were included. After a median follow-up of 117 (interquartile range 106-132) months, 95 (17%) patients died. We observed no differences in baseline LVEF and peak troponin levels between survivors and non-survivors. However, non-survivors showed more impaired GLS at all layers (epicardium: -11.9 ± 2.8% vs. -13.4 ± 2.8%; mid-myocardium: -14.2 ± 3.2% vs. -15.6 ± 3.2%; endocardium: -16.5 ± 3.7% vs. -17.7 ± 3.6%, p <0.05, for all). On multivariable analysis, increasing age (hazard ratio 1.095; p<0.001) and impaired LV GLS of the epicardial layer (hazard ratio 1.085; p = 0.047) were independently associated with higher risk of all-cause mortality. In addition, LV GLS at the epicardium had incremental prognostic value for all-cause mortality (χ2 = 114, p = 0.044). In conclusion, in contemporary STEMI patients with mildly reduced or preserved LVEF, ageing and reduced LV GLS of the epicardium (reflecting transmural scar formation) were independently associated with all-cause mortality after adjusting for clinical and echocardiographic variables.

Sex differences in coronary plaque changes assessed by serial computed tomography angiography.

Long-term data on sex-differences in coronary plaque changes over time is lacking in a low-to-intermediate risk population of stable coronary artery disease (CAD). The aim of this study was to evaluate the role of sex on long-term plaque progression and evolution of plaque composition. Furthermore, the influence of menopause on plaque progression and composition was also evaluated. Patients that underwent a coronary computed tomography angiography (CTA) were prospectively included to undergo a follow-up coronary CTA. Total and compositional plaque volumes were normalized using the vessel volume to calculate a percentage atheroma volume (PAV). To investigate the influence of menopause on plaque progression, patients were divided into two groups, under and over 55 years of age. In total, 211 patients were included in this analysis, 146 (69%) men. The mean interscan period between baseline and follow-up coronary CTA was 6.2 ± 1.4 years. Women were older, had higher HDL levels and presented more often with atypical chest pain. Men had 434 plaque sites and women 156. On a per-lesion analysis, women had less fibro-fatty PAV compared to men (ß -1.3 ± 0.4%; p < 0.001), with no other significant differences. When stratifying patients by 55 years age threshold, fibro-fatty PAV remained higher in men in both age groups (p < 0.05) whilst women younger than 55 years demonstrated more regression of fibrous (ß -0.8 ± 0.3% per year; p = 0.002) and non-calcified PAV (ß -0.7 ± 0.3% per year; p = 0.027). In a low-to-intermediate risk population of stable CAD patients, no significant sex differences in total PAV increase over time were observed. Fibro-fatty PAV was lower in women at any age and women under 55 years demonstrated significantly greater reduction in fibrous and non-calcified PAV over time compared to age-matched men. (ClinicalTrials.gov number, NCT04448691.).

Posterior Left Atrial Adipose Tissue Attenuation Assessed by Computed Tomography and Recurrence of Atrial Fibrillation After Catheter Ablation.

[Figure: see text].

Global Left Ventricular Myocardial Work Efficiency and Long-Term Prognosis in Patients After ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Left ventricular (LV) global longitudinal strain has demonstrated incremental prognostic value over LV ejection fraction in patients with ST-segment-elevation myocardial infarction. However, LV global longitudinal strain does not take into consideration the effect of afterload. Novel speckle-tracking echocardiographic indices of myocardial work integrate blood pressure measurements (afterload) with LV global longitudinal strain. The present study aimed to investigate the prognostic value of global LV myocardial work efficiency (GLVMWE; reflecting LV performance) obtained from pressure-strain loops with echocardiography in patients with ST-segment-elevation myocardial infarction. METHODS: A total of 507 ST-segment-elevation myocardial infarction patients (mean age, 61±11 years; 76% men) were retrospectively analyzed. LV ejection fraction and GLVMWE were measured by transthoracic echocardiography within 48 hours of admission. GLVMWE was defined as the ratio of constructive work divided by the sum of constructive and wasted work in all LV segments and expressed as a percentage. Spline curve analysis was used to define the association between reduced GLVMWE and all-cause death. RESULTS: After a median follow-up of 80 months (interquartile range, 67-97 months), 40 (8%) patients died. Patients with reduced GLVMWE (<86%) showed higher cumulative rates of all-cause mortality (17.5% versus 4.7%; log-rank P<0.001) in comparison with patients with preserved GLVMWE (≥86%). Reduced GLVMWE (<86%) showed an independent association with all-cause mortality (hazard ratio, 3.167 [95% CI, 1.679-5.972]; P<0.001). CONCLUSIONS: Reduced GLVMWE (<86%) measured by transthoracic echocardiography within 48 hours of admission in ST-segment-elevation myocardial infarction patients is associated with worse long-term survival.

Relationship between coronary artery calcification and myocardial ischemia on computed tomography myocardial perfusion in patients with stable chest pain.

BACKGROUND: Coronary artery calcium (CAC) score has shown to provide incremental prognostic information when added to the Framingham risk score. Although the relation between CAC and myocardial ischemia has been evaluated, there has been little evaluation of the relationship between CAC score and inducible myocardial ischemia on computed tomography myocardial perfusion (CTP). METHODS AND RESULTS: Patients who were referred with stable chest pain from the outpatient clinic and who underwent non-contrast computed tomography scan, coronary computed tomography angiography, and adenosine stress CTP were included in this study. CAC score was subdivided in four groups (1 to 99; 100 to 399, 400 to 999, and ≥ 1000). Inducible myocardial ischemia was considered when reversible perfusion defects were observed in ≥ 1 segment. A total of 131 patients (age 62 ± 9.4 years; 56% male) were included. The median CAC score was 241 (73 to 539). Forty-nine patients (37%) had evidence of inducible myocardial ischemia. The presence of inducible myocardial ischemia increased with increasing CAC score from 22% in the CAC score 1 to 99 subgroup to 35, 47, and 65% in the 100 to 399, 400 to 999, and ≥ 1000 CAC score subgroup, respectively. In multivariable analysis CAC score was the only determinant that significantly predicted the presence of inducible myocardial ischemia on CTP. CONCLUSIONS: In a population of symptomatic patients, the majority of patients with extensive calcification had evidence of inducible myocardial ischemia on CTP. CAC score was the only independent predictor of inducible myocardial ischemia on CTP.

Left ventricular myocardial work in the culprit vessel territory and impact on left ventricular remodelling in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

AIMS: Adverse left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. Global and regional LV myocardial work (LVMW) derived from speckle tracking echocardiographic strain data in combination with non-invasive blood pressure recordings could provide information for prediction of LV remodelling after STEMI. The aim of the study was to assess the predictive value of global and regional LVMW for LV remodelling before discharge in patients with STEMI. METHODS AND RESULTS: Three-hundred and fifty STEMI patients treated with primary percutaneous coronary intervention (PCI) were included [265 men (76%), mean age: 61 ± 10 years]. Clinical variables, conventional echocardiographic parameters, global and regional measures of myocardial work index (MWI), and myocardial work efficiency were recorded before discharge. The primary endpoint was early LV remodelling defined as increase in LV end-diastolic volume (LVEDV) ≥20% at 3 months after STEMI. Eighty-seven patients (25%) showed early LV remodelling. The global and regional LVMW in the culprit territory were significantly lower in patients with early LV remodelling. Peak troponin I (OR 1.109, 95% CI 1.046-1.177; P = 0.001), LVEDV (OR 0.972, 95% CI 0.959-0.984; P < 0.001) and regional MWI in the culprit vessel territory (OR 0.602, 95% CI 0.383-0.945; P = 0.027) were independently associated with early LV remodelling. CONCLUSION: In STEMI patients treated with primary PCI and optimal medical therapy, the regional cardiac work index in the culprit vessel territory before discharge is independently associated with early adverse LV remodelling.

Right ventricular myocardial work: proof-of-concept for non-invasive assessment of right ventricular function.

AIMS: Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function utilizing RV pressure-strain loops. This study aimed to explore the relationship between RVMW and invasive indices of right heart catheterization (RHC) in a cohort of patients with heart failure with reduced left ventricular ejection fraction (HFrEF), and to compare values of RVMW with those of a group of patients without cardiovascular disease. METHODS AND RESULTS: Non-invasive analysis of RVMW was performed in 22 HFrEF patients [median age 63 (59-67) years] who underwent echocardiography and invasive RHC within 48 h. Conventional RV functional measurements, RV global constructive work (RVGCW), RV global work index (RVGWI), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were analysed and compared with invasively measured stroke volume and stroke volume index. Non-invasive analysis of RVMW was also performed in 22 patients without cardiovascular disease to allow for comparison between groups. None of the conventional echocardiographic parameters of RV systolic function were significantly correlated with stroke volume or stroke volume index. In contrast, one of the novel indices derived non-invasively by pressure-strain loops, RVGCW, demonstrated a moderate correlation with invasively measured stroke volume and stroke volume index (r = 0.63, P = 0.002 and r = 0.59, P = 0.004, respectively). RVGWI, RVGCW, and RVGWE were significantly lower in patients with HFrEF compared to a healthy cohort, while values of RVGWW were significantly higher. CONCLUSION: RVGCW is a novel parameter that provides an integrative analysis of RV systolic function and correlates more closely with invasively measured stroke volume and stroke volume index than other standard echocardiographic parameters.

Left ventricular mechanical dispersion in ischaemic cardiomyopathy: association with myocardial scar burden and prognostic implications.

AIMS: Left ventricular (LV) mechanical dispersion (MD) may result from heterogeneous electrical conduction and is associated with adverse events. The present study investigated (i) the association between LV MD and the extent of LV scar as assessed with contrast-enhanced cardiac magnetic resonance (CMR) and (ii) the prognostic implications of LV MD in patients after ST-segment elevation myocardial infarction. METHODS AND RESULTS: LV MD was calculated by echocardiography and myocardial scar was analysed on CMR data retrospectively. Infarct core and border zone were defined as ≥50% and 35-50% of maximal signal intensity, respectively. Patients were followed for the occurrence of the combined endpoint (all-cause mortality and appropriate implantable cardioverter-defibrillator therapy). In total, 96 patients (87% male, 57 ± 10 years) were included. Median LV MD was 53.5 ms [interquartile range (IQR) 43.4-62.8]. On CMR, total scar burden was 11.4% (IQR 3.8-17.1%), infarct core tissue 6.2% (IQR 2.0-12.7%), and border zone was 3.5% (IQR 1.5-5.7%). Correlations were observed between LV MD and infarct core (r = 0.517, P < 0.001), total scar burden (r = 0.497, P < 0.001), and border zone (r = 0.298, P = 0.003). In total, 14 patients (15%) reached the combined endpoint. Patients with LV MD >53.5 ms showed higher event rates as compared to their counterparts. Finally, LV MD showed the highest area under the curve for the prediction of the combined endpoint. CONCLUSION: LV MD is correlated with LV scar burden. In addition, patients with prolonged LV MD showed higher event rates. Finally, LV MD provided the highest predictive value for the combined endpoint when compared with other parameters.

Noninvasive Myocardial Work Indices 3 Months after ST-Segment Elevation Myocardial Infarction: Prevalence and Characteristics of Patients with Postinfarction Cardiac Remodeling.

BACKGROUND: Assessment of left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is pivotal for patient management. Noninvasive myocardial work indices obtained from echocardiography-derived strain-pressure loops provide a new tool that permits characterization of LV mechanics. We aimed at characterizing myocardial work indices in patients with LV remodeling after STEMI versus patients without remodeling. METHODS: Six-hundred STEMI patients were retrospectively analyzed (456 men, mean age: 61 ± 11 years) and divided according to the presence of LV remodeling 3 months after the index admission (≥20% increase in LV end-diastolic volume). Noninvasive myocardial work indices were measured at 3 months after STEMI. RESULTS: LV remodeling was observed in 150 patients (25%) who showed more impaired global myocardial work indices compared with their counterparts: work index (1,708 ± 522 mm Hg% vs 1,979 ± 450 mm Hg%; P < .001), constructive work (1,941 ± 598 mm Hg% vs 2,272 ± 519 mm Hg%; P < .001), and work efficiency (92% [range 88%-96%] vs 95% [range 93%-96%]; P < .001). In addition, patients with LV remodeling had significantly increased wasted work (116 mm Hg% [range 73-184 mm Hg%] vs 91 mm Hg% [range 61-132 mm Hg%]; P < .001). The frequency of impaired global work index, constructive and work efficiency, and increased wasted work was significantly higher among patients with LV remodeling compared with their counterparts: 21.3%, 34.7%, 34.7%, and 14.0%, respectively, versus 5.3%, 9.6%, 8.9%, and 4.9%, respectively (P < .001). CONCLUSIONS: At 3-month follow-up after STEMI, patients with LV remodeling revealed more impaired myocardial work indices compared with patients without LV remodeling. The prevalence of impaired myocardial work indices was higher among patients with LV remodeling compared with patients without.

Myocardial Work in Nonobstructive Hypertrophic Cardiomyopathy: Implications for Outcome.

BACKGROUND: Noninvasive left ventricular (LV) pressure-strain loop analysis is emerging as a new echocardiographic method to evaluate LV function, integrating longitudinal strain by speckle-tracking analysis and sphygmomanometrically measured blood pressure to estimate myocardial work. The aims of this study were (1) to describe global and segmental myocardial work in patients with hypertrophic cardiomyopathy (HCM), (2) to assess the correlation between myocardial work and other echocardiographic parameters, and (3) to evaluate the association of myocardial work with adverse outcomes. METHODS: One hundred ten patients with nonobstructive HCM (mean age, 55 ± 15 years; 66% men), with different phenotypes (apical, concentric, and septal hypertrophy), and 35 age- and sex-matched healthy control subjects were included. The following myocardial work indices were included: myocardial work index, constructive work (CW), wasted work, and cardiac efficiency. The combined end point included all-cause mortality, heart transplantation, heart failure hospitalization, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator therapy. RESULTS: Mean global CW (1,722 ± 602 vs 2,274 ± 574 mm Hg%, P < .001), global cardiac efficiency (93% [89%-95%] vs 96% [96%-97%], P < .001), and global MWI (1,534 ± 551 vs 1,929 ± 473 mm Hg%) were significantly reduced, while global wasted work (104 mm Hg% [66-137 mm Hg%] vs 71 mm Hg% [49-92 mm Hg%], P < .001) was increased in patients with HCM compared with control subjects. Segmental impairment in CW colocalized with maximal wall thickness (HCM phenotype), and global CW correlated with LV wall thickness (r = -0.41, P < .001), diastolic function (r = -0.27, P = .001), and QRS duration (r = -0.28, P = .001). Patients with global CW > 1,730 mm Hg% (the median value) experienced better event-free survival than those with global CW < 1,730 mm Hg% (P < .001). CONCLUSIONS: Myocardial work, assessed noninvasively using echocardiography and blood pressure measurement, is reduced in patients with nonobstructive HCM; it correlates with maximum LV wall thickness and is significantly associated with a worse long-term outcome.