The relationship between coronary artery calcium and layer-specific global longitudinal strain in patients with suspected coronary artery disease.

PURPOSE: Layer-specific global longitudinal strain (GLS) may provide important insights in patients with suspected coronary artery disease (CAD). We aimed to investigate the association between layer-specific GLS and coronary artery calcium score (CACS) in patients suspected of CAD. METHODS: We performed a retrospective study of patients suspected of CAD who underwent both an echocardiogram and cardiac computed tomography (median 42 days between). Layer-specific (endocardial-, whole-layer-, and epicardial-) GLS was measured using speckle tracking echocardiography. We assessed the continuous association between layer-specific GLS and CACS by negative binomial regression, and the association with high CACS (≥400) using logistic regression. RESULTS: Of the 496 patients included (mean age 59 years, 56% male), 64 (13%) had a high CACS. Those with high CACS had reduced GLS in all layers compared to those with CACS < 400 (endocardial GLS: -20.5 vs. -22.7%, whole-layer GLS: -17.7 vs. -19.4%, epicardial GLS: -15.3 vs. -16.9%, p < .001 for all). Negative binomial regression revealed a significant continuous association showing increasing CACS with worsening GLS in all layers, which remained significant after multivariable adjustment including SCORE chart risk factors. All layers of GLS were associated with high CACS in univariable analyses, which was consistent after multivariable adjustment (endocardial GLS: OR = 1.11 (1.03-1.20); whole-layer GLS: OR = 1.14 (1.04-1.24); epicardial GLS: OR = 1.16 (1.05-1.29), per 1% absolute decrease). CONCLUSION: In this study population with patients suspected of CAD and normal systolic function, impaired layer-specific GLS was continuously associated with increasing CACS, and decreasing GLS in all layers were associated with presence of high CACS.

High Lipoprotein(a) May Explain One-Quarter of Clinical Familial Hypercholesterolemia Diagnoses in Danish Lipid Clinics.

CONTEXT: Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH). OBJECTIVE: We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH. METHODS: Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a). RESULTS: We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a). CONCLUSION: Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.

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).

Myocardial performance index is associated with cardiac computed tomography findings in patients with suspected coronary artery disease.

BACKGROUND: Studies suggest cardiac time intervals to be associated with cardiac ischemia. A novel method to assess cardiac time intervals by tissue Doppler echocardiography has been proposed. Cardiac time intervals can assess the myocardial performance index (MPI), which quantifies the proportion of time spent contributing effective myocardial work. We hypothesized that MPI associates with coronary artery lesions detected by cardiac computed tomography (CT) in patients suspected of coronary artery disease (CAD). METHODS: We investigated patients referred for cardiac CT under suspicion of CAD who had an echocardiogram performed. Curved m-mode tissue Doppler imaging was used to measure cardiac time intervals and MPI. The outcome was coronary artery lesions, defined as a calcium score > 400 and/or coronary artery stenosis (>70% luminal narrowing). Logistic regression was applied with multivariable models including: (a) SCORE chart risk factors and (b) SCORE chart risk factors, body mass index, dyslipidemia, familial history of CAD, diabetes mellitus, LVEF, and left ventricular mass index. RESULTS: Of 404 patients, 41 (10%) had a coronary artery lesion. Overall, 42% were male, mean age was 58 years, and LVEF was 58%. Patients with coronary artery lesions exhibited higher MPI than those without (0.52 vs. 0.44, P < .001). MPI associated with coronary artery lesions in unadjusted analyses (OR = 1.69 [1.30-2.19], per 0.1 increase), and this association persisted when adjusted for SCORE chart risk factors (OR = 1.55 [1.16-2.07], P = .003, per 0.1 increase), and additional risk factors (OR = 1.64 [1.11-2.41], P = .013, per 0.1 increase). CONCLUSION: Curved m-mode-derived MPI is associated with coronary artery lesions detected by cardiac CT in suspected CAD patients.

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

Postsystolic shortening on echocardiography as a gateway to cardiac computed tomography in patients with suspected stable angina pectoris.

Postsystolic shortening (PSS) by speckle-tracking echocardiography (STE) is a marker of myocardial ischemia and may improve diagnostic strategy. We sought to evaluate if PSS is associated with the coronary artery calcium score (CACS) and stenosis by computed tomography angiography (CTA) in patients with suspected stable angina pectoris (SAP). We retrospectively studied 437 SAP patients (age 58 ± 11 years, 41% male) who underwent STE, evaluation of CACS and assessment of significant stenosis (≥ 50%) by CTA. The postsystolic index (PSI) was defined as follows: 100x([peak negative strain cardiac cycle - peak negative strain systole])/peak negative strain cardiac cycle. A wall had PSS if any segment within the wall had a PSI ≥ 20%. We defined categories for walls with PSS: 0, 1, 2 and ≥ 3, and CACS: 0, 1-100, 101-400 and > 400. Each additional wall with PSS was associated with a 43% relative increase in CACS (95%CI +9% to +87%, P = 0.010), while each 1% absolute increase in the PSI was associated with a 9% relative increase in CACS (95%CI +1% to +18%, P = 0.031). Walls with PSS (OR 1.81 per 1 wall increase, 95%CI 1.27-2.59, P = 0.001) and the PSI (OR 1.12 per 1% increase, 95%CI 1.04-1.21, P = 0.004) were associated with the occurrence of CACS > 400. Additionally, walls with PSS (OR 1.53 per 1 wall increase, 95%CI 1.21-1.93, P < 0.001) was a predictor of significant stenosis by CTA. PSS is associated with CACS and significant stenosis by CTA in patients with SAP and may aid in the selection of patients referred for cardiac computed tomography.

Echocardiography improves prediction of major adverse cardiovascular events in a population with type 1 diabetes and without known heart disease: the Thousand & 1 Study.

AIMS/HYPOTHESIS: Cardiovascular disease is the most common comorbidity in type 1 diabetes. However, current guidelines do not include routine assessment of myocardial function. We investigated whether echocardiography provides incremental prognostic information in individuals with type 1 diabetes without known heart disease. METHODS: A prospective cohort of individuals with type 1 diabetes without known heart disease was recruited from the outpatient clinic. Follow-up was performed through Danish national registers. The association of echocardiography with major adverse cardiovascular events (MACE) and the incremental prognostic value when added to the clinical Steno T1D Risk Engine were examined. RESULTS: A total of 1093 individuals were included: median (interquartile range) age 50.2 (39.2-60.3) years and HbA1c 65 (56-74) mmol/mol; 53% men; and mean (SD) BMI 25.5 (3.9) kg/m2 and diabetes duration 25.8 (14.6) years. During 7.5 years of follow-up, 145 (13.3%) experienced MACE. Echocardiography significantly and independently predicted MACE: left ventricular ejection fraction (LVEF) <45% (n = 18) vs ≥45% (n = 1075), HR (95% CI) 3.93 (1.91, 8.08), p < 0.001; impaired global longitudinal strain (GLS), 1.65 (1.17, 2.34) (n = 263), p = 0.005; diastolic mitral early velocity (E)/early diastolic tissue Doppler velocity (e') <8 (n = 723) vs E/e' 8-12 (n = 285), 1.59 (1.04, 2.42), p = 0.031; and E/e' <8 vs E/e' ≥12 (n = 85), 2.30 (1.33, 3.97), p = 0.003. In individuals with preserved LVEF (n = 1075), estimates for impaired GLS were 1.49 (1.04, 2.15), p = 0.032; E/e' <8 vs E/e' 8-12, 1.61 (1.04, 2.49), p = 0.033; and E/e' <8 vs E/e' ≥12, 2.49 (1.41, 4.37), p = 0.001. Adding echocardiographic variables to the Steno T1D Risk Engine significantly improved risk prediction: Harrell's C statistic, 0.791 (0.757, 0.824) vs 0.780 (0.746, 0.815), p = 0.027; and net reclassification index, 52%, p < 0.001. CONCLUSIONS/INTERPRETATION: In individuals with type 1 diabetes without known heart disease, echocardiography significantly improves risk prediction over and above guideline-recommended clinical risk factors alone and could have a role in clinical care.

Coronary microvascular dysfunction is associated with cardiac time intervals in women with angina and no obstructive coronary artery disease: An iPOWER substudy.

BACKGROUND: Coronary microvascular dysfunction (CMD) may cause angina in the absence of obstructive coronary artery disease (CAD) and increases the risk of future adverse cardiovascular events. Transthoracic Doppler echocardiography (TTDE) with pharmacological stress can assess coronary flow velocity reserve (CFVR), a measure of coronary microvascular function. However, simpler methods would be preferable for diagnosing CMD. Therefore, we examined the relationship between CFVR and cardiac time intervals measured by TTDE in a cohort of women with angina and no obstructive CAD. METHODS: In a prospective cohort study, we included 389 women with angina, left ventricular ejection fraction > 45%, and no obstructive CAD. CMD was defined as CFVR < 2.0. The study population was divided into three groups according to cutoff values of CFVR < 2, 2 ≤ CFVR ≤ 2.5, and CFVR > 2.5. Isovolumic contraction time (IVCT), ejection time (ET), and isovolumic relaxation time (IVRT) were measured by tissue Doppler M-mode, and the myocardial performance index (MPI = (IVCT + IVRT)/ET) was calculated. RESULTS: Coronary microvascular dysfunction was associated with increasing age, hypertension, higher resting heart rate, and lower diastolic blood pressure. Moreover, CMD was associated with higher E/e' ratio (P = 0.002) and longer IVCT (P < 0.001), higher MPI (P < 0.001) and shorter ET (P = 0.002), but not with IVRT or conventional measures of left ventricular geometry, mass, and function. In multivariable analysis, longer IVCT (P < 0.001) and higher MPI (P = 0.002) remained associated with CMD. CONCLUSION: In women with angina and no obstructive CAD, CMD is associated with longer IVCT and higher MPI indicating a link between CMD and subtle alternations of systolic and combined measures of cardiac time intervals.

Prediction of obstructive coronary artery disease and prognosis in patients with suspected stable angina.

AIMS: We hypothesized that the modified Diamond-Forrester (D-F) prediction model overestimates probability of coronary artery disease (CAD). The aim of this study was to update the prediction model based on pre-test information and assess the model's performance in predicting prognosis in an unselected, contemporary population suspected of angina. METHODS AND RESULTS: We included 3903 consecutive patients free of CAD and heart failure and suspected of angina, who were referred to a single centre for assessment in 2012-15. Obstructive CAD was defined from invasive angiography as lesion requiring revascularization, >70% stenosis or fractional flow reserve <0.8. Patients were followed (mean follow-up 33 months) for myocardial infarction, unstable angina, heart failure, stroke, and death. The updated D-F prediction model overestimated probability considerably: mean pre-test probability was 31.4%, while only 274 (7%) were diagnosed with obstructive CAD. A basic prediction model with age, gender, and symptoms demonstrated good discrimination with C-statistics of 0.86 (95% CI 0.84-0.88), while a clinical prediction model adding diabetes, family history, and dyslipidaemia slightly improved the C-statistic to 0.88 (0.86-0.90) (P for difference between models <0.0001). Quartiles of probability of CAD from the clinical prediction model provided good diagnostic and prognostic stratification: in the lowest quartiles there were no cases of obstructive CAD and cumulative risk of the composite endpoint was less than 3% at 2 years. CONCLUSION: The pre-test probability model recommended in current ESC guidelines substantially overestimates likelihood of CAD when applied to a contemporary, unselected, all-comer population. We provide an updated prediction model that identifies subgroups with low likelihood of obstructive CAD and good prognosis in which non-invasive testing may safely be deferred.

Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. METHODS: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. RESULTS: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023). CONCLUSIONS: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Coronary microvascular dysfunction and myocardial contractile reserve in women with angina and no obstructive coronary artery disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function at rest and during stress. We investigated whether CMD was associated with left ventricular diastolic and systolic function at rest and during pharmacologically induced hyperemic stress. METHODS: In a prospective cohort study, we included 963 women with angina, left ventricular ejection fraction (LVEF) >45%, and an invasive coronary angiogram without significant stenosis (<50%). Parameters of left ventricular diastolic function, LVEF, speckle tracking-derived global longitudinal strain (GLS), and coronary flow velocity reserve (CFVR) were assessed by transthoracic echocardiography at rest and during dipyridamole stress. The GLS and LVEF reserves were defined as the absolute increases in GLS and LVEF during stress. RESULTS: Coronary flow velocity reserve (CFVR) was measured in 919 women of whom 26% had CMD (defined as CFVR < 2). Coronary microvascular dysfunction (CMD) was associated with higher age and a higher resting heart rate. Women with CMD had a reduced GLS reserve (P = .005), while we found no association between CFVR and LVEF at rest, GLS at rest, or the LVEF reserve, respectively. Global longitudinal strain (GLS) reserve remained associated with CFVR (P = .002) in a multivariable regression analysis adjusted for age, hemodynamic variables, and GLS at rest. In age-adjusted analysis, women with low CFVR had no signs of left ventricular diastolic dysfunction measured by echocardiography at rest. CONCLUSION: The GLS reserve was significantly lower in women with CMD. The mechanisms underlying the association between CMD and GLS reserve warrant further study.

Low diagnostic yield of non-invasive testing in patients with suspected coronary artery disease: results from a large unselected hospital-based sample.

Aims: Stable angina is the most common presentation of heart disease and has a good prognosis. With declining coronary artery disease (CAD), rates a diagnostic approach balancing costs and benefits is a challenge, particularly in women. This study describes the real-life diagnostic workup in a large hospital to explore whether the diagnostic approach may be improved. Methods and results: We identified 4028 patients free of CAD, referred for and assessed with non-invasive (NIT) or invasive test for stable suspected CAD in 2012-15. In both the sexes, the majority (>85%) presented with chest pain as primary symptom. Women had more non-angina (60.2 vs. 54.5%) and less typical angina (8.2 vs. 11.8%, P < 0.001). Despite a mean pretest probability of 20.9% in women and 45.1% in men (P < 0.001), only 69 (3.1%) women and 190 men (10.4%) were diagnosed with obstructive CAD. In all, 93% underwent a NIT and 80% of these were normal. Among the 1238 men and 1595 women with non-angina or dyspnoea, only 6.1% and 2.9%, respectively, had positive NIT. After multiple adjustments, women remained less likely to have positive NIT [odds ratio (OR) 0.42 95% confidence interval (95% CI 0.32-0.56)] and given a positive test also less likely to have obstructive CAD [OR 0.30 (0.17-0.52)]. The C-statistics for predicting positive NIT was 0.77 (0.72-0.82) in women and 0.77 (0.74-0.80) in men. Conclusion: These data confirm the very low diagnostic yield of non-invasive and invasive assessment of CAD in current clinical practice, particularly in women and in patients with atypical symptoms. Data call for a more rational approach to avoid unnecessary testing.

Regional Longitudinal Myocardial Deformation Provides Incremental Prognostic Information in Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI). The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information. METHOD: In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI) and two-dimensional strain echocardiography (2DSE). RESULTS: During a median-follow-up of 5.3 (IQR 2.5-6.1) years the primary endpoint (death, heart failure or a new MI) was reached by 145 (38.9%) patients. After adjustment for significant confounders (including conventional echocardiographic parameters) and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS) remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell's c-statistics: 0.63 vs. 0.67, p = 0.032). In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p<0.05 for all deformation parameters). CONCLUSION: Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse outcome.

Early myocardial impairment in type 1 diabetes patients without known heart disease assessed with tissue Doppler echocardiography: The Thousand & 1 study.

PURPOSE: Cardiovascular disease is the most common cause of mortality in type 1 diabetes; patients with albuminuria are at greatest risk. We investigated myocardial function and premature myocardial impairment in type 1 diabetes patients with and without albuminuria compared to controls. METHODS: This study included a cross-sectional survey of 1093 type 1 diabetes patients from Steno Diabetes Center and 200 healthy controls. Conventional and tissue Doppler echocardiographic measurements were analysed in multivariable models in normoalbuminuria (n = 760), microalbuminuria (n = 227) and macroalbuminuria (n = 106). Investigators were blinded to degree of albuminuria. RESULTS: For the type 1 diabetes patients, mean age was 49.6 years, 53% were men and mean diabetes duration was 25.5 years. In multivariable models systolic velocity s' did not differ between type 1 diabetes patients with normoalbuminuria and controls (ß-coefficient [95% confidence interval]: -0.17 [-0.41; 0.08], p = 0.19), but was impaired between controls and microalbuminuria (-0.53 [-0.84; -0.23], p = 0.001) and macroalbuminuria (-0.59 [-0.96; -0.22], p = 0.002). Diastolic measurements (e', a', e'/a', and E/e') were all significantly impaired in type 1 diabetes, for example, e'/a': normoalbuminuria, microalbuminuria and macroalbuminuria versus controls: -0.38 [-0.52; -0.23], p < 0.001; -0.49 [-0.67; -0.32], p < 0.001; and -0.81 [-1.03; -0.59], p < 0.001. In age-related analyses, myocardial impairment occurred prematurely in type 1 diabetes compared to controls (e.g. E/e' = 8; 9.2 years [normoalbuminuria], 17.3 years [microalbuminuria] and 41.4 years [macroalbuminuria] prematurely, respectively). CONCLUSION: In type 1 diabetes patients with albuminuria, both systolic and diastolic functions are impaired, whereas in patients without albuminuria only diastolic function is affected. Myocardial impairment is detectable many years prematurely in type 1 diabetes, especially in patients with albuminuria.

Abnormal echocardiography in patients with type 2 diabetes and relation to symptoms and clinical characteristics.

OBJECTIVES: We aimed to determine the prevalence of echocardiographic abnormalities and their relation to clinical characteristics and cardiac symptoms in a large, contemporary cohort of patients with type 2 diabetes. RESULTS: A total of 1030 patients with type 2 diabetes participated. Echocardiographic abnormalities were present in 513 (49.8%) patients, mainly driven by a high prevalence of diastolic dysfunction 178 (19.4%), left ventricular hypertrophy 213 (21.0%) and left atrial enlargement, 200 (19.6%). The prevalence increased markedly with age from 31.1% in the youngest group (<55 years) to 73.9% in the oldest group (>75 years) (p < 0.001) and was equally distributed among the sexes (p = 0.76). In univariate analyses, electrocardiographic abnormalities, age, body mass index, known coronary heart disease, hypertension, albuminuria, diabetes duration and creatinine were associated with abnormal echocardiography along with dyspnoea and characteristic chest pain (p < 0.05 for all). Neither of the cardiac symptoms nor clinical characteristics had sufficient sensitivity and specificity to accurately identify patients with abnormal echocardiography. CONCLUSION: Echocardiographic abnormalities are very common in outpatients with type 2 diabetes, but neither cardiac symptoms nor clinical characteristics are effective to identify patients with echocardiographic abnormalities.

Coronary Flow Velocity Reserve Assessed by Transthoracic Doppler: The iPOWER Study: Factors Influencing Feasibility and Quality.

BACKGROUND: Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography is a noninvasive measure of microvascular function, but it has not achieved widespread use, mainly because of concerns of validity and feasibility. The aim of this study was to describe the feasibility and factors associated with the quality of CFVR obtained in a large prospective study of women suspected of having microvascular disease. METHODS: Women with angina-like chest pain and no obstructive coronary artery disease on coronary angiography (<50% stenosis) were consecutively examined by transthoracic Doppler echocardiography of the left anterior descending coronary artery to measure CFVR (n = 947). Quality was evaluated on the basis of (1) identification of the left anterior descending coronary artery, (2) maintained probe position throughout the examination, (3) visibility and configuration of the left anterior descending coronary artery in two-dimensional color Doppler mode, and (4) gradual, consistent increases of characteristic, well-defined flow velocity curves in pulsed-wave mode. RESULTS: The mean age (SD) was 62.1 ± 9.7 years. On the basis of the evaluations, patients were divided into four groups according to quality score: nonfeasible (n = 28 [3%]), low quality (n = 80 [8%]), medium quality (n = 451 [48%]), and high quality (n = 388 [41%]). Quality score was associated with diabetes (P < .01), body mass index (P = .02), waist circumference (P = .05), nonsignificant atherosclerosis on coronary angiography (P = .03), and operator experience (P < .01). Low examination quality was associated with lower CFVR (P = .03), also after multivariate adjustment. CONCLUSIONS: Transthoracic Doppler echocardiographic measurement of CFVR is highly feasible and of good quality in experienced hands. However, CFVR is possibly underestimated when examination quality is low. Awareness of pitfalls and potential bias may improve the validity and interpretation of the measures obtained.

Predicting Paroxysmal Atrial Fibrillation in Cerebrovascular Ischemia Using Tissue Doppler Imaging and Speckle Tracking Echocardiography.

BACKGROUND: Often the underlying cause of cerebral ischemia (CI) cannot be found during a routine diagnostic investigation, but paroxysmal atrial fibrillation (PAF) could be the culprit. AIM: The objective of the study is to investigate whether advanced echocardiography improves the diagnostic approach for PAF in CI. METHODS: The study included 286 CI patients with an echocardiogram in sinus rhythm. Patients were divided by PAF occurrence (PAF: n = 86, non-PAF: n = 200). PAF was defined as 1 or more reported episodes of atrial fibrillation. Echocardiograms consisted of conventional measures, tissue Doppler imaging (TDI), and speckle tracking. TDI was performed to acquire myocardial peak velocities during systole/ventricular contraction (global s'), early diastole/ventricular filling (global e'), and late diastole/atrial contraction (global a'). Speckle tracking was performed for myocardial strain analysis, thereby retrieving global longitudinal strain and global strain rate (s, e, a) values. RESULTS: Patients with PAF exhibited significantly impaired atrial contractile measures: global a' (-7.0 cm/second versus -5.7 cm/second, P < .001) and global strain rate a (.97 second(-1) versus .81 second(-1), P < .001). Both were univariable markers of PAF, and along with age remained the only independent significant determinants of PAF after multivariable logistic regression. Area under the curve (AUC) for age, global a', and global strain rate a significantly exceeded AUC for age alone (.79 versus .76, P = .032). Cutoff values with the highest sensitivity and specificity for these 3 parameters improved the diagnostic accuracy (sensitivity = 97%, specificity = 32%, negative predictive value = 95%, and positive predictive value = 38%). CONCLUSIONS: Atrial contractile measures by advanced echocardiography are significant determinants of PAF in CI. However, there is no discriminatory power to make them clinically useful at the current moment.

Diastolic myocardial dysfunction by tissue Doppler imaging predicts mortality in patients with cerebral infarction.

Several clinical prediction score models have been investigated for predicting mortality in patients with cerebral infarction. However, none of these include echocardiographic measures. Our objective was to evaluate the prognostic value of tissue Doppler imaging (TDI) of the myocardium in patients with cerebral infarction. Two hundred forty-four patients with cerebral infarction and subsequent echocardiographic examination in sinus rhythm were identified. Using TDI in three apical projections, longitudinal mitral annular velocities were obtained in six segments. Cox regression models, C-statistics and reclassification analysis were performed for global and segmental e'. During a median follow-up of 3 years 42 patients died. Patients who died had significantly impaired systolic and diastolic function (determined by LVEF and E/e'). The risk of dying increased with decreasing global e', being approximately 13 times higher for patients in the lowest tertile compared to patients in the highest tertile (HR 13.4 [3.2;56.3], p < 0.001). Patients with significantly impaired global e' showed increased mortality after multivariable adjustment for: LVEF, E/e', age, gender, heart failure, chronic obstructive pulmonary disease, prior cerebral infarction, ischemic heart disease, cancer, hypertension, hypercholesterolemia, carotid stenosis, mitral regurgitation, liver disease and thromboembolisms (HR 1.9 [1.1;3.2]), per 1 cm/s decrease, p < 0.05). Similar pattern was seen in segmental analyses of the e'. In contrast to e', no conventional echocardiographic parameters remained independent predictors of mortality after multivariable adjustment. Diastolic myocardial dysfunction determined as e' by TDI is a significant predictor of mortality in patients with cerebral infarction. Applying this parameter can aid the prognostic assessment after cerebral infarction.

Global longitudinal strain is not impaired in type 1 diabetes patients without albuminuria: the Thousand & 1 study.

OBJECTIVES: The purpose of this study was to investigate if systolic myocardial function is reduced in all patients with type 1 diabetes (T1DM) or only in patients with albuminuria. BACKGROUND: Heart failure is a common cause of mortality in T1DM, and a specific diabetic cardiomyopathy has been suggested. It is not known whether myocardial dysfunction is a feature of T1DM per se or primarily associated with diabetes with albuminuria. METHODS: This cross-sectional study compared 1,065 T1DM patients without known heart disease from the outpatient clinic at the Steno Diabetes Center with 198 healthy control subjects. Conventional echocardiography and global longitudinal strain (GLS) by 2-dimensional speckle-tracking echocardiography was performed and analyzed in relation to normoalbuminuria (n = 739), microalbuminuria (n = 223), and macroalbuminuria (n = 103). Data were analyzed in univariable and multivariable linear regression models adjusted for confounding factors including conventional risk factors, medication, and systolic and diastolic dysfunction. Investigators were blinded to degree of albuminuria. RESULTS: Mean age was 49.5 years, 52% men, mean glycated hemoglobin 8.2% (66 mmol/mol), mean body mass index 25.5 kg/m(2), and mean diabetes duration 26.1 years. In unadjusted analyses, GLS differed significantly between T1DM patients and control subjects (p = 0.02). When stratified by degrees of albuminuria, the difference in GLS compared with control subjects was -18.8 ± 2.5% versus -18.5 ± 2.5% for normoalbuminuria (p = 0.28), versus -17.9 ± 2.7% for microalbuminuria (p = 0.001), and versus -17.4 ± 2.9% for macroalbuminuria (p < 0.001). Multivariable analyses, including clinical characteristics, diastolic and systolic dysfunction, and use of medication, did not change this relationship. CONCLUSIONS: Systolic function assessed by GLS was reduced in T1DM compared with control subjects. This difference, however, was driven solely by decreased GLS in T1DM patients with albuminuria. T1DM patients with normoalbuminuria have systolic myocardial function similar to healthy control subjects. These findings do not support the presence of specific diabetic cardiomyopathy without albuminuria.

Systolic and Diastolic Function by Tissue Doppler Imaging Predicts Mortality in Patients with Atrial Fibrillation.

AIM: Tissue Doppler Imaging (TDI) detects early signs of left ventricular dysfunction. The prognostic potential of TDI in patients with atrial fibrillation (AF) has, however, not yet been clarified. This study evaluates the prognostic value of TDI in patients with atrial fibrillation. METHODS AND RESULTS: In total, echocardiograms from 313 patients with AF during examination were analyzed offline. Longitudinal systolic velocity (s'), early diastolic velocity (e') and longitudinal displacement (LD) were measured by color TDI. During a median follow-up of 891 days, 64 patients (20%) died. TDI was significantly associated with all-cause mortality, and the risk of dying increased significantly per 1 cm/s decrease in s' (HR of 1.31, 95% CI 1.05-1.63; p=0.018) and e' (HR of 1.17, 95% CI 1.01-1.35; p=0.038) respectively, even after adjustment for age, gender, heart rate, aortic stenosis, DM and LVEF quartiles. LD also proved to be a significant predictor of outcome after multivariate adjustment (HR 1.23; 95% CI 1.05-1.44; p=0.012). The population was stratified according to high or low s' and e'. Patients with low s' and e' had more than three times the risk of mortality compared to the patients with high s' and e' (HR 3.64; 95% CI 1.83-7.26; p<0.001) and remained in significantly higher risk after adjustment for various risk factors. CONCLUSIONS: Both systolic and diastolic performance, as assessed by TDI, are strong predictors of mortality in patients with atrial fibrillation, and especially the combination of systolic and diastolic dysfunction is a significant prognostic marker.