Aortic Root Dimension Using Transthoracic Echocardiography: Results from the Copenhagen City Heart Study.

Findings regarding the relation between aortic size and risk factors are heterogeneous. This study aimed to generate new insights from a population-based adult cohort on aortic root dimensions and their association with age, anthropometric measures, and cardiac risk factors and evaluate the incidence of acute aortic events. Participants from the fifth examination round of the Copenhagen City Heart study (aged 20 to 98 years) with applicable echocardiograms and no history of aortic disease or valve surgery were included. Aorta diameter was assessed at the annulus, sinus of Valsalva, sinotubular junction, and the tubular part of the ascending aorta. The study population comprised 1,796 men and 2,316 women; mean age: 56.4 ± 17.0 and 56.9 ± 18.1 years, respectively. Men had larger aortic root diameters than women regardless of height indexing (p <0.01). Age, height, weight, systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, hypertension, diabetes, ischemic heart disease, and smoking were positively correlated with aortic sinus diameter in the crude and gender-adjusted analyses. However, after full adjustment, only height, weight, and diastolic blood pressure remained significantly positively correlated with aortic sinus diameter (p <0.001). For systolic blood pressure and pulse pressure, the correlation was inverse (p <0.001). During follow-up (median 5.4 [quartile 1 to quartile 3 4.5 to 6.3] years), the incidence rate of first-time acute aortic events was 13.6 (confidence interval 4.4 to 42.2) per 100,000 person-years. In conclusion, beyond anthropometric measures, age, and gender, diastolic blood pressure was the only cardiac risk factor that was independently correlated with aortic root dimensions. The number of aortic events during follow-up was low.

Computed tomography or chest X-ray to assess pulmonary congestion in dyspnoeic patients with acute heart failure.

AIMS: While computed tomography (CT) is widely acknowledged as superior to chest radiographs for acute diagnostics, its efficacy in diagnosing acute heart failure (AHF) remains unexplored. This prospective study included consecutive patients with dyspnoea undergoing simultaneous low-dose chest CT (LDCT) and chest radiographs. Here, we aimed to determine if LDCT is superior to chest radiographs to confirm pulmonary congestion in dyspnoeic patients with suspected AHF. METHODS AND RESULTS: An observational, prospective study, including dyspnoeic patients from the emergency department. All patients underwent concurrent clinical examination, laboratory tests, echocardiogram, chest radiographs, and LDCT. The primary efficacy measure to compare the two radiological methods was conditional odds ratio (cOR). The primary outcome was adjudicated AHF, ascertained by comprehensive expert consensus. The secondary outcome, echo-bnp AHF, was an objective AHF diagnosis based on echocardiographic cardiac dysfunction, elevated cardiac filling pressure, loop diuretic administration, and NT-pro brain natriuretic peptide > 300 pg/mL. Of 228 dyspnoeic patients, 64 patients (28%) had adjudicated AHF, and 79 patients (35%) had echo-bnp AHF. Patients with AHF were older (78 years vs. 73 years), had lower left ventricular ejection fraction (36% vs. 55%), had higher elevated left ventricular filling pressures (98% vs. 18%), and had higher NT-pro brain natriuretic peptide levels (3628 pg/mL vs. 470 pg/mL). The odds to diagnose adjudicated AHF and echo-bnp AHF were up to four times greater using LDCT (cOR: 3.89 [2.15, 7.06] and cOR: 2.52 [1.45, 4.38], respectively). For each radiologic sign of pulmonary congestion, the LDCT provided superior or equivalent results as the chest radiographs, and the interrater agreement was higher using LDCT (kappa 0.88 [95% CI: 0.81, 0.95] vs. 0.73 [95% CI: 0.63, 0.82]). As first-line imaging modality, LDCT will find one additional adjudicated AHF in 12.5 patients and prevent one false-positive in 20 patients. Similar results were demonstrated for echo-bnp AHF. CONCLUSIONS: In consecutive dyspnoeic patients admitted to the emergency department, LDCT is significantly better than chest radiographs in detecting pulmonary congestion.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Aorta-right ventricular fistula after transcatheter aortic valve replacement.

Aortic-to-right ventricle fistula is a rare complication after transcatheter aortic valve implantation (TAVI). In this case report, an 87-year-old male was admitted with signs of congestion six weeks after TAVI. Two days later, he developed severe epigastric and back pain, elevated D-dimer, lactic acidosis and renal failure. Transthoracic echocardiography revealed a progressing aortic-to-right ventricle fistula which in retrospect had been present since the TAVI-procedure. The patient died despite supportive treatment.

Left atrial late gadolinium enhancement in patients with ischaemic stroke.

AIMS: To evaluate the extent of left atrial (LA) fibrosis in patients with a recent stroke without atrial fibrillation and controls without established cardiovascular disease. METHODS AND RESULTS: This prospectively designed study used cardiac magnetic resonance to detect LA late gadolinium enhancement as a proxy for LA fibrosis. Between 2019 and 2021, we consecutively included 100 patients free of atrial fibrillation with recent ischaemic stroke (<30 days) and 50 age- and sex-matched controls. LA fibrosis assessment was achieved in 78 patients and 45 controls. Blinded to the cardiac magnetic resonance results, strokes were adjudicated according to modified Trial of Org 10172 in Acute Stroke Treatment classification as undetermined aetiology (n = 42) or as attributable to large- or small-vessel disease (n = 36). Patients with stroke had a larger extent of LA fibrosis [6.9%, interquartile range (IQR) 3.6-15.4%] than matched controls (4.2%, IQR 2.3-7.5%; P = 0.007). No differences in LA fibrosis were observed between patients with stroke of undetermined aetiology and those with large- or small-vessel disease (6.6%, IQR 3.8-16.0% vs. 6.9%, IQR 3.4-14.6%; P = 0.73). CONCLUSION: LA fibrosis was more extensive in patients with stroke than in age- and sex-matched controls. A similar extent of LA fibrosis was observed in patients with stroke of undetermined aetiology and stroke classified as attributable to large- or small-vessel disease. Our findings suggest that LA structural abnormality is more frequent in patients with stroke than in controls independent of aetiological classification.

Remote dielectric sensing to detect acute heart failure in patients with dyspnoea: a prospective observational study in the emergency department.

Aims: Remote dielectric sensing (ReDS) enables quick estimation of lung fluid content. To examine if ReDS is superior to other methods in detecting acute heart failure. Methods and results: We included consecutive patients with dyspnoea from the emergency departments at Bispebjerg Hospital, Copenhagen, and performed ReDS, low-dose chest computed tomography (CT), echocardiogram, lung ultrasound, NT-Pro-brain natriuretic peptide (NT-proBNP), and a Boston score evaluation (chest X-ray and clinical signs). ReDS values >35% were used as a cut-off to diagnose pulmonary congestion. Acute heart failure was adjudicated by experts' review of health records but independently of ReDS values. Sub-analyses investigated ReDS in acute heart failure patients with congestion on CT. We included 97 patients within a median of 4.8 h from admittance: 25 patients (26%) were ReDS-positive and 39 (40%) had adjudicated acute heart failure (21 with and 18 without CT congestion). Heart failure patients had median ReDS 33%, left ventricular ejection fraction 48%, and NT-proBNP 2935 ng/L. A positive ReDS detected heart failure with 46% sensitivity, 88% specificity, and 71% accuracy. The AUC for ReDS was like the Boston score (P = 0.88) and the lung ultrasound score (P = 0.74). CT-congested heart failure patients had higher ReDS values than patients without heart failure (median 38 vs. 28%, P < 0.001). Heart failure patients without CT-congestion had ReDS values like patients without heart failure (mean 30 vs. 28%, P = 0.07). Conclusion: ReDS detects acute heart failure similarly to the Boston score and lung ultrasound score, and ReDS primarily identifies the acute heart failure patients who have congestion on a chest CT.

Left Atrial Volumes and Function, and Long-Term Incidence of Ischemic Stroke in the General Population.

Background Left atrial (LA) volumes and emptying fraction in the general population may address structural and functional aspects of atrial cardiomyopathy associated with long-term risk of ischemic stroke in the absence of atrial fibrillation or prior stroke. We investigated the association between LA volumes and function and ischemic stroke. Methods and Results In a community-based cohort, we measured LA minimal volume, LA maximal volume, and LA emptying fraction by transthoracic echocardiography. The primary end point was ischemic stroke. Participants with known atrial fibrillation or prior ischemic stroke were excluded, which resulted in 1866 participants. The mean age was 58±16 years, and 57% were women. During a median follow-up of 16.5 years (interquartile range: 11.4-16.8 years), 176 (9.4%) ischemic strokes occurred. In multivariable cause-specific regression models and competing risk models with death as a competing risk, LA emptying fraction was associated with ischemic stroke (hazard ratio [HR], 1.14 per 10% decrease [95% CI, 1.02-1.28]) and (subdistribution HR, 1.14 [95% CI, 1.01-1.29]). This association remained when adjusting for participants who developed atrial fibrillation during follow-up (HR, 1.12 per 10% decrease [95% CI, 1.00-1.26]). Indexed LA volumes were not associated with ischemic stroke in the same models. LA emptying fraction and indexed LA volumes were not associated with all-cause mortality. Conclusions Lower LA emptying fraction measured by transthoracic echocardiography was associated with future ischemic stroke independently of incident atrial fibrillation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02993172.

Atrial cardiomyopathy in patients with ischaemic stroke: a cross-sectional and prospective cohort study-the COAST study.

INTRODUCTION: Despite workup for the aetiology of ischaemic stroke, about 25% of cases remain unexplained. Paroxysmal atrial fibrillation is typically suspected but often not detected. Even if atrial fibrillation (AF) is detected, the quantitative threshold of clinically relevant AF remains unclear. Emerging evidence suggests that left atrial (LA) functional and structural abnormalities may convey a risk of ischaemic stroke in which AF is only one of several features. These abnormalities have been termed 'atrial cardiomyopathy'. This study uses cardiac magnetic resonance (CMR) to evaluate atrial cardiomyopathy among patients with stroke of undetermined aetiology compared with those with an attributable mechanism and controls without established cardiovascular disease. METHODS AND ANALYSIS: This cross-sectional and prospective cohort study included 100 patients with recent ischaemic stroke and 50 controls with no established cardiovascular disease. The study will assess LA structural and functional abnormalities with CMR. Inclusion began in March 2019, and follow-up is planned to be complete in January 2023. There are two scheduled follow-ups: (1) 18 months after individual inclusion, counting from the index diagnostic MRI of the brain, (2) end of study follow-up at 18 months after inclusion of the last patient, assessing the incidence of recurrent ischaemic stroke, AF and cardiovascular death. The primary endpoint is the extent of CMR-assessed atrial fibrosis in the LA at baseline. The study is powered to detect a difference of 6% fibrosis between stroke of undetermined aetiology and stroke of known mechanism with a SD of 9%, a significance level of 0.05, and power of 80%. ETHICS AND DISSEMINATION: This study has been approved by the Danish National Committee on Health Research Ethics (H-18055313). All participants in the study signed informed consent. Results from the study will be published in peer-reviewed journals regardless of the outcome. TRIAL REGISTRATION NUMBER: NCT03830983.

Chest computed tomography features of heart failure: A prospective observational study in patients with acute dyspnea.

BACKGROUND: Pulmonary congestion is a key component of heart failure (HF) that chest computed tomography (CT) can detect. However, no guideline describes which of many anticipated CT signs are most associated with HF in patients with undifferentiated dyspnea. METHODS: In a prospective observational single-center study, we included consecutive patients ≥ 50 years admitted with acute dyspnea to the emergency department. Patients underwent immediate clinical examination, blood sampling, echocardiography, and CT. Two radiologists independently evaluated all images. Acute HF (AHF) was adjudicated by an expert panel blinded to radiology images. LASSO and logistic regression identified the independent CT signs of AHF. RESULTS: Among 232 patients, 102 (44%) had AHF. Of 18 examined CT signs, 5 were associated with AHF (multivariate odds ratio, 95% confidence interval): enlarged heart (20.38, 6.86-76.16), bilateral interlobular thickening (11.67, 1.78-230.99), bilateral pleural effusion (6.39, 1.98-22.85), and increased vascular diameter (4.49, 1.08-33.92). Bilateral ground-glass opacification (2.07, 0.95-4.52) was a consistent fifth essential sign, although it was only significant in univariate analysis. Eighty-eight (38%) patients had none of the five CT signs corresponding to a 68% specificity and 86% sensitivity for AHF, while two or more of the five CT signs occurred in 68 (29%) patients, corresponding to 97% specificity and 67% sensitivity. A weighted score based on these five CT signs had an 0.88 area under the curve to detect AHF. CONCLUSIONS: Five CT signs seem sufficient to assess the risk of AHF in the acute setting. The absence of these signs indicates a low probability, one sign makes AHF highly probable, and two or more CT signs mean almost certain AHF.

Excessive supraventricular ectopic activity and risk of incident atrial fibrillation in a consecutive population referred to ambulatory cardiac monitoring.

BACKGROUND: Excessive supraventricular ectopic activity (ESVEA), defined as ≥720 premature atrial contractions (PAC) per day or any runs of ≥20 PACs, has been proposed as a surrogate marker for paroxysmal atrial fibrillation (PAF). OBJECTIVE: We aimed to estimate the prognostic impact of ESVEA on the future development of PAF in consecutive patients referred to ambulatory cardiac monitoring. METHODS: The cohort consists of a population with comorbidities referred to 48-hour ambulatory electrocardiogram aged 30-98 (n = 1316) between 2009 and 2011. After exclusion of known or current atrial fibrillation (AF) (n = 527) and patients with pacemakers (n = 7), 782 patients were included, with a median follow-up of 8.1 years. Events of incident AF and death were retrieved from patient records. RESULTS: Mean age was 58.6 ± 15.5 years and 56.5% were women. A total of 101 patients had ESVEA at baseline (12.9%). During follow-up, 69 (8.9%) developed incidental AF. Twenty-three patients with ESVEA developed AF (23%). Incidence rate of AF in patients with and without ESVEA was 37.1/1000 person-years and 9.1 per 1000 person-years, respectively (P < .001). ESVEA was associated with incident AF after adjustment for potential confounders in Cox regression analysis (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.40-4.09) and in competing risk analysis with death as competing risk (subdistribution HR: 2.35; 95% CI: 1.30-4.17). CONCLUSION: ESVEA increases the risk of incident AF substantially in a population referred to ambulatory cardiac monitoring.

Myocardial CT perfusion compared with transthoracic Doppler echocardiography in evaluation of the coronary microvascular function: An iPOWER substudy.

BACKGROUND: A significant number of women with angina and no obstructive coronary artery disease (CAD; <50% stenosis) have coronary microvascular dysfunction (CMD) which carries an adverse cardiovascular prognosis. Coronary microvascular function can be evaluated by transthoracic Doppler echocardiography (TTDE) as a coronary flow velocity reserve (CFVR) and by static CT myocardial perfusion (CTP) as a myocardial perfusion reserve (MPR). Whether these methods are correlated is not known. We assessed the correlation between CFVR and MPR and investigated whether women with angina, CMD and no obstructive CAD have reduced MPR compared with asymptomatic women. METHODS: Static CTP with adenosine-induced vasodilation and TTDE of the left anterior descending artery with dipyridamole-induced vasodilation were successfully performed and analysed in 99 women with stable angina and no obstructive CAD and 33 asymptomatic women with no obstructive CAD. CMD was defined as CFVR < 2. RESULTS: Correlation between rate-pressure product corrected MPR and CFVR was weak but significant (r = .23; p = .007). MPR was highest among asymptomatic women with normal CFVR (median [interquartile range; IQR] 158 [145-181] %). Symptomatic women with normal CFVR had reduced MPR (148 [134-162] %; age-adjusted p < .001); however, the lowest MPR was found in symptomatic women with CMD (140 [129-164] %; age-adjusted p < .001), independent of cardiovascular risk factors and haemodynamic parameters (p = .017). CONCLUSION: Women with angina, CMD and no obstructive CAD had markedly diminished MPR compared with asymptomatic women. Correlation between CFVR and MPR was weak, suggesting that CTP and TTDE are not interchangeable for detection of CMD.

The impact of cardiovascular risk factors on global longitudinal strain over a decade in the general population: the copenhagen city heart study.

Global longitudinal strain (GLS) declines throughout adult-life as the LV remodels and adapts. Information on the impact of cardiac risk factors such as male sex, obesity, smoking status, hypertension, hypercholesterolemia, and diabetes on GLS. over time has not yet been investigated. The present prospective longitudinal study included 689 participants of the 4th and 5th Copenhagen City Heart Study who had GLS measured at both timepoints. Mean age was 51 years and 45% were male. All participants underwent two echocardiographic examinations median 10.4 (IQR: 10.2, 10.9) years apart. Average decline in GLS during follow-up was -0.7%. High age, male sex, high body mass index, and mean arterial blood pressure (MAP) proved to be significantly associated with an accelerated decline in GLS. In a multivariable regression model including all the investigated cardiovascular risk factors, age (stand. ß-coef. = -0.10, P = 0.005), male sex (stand. ß-coef. = -0.16, P < 0.001), and MAP (stand. ß-coef. = -0.07, P = 0.009) were independent predictors of an accelerated decline in GLS during a 10-year period. Finally, the investigated risk factors had different regional impact after the same multivariable adjustments. Male sex had a significant impact on changes in longitudinal strain at the apical, mid-wall and basal segments, meanwhile MAP and age only accelerated changes in the mid-wall and basal longitudinal strain. In the general population age, male sex, and MAP are independent predictors of an accelerated decline in GLS over a 10-year period. Furthermore, MAP, male sex and age had different regional impact.

Relationship between left atrial strain, diastolic dysfunction and subclinical atrial fibrillation in patients with cryptogenic stroke: the SURPRISE echo substudy.

Paroxysmal atrial fibrillation (PAF) may be the cause of a substantial part of cryptogenic strokes (CS). Echocardiography could assist risk stratification for PAF to select patients in need of prolonged rhythm monitoring. We aimed to assess the value of left atrial (LA) strain and a revised diastolic dysfunction (DDF) model with LA strain for predicting PAF. This was a prospective study of 56 CS patients who had a cardiac monitor implanted for 3 year monitoring for PAF, and an echocardiogram performed prior to monitoring. Conventional echocardiography, global longitudinal strain (GLS) and LA strain were performed. LA speckle tracking provided the LA reservoir strain (LAs). Patients were stratified into high versus low LAs by ROC curves (28.2%), and this cut-off was used to refine DDF grading. During follow-up of median 20 months, 13 (23%) patients were diagnosed with PAF. No conventional echocardiographic parameters differed between patients who developed PAF and those without PAF. However, LAs was significantly impaired in PAF patients (LAs: 30 vs. 27% for non-PAF and PAF, p = 0.046). Low LAs significantly predicted PAF independent of LA volume and GLS [OR 5.88 (1.30; 26.55), p = 0.021]. Revised DDF grading significantly predicted PAF, even when adjusted for the CHADS2 risk-score (OR 1.88 [1.01;3.50], per increase in DDF grade, p for trend = 0.047), which was not the case for conventional DDF grading. In conclusion, LAs associates with PAF independent of GLS and LA size, and may be used to improve the performance of DDF grading for identifying PAF in CS patients.

Overlap between angina without obstructive coronary artery disease and left ventricular diastolic dysfunction with preserved ejection fraction.

BACKGROUND: A link between angina with no obstructive coronary artery disease (CAD) and heart failure with preserved left ventricular ejection fraction has been proposed, but evidence in support of this is lacking. In a cross-sectional study, we investigated whether left ventricular diastolic function in women with angina pectoris and no obstructive CAD differed from a reference population. METHODS: We included 956 women with angina and <50% coronary artery stenosis at invasive coronary angiography. Women with cardiovascular risk factors, but no history of chest pain or cardiac disease served as controls (n = 214). Left ventricular diastolic function was assessed by transthoracic echocardiography. RESULTS: The women with angina were slightly older, had higher body mass index, higher heart rate, and more had diabetes compared with controls while systolic blood pressure was lower. In age-adjusted analyses, angina patients had significantly lower E/A (Estimated difference -0.13, 95% CI: -0.17; -0.08), higher left ventricular mass index (5.73 g/m2, 95% CI: 3.71; 7.75), left atrial volume index (2.34 ml/m2, 95% CI: 1.23; 3.45) and E/e' (0.68, 95% CI: 0.30; 1.05) and a larger proportion had higher estimated left ventricular filling pressure (17% versus 6%, p = 0.001). No between group differences were seen for e' or deceleration time. After adjustment for known cardiovascular risk factors, between group differences for echocardiographic parameters remained statistically significant. CONCLUSIONS: Patients with angina and no obstructive CAD had a more impaired left ventricular diastolic function compared with an asymptomatic reference population. This suggests some common pathophysiological pathway between the two syndromes.

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.

Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina: A randomized placebo-controlled trial.

OBJECTIVE: Studies have suggested a beneficial effect of angiotensin-converting enzyme (ACE) inhibition. To explore whether the ACE inhibitor ramipril has a direct effect on the microvasculature beyond the blood pressure (BP) lowering effect, we investigated whether ramipril improved coronary microvascular function in normotensive women with coronary microvascular dysfunction (CMD). METHODS: We included 63 normotensive women with angina, no epicardial stenosis>50% and CMD defined as a coronary flow velocity reserve (CFVR)<2.2 assessed by adenosine stress-echocardiography in a randomized double-blinded, superiority trial with 1:1 allocation to placebo or ramipril (maximum dose 10 mg depending on blood pressure) for 24±6 weeks. Primary outcome was CFVR. Secondary outcomes were left ventricular systolic and diastolic function and symptoms evaluated by Seattle Angina Questionnaire (clinicaltrials.gov, NCT02525081). RESULTS: Follow-up was available on 55 patients. BP remained unchanged during treatment in both groups. CFVR improved in both the ramipril (p = 0.004) and placebo group (p = 0.026) with no difference between groups (p = 0.63). Symptoms improved in both groups with no significant between-group differences. No changes were detected in parameters of systolic and diastolic function. No serious adverse reactions were reported. CONCLUSIONS: In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction.

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.

Usefulness of left ventricular speckle tracking echocardiography and novel measures of left atrial structure and function in diagnosing paroxysmal atrial fibrillation in ischemic stroke and transient ischemic attack patients.

Asymptomatic paroxysmal atrial fibrillation (PAF) is often assumed to be the cause of cryptogenic ischemic strokes (IS) and transient ischemic attacks (TIA). We examined the usefulness of measures obtained by 2D speckle tracking echocardiography and novel left atrial measurements, in the diagnosis of PAF in patients with IS and TIA. We retrospectively included 205 patients who after acute IS or TIA underwent an echocardiogram in sinus rhythm. Patients were designated as PAF-patients if they had one or more reported incidents of AF before or after their echocardiographic examination. None of the conventional echocardiographic parameters were significantly associated with PAF. Of the speckle tracking measurements, only early diastolic strain rate (0.7±0.2 s-1 vs. 0.8±0.3 s-1, p = 0.048) and global longitudinal displacement (GLD) (3.15 ± 1.40 mm vs. 3.87 ± 1.56 mm, p = 0.007) proved significantly different. Of the left atrial parameters both minimal and maximal left atrium volume divided by left ventricular length (min LAV/LVL and max LAV/LVL, respectively) were significantly impaired (min LAV/LVL: 3.7 ± 2.1 cm2 vs. 2.8 ± 1.11 cm2, p = 0.012; max LAV/LVL: 6.6 ± 3.1 cm2 vs. 5.6 ± 1.7 cm2, p = 0.012). GLD, min max LAV/LVL proved significant after adjustment for age, gender, CHA2DS2-VASc and NIHSS. By combining information regarding age, GLD, min and max LAV/LVL the diagnostic accuracy of PAF improved, resulting in a significantly increased area under the curve (p = 0.037). In patients with IS and TIA GLD, min and max LAV/LVL were independently associated with the presence of PAF.

Transthoracic Doppler echocardiography compared with positron emission tomography for assessment of coronary microvascular dysfunction: The iPOWER study.

BACKGROUND: Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR. METHODS: From a cohort of women with angina and no obstructive coronary artery stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals. RESULTS: MBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR) was 2.68 (2.29-3.10) and CFVR (IQR) was 2.31 (1.89-2.72). Pearson's correlation coefficient was 0.36 (p<0.01). Limits of agreement (2·standard deviation) assessed by the Bland-Altman (confidence interval, CI) method was 1.49 (1.29;1.69) and unaffected by time-interval between examinations. Results were similar when adjusting for rate pressure product or focusing on perfusion of the left anterior descending artery region. Limits of agreement (CI) for repeated CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68) and 0.48 (0.22; 0.74), respectively. CONCLUSION: CFVR had a good repeatability, but the agreement between CFVR and MBFR was modest. Divergence could be due to methodology differences; TTDE estimates flow velocities whereas PET estimates myocardial blood flow.