High Resting Coronary Flow Velocity by Echocardiography Is Associated With Worse Survival in Patients With Chronic Coronary Syndromes.

BACKGROUND: Resting coronary flow velocity (CFV) in the mid-distal left anterior descending coronary artery can be easily assessed with transthoracic echocardiography. In this observational study, the authors sought to assess the relationship between resting CFV, CFV reserve (CFVR), and outcome in patients with chronic coronary syndromes. METHODS AND RESULTS: In a prospective multicenter study design, the authors retrospectively analyzed 7576 patients (age, 66±11 years; 4312 men) with chronic coronary syndromes and left ventricular ejection fraction ≥50% referred for dipyridamole stress echocardiography. Recruitment (years 2003-2021) involved 7 accredited laboratories, with interobserver variability <10% for CFV measurement at study entry. Baseline peak diastolic CFV was obtained by pulsed-wave Doppler in the mid-distal left anterior descending coronary artery. CFVR (abnormal value ≤2.0) was assessed with dipyridamole. All-cause death was the only end point. The mean CFV of the left anterior descending coronary artery was 31±12 cm/s. The mean CFVR was 2.32±0.60. During a median follow-up of 5.9±4.3 years, 1121 (15%) patients died. At multivariable analysis, resting CFV ≥32 cm/s was identified by a receiver operating curve as the best cutoff and was independently associated with mortality (hazard ratio [HR], 1.24 [95% CI, 1.10-1.40]; P<0.0001) together with CFVR ≤2.0 (HR, 1.78 [95% CI, 1.57-2.02]; P<0.0001), age, diabetes, history of coronary surgery, and left ventricular ejection fraction. When both CFV and CFVR were considered, the mortality rate was highest in patients with resting CFV ≥32 cm/s and CFVR ≤2.0 and lowest in patients with resting CFV <32 cm/s and CFVR >2.0. CONCLUSIONS: High resting CFV is associated with worse survival in patients with chronic coronary syndromes and left ventricular ejection fraction ≥50%. The value is independent and additive to CFVR. The combination of high resting CFV and low CFVR is associated with the worst survival.

Multiple Phenotypes of Chronic Coronary Syndromes Identified by ABCDE Stress Echocardiography.

BACKGROUND: Regional wall motion abnormality is considered a sensitive and specific marker of ischemia during stress echocardiography (SE). However, ischemia is a multifaceted entity associated with either coronary artery disease (CAD) or angina with normal coronary arteries, a distinction difficult to make using a single sign. The aim of this study was to evaluate the diagnostic potential of the five-step ABCDE SE protocol for CAD detection. METHODS: From the 2016-2022 Stress Echo 2030 study data bank, 3,229 patients were selected (mean age, 66 ± 12 years; 2,089 men [65%]) with known CAD (n = 1,792) or angina with normal coronary arteries (n = 1,437). All patients were studied using both the ABCDE SE protocol and coronary angiography, within 3 months. In step A, regional wall motion abnormality is assessed; in step B, B-lines and diastolic function; in step C, left ventricular contractile reserve; in step D, coronary flow velocity reserve in the left anterior descending coronary artery; and in step E, heart rate reserve. RESULTS: SE response ranged from a score of 0 (all steps normal) to a score of 5 (all steps abnormal). For CAD, rates of abnormal results were 347 for step A (19.4%), 547 (30.5%) for step B, 720 (40.2%) for step C, 615 (34.3%) for step D, and 633 (35.3%) for step E. For angina with normal coronary arteries, rates of abnormal results were 81 (5.6%) for step A, 429 (29.9%) for step B, 432 (30.1%) for step C, 354 (24.6%) for step D, and 445 (31.0%) for step E. The dominant "solitary phenotype" was step B in 109 patients (9.1%). CONCLUSIONS: Stress-induced ischemia presents with a wide range of diagnostic phenotypes, highlighting its complex nature. Using a comprehensive approach such as the advanced ABCDE score, which combines multiple markers, proves to be more valuable than relying on a single marker in isolation.

"Bronchogenic cyst impersonating a pericardial lesion": A case report.

A 32-year-old female presented with palpitations and chest discomfort. The patient had a history of pericardiotomy due to pericardial effusion. Multimodal imaging, including echocardiography, cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) showed a single mass in the pericardium as the cause of the symptoms. Furthermore, its location and potential complications were accurately defined. The patient underwent a successful surgical resection of the pericardial cyst, microscopic histopathological examination was compatible with a bronchogenic cyst, a very rare congenital malformation. The article discusses the rarity of bronchogenic cysts in the pericardium and the importance of accurate diagnosis and appropriate treatment.

Sinus node dysfunction during transcatheter assessment and stent correction of sinus venosus atrial septal defects.

Covered stent correction of a superior sinus venosus atrial septal defect is increasingly performed as an alternative to surgical repair. While sinus node dysfunction requiring pacemaker implantation may be required after surgical repair, this has not been previously reported after covered stent implantation. We reviewed the experience in two interventional centers. Balloon inflation in the superior vena cava was used to confirm the anomalous pulmonary vein drainage would be unobstructed after stent implantation. During balloon testing in 62 consecutive patients, we assessed gradients across the pulmonary vein to left atrium while monitoring the rhythm. We observed the outcomes after covered stent correction in 51 patients. In a single patient, significant bradycardia and pauses developed on repeat balloon testing and the procedure was abandoned without stent implantation. In another patient, there was no sign of sinus node dysfunction during balloon testing but several hours after stent implantation, the patient became symptomatic from sinus bradycardia and pauses and had a pacemaker implanted 3 days later. Over a year later there are some signs of improvement in sinus node function. While sinus node dysfunction has not been described previously during balloon testing or after stent implantation, this report demonstrates for the first time that it may occur. Larger registries are therefore required to monitor for this uncommon complication.

Pulmonary Congestion During Exercise Stress Echocardiography in Ischemic and Heart Failure Patients.

BACKGROUND: Lung ultrasound detects pulmonary congestion as B-lines at rest, and more frequently, during exercise stress echocardiography (ESE). METHODS: We performed ESE plus lung ultrasound (4-site simplified scan) in 4392 subjects referred for semi-supine bike ESE in 24 certified centers in 9 countries. B-line score ranged from 0 (normal) to 40 (severely abnormal). Five different populations were evaluated: control subjects (n=103); chronic coronary syndromes (n=3701); heart failure with reduced ejection fraction (n=395); heart failure with preserved ejection fraction (n=70); ischemic mitral regurgitation ≥ moderate at rest (n=123). In a subset of 2478 patients, follow-up information was available. RESULTS: During ESE, B-lines increased in all study groups except controls. Age, hypertension, abnormal ejection fraction, peak wall motion score index, and abnormal heart rate reserve were associated with B-lines in multivariable regression analysis. Stress B lines (hazard ratio, 2.179 [95% CI, 1.015-4.680]; P=0.046) and ejection fraction <50% (hazard ratio, 2.942 [95% CI, 1.268-6.822]; P=0.012) were independent predictors of all-cause death (n=29 after a median follow-up of 29 months). CONCLUSIONS: B-lines identify the pulmonary congestion phenotype at rest, and more frequently, during ESE in ischemic and heart failure patients. Stress B-lines may help to refine risk stratification in these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03049995.

Mitral valve prolapse in patients with atrial septal defect: A quantitative three-dimensional echocardiographic analysis.

INTRODUCTION AND OBJECTIVES: Mitral valve (MV) prolapse is highly prevalent in patients with atrial septal defect (ASD). Abnormal left ventricular geometry has been proposed as the main mechanism of MV prolapse in ASD, however, the changes in the morphology of the MV apparatus remain to be clarified. Our aim was to assess the MV geometry in patients with ASD and MV prolapse. METHODS: We evaluated 99 patients (73% female, median age 40 years) with ASD who underwent a three-dimensional transesophageal echocardiogram. Three-dimensional analysis of the MV was done using dedicated automated software. Transthoracic echocardiographic parameters were assessed post ASD closure in 28 patients. RESULTS: MV prolapse was found in 39% of patients. Although smaller left ventricular dimensions and greater interatrial shunt were found in patients with MV prolapse compared with those without prolapse, there was no difference in the subvalvular parameters. MV prolapse was associated with larger mitral anterior-posterior diameter, anterolateral-posteromedial diameter, anterior perimeter, posterior perimeter, total perimeter, and anterior leaflet area (all p < 0.05). Mitral regurgitation was more frequent in patients with MV prolapse (80 vs. 48%, p = 0.002). CONCLUSIONS: In patients with ASD, the main mechanism of MV prolapse is the presence of an organic primary process of the MV apparatus (excessive anterior mitral leaflet tissue and mitral annular enlargement).

Postoperative intermittent dysfunction of mitral valve prosthesis of unclear etiology identified by three-dimensional echocardiography.

A 56-year-old patient with rheumatic heart disease and atrial fibrillation underwent mitral valve replacement with a mechanical prosthesis. The 3D perioperative echocardiogram showed an intermittent immobile medial disk without hemodynamic repercussion in the intensive care unit. The patient was taken back to the operating room and surgeons could not identify the cause. An enlarged left atrium and the size of the prosthetic valve was thought to have precipitated this condition. The heart team decided a biological prosthetic valve replacement would be performed. This case emphasizes the important role of the perioperative 3D echocardiogram in the detection of immediate surgical complications.

Vasodilator Strain Stress Echocardiography in Suspected Coronary Microvascular Angina.

Background: In patients with Ischemia and non-obstructive coronary artery stenosis (INOCA) wall motion is rarely abnormal during stress echocardiography (SE). Our aim was to determine if patients with INOCA and reduced coronary flow velocity reserve (CVFR) have altered cardiac mechanics using two-dimensional speckle-tracking echocardiography (2DSTE) during SE. Methods: In a prospective, multicenter, international study, we recruited 135 patients with INOCA. Overall, we performed high dose (0.84 mg/kg) dipyridamole SE with combined assessment of CVFR and 2DSTE. The population was divided in patients with normal CVFR (>2, group 1, n = 95) and abnormal CVFR (≤2, group 2, n = 35). Clinical and 2DSTE parameters were compared between groups. Results: Feasibility was high for CFVR (98%) and 2DSTE (97%). A total of 130 patients (mean age 63 ± 12 years, 67 women) had complete flow and strain data. The two groups showed similar 2DSTE values at rest. At peak SE, Group 1 patients showed lower global longitudinal strain (p < 0.007), higher mechanical dispersion (p < 0.0005), lower endocardial (p < 0.001), and epicardial (p < 0.0002) layer specific strain. Conclusions: In patients with INOCA, vasodilator SE with simultaneous assessment of CFVR and strain is highly feasible. Coronary microvascular dysfunction is accompanied by an impairment of global and layer-specific deformation indices during stress.

Left atrial volume changes during exercise stress echocardiography in heart failure and hypertrophic cardiomyopathy.

OBJECTIVE: We aimed to assess feasibility and functional correlates of left atrial volume index (LAVI) changes during exercise stress echocardiography (ESE). METHODS: ESE on a bike or treadmill was performed in 363 patients with heart failure with preserved ejection fraction (HFpEF, n = 173), reduced ejection fraction (HFrEF, n = 59), or hypertrophic cardiomyopathy (HCM, n = 131). The LAVI stress-rest increase ≥6.8 ml/m2 was defined as dilation. RESULTS: LAVI measurements were feasible in 100%. LAVI did not change in HFrEF being at rest 32 (25-45) vs at stress 36 (24-54) ml/m2, P = NS and in HCM at rest 35 (26-48) vs at stress 38 (28-48) ml/m2, P = NS, whereas it decreased in HFpEF from 30 (24-40) to 29 (21-37) ml/m2 at stress, P = 0.007. LA dilation occurred in 107 (30%) patients (27% with treadmill vs 33% with bike ESE, P = NS): 26 with HFpEF (15%), 26 with HFrEF (44%), and 55 with HCM (42%) with P < 0.001 for HFrEF and HCM vs HFpEF. A multivariate analysis revealed as the predictors for LAVI dilation E/e' > 14 at rest with odds ratio (OR) 4.4, LVEF <50% with OR 2.9, and LAVI at rest <35 ml/m2 with OR 2.7. CONCLUSION: The LAVI assessment during ESE was highly feasible and dilation equally frequent with a treadmill or bike. LA dilation was three-fold more frequent in HCM and HFrEF and could be predicted by increased resting E/e' and impaired EF as well as smaller baseline LAVI.

Feasibility and value of two-dimensional volumetric stress echocardiography.

BACKGROUND: Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). METHODS: We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). RESULTS: Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. CONCLUSIONS: Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Homozygous Fukutin Missense Mutation in Two Mexican Siblings with Dilated Cardiomyopathy

ABSTRACT Background: Fukuyama congenital muscular dystrophy (FCMD) is the most common form of a group of autosomal recessive disorders characterized by altered α-dystroglycan glycosylation and caused by FKTN gene mutations. However, mutations of this gene may cause a broad range of phenotypes, including Walker-Warburg syndrome, muscle-brain-eye disease, FCMD, limb-girdle muscular dystrophy without mental retardation, and cardiomyopathy with no or minimal skeletal muscle weakness. Objective: Our purpose was to describe two siblings who died at a young age with dilated cardiomyopathy (DCM), no muscle weakness, or atrophy, and were homozygous for a FKTN missense mutation. Methods: Site-directed next-generation sequencing (NGS) was performed. Pathogenicity of variants of interest was established according to the American College of Medical Genetics (ACMG) criteria, and all available first-degree relatives were screened for mutations by Sanger sequencing. Results: NGS revealed a homozygous FKTN variant in the index case (p.Gly424Ser, rs752358445), classified as likely pathogenic by ACMG criteria. Both parents and an unaffected brother were heterozygous carriers. Since the siblings had no apparent skeletal muscle weakness or central nervous system involvement, FKTN mutations were not initially suspected. Conclusions: This is the first report demonstrating that heterozygous individuals for the FKTN p.Gly424Ser mutation were healthy, while two homozygous brothers suffered severe DCM, strongly suggesting that this FKTN mutation is a rare cause of autosomal recessive DCM.

Right Ventricular Longitudinal Strain Predicts Low-Cardiac- Output Syndrome After Surgical Aortic Valve Replacement in Patients With Preserved and Mid-range Ejection Fraction.

OBJECTIVES: The aim of this study was to analyze whether right ventricular free wall longitudinal strain (RVFWSL) could be a predictor of low-cardiac-output syndrome (LCOS) after surgical aortic valve replacement (SAVR) in patients with left ventricular ejection fraction ≥40%. DESIGN: Prospective, observational study. SETTING: The study was conducted at a third level university hospital. PARTICIPANTS: The study comprised 75 patients with severe aortic stenosis and LVEF ≥40% who underwent SAVR. The primary outcome was the occurrence of LCOS, and secondary outcomes were in-hospital mortality, hospital stay, or vasoplegic syndrome. INTERVENTIONS: Patients were divided into two groups (LCOS and no LCOS), and RVFWSL was analyzed to determine whether it is a predictor for LCOS. In addition, a receiver operating characteristic curve also was constructed, and the best cutoff value to predict LCOS was found. Furthermore, the reproducibility of RVFWSL measurements was evaluated. MEASUREMENT AND MAIN RESULTS: The incidence of LCOS was 20% in the present study's cohort. After multivariate analysis, cross-clamp time (odds ratio 1.06, 95% confidence interval 1.02-1.11; p = 0.002) and RVFWSL (odds ratio 1.41, 95% confidence interval 1.07-1.87; p = 0.015) were the only predictors of LCOS. However, RVFWSL did not show association with secondary outcomes (p > 0.05 for all). The area under the curve of RVFWSL to predict LCOS was 0.75, and the best cutoff value was -17.3%, with a sensitivity of 86.7% and specificity of 61.7%. CONCLUSIONS: RVFWSL seems to be a predictor of LCOS in patients with severe aortic stenosis and LVEF ≥40% undergoing SAVR. RVFWSL less than -17.3% may identify patients at increased risk for LCOS.

Feasibility and functional correlates of left atrial volume changes during stress echocardiography in chronic coronary syndromes.

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12 years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = - 0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8 ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293-5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111-4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

Homozygous Fukutin Missense Mutation in Two Mexican Siblings with Dilated Cardiomyopathy.

BACKGROUND: Fukuyama congenital muscular dystrophy (FCMD) is the most common form of a group of autosomal recessive disorders characterized by altered α-dystroglycan glycosylation and caused by FKTN gene mutations. However, mutations of this gene may cause a broad range of phenotypes, including Walker-Warburg syndrome, muscle-brain-eye disease, FCMD, limbgirdle muscular dystrophy without mental retardation, and cardiomyopathy with no or minimal skeletal muscle weakness. OBJECTIVE: Our purpose was to describe two siblings who died at a young age with dilated cardiomyopathy (DCM), no muscle weakness, or atrophy, and were homozygous for a FKTN missense mutation. METHODS: Site-directed next-generation sequencing (NGS) was performed. Pathogenicity of variants of interest was established according to the American College of Medical Genetics (ACMG) criteria, and all available first-degree relatives were screened for mutations by Sanger sequencing. RESULTS: NGS revealed a homozygous FKTN variant in the index case (p.Gly424Ser, rs752358445), classified as likely pathogenic by ACMG criteria. Both parents and an unaffected brother were heterozygous carriers. Since the siblings had no apparent skeletal muscle weakness or central nervous system involvement, FKTN mutations were not initially suspected. CONCLUSIONS: This is the first report demonstrating that heterozygous individuals for the FKTN p.Gly424Ser mutation were healthy, while two homozygous brothers suffered severe DCM, strongly suggesting that this FKTN mutation is a rare cause of autosomal recessive DCM.