Left atrial 4D flow cardiovascular magnetic resonance: a reproducibility study in sinus rhythm and atrial fibrillation.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows sophisticated quantification of left atrial (LA) blood flow, and could yield novel biomarkers of propensity for intra-cardiac thrombus formation and embolic stroke. As reproducibility is critically important to diagnostic performance, we systematically investigated technical and temporal variation of LA 4D flow in atrial fibrillation (AF) and sinus rhythm (SR). METHODS: Eighty-six subjects (SR, n = 64; AF, n = 22) with wide-ranging stroke risk (CHA2DS2VASc 0-6) underwent LA 4D flow assessment of peak and mean velocity, vorticity, vortex volume, and stasis. Eighty-five (99%) underwent a second acquisition within the same session, and 74 (86%) also returned at 30 (27-35) days for an interval scan. We assessed variability attributable to manual contouring (intra- and inter-observer), and subject repositioning and reacquisition of data, both within the same session (same-day scan-rescan), and over time (interval scan). Within-subject coefficients of variation (CV) and bootstrapped 95% CIs were calculated and compared. RESULTS: Same-day scan-rescan CVs were 6% for peak velocity, 5% for mean velocity, 7% for vorticity, 9% for vortex volume, and 10% for stasis, and were similar between SR and AF subjects (all p > 0.05). Interval-scan variability was similar to same-day scan-rescan variability for peak velocity, vorticity, and vortex volume (all p > 0.05), and higher for stasis and mean velocity (interval scan CVs of 14% and 8%, respectively, both p < 0.05). Longitudinal changes in heart rate and blood pressure at the interval scan in the same subjects were associated with significantly higher variability for LA stasis (p = 0.024), but not for the remaining flow parameters (all p > 0.05). SR subjects showed significantly greater interval-scan variability than AF patients for mean velocity, vortex volume, and stasis (all p < 0.05), but not peak velocity or vorticity (both p > 0.05). CONCLUSIONS: LA peak velocity and vorticity are the most reproducible and temporally stable novel LA 4D flow biomarkers, and are robust to changes in heart rate, blood pressure, and differences in heart rhythm.

Echocardiographic features of post-transcatheter aortic valve implantation thrombosis and endocarditis.

BACKGROUND: Transcatheter heart valve thrombosis (THV-t) and endocarditis (THV-e) are relevant complications after transcatheter aortic valve implantation (TAVI). Transcatheter heart valve (THV) dysfunction definition is mostly based on Doppler (stenosis/regurgitation) without considering leaflets characteristics. PURPOSE: To evaluate the additional diagnostic value of leaflets echocardiographic features over Doppler when prosthetic valve complication is suspected. METHODS: Among 621 post-TAVI patients, 128 cases with probable valve complication were identified. THV-t was finally diagnosed in 13 patients (10%) and THV-e in 8 (6%), while the remaining 107 (84%) had no definitive diagnosis of thrombosis/endocarditis (THV-no). We analyzed at 2 time points (baseline and follow-up) both traditional Doppler parameters and leaflets morpho-functional features. RESULTS: Both Doppler and leaflets parameters showed high sensitivity (sensitivity 92%) and low specificity (ranging from specificity 32% to 74%) in detecting THV-t. Interestingly, the combination of mean aortic pressure gradient ≥20 mm Hg and leaflet thickening significantly improved the specificity of echocardiography for diagnosis of THV thrombosis (specificity 94%). On the other hand, echocardiographic diagnosis of THV endocarditis remained limited by very low sensitivity despite showing high specificity. CONCLUSIONS: The combination of Doppler and leaflets parameters can improve the echocardiographic diagnosis of THV thrombosis in post-TAVI patients with suspicious symptoms, via a significant increase in the overall test specificity. This would potentially allow more rational gatekeeping to more expensive/invasive diagnostic examinations (eg, CT scan) or therapeutic trials (eg, unnecessary anticoagulation).

PlaCor PRT measurement of shear-activated platelet aggregate formation in stable patients treated with single and dual antiplatelet therapy.

Shear forces play a key role in thrombus formation and shear-based tests may better reflect physiological conditions in vivo compared with agonist-based tests. We evaluated the PlaCor PRT®, a novel platelet reactivity test based on shear-induced platelet aggregation, in patients with stable coronary artery disease (CAD) treated with single (SAPT) and dual antiplatelet therapy (DAPT). We examined 100 patients with multiple risk factors for CAD and/or documented stable CAD: 38 treated with SAPT, aspirin 100 mg qd, 62 treated with DAPT, aspirin 100 mg + clopidogrel 75 mg qd, compared with age- and sex-matched healthy volunteers without antiplatelet therapy (HV, n = 35). Measures of shear-induced platelet aggregation were performed with the PlaCor PRT®. In 25 patients in SAPT, the PlaCor test was also performed before and after a 12-hour-loading dose of clopidogrel 600 mg. The mean ± SD PRT time (seconds) in HV was 78 ± 13 and was significantly lower compared with SAPT (118 ± 16, p = 0.030) and to DAPT patients (242 ± 11, p < 0.0001). A statistically significant difference was also reported between SAPT and DAPT patients (p < 0.0001). After a loading dose of clopidogrel, the PRT time of SAPT patients increased significantly from 112 ± 20 to 254 ± 17, p < 0.0001. 2.7 and 26% of patients were considered as "poor responders" to single and dual antiplatelet therapy, respectively. This study shows that in patients with multiple risk factors for CAD and/or documented stable CAD, SAPT and DAPT play an important role in reducing platelet aggregation mediated by shear forces as evaluated with the novel PlaCor PRT®. Further studies will be required to confirm and assess the extent of these findings in patients with acute coronary syndromes.

Reduced Left Atrial Rotational Flow Is Independently Associated With Embolic Brain Infarcts.

BACKGROUND: Up to 25% of embolic strokes occur in individuals without atrial fibrillation (AF) or other identifiable mechanisms. OBJECTIVES: This study aims to assess whether left atrial (LA) blood flow characteristics are associated with embolic brain infarcts, independently of AF. METHODS: The authors recruited 134 patients: 44 with a history of ischemic stroke and 90 with no history of stroke but CHA2DS2VASc score ≥1. Cardiac magnetic resonance (CMR) evaluated cardiac function and LA 4-dimensional flow parameters, including velocity and vorticity (a measure of rotational flow), and brain magnetic resonance imaging (MRI) was performed to detect large noncortical or cortical infarcts (LNCCIs) (likely embolic), or nonembolic lacunar infarcts. RESULTS: Patients (41% female; age 70 ± 9 years) had moderate stroke risk (median CHA2DS2VASc = 3, Q1-Q3: 2-4). Sixty-eight (51%) had diagnosed AF, of whom 58 (43%) were in AF during CMR. Thirty-nine (29%) had ≥1 LNCCI, 20 (15%) had ≥1 lacunar infarct without LNCCI, and 75 (56%) had no infarct. Lower LA vorticity was significantly associated with prevalent LNCCIs after adjustment for AF during CMR, history of AF, CHA2DS2VASc score, LA emptying fraction, LA indexed maximum volume, left ventricular ejection fraction, and indexed left ventricular mass (OR: 2.06 [95% CI: 1.08-3.92 per SD]; P = 0.027). By contrast, LA flow peak velocity was not significantly associated with LNCCIs (P = 0.21). No LA parameter was associated with lacunar infarcts (all P > 0.05). CONCLUSIONS: Reduced LA flow vorticity is significantly and independently associated with embolic brain infarcts. Imaging LA flow characteristics may aid identification of individuals who would benefit from anticoagulation for embolic stroke prevention, regardless of heart rhythm.

Time to TAVI: streamlining the pathway to treatment.

INTRODUCTION: Severe aortic stenosis is a major cause of morbidity and mortality. The existing treatment pathway for transcatheter aortic valve implantation (TAVI) traditionally relies on tertiary Heart Valve Centre workup. However, this has been associated with delays to treatment, in breach of British Cardiovascular Intervention Society targets. A novel pathway with emphasis on comprehensive patient workup at a local centre, alongside close collaboration with a Heart Valve Centre, may help reduce the time to TAVI. METHODS: The centre performing local workup implemented a novel TAVI referral pathway. Data were collected retrospectively for all outpatients referred for consideration of TAVI to a Heart Valve Centre from November 2020 to November 2021. The main outcome of time to TAVI was calculated as the time from Heart Valve Centre referral to TAVI, or alternative intervention, expressed in days. For the centre performing local workup, referral was defined as the date of multidisciplinary team discussion. For this centre, a total pathway time from echocardiographic diagnosis to TAVI was also evaluated. A secondary outcome of the proportion of referrals proceeding to TAVI at the Heart Valve Centre was analysed. RESULTS: Mean±SD time from referral to TAVI was significantly lower at the centre performing local workup, when compared with centres with traditional referral pathways (32.4±64 to 126±257 days, p<0.00001). The total pathway time from echocardiographic diagnosis to TAVI for the centre performing local workup was 89.9±67.6 days, which was also significantly shorter than referral to TAVI time from all other centres (p<0.003). Centres without local workup had a significantly lower percentage of patients accepted for TAVI (49.5% vs 97.8%, p<0.00001). DISCUSSION: A novel TAVI pathway with emphasis on local workup within a non-surgical centre significantly reduced both the time to TAVI and rejection rates from a Heart Valve Centre. If adopted across the other centres, this approach may help improve access to TAVI.

Effect of Weight Loss on Early Left Atrial Myopathy in People With Obesity But No Established Cardiovascular Disease.

Background Obesity is associated with left atrial (LA) remodeling (ie, dilatation and dysfunction) which is an independent determinant of future cardiovascular events. We aimed to assess whether LA remodeling is present in obesity even in individuals without established cardiovascular disease and whether it can be improved by intentional weight loss. Methods and Results Forty-five individuals with severe obesity without established cardiovascular disease (age, 45±11 years; body mass index; 39.1±6.7 kg/m2; excess body weight, 51±18 kg) underwent cardiac magnetic resonance for quantification of LA and left ventricular size and function before and at a median of 373 days following either a low glycemic index diet (n=28) or bariatric surgery (n=17). Results were compared with those obtained in 27 normal-weight controls with similar age and sex. At baseline, individuals with obesity displayed reduced LA reservoir function (a marker of atrial distensibility), and a higher mass and LA maximum volume (all P<0.05 controls) but normal LA emptying fraction. On average, weight loss led to a significant reduction of LA maximum volume and left ventricular mass (both P<0.01); however, significant improvement of the LA reservoir function was only observed in those at the upper tertile of weight loss (≥47% excess body weight loss). Following weight loss, we found an average residual increase in left ventricular mass compared with controls but no residual significant differences in LA maximum volume and strain function (all P>0.05). Conclusions Obesity is linked to subtle LA myopathy in the absence of overt cardiovascular disease. Only larger volumes of weight loss can completely reverse the LA myopathic phenotype.

The impact of atrial fibrillation and stroke risk factors on left atrial blood flow characteristics.

AIMS: Altered left atrial (LA) blood flow characteristics account for an increase in cardioembolic stroke risk in atrial fibrillation (AF). Here, we aimed to assess whether exposure to stroke risk factors is sufficient to alter LA blood flow even in the presence of sinus rhythm (SR). METHODS AND RESULTS: We investigated 95 individuals: 37 patients with persistent AF, who were studied before and after cardioversion [Group 1; median CHA2DS2-VASc = 2.0 (1.5-3.5)]; 35 individuals with no history of AF but similar stroke risk to Group 1 [Group 2; median CHA2DS2-VASc = 3.0 (2.0-4.0)]; and 23 low-risk individuals in SR [Group 3; median CHA2DS2-VASc = 0.0 (0.0-0.0)]. Cardiac function and LA flow characteristics were evaluated using cardiac magnetic resonance. Before cardioversion, Group 1 displayed impaired left ventricular (LV) and LA function, reduced LA flow velocities and vorticity, and a higher normalized vortex volume (all P < 0.001 vs. Groups 2 and 3). After restoration of SR at ≥4-week post-cardioversion, LV systolic function and LA flow parameters improved significantly (all P < 0.001 vs. pre-cardioversion) and were no longer different from those in Group 2. However, in the presence of SR, LA flow peak and mean velocity, and vorticity were lower in Groups 1 and 2 vs. Group 3 (all P < 0.01), and were associated with impaired LA emptying fraction (LAEF) and LV diastolic dysfunction. CONCLUSION: Patients at moderate-to-high stroke risk display altered LA flow characteristics in SR in association with an LA myopathic phenotype and LV diastolic dysfunction, regardless of a history of AF.

Progression of myocardial fibrosis in hypertrophic cardiomyopathy: mechanisms and clinical implications.

Aims: Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results: Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (

Three-dimensional speckle tracking longitudinal strain is related to myocardial fibrosis determined by late-gadolinium enhancement.

Three-dimensional (3D) speckle tracking echocardiography (STE) is a reliable clinical tool for accurate measurements of left ventricular (LV) volumes and ejection fraction (EF). In this prospective study, we sought to identify an association between 3DSTE longitudinal strain abnormalities and areas of late gadolinium enhancement (LGE). In 50 patients (52 ± 18.5 years old) referred to our hospital for clinically indicated CMR, 3D full-volume trans-thoracic acquisitions on apical views were performed within 1 h of CMR, in order to obtain LV volumes and ejection fraction as well as global and segmental peak systolic longitudinal strain. Relative amount of fibrosis was defined based on LGE CMR with grey-scale threshold of 5 standard deviations above the mean signal intensity of the normal remote myocardium. We found a moderate positive correlation between global longitudinal strain (GLS) by 3DSTE and LGE proportion (r = 0.465, p = 0.001). The area under the receiver operating characteristic curve was 0.79. In addition, abnormal GLS could detect LGE-determined myocardial fibrosis with a sensitivity of 84.6%, a specificity of 84.8%, a positive predictive value of 69% and negative predictive value of 93%, considering an optimal GLS cut-off value of - 15.25%. Regarding 3DSTE capacity of localizing segmental LGE involvement, about 70% of LGE-positive segments presented a concomitant longitudinal strain reduction. This prospective study shows that 3DSTE longitudinal deformation is moderately associated with the extent of myocardial fibrosis, with a promising potential role in ruling out prognostically relevant fibrosis as detected by LGE.

Stepwise use of circulatory support devices in a patient refractory to cardiopulmonary resuscitation.

This case describes the management of a patient admitted to an emergency department with general malaise, who deteriorated into cardiac arrest and refractory to advanced life support measures. After extracorporeal cardiopulmonary resuscitation (eCPR) with veno-arterial extracorporeal membrane oxygenation in association with an Impella 2.5 device, the patient underwent cardiac surgery (tissue aortic valve replacement, coronary artery bypass grafting and implantation of short-term paracorporeal left ventricular assist device). Subsequently a long-term LVAD was implanted and the patient was successfully discharged shortly afterwards. This report illustrates the challenges of 'clinical decision making' in a complex patient utilising a wide range of left ventricular support mechanical devices with varying degrees of invasiveness, whilst also reflecting on the current financial and economic considerations in utilizing this type of care pathway.

Long-term clinical outcomes of patients with rheumatoid arthritis and concomitant coronary artery disease.

BACKGROUND: Rheumatoid arthritis (RA) is associated with high morbidity and mortality predominately due to increased cardiovascular risk. Few reports are available regarding the management of coronary artery disease (CAD) in RA patients and the long-term clinical outcomes after coronary revascularization. METHODS AND RESULTS: All consecutive patients with RA were identified by retrospective review at a rheumatology tertiary center in Milan, Italy between 2001 and 2013. RA patients affected by significant CAD (RA-CAD+) were prospectively followed for major adverse cardiovascular and cerebrovascular events (MACCE) after percutaneous coronary revascularization (RA-PCI), coronary artery bypass grafting (RA-CABG) or medical therapy (RA-MT). Among 936 patients with RA, the presence of clinically significant CAD was found in 5.6% (53 patients, RA-CAD+). Of these, 32 patients (60%) underwent PCI (RA-PCI), 10 patients (19%) underwent CABG (RA-CABG) and 11 patients (21%) treated with MT (RA-MT). After a mean follow-up of 9±7 years, the rate of MACCE was 56% in RA-PCI patients, 50% in RA-CABG and 27% in RA-MT patients (P=0.184). The high MACCE rate was mainly driven by repeat coronary revascularization (47%) in the RA-PCI group and high rate of strokes (30%) in RA-CABG patients. CONCLUSION: In patients with rheumatoid arthritis and concomitant coronary artery disease (RA-CAD+), we observed at long-term follow-up a high MACCE rate, predominantly in those who underwent coronary revascularization.

Mechanical dyssynchrony and deformation imaging in patients with functional mitral regurgitation.

Chronic functional mitral regurgitation (FMR) is a frequent finding of ischemic heart disease and dilated cardiomyopathy (DCM), associated with unfavourable prognosis. Several pathophysiologic mechanisms are involved in FMR, such as annular dilatation and dysfunction, left ventricle (LV) remodeling, dysfunction and dyssynchrony, papillary muscles displacement and dyssynchrony. The best therapeutic choice for FMR is still debated. When optimal medical treatment has already been set, a further option for cardiac resynchronization therapy (CRT) and/or surgical correction should be considered. CRT is able to contrast most of the pathophysiologic determinants of FMR by minimizing LV dyssynchrony through different mechanisms: Increasing closing forces, reducing tethering forces, reshaping annular geometry and function, correcting diastolic MR. Deformation imaging in terms of two-dimensional speckle tracking has been validated for LV dyssynchrony assessment. Radial speckle tracking and three-dimensional strain analysis appear to be the best methods to quantify intraventricular delay and to predict CRT-responders. Speckle-tracking echocardiography in patients with mitral valve regurgitation has been usually proposed for the assessment of LV and left atrial function. However it has also revealed a fundamental role of intraventricular dyssynchrony in determining FMR especially in DCM, rather than in ischemic cardiomyopathy in which MR severity seems to be more related to mitral valve deformation indexes. Furthermore speckle tracking allows the assessment of papillary muscle dyssynchrony. Therefore this technique can help to identify optimal candidates to CRT that will probably demonstrate a reduction in FMR degree and thus will experience a better outcome.

Role of cardiac dyssynchrony and resynchronization therapy in functional mitral regurgitation.

Functional mitral regurgitation (FMR) is a common complication of left ventricle (LV) dysfunction and remodelling. Recently, it has been recognized as an independent prognostic factor in both ischaemic and non-ischaemic LV dysfunctions. In this review article, we discuss the mechanisms through which cardiac dyssynchrony is involved in FMR pathophysiologic cascade and how cardiac resynchronization therapy (CRT) can have therapeutic effects on FMR by reverting specific dyssynchrony pathways. We analyse recent clinical trials focusing on CRT impact on FMR in 'real-world' patients, the limits and future perspectives that could eventually generate new predictors of CRT response in terms of FMR reduction. Finally, we propose a practical diagnostic and therapeutic strategy for the management of symptomatic patients with severe LV dysfunction and concomitant 'prognostic' FMR.

One-year outcome of biolimus eluting stent with biodegradable polymer in all comers: the Italian Nobori Stent Prospective Registry.

OBJECTIVES: INSPIRE-1 (Italian Nobori Stent ProspectIve REgistry-1) was designed and conducted to assess clinical performance of Nobori biolimus A9-eluting stent (BES) implantation in an unrestricted "real-world" cohort of patients. METHODS: Unrestricted consecutive high-risk patients treated with BES with biodegradable polymer (Nobori, Terumo, Tokyo, Japan) between February 2008 and July 2012 were prospectively enrolled in an independent multicenter registry and divided in two groups: complex and non complex lesions. RESULTS: 1066 patients (1589 lesions) treated with Nobori BES were analyzed. The majority of patients (57%) were treated for at least one complex lesion and presented a high-risk clinical profile (previous CABG 17.6%, diabetes mellitus 33.1%, chronic kidney disease 14.3%). Angiographic success rate was achieved in 96.2% cases. At 1 year, the primary endpoint, (composite of cardiac death, myocardial infarction, and clinically driven target vessel revascularization), occurred in 39 (4.0%) patients, and was higher in the complex lesions (5.2% vs. 2.5%, P = 0.032). Target lesion failure (TLF, secondary endpoint) occurred in 45 (4.6%) patients, and was more frequent in the complex lesions group (6.2% vs. 2.7%, P = 0.011), mainly due to a higher incidence of any target lesion revascularization (4.8% vs. 2.7%; P = 0.095). Definite and probable stent thrombosis (ST) rate was 0.6% and 0.5% respectively, with no difference between groups. CONCLUSIONS: In unrestricted daily practice, BESs were implanted predominantly in high risk patients with complex lesions. Despite this, the Nobori BES was associated with a relatively low rate of primary endpoint and TLF, with a higher risk in patients with complex lesions.