Effect of active vitamin-D on left ventricular mass index: Results of a randomized controlled trial in type 2 diabetes and chronic kidney disease.

BACKGROUND: Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD). METHODS: We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n = 19, placebo n = 26). RESULTS: Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints. CONCLUSIONS: The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.

Updated knowledge and practical implementations of stress echocardiography in ischemic and non-ischemic cardiac diseases: An expert consensus of the Working Group of Echocardiography of the Hellenic Society of Cardiology.

Stress echocardiography (SE) is a well established and valid technique, widely used for the diagnostic evaluation of patients with ischemic and nonischemic cardiac diseases. This statement of the Echocardiography Working Group of the Hellenic Society of Cardiology summarizes the consensus of the writing group regarding the applications of SE, based on the expertise of their members and on a critical review of present medical literature. The main objectives of the consensus document include a comprehensive review of SE methodology and training-which focus on the preparation, the protocols used, the analysis of the SE images, and updated, evidence-based knowledge about SE applications on ischemic and nonischemic heart diseases, such as in cardiomyopathies, heart failure, and valvular heart disease.

Emerging role of cardiac computed tomography in heart failure.

Despite medical advancements, the prognosis of patients with heart failure remains poor. While echocardiography and cardiac magnetic resonance imaging remain at the forefront of diagnosing and monitoring patients with heart failure, cardiac computed tomography (CT) has largely been considered to have a limited role. With the advancements in scanner design, technology, and computer processing power, cardiac CT is now emerging as a valuable adjunct to clinicians managing patients with heart failure. In the current manuscript, we review the current applications of cardiac CT to patients with heart failure and also the emerging areas of research where its clinical utility is likely to extend into the realm of treatment, procedural planning, and advanced heart failure therapy implementation.

Clinical value of dark-blood late gadolinium enhancement cardiovascular magnetic resonance without additional magnetization preparation.

BACKGROUND: For two decades, bright-blood late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been considered the reference standard for the non-invasive assessment of myocardial viability. While bright-blood LGE can clearly distinguish areas of myocardial infarction from viable myocardium, it often suffers from poor scar-to-blood contrast, making subendocardial scar difficult to detect. Recently, we proposed a novel dark-blood LGE approach that increases scar-to-blood contrast and thereby improves subendocardial scar conspicuity. In the present study we sought to assess the clinical value of this novel approach in a large patient cohort with various non-congenital ischemic and non-ischemic cardiomyopathies on both 1.5 T and 3 T CMR scanners of different vendors. METHODS: Three hundred consecutive patients referred for clinical CMR were randomly assigned to a 1.5 T or 3 T scanner. An entire short-axis stack and multiple long-axis views were acquired using conventional phase sensitive inversion recovery (PSIR) LGE with TI set to null myocardium (bright-blood) and proposed PSIR LGE with TI set to null blood (dark-blood), in a randomized order. The bright-blood LGE and dark-blood LGE images were separated, anonymized, and interpreted in a random order at different time points by one of five independent observers. Each case was analyzed for the type of scar, per-segment transmurality, papillary muscle enhancement, overall image quality, observer confidence, and presence of right ventricular scar and intraventricular thrombus. RESULTS: Dark-blood LGE detected significantly more cases with ischemic scar compared to conventional bright-blood LGE (97 vs 89, p = 0.008), on both 1.5 T and 3 T, and led to a significantly increased total scar burden (3.3 ± 2.4 vs 3.0 ± 2.3 standard AHA segments, p = 0.015). Overall image quality significantly improved using dark-blood LGE compared to bright-blood LGE (81.3% vs 74.0% of all segments were of highest diagnostic quality, p = 0.006). Furthermore, dark-blood LGE led to significantly higher observer confidence (confident in 84.2% vs 78.4%, p = 0.033). CONCLUSIONS: The improved detection of ischemic scar makes the proposed dark-blood LGE method a valuable diagnostic tool in the non-invasive assessment of myocardial scar. The applicability in routine clinical practice is further strengthened, as the present approach, in contrast to other recently proposed dark- and black-blood LGE techniques, is readily available without the need for scanner adjustments, extensive optimizations, or additional training.

A Kaleidoscope heart.

In the current manuscript, we report an unusual case of a young 18-year-old woman who survived an out-of-hospital cardiac arrest secondary to Bland-White-Garland syndrome. Her transthoracic echocardiogram showed an abnormal color Doppler flow-pattern within the myocardium indicative of coronary fistulous flow that prompted further evaluation with coronary CT angiography, which confirmed the diagnosis. Our case serves not only as a reminder to consider coronary artery anomalies as a cause of sudden cardiac death in young individuals but also as a prompt to investigate unusual echocardiographic findings with alternative imaging when the diagnosis may not be initially clear.

Circulating progenitor cells and their interaction with platelets in patients with an acute coronary syndrome.

CD34+ cells expressing KDR (CD34+/KDR+) represent a small proportion of circulating progenitor cells that have the capacity to interact with platelets and to differentiate into mature endothelial cells, thus contributing to vascular homeostasis and regeneration as well as to re-endothelialization. We investigated the levels of CD34+ and CD34+/KDR+ progenitor cells as well as their interaction with platelets in acute coronary syndrome (ACS) patients before the initiation (baseline) of their treatment with a P2Y12 receptor antagonist, and at 5-days post-treatment (follow-up). Sixty-seven consecutive ACS patients and thirty healthy subjects (controls) participated in the study. On admission, all patients received 325 mg aspirin, followed by 100 mg/day and then were loaded either with 600 mg clopidogrel or 180 mg ticagrelor, followed by 75 mg/day (n = 36) or 90 mg × 2/day (n = 31), respectively. The levels of circulating CD34+ and CD34+/KDR+ progenitor cells, as well as their interaction with platelets, were determined by flow cytometry, before and after activation with ADP, in vitro. The circulating levels of CD34+ and CD34+/KDR+ cells in both patient groups at baseline were lower compared with controls while they were significantly increased at 5-days of follow-up in both groups, this increase being more pronounced in the ticagrelor group. The platelet/CD34+ (CD61+/CD34+) conjugates were higher at baseline and reduced at follow-up while the platelet/KDR+ (CD61+/KDR+) conjugates were lower at baseline and increased at follow-up, both changes being more pronounced in the ticagrelor group. ADP activation of control samples significantly increased the KDR expression by CD34+ cells and the CD61+/KDR+ conjugates, these parameters being unaffected in patients at baseline but increased at follow-up. Short-term dual antiplatelet therapy in ACS patients restores the low platelet/KDR+ conjugates and CD34+ cell levels and improves the low membrane expression levels of KDR in these cells, an effect being more pronounced in ticagrelor-treated patients. This may represent a pleiotropic effect of antiplatelet therapy towards vascular endothelial regeneration.

Comparison of Triflusal with Aspirin in the Secondary Prevention of Atherothrombotic Events; Α Randomised Clinical Trial.

BACKGROUND: Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events. OBJECTIVE: We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor. METHODS: Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p<0.001). Regarding the primary safety endpoints, patients on triflusal treatment were 50% less likely to develop bleeding events according to the BARC criteria, and especially any clinically overt sign of haemorrhage that requires diagnostic studies, hospitalisation or special treatment (BARC type 2). CONCLUSION: The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).

Importance of operator training and rest perfusion on the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance.

BACKGROUND: Clinical evaluation of stress perfusion cardiovascular magnetic resonance (CMR) is currently based on visual assessment and has shown high diagnostic accuracy in previous clinical trials, when performed by expert readers or core laboratories. However, these results may not be generalizable to clinical practice, particularly when less experienced readers are concerned. Other factors, such as the level of training, the extent of ischemia, and image quality could affect the diagnostic accuracy. Moreover, the role of rest images has not been clarified. The aim of this study was to assess the diagnostic accuracy of visual assessment for operators with different levels of training and the additional value of rest perfusion imaging, and to compare visual assessment and automated quantitative analysis in the assessment of coronary artery disease (CAD). METHODS: We evaluated 53 patients with known or suspected CAD referred for stress-perfusion CMR. Nine operators (equally divided in 3 levels of competency) blindly reviewed each case twice with a 2-week interval, in a randomised order, with and without rest images. Semi-automated Fermi deconvolution was used for quantitative analysis and estimation of myocardial perfusion reserve as the ratio of stress to rest perfusion estimates. RESULTS: Level-3 operators correctly identified significant CAD in 83.6% of the cases. This percentage dropped to 65.7% for Level-2 operators and to 55.7% for Level-1 operators (p < 0.001). Quantitative analysis correctly identified CAD in 86.3% of the cases and was non-inferior to expert readers (p = 0.56). When rest images were available, a significantly higher level of confidence was reported (p = 0.022), but no significant differences in diagnostic accuracy were measured (p = 0.34). CONCLUSIONS: Our study demonstrates that the level of training is the main determinant of the diagnostic accuracy in the identification of CAD. Level-3 operators performed at levels comparable with the results from clinical trials. Rest images did not significantly improve diagnostic accuracy, but contributed to higher confidence in the results. Automated quantitative analysis performed similarly to level-3 operators. This is of increasing relevance as recent technical advances in image reconstruction and analysis techniques are likely to permit the clinical translation of robust and fully automated quantitative analysis into routine clinical practice.

Left ventricular outflow obstruction predicts increase in systolic pressure gradients and blood residence time after transcatheter mitral valve replacement.

Left ventricular outflow tract (LVOT) obstruction is a relatively common consequence of transcatheter mitral valve replacement (TMVR). Although LVOT obstruction is associated with heart failure and adverse remodelling, its effects upon left ventricular hemodynamics remain poorly characterised. This study uses validated computational models to identify the LVOT obstruction degree that causes significant changes in ventricular hemodynamics after TMVR. Seven TMVR patients underwent personalised flow simulations based on pre-procedural imaging data. Different virtual valve configurations were simulated in each case, for a total of 32 simulations, and the resulting obstruction degree was correlated with pressure gradients and flow residence times. These simulations identified a threshold LVOT obstruction degree of 35%, beyond which significant deterioration of systolic function was observed. The mean increase from baseline (pre-TMVR) in the peak systolic pressure gradient rose from 5.7% to 30.1% above this threshold value. The average blood volume staying inside the ventricle for more than two cycles also increased from 4.4% to 57.5% for obstruction degrees above 35%, while the flow entering and leaving the ventricle within one cycle decreased by 13.9%. These results demonstrate the unique ability of modelling to predict the hemodynamic consequences of TMVR and to assist in the clinical decision-making process.

Automated quantification of mitral valve geometry on multi-slice computed tomography in patients with dilated cardiomyopathy - Implications for transcatheter mitral valve replacement.

OBJECTIVES: The primary aim of this study was to quantify the dimensions and geometry of the mitral valve complex in patients with dilated cardiomyopathy and significant mitral regurgitation. The secondary aim was to evaluate the validity of an automated segmentation algorithm for assessment of the mitral valve compared to manual assessment on computed tomography. BACKGROUND: Transcatheter mitral valve replacement (TMVR) is an evolving technique which relies heavily on the lengthy evaluation of cardiac computed tomography (CT) datasets. Limited data is available on the dimensions and geometry of the mitral valve in pathological states throughout the cardiac cycle, which may have implications for TMVR device design, screening of suitable candidates and annular sizing prior to TMVR. METHODS: A retrospective study of 15 of patients with dilated cardiomyopathy who had undergone full multiphase ECG gated cardiac CT. A comprehensive evaluation of mitral valve geometry was performed at 10 phases of the cardiac cycle using the recommended D-shaped mitral valve annulus (MA) segmentation model using manual and automated CT interpretation platforms. Mitral annular dimensions and geometries were compared between manual and automated methods. RESULTS: Mitral valve dimensions in patients with dilated cardiomyopathy were similar to previously reported values (MAarea Diastole: 12.22 ±â€¯1.90 cm2), with dynamic changes in size and geometry between systole and diastole of up to 5%. The distance from the centre of the MA to the left ventricular apex demonstrated moderate agreement between automated and manual methods (ρc = 0.90) with other measurements demonstrating poor agreement between the two methods (ρc = 0.75-0.86). CONCLUSIONS: Variability of mitral valve annulus measurements are small during the cardiac cycle. Novel automated algorithms to determine cardiac cycle variations in mitral valve geometry may offer improved segmentation accuracy as well as improved CT interpretation times.

Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis.

BACKGROUND: Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. METHODS AND RESULTS: Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126-2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19-6.78]; P<0.001) after adjustment for age, sex, peak velocity, and aortic valve area. Among 210 (23%) patients with discordant echocardiographic assessments, there was considerable heterogeneity in CT-AVC scores, which again were an independent predictor of clinical outcomes (hazard ratio, 3.67 [95% confidence interval, 1.39-9.73]; P=0.010). CONCLUSIONS: Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.

Transcatheter mitral valve replacement in mitral annulus calcification - "The art of computer simulation".

There is considerable interest in transcatheter prosthetic valve treatment for mitral valve disease in high-risk individuals. Although the presence of mitral annular calcium (MAC) may provide an anchoring zone for such devices, results to date have been modest with reported technical failure rates approaching 30% in specialist centers. This in part relates to the risk of left ventricular outflow tract obstruction and device dislodgment but also to the lack of specific imaging guidelines to plan for such procedures. We present the use of finite element analysis and computer simulation based on cardiac CT in three patients with severe MAC in whom transcatheter devices were considered. In the first two cases, the computer simulations were performed after the clinical procedure and were concordant with the clinical outcome. For the third case, computer simulation was performed prior to the clinical procedure. This indicated unsuitability for transcatheter device deployment and a subsequent medical management was adopted. Overall, our initial results suggest that computer simulation may have the potential to improve patient selection for transcatheter mitral valve replacement in the presence of significant MAC.

Remodelling of the aorta after a catheter-induced acute aortic dissection.

Iatrogenic acute aortic dissection during percutaneous coronary intervention is an extremely rare but critical complication. Although sealing the entry point with a coronary stent is an option to treat localized dissections, more extensive cases may require surgical intervention. We present a case of Type A aortic dissection that occurred during an angioplasty of a chronically occluded right coronary artery. Despite the extent of the dissection, a 'watch-and-wait' strategy was chosen, and repeated imaging a few days later revealed that the aorta had been remodelled to its normal anatomy.

The Doppler paradox.

Obstructive prosthetic valve thrombosis (PVT) is a rare but severe complication that usually occurs in the presence of suboptimal anticoagulation. Although fluoroscopy is commonly used to detect abnormal leaflet motion as a surrogate marker for PVT, its inability to directly visualize adjacent tissue and valve physiology leaves it susceptible to miss clinically important PVT. In this manuscript, we report the case of a 54-year-old woman with a mechanical mitral valve who was admitted to our institute with exertional dyspnea. Although valve fluoroscopy was normal, subsequent 3D echocardiography and ECG-gated multiphase computed tomography confirmed the presence of PVT that was subsequently treated successfully with surgical replacement. Our case demonstrates the utility of multimodality imaging in establishing PVT in patients with abnormal prosthetic valve physiology and progressive symptoms.

Dynamic platelet adhesion in patients with an acute coronary syndrome: The effect of antiplatelet therapy.

Platelet adhesion and aggregation are key functions leading to thrombus formation. The effect of aspirin, clopidogrel, and ticagrelor on platelet aggregation has been well established, however, there is limited data on the effect of these drugs on platelet adhesion. We therefore evaluated the effect of these drugs on platelet adhesion in acute coronary syndrome (ACS) patients. Citrated blood was collected from 50 ACS patients loaded with 325 mg of aspirin (baseline) and at 5 days after the administration of aspirin 100 mg/day and clopidogrel (600 mg loading dose, 75 mg/day) (n = 26) or ticagrelor (180 mg loading dose, 90 mg × 2/day) (n = 24). High on-treatment platelet reactivity (HTPR) to clopidogrel was estimated by vasodilator stimulated phosphoprotein (VASP) phosphorylation assay. Platelet adhesion to collagen was studied for 6 min under high shear stress and was evaluated using the time to platelet recruitment (TPR), the perimeter and average area of each adherent object, number of adherent objects, and the total percent of surface coverage (SC%). Six ACS patients exhibited HTPR to clopidogrel and excluded from the platelet adhesion assays. TPR and SC% values were similar among patient groups at baseline and controls. However, all other adhesion parameters were different in ACS patients, indicating the formation of more aggregates in regard to controls. At 5 days post-treatment with either clopidogrel or ticagrelor, the TPR values were increased and the SC% values were reduced to a similar extent compared with baseline. However, significant differences were observed in the ticagrelor group in the perimeter, number of adherent objects, and the average area of each adherent object indicating a more potent inhibition of adherence-induced platelet aggregation than clopidogrel. In conclusion, aspirin does not affect platelet adherence to collagen, whereas clopidogrel and ticagrelor inhibit to a similar extent dynamic platelet adhesion at 5 days post-treatment in ACS patients. However, ticagrelor exhibits a greater inhibitory effect on reducing adhesion-induced platelet aggregation.