Maja Čikeš

Beyond ejection fraction: an integrative approach for assessment of cardiac structure and function in heart failure.

Left ventricular ejection fraction (LVEF) has been the central parameter used for diagnosis and management in patients with heart failure. A good predictor of adverse outcomes in heart failure when below ∼45%, LVEF is less useful as a marker of risk as it approaches normal. As a measure of cardiac function, ejection fraction has several important limitations. Calculated as the stroke volume divided by end-diastolic volume, the estimation of ejection fraction is generally based on geometric assumptions that allow for assessment of volumes based on linear or two-dimensional measurements. Left ventricular ejection fraction is both preload- and afterload-dependent, can change substantially based on loading conditions, is only moderately reproducible, and represents only a single measure of risk in patients with heart failure. Moreover, the relationship between ejection fraction and risk in patients with heart failure is modified by factors such as hypertension, diabetes, and renal function. A more complete evaluation and understanding of left ventricular function in patients with heart failure requires a more comprehensive assessment: we conceptualize an integrative approach that incorporates measures of left and right ventricular function, left ventricular geometry, left atrial size, and valvular function, as well as non-imaging factors (such as clinical parameters and biomarkers), providing a comprehensive and accurate prediction of risk in heart failure.

Myocardial motion and deformation: What does it tell us and how does it relate to function?

The assessment of cardiac pump function and the potential of local myocardium to contribute to the overall performance are of great importance in many cardiovascular abnormalities. Assessing intrinsic cardiac function requires obtaining information on the true contractility of the heart muscle, assessed locally but interpreted in the context of its contribution to the global ejection performance and potential to adapt to changing circumstances. Contemporary imaging techniques offer the possibility of noninvasive quantification of myocardial deformation. These new clinical tools are attractive to use for the assessment of ventricular function. However, it is of great importance to understand cardiac mechanics – a complex interplay between the tissue structure/shape, force development, and interaction with the environment/neighbors – to interpret alterations in deformation and to extract clinically relevant conclusions. The combination of insight into the measurement techniques and their limitations, together with knowledge of myocardial mechanics and physiology, opens new perspectives to improve the assessment and management of fetal, pediatric, and adult patients.

Differentiation Between Fresh and Old Left Ventricular Thrombi by Deformation Imaging

Background—Noninvasive echocardiographic differentiation between old and fresh left ventricular thrombi after myocardial infarction would be of clinical importance to estimate the risk for embolization and the necessity of anticoagulation. Methods and Results—Fifty-two patients, aged 41 to 87 years, with a thrombus after myocardial infarction were included in this 2-part study: In substudy-I, 20 patients, 10 each with a definite diagnosis of fresh or old thrombus, were included. In the subsequent prospective substudy-II, 32 consecutive patients with an incident thrombus after myocardial infarction but unknown thrombus age were started on phenprocoumon and followed for 6 months. Data on medical history, standard echocardiography, strain-rate (SR) imaging and magnetic resonance tomography were analyzed. In substudy-I, analysis of thrombus deformation revealed the most rapid change in SR during the isovolumetric relaxation period when cavity pressure decreases rapidly. Fresh (range: 5–27 days) and old thrombi (4–26 months) could be discriminated without overlap by peak SR during the isovolumetric relaxation period, using a cutoff value of 1 s−1. Applying this threshold value in substudy-II, 17 thrombi were echocardiographically classified as fresh (=SR ≥1 s−1) and 15 as old. After 6 months in the fresh thrombus group, 16 of 17 thrombi had disappeared (94%), and in 1 patient the thrombus size was diminished by >50% (now presenting an old thrombus SR pattern). In contrast, 14 of the 15 old thrombi remained unchanged in size and deformation (1 thrombus disappeared). Conclusions—Fresh and old intracavitary thrombi can be reliably differentiated by deformation imaging. In fresh thrombi, anticoagulation with phenprocoumon results in thrombus resolution in most patients.

Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis.

Development of cardiac allograft vasculopathy represents the major determinant of long-term survival in patients after heart transplantation. Due to graft denervation, these patients seldom present with classic symptoms of angina pectoris, and the first clinical presentations are progressive heart failure or sudden cardiac death. Although coronary angiography remains the routine technique for coronary artery disease detection, it is not sensitive enough for screening purposes. This is especially the case in the first year after transplantation when diffuse and concentric vascular changes can be easily detected only by intravascular ultrasound. The treatment of the established vasculopathy is disappointing, so the primary effort should be directed toward early prevention and diagnosis. Due to diffuse vascular changes, revascularization procedures are restricted only to a relatively small proportion of patients with favorable coronary anatomy. Percutaneous coronary intervention is preferred over surgical revascularization since it leads to better acute results and patient survival. Although there is no proven long-term advantage of drug-eluting stents for the treatment of in-stent restenosis, they are preferred over bare-metal stents. Severe vasculopathy has a poor prognosis and the only definitive treatment is retransplantation. This article reviews the present knowledge on the pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft vasculopathy.

Pretransplant and perioperative predictors of early heart transplantation outcomes

Aim To identify predictors of 3-month mortality after heart transplantation in a Croatian academic center. Methods A retrospective review of institutional database identified 117 heart transplantations from January 2008 to July 2014. Two children <14 years were excluded from the study. The remaining 115 patients were dichotomized into survivors and non-survivors adjudicated at 3-months postoperatively, and their demographic, clinical, and longitudinal hemodynamic data were analyzed. Results 3-month survival after heart transplantation was 86%. Non-survivors were older (59u2009±u20098 vs 50u2009±u200914 years, Pu2009=u20090.009), more likely to have previous cardiac surgery (44% vs 19%; odds ratio [OR] 3.28, 95% confidence interval [CI] 1.08-9.90; Pu2009=u20090.029), lower body mass index (BMI) (25u2009±u20094 vs 28u2009±u20092 kg/m2, Pu2009=u20090.001), and be diabetics (44% vs 23%; OR 2.57, 95% CI 0.86-7.66; Pu2009=u20090.083). Creatinine clearance was marginally superior among survivors (59u2009±u200919 vs 48u2009±u200920 mL/min, Pu2009=u20090.059). Donor age and sex did not affect outcomes. Non-survivors were more likely to have had ischemic cardiomyopathy (69% vs 32%, Pu2009=u20090.010). Postoperative utilization of epinephrine as a second line inotropic agent was a strong predictor of mortality (63% vs 7%; OR 21.91; 95% CI 6.15-78.06; Pu2009<u20090.001). Serum lactate concentrations were consistently higher among non-survivors, with the difference being most pronounced 2 hours after cardiopulmonary bypass (9.8u2009±u20093.5 vs 5.2u2009±u20093.2 mmol/L, Pu2009<u20090.001). The donor hearts exhibited inferior early hemodynamics in non-survivors (cardiac index 3.0u2009±u20091.0 vs 4.0u2009±u20091.1 L/min/m2, Pu2009=u20090.001), stroke volume (49u2009±u200924 vs 59u2009±u200919 mL, Pu2009=u20090.063), and left and right ventricular stroke work indices (18u2009±u20098 vs 30u2009±u200911 g/beat/m2, Pu2009<u20090.001 and 5u2009±u20093 vs 7u2009±u20094 g/beat/m2, Pu2009=u20090.060, respectively). Non-survivors were more likely to require postoperative re-sternotomy (50% vs 12%; OR 7.25, 95% CI 2.29-22.92; Pu2009<u20090.001), renal replacement therapy (RRT) (69% vs 9%; OR 22.00, 95% CI 6.24-77.54; Pu2009<u20090.001), and mechanical circulatory assistance (MCS) (44% vs 5%; OR 14.62, 95% CI 3.84-55.62; Pu2009<u20090.001). Binary logistic regression revealed recipient age (Pu2009=u20090.024), serum lactates 2 hours after CPB (Pu2009=u20090.007), and epinephrine use on postoperative day 1 (Pu2009=u20090.007) to be independently associated with 3-month mortality. Conclusion Pretransplant predictors of adverse outcome after heart transplantation were recipient age, lower BMI, ischemic cardiomyopathy, reoperation and diabetes. Postoperative predictors of mortality were inferior donor heart hemodynamics, epinephrine use, and serum lactate concentrations. Non-survivors were more likely to require re-sternotomy, MCS, and RRT.

Image registration and atlas-based segmentation of cardiac outflow velocity profiles

Cardiovascular disease is the leading cause of death worldwide and for this reason computer-based diagnosis of cardiac diseases is a very important task. In this article, a method for segmentation of aortic outflow velocity profiles from cardiac Doppler ultrasound images is presented. The proposed method is based on the statistical image atlas derived from ultrasound images of healthy volunteers. The ultrasound image segmentation is done by registration of the input image to the atlas, followed by a propagation of the segmentation result from the atlas onto the input image. In the registration process, the normalized mutual information is used as an image similarity measure, while optimization is performed using a multiresolution gradient ascent method. The registration method is evaluated using an in-silico phantom, real data from 30 volunteers, and an inverse consistency test. The segmentation method is evaluated using 59 images from healthy volunteers and 89 images from patients, and using cardiac parameters extracted from the segmented image. Experimental validation is conducted using a set of healthy volunteers and patients and has shown excellent results. Cardiac parameter segmentation evaluation showed that the variability of the automated segmentation relative to the manual is comparable to the intra-observer variability. The proposed method is useful for computer aided diagnosis and extraction of cardiac parameters.

A method for registration and model-based segmentation of Doppler ultrasound images

Morphological changes of Doppler ultrasound images are an important source of information for diagnosis of cardiovascular diseases. Quantification of these flow profiles requires segmentation of the ultrasound images. In this article, we propose a new model-based method for segmentation of (aortic outflow) velocity profiles. The method is based on a procedure for registration using a geometric transformation specifically designed for matching Doppler ultrasound profiles. After manual segmentation of a model image, the model image is temporarily registered to a new image using two manually defined points in time. Next, a non-rigid registration was carried out in the velocity direction. As a similarfity measure normalized mutual information is used, while optimization is performed by a genetic algorithm. The registration method is experimentally validated using an in-silico image phantom, and showed an accuracy of 5.4%. The model based on segmentation is evaluated in a seris of aortic outflow Doppler ultrasound images from 30 normal volunteers. Comparing the automated method to the manual delineation by an expert cardiologist the method proved accurate to 6.6%. The experimental results confirm the accuracy of the approach and shows that the method can be used for the segmentation of the clinically obtained aortic outflow velocity profiles.

Impact of reduced creatinine clearance on early heart transplantation outcomes: A propensity score adjusted analysis

We aimed to determine the independent effect of preoperative creatinine clearance (CrCl) on HTx outcomes. Patients and Methods: 220 patients underwent HTx in Croatia from 2008 to 2014. Four patients were excluded due to missing data. Patients were dichotomized according to a CrCl cut-off value of 50 ml/ min (Group A: CrCl≤50 ml/min; Group B: CrCl>50 ml/min). Sixty-three patients (29%) had a CrCl≤50 ml/ min. Propensity score (PS) adjustment was performed by accounting for recipient age and gender, AF, smoking, ischemic time, CPB time, BMI, mechanical circulatory assistance (MCS) and reoperation. Results: Patients in Group A were older (56±11 vs. 49±12 years, P<0.001) and had longer donor ischemic times (197±65 vs. 162±62 min, P<0.001). No significant differences were noted in recipient gender (48/63 (76%) vs. 125/153 (82%) male, P=0.355), donor age (39±13 vs. 39±12 years, P=0.875), donor gender (46/63 (73%) vs. 100/153 (65%) male, P=0.338), PVR (213±107 vs. 188±96 dyn*s*cm −5 , P=0.145), diabetes (18/63 (29%) vs. 34/153 (22%), P=0.382), reoperation (18/63 (29%) vs. 34/153 (22%), P=0.382), CPB duration (175±62 vs. 158±56 min, P=0.06) or preoperative MCS (6/63 (10%) vs. 17/153 (11%), P=0.813). Six-month mortality was higher in patients with a CrCl≤50 ml/min (18/63 (29%) vs. 19/153 (12%); unadjusted OR 2.82 [95% CI 1.36-5.84]; P=0.009). Similarly, group A patients were more likely to require renal replacement therapy (RRT) (16/63 (25%) vs. 17/153 (11%); OR 2.72 (1.28-5.82); P=0.012). After PS adjustment these differences remained significant for both 6-month mortality and RRT (OR 2.44 [95% CI 1.09-5.49]; P=0.030 and OR 3.36 [95% CI 1.43-7.92]; P=0.005, respectively). Con Clusions: Patients with a CrCl≤50 ml/min undergoing isolated HTx had inferior 6-month survival and required RRT more commonly. The impact of CrCl remained significant after adjustment for multiple perioperative covariates. Hrvoje Gasparovic 1

Impact of Remote Ischemic Preconditioning Preceding Coronary Artery Bypass Grafting on Inducing Neuroprotection (RIPCAGE trial)

Background: Neurological complications after coronary artery bypass grafting (CABG) reduce quality of life, increase mortality, and inflate resource utilization. The risk of postoperative neurological complications parallels the increasing risk burden of the contemporary patient population. We evaluated the efficacy of remote ischemic preconditioning (RIPC) on inducing neuroprotection. Methods: Seventy patients undergoing first‐time CABG were randomly assigned to RIPC or a sham procedure. Structural brain magnetic resonance imaging (MRI) was complemented with functional connectivity MRI to gain a whole‐brain global connectivity analysis. Paired neurocognitive and MRI data were acquired pre‐ and postoperatively. The primary end point was a composite of new ischemic brain lesions and neurocognitive impairment. Secondary end points included brain connectivity profiles, pooled ischemic volumes, and individual components of the primary outcome. The Shapiro–Wilk test was used to determine whether a data set followed a normal distribution. The Fisher exact test was used to calculate the measures of association for categorical variables, whereas continuous data were tested with either the Mann–Whitney U test or the Student t test. Results: There was no between‐group difference in the incidence of the primary end point (9 [27%] in the RIPC group vs 8 [24%] in the control group, odds ratio, 1.17 [95% confidence interval, 0.34‐4.06]; P = 1.0). Although RIPC did not reduce the incidence of brain ischemia (8/33 [24%] vs 7/33 [21%]; P = 1.0), the pooled ischemic volume was lower in the RIPC group (157 [interquartile range, 125‐231] vs 777 [interquartile range, 564‐965] mm3; P = .004). Postoperative neurocognition was marginally superior in the RIPC group as evidenced by a lower absolute number of abnormal neurocognitive tests in the RIPC group (7/99 [7%] vs 16/99 [16%]; odds ratio, 0.40 [95% confidence interval, 0.14‐1.09]; P = .074). Robust reductions of functional connectivity profiles for the associative thalamus were documented in both groups, irrespective of RIPC (RIPC group, t = 3.31; P < .01; and the control group, t = 3.52; P < .01). Conclusions: Silent brain ischemia occurs frequently after CABG. RIPC did not reduce the incidence of the primary outcome. However, RIPC significantly reduced the pooled volume of ischemic brain lesions. Surgery adversely affected global brain connectivity, with RIPC conferring no demonstrable protection. The association of RIPC with superior neurocognitive test scores failed to cross the threshold for significance. Graphical abstract Figure. No Caption available.

Drug-Eluting Balloons–A New Tool in the Treatment of Cardiac Allograft Vasculopathy: A Case Series

Percutaneous coronary intervention in patients with cardiac allograft vasculopathy is burdened with a lot of difficulties. Although they have allowed significant progress in comparison with plain balloon angioplasty and bare metal stents, drug-eluting stents have not fully overcome problems of diffuse lesions and small-vessel disease that are so common in transplant coronary artery disease. There is growing evidence that drug-eluting balloons might be a better choice for patients with small vessel atherosclerotic coronary disease and yet there is no experience with this technology in patients with cardiac allograft vasculopathy. Herein we report a case series of successful percutaneous coronary interventions in patients with cardiac allograft vasculopathy.